rifampin and Leprosy

Leprosy is a neglected, infectious, granulomatous and chronic disease caused by the pathological agent. This study aims to analyze the technological evolution of the pharmaceutical treatment of leprosy, aimed at children. A review of patents around the world was conducted to look for technical and clinical aspects of formulations and devices.. Innovative formulations for pediatric patients were classified according to the routes of administration as oral, inhalable, injectable and transdermal. The formulations were organized as alternatives for pediatric therapy, taking into account the physicochemical aspects of drugs and the physiological aspects of pediatric patients. Among the difficulties for the patented formulations to reach the market, of special note is the low stability of the physicochemical characteristics of the drugs. Optimization of formulations would favor the pediatric treatment of leprosy, aiming at therapeutic success.

Topics: Child; Humans; Leprostatic Agents; Leprosy; Patents as Topic; Pharmaceutical Preparations; Rifampin

The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations.. All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score.. Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens.. The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction.. All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Leprosy, Multibacillary; Network Meta-Analysis; Rifampin

As the only bactericidal drug in multidrug therapy is rifampicin, monitoring of antimicrobial resistance is important in leprosy patients. Therefore, we conducted a meta-analysis on the resistance of Mycobacterium leprae (M. leprae) to rifampicin and estimated drug resistance in different therapeutic states and regions.. Embase, Medline, PubMed, and Web of Science were searched to identify studies between 1 January 1993 and 1 January 2022. Two independent reviewers extracted study data. Pooled cumulative incidences were computed using random-effects meta-analyses.. We included 32 papers describing the resistance of M. leprae to rifampicin (pooled cumulative incidences, 11% [95% confidence interval {CI}, 7% to 15%]). Therapeutic states and regional distribution were obtained for subgroup analyses. A total of 51 of 1135 new cases (pooled incidence, 10% [95% CI, 5% to 16%]) and 81 of 733 relapsed cases (pooled incidence, 20% [95% CI, 13% to 27%]) had rifampicin resistance. A total of 139 participants, including 11 patients with rifampicin resistance (pooled incidence, 42% [95% CI, -21% to 105%]), were nonresponsive and intractable cases. The incidence of rifampicin resistance was highest in the Western Pacific (pooled incidence, 21% [95% CI, 13% to 29%]) and lowest in the Americas (pooled incidence, 4% [95% CI, 1% to 7%]).. Drug resistance testing and a robust and rigorous surveillance system are recommended to detect the prevalence of drug resistance in leprosy.

Topics: Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Prevalence; Rifampin

In the past 15 years, the decline in annually detected leprosy patients has stagnated. To reduce the transmission of Mycobacterium leprae, the World Health Organization recommends single-dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients. Various approaches to administer SDR-PEP have been piloted. However, requirements and criteria to select the most suitable approach were missing. The aims of this study were to develop an evidence-informed decision tool to support leprosy programme managers in selecting an SDR-PEP implementation approach, and to assess its user-friendliness among stakeholders without SDR-PEP experience.. The development process comprised two phases. First, a draft tool was developed based on a literature review and semi-structured interviews with experts from various countries, organisations and institutes. This led to: an overview of existing SDR-PEP approaches and their characteristics; understanding the requirements and best circumstances for these approaches; and, identification of relevant criteria to select an approach. In the second phase the tool's usability and applicability was assessed, through interviews and a focus group discussion with intended, inexperienced users; leprosy programme managers and non-governmental organization (NGO) staff.. Five SDR-PEP implementation approaches were identified. The levels of endemicity and stigma, and the accessibility of an area were identified as most relevant criteria to select an approach. There was an information gap on cost-effectiveness, while successful implementation depends on availability of resources. Five basic requirements, irrespective of the approach, were identified: stakeholder support; availability of medication; compliant health system; trained health staff; and health education. Two added benefits of the tool were identified: its potential value for advocacy and for training.. An evidence-informed SDR-PEP decision tool to support the selection of implementation approaches for leprosy prevention was developed. While the tool was evaluated by potential users, more research is needed to further improve the tool, especially health-economic studies, to ensure efficient and cost-effective implementation of SDR-PEP.

Topics: Decision Making; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin

Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85-12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46-15.33) vs. 6.59% (3.66-9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65-9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82-18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02-5.77), 3.66% (95% CI: 2.41-4.90) and 1.28% (95% CI: 0.87-1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83-2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.

Topics: Amino Acids; Dapsone; Drug Resistance, Bacterial; Humans; Leprostatic Agents; Leprosy; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae; Ofloxacin; Rifampin

Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities.. The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates.. Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported.. Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established.. Novartis Foundation.

Topics: Feasibility Studies; Humans; Leprostatic Agents; Leprosy; Post-Exposure Prophylaxis; Precision Medicine; Public Health; Rifampin

Vaccination and single-dose rifampin are the main proven effective intervention types for preventing leprosy among contacts of Mycobacterium leprae endemic areas. Currently, no high-quality evidence is available regarding the best prophylactic intervention.. Our primary study aim is to detect the most effective prophylactic intervention for the prevention of leprosy.. In May 2019, 12 databases were searched systematically. Updated search terms were developed in March 2020 to complete an updated search. All randomized controlled trials (RCTs) comparing the different types of chemoprophylactic and immunoprophylactic interventions in leprosy prevention were included. Our participants were contacts of patients with leprosy or people residing in leprosy endemic communities. We searched for different types of chemoprophylactic and immunoprophylactic interventions used in leprosy prevention. We used network meta-analysis and meta-analysis. Quality assessment was performed using Cochrane Risk of Bias for included RCTs, in which all included RCTs were rated to be low to moderate risk. We registered our protocol in Prospero with ID CRD42019143207.. Among 11 included studies (326 264 patients) from original and updated search terms, eight were eligible for network meta-analysis (NMA) while four were eligible for MA. Findings suggest that Bacillus Calmette-Guérin (BCG) vaccination was the most effective intervention compared to placebo (risk ratios (RRs) 0.49 (0.30, 0.80), p 0.77), followed by combined BCG vaccination and single-dose rifampicin (SDR) with similarly low values (RR 48%, p 0.77). BCG revaccination was the least effective intervention compared to placebo (RR 1.08 (0.36, 3.22), p 0.26).. Compared to placebo, the BCG vaccine was the most effective prophylactic intervention. The combination of BCG vaccination + SDR had nearly the same efficacy as BCG vaccination alone, while BCG revaccination was the least effective. Thus, vaccination proved to be a more effective treatment than SDR alone. A well-designed multicenter RCT is warranted to evaluate the safety of these vaccines.

Topics: BCG Vaccine; Chemoprevention; Humans; Leprosy; Network Meta-Analysis; Randomized Controlled Trials as Topic; Rifampin

Leprosy is a chronic infectious disease caused my Mycobacterium leprae that primarily affects peripheral nervous system and extremities and is prevalent in tropical countries. Treatment for leprosy with multidrug regimens is very effective compared to monotherapy especially in multibacillary cases. The three major antileprosy drugs currently in use are 4, 4'-diaminodiphenyl sulfone (DDS, dapsone), rifampicin, and clofazimine. During multidrug therapy, the potent antibiotic rifampicin induces the metabolism of dapsone, which results in decreased plasma half-life of dapsone and its metabolites. Furthermore, rifampicin induces its own metabolism and decreases its half-life during monotherapy. Rifampicin upregulates several hepatic microsomal drug-metabolizing enzymes, especially cytochrome P450 (CYP) family that in turn induce the metabolism of dapsone. Clofazimine lacks significant induction of any drug-metabolizing enzyme including CYP family and does not interact with dapsone metabolism. Rifampicin does not induce clofazimine metabolism during combination treatment. Administration of dapsone in the acetylated form (acedapsone) can release the drug slowly into circulation up to 75 days and could be useful for the effective treatment of paucibacillary cases along with rifampicin. This review summarizes the major aspects of antileprosy drug metabolism and drug interactions and the role of cytochrome P450 family of drug metabolizing enzymes, especially CYP3A4 during multidrug regimens for the treatment of leprosy.

Topics: Acedapsone; Biological Availability; Biotransformation; Clofazimine; Cytochrome P-450 CYP3A; Dapsone; Drug Interactions; Drug Therapy, Combination; Half-Life; Humans; Leprostatic Agents; Leprosy; Metabolic Clearance Rate; Metabolic Networks and Pathways; Mycobacterium leprae; Rifampin

Mycobacterium leprae is known to cause leprosy, a neurological and dermatological disease. In the past 20 years, 16 million leprosy cases have been recorded and more than 200,000 new cases were registered each year, indicating that the disease is still progressing without hindrance. M. leprae, an intracellular bacterium, infects the Schwann cells of the peripheral nervous system. Several types of leprosy have been described, including indeterminate, tuberculoid, borderline tuberculoid, mid-borderline, borderline lepromatous and lepromatous, and three different forms of leprosy reactions, namely type 1, 2 and 3, have been designated. Microscopic detection, serological diagnostic test, polymerase chain reaction and flow tests are employed in the diagnosis of leprosy. The recommended treatment for leprosy consists of rifampicin, dapsone, clofazimine, ofloxacin and minocycline and vaccines are also available. However, relapse may occur after treatment has been halted and hence patients must be educated on the signs of relapse to allow proper treatment and reduce severity. In this review, we depict the current understanding of M. leprae pathogenicity, clinical aspects and manifestations. Transmission of leprosy, diagnosis and treatment are also discussed.

Topics: Humans; Leprosy; Mycobacterium leprae; Polymerase Chain Reaction; Rifampin; Serologic Tests

Today, the emergence of the phenomenon of drug or multidrug-resistance for community-associated diseases represents a major concern in the world. In these contexts, the chronic infectious disease, leprosy, grounded by a slow-growing bacterium called Mycobacterium leprae or Mycobacterium lepromatosis is a leadingcause of severe disfiguring skin sores and nerve damage in the arms, legs, and skin areas around the body. Even, over 200,000 new leprosy cases are being accounted every year along with the relapsed leprosy cases. Nonetheless, this has been considered a curable disease with a higher dose of multidrug therapy (MDT) for a long period of time. The prolonged action of a high dose of combination drugs administration may cause an adverse reaction that can significantly affect patient compliance, particularly the outbreak of multidrug-resistance in the infected person. To overcome these shortfalls or prevent the resistance-associated problems, researchers are diligently involved in the structural modifications of the clinically used anti-leprosy drugs or the allied compounds for the structure-antimycobacterial activity relationship study. This review article described the detailed synthesis and biological assays of different anti-leprosy compounds reported by several research groups.

Topics: Humans; Leprostatic Agents; Leprosy; Structure-Activity Relationship

MJ is a janitor working in an office building for the past 5 years. He sustained a third-degree burn with a secondary infection and was sent to the county hospital. He was diagnosed with leprosy. The employees in the office building were concerned with the risk of transmission. This article reviews leprosy, and implications for occupational health nurses are discussed.

Topics: Dapsone; Diagnosis, Differential; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Occupational Health Nursing; Rifampin

Leprosy is present in more than 100 countries, where it remains a major cause of peripheral neuropathy and disability. Attempts to eliminate the disease have faced various obstacles, including characteristics of the causative bacillus Mycobacterium leprae: the long incubation period, limited knowledge about its mode of transmission, and its poor growth on culture media. Fortunately, the leprosy bacillus is sensitive to several antibiotics. The first antibiotic to be widely used for leprosy treatment was dapsone in the 1950s, which had to be taken over several years and was associated with increasing bacterial resistance. Therefore, in 1981, WHO recommended that all registered patients with leprosy should receive combination therapy with three antibiotics: rifampicin, clofazimine, and dapsone. Global implementation of this highly effective multidrug therapy took about 15 years. In 1985, 5·3 million patients were receiving multidrug therapy; by 1991, this figure had decreased to 3·1 million (a decrease of 42%) and, by 2000, to 597 232 (a decrease of almost 90%). This reduction in the number of patients registered for treatment was due to shortening of the treatment regimen and achievement of 100% coverage with multidrug therapy. This achievement, which owed much to WHO and the donors of the multidrug therapy components, prompted WHO in 1991 to set a global target of less than one case per 10 000 population by 2000 to eliminate the disease as a public health problem. All but 15 countries achieved this target. Since 2000, about 250 000 new cases of leprosy have been detected every year. We believe an all-out campaign by a global leprosy coalition is needed to bring that figure down to zero.

Topics: Clofazimine; Dapsone; Disease Eradication; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin

Individuals in contact with patients who have leprosy have an increased risk of disease exposure, which reinforces the need for chemoprophylactic measures, such as the use of rifampicin.. The objective of the review was to synthesize the best available evidence regarding the effectiveness of rifampicin chemoprophylaxis for contacts with patients with leprosy, and to synthesize the best available evidence on the experience and acceptability of rifampicin chemoprophylaxis as reported by the contacts and health professionals involved in the treatment of leprosy or Hansen's disease.. In the quantitative component, individuals in contact with leprosy patients were included. In the qualitative component, in addition to contacts, health professionals who were in the practice of treating leprosy were included.. The quantitative component considered as an intervention rifampicin at any dose, frequency and mode of administration, and rifampicin combination regimens.The qualitative component considered as phenomena of interest the experience and acceptability of rifampicin chemoprophylaxis.. The quantitative component considered experimental and observational studies whereas the qualitative component considered studies that focused on qualitative data, including but not limited to, designs such as phenomenology, grounded theory, ethnography and action-research.. The quantitative component considered studies that reported on outcomes such as the development of clinical leprosy in the contacts of patients who had leprosy, incidence rates, adverse effects and safety/harmful effects of the intervention.. A three-step strategy for published and unpublished literature was used. The search for published studies included: PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Scopus, Web of Science, National Institute for Health and Clinical Excellence, Latin American and Caribbean Health Sciences Literature; and Google Scholar and EVIPnet for unpublished studies. Studies published from the time of the respective database inception to January 2016 in English, Spanish, Portuguese, Japanese and Chinese were considered.. Two reviewers independently assessed the studies for methodological quality using standardized critical appraisal instruments from the Joanna Briggs Institute.. Standardized data extraction tools developed by the Joanna Briggs Institute were used to extract quantitative and qualitative data from papers included in the review.. Due to clinical and methodological heterogeneity in the interventions of the included studies, no statistical meta-analysis was possible. Quantitative and qualitative research findings are presented in narrative form.. Following critical appraisal, eight studies were included in this review, seven quantitative and one qualitative. The reduction in incidence of leprosy, using one dose of rifampicin in the first two years, was 56.5%; in the follow up period of one to four years, the reduction was 34.9%. The combination of rifampicin and the Bacillus Calmette-Guérin vaccine showed a preventative effect of 80% against the disease. The only controlled clinical trial using two doses of rifampicin was community-based and did not indicate effectiveness of the intervention. The qualitative findings showed social acceptability of rifampicin.. Chemoprophylaxis with one dose of rifampicin is found to be effective in preventing contacts of leprosy patients from contracting the disease. Also, there is indication that this strategy is socially accepted.

Topics: Chemoprevention; Health Personnel; Humans; Leprostatic Agents; Leprosy; Rifampin

Topics: Humans; Leprostatic Agents; Leprosy; Rifampin; Treatment Outcome

Leprosy is a chronic disease with many clinical manifestations, which affect mainly the skin, the peripheral nerves, mucosa of the upper respiratory tract and the eyes. Although global elimination of leprosy was achieved globally in the year 2000 and the disease is actually rare in most parts of the world, a low but constant number of more than 200,000 new cases are still registered each year. Leprosy is caused by two acid-resistant, slow multiplying Gram-positive bacteria, i. e., Mycobacterium leprae and the recently discovered M. lepromatosis. The transmission routes of these pathogens are not completely understood. All forms of leprosy can be treated with long-lasting antibacterial combination therapy using dapsone and rifampicin and – in cases of multibacillar leprosy – clofazimin. Using this multi-drug approach, leprosy has been shown to be curable in most cases. However, immunological sequelae (leprosy reactions), which may appear during therapy or even several years later, are frequently difficult to treat. Although leprosy has been eliminated in most countries, its complete eradication is extremely unlikely.

Topics: Animals; Armadillos; Clofazimine; Cross-Sectional Studies; Dapsone; Disease Reservoirs; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.

Topics: Drug Resistance, Bacterial; Humans; Leprostatic Agents; Leprosy; Mycobacterium tuberculosis; Post-Exposure Prophylaxis; Rifampin; Risk; Tuberculosis, Multidrug-Resistant

Leprosy is an infectious disease that has now been reported for more than 2000 years. The leprosy elimination goal set by the World Health Organization (WHO), i.e. a global prevalence rate <1 patient per 10,000 population, was achieved in the year 2000, but more than 200,000 new case patients are still reported each year, particularly in India, Brazil, and Indonesia. Leprosy is a specific infection: (i) it is a chronic infection primarily affecting the skin and peripheral nerves, (ii) Mycobacterium leprae is one of the last bacterial species of medical interest that cannot be cultured in vitro (mainly because of its reductive genome evolution), and (iii) transmission and pathophysiological data is still limited. The various presentations of the disease (Ridley-Jopling and WHO classifications) are correlated with the patient's immune response, bacillary load, and by the delay before diagnosis. Multidrug therapy (dapsone, rifampicin, with or without clofazimine) has been recommended since 1982 as the standard treatment of leprosy; 6 months for patients presenting with paucibacillary leprosy and 12 months for patients presenting with multibacillary leprosy. The worldwide use of leprosy drugs started in the 1980s and their free access since 1995 contributed to the drastic decline in the number of new case patients. Resistant strains are however emerging despite the use of multidrug therapy; identifying and monitoring resistance is still necessary.

Topics: Antibodies, Bacterial; Bacteriological Techniques; Biopsy; Clofazimine; Dapsone; Drug Resistance, Bacterial; Drug Utilization; Genome, Bacterial; Global Health; History, 16th Century; History, 17th Century; History, 18th Century; History, Ancient; Humans; Leprostatic Agents; Leprosy; Molecular Diagnostic Techniques; Mycobacterium leprae; Phylogeny; Prevalence; Rifampin; Risk Factors

As for the Mycobacterium leprae which is a causative agent of Hansen's disease, many studies had been done since it was identified in 1873. However, those studies, at the same time, experienced many struggles because of the difficulty of culture of M. leprae on the artificial growth media. Hence, the study of Hansen's disease progressed by taking the knowledge from the study of tuberculosis caused by the bacteria belonging to the same genus, genus Mycobacterium. For instance, the knowledge of mutations in specific genes responsible for rifampicin- and quinolone-resistance in M. tuberculosis led the elucidation of drug-resistant acquisition mechanism of M. leprae. Similarly, it is necessary for the researcher of Hansen's disease to get important information from the latest topic of the tuberculosis study and utilize them to the study of the disease.

Topics: Antibiotics, Antitubercular; DNA Gyrase; Drug Resistance, Microbial; Humans; Leprosy; Molecular Biology; Mutation; Mycobacterium leprae; Mycobacterium tuberculosis; Quinolones; Research; Rifampin; Tuberculosis

A review of the records of patients seen between 2004 and 2011 at the Dermatology Clinic of the São Paulo University Medical School showed that only two leprosy patients had been co-infected with tuberculosis (TB). One patient showed a type 1 leprosy reaction during the first 3 months of treatment of pleural TB and in the other patient, pulmonary TB was diagnosed during the first 3 months of treatment of a type 1 leprosy reaction. Both patients showed normal cellular immune response tests, including those of the interferon-gamma (IFN-γ)/interleukin 12 (IL-12) axis. Although both mycobacterial infections are endemic in developing countries like Brazil, the co-infection has hardly been reported in the last decade. There is no suitable explanation for this observation. The reports on the interaction between the two mycobacteria are highly speculative: some studies suggest that leprosy, especially the anergic form, would predispose to TB, whereas other investigations suggested an antagonism between the two diseases.

Topics: Adult; Brazil; Coinfection; Female; Humans; Immunity, Cellular; Interferon-gamma; Interleukin-12; Isoniazid; Leprosy; Male; Middle Aged; Prednisone; Pyrazinamide; Rifampin; Treatment Outcome; Tuberculosis, Pleural; Tuberculosis, Pulmonary; White People

Daily rifampin therapy is associated with minimal adverse effects, but administration on an intermittent or interrupted basis has been associated with severe immunoallergic reactions such as hemolytic anemia, acute renal failure, and disseminated intravascular coagulation. We describe a patient with Mycobacterium leprae infection who experienced recurrent episodes of disseminated intravascular coagulation after intermittent exposures to rifampin, and review eight previously reported cases of rifampin-associated disseminated intravascular coagulation. In six (75%) cases, previous exposure to rifampin was reported and seven (87.5%) patients were receiving the medication on an intermittent or interrupted basis. Clinical features of rifampin-associated disseminated intravascular coagulation included fever, hypotension, abdominal pain, and vomiting within hours of ingestion. Average time to reaction was 3-6 doses if rifampin was being administered on a monthly schedule. Three (37.5%) of eight reported cases were fatal. A complete history of previous exposure to rifampin is recommended before intermittent therapy with this medication.

Topics: Abdominal Pain; Aged; Anemia, Hemolytic; Disseminated Intravascular Coagulation; Dose-Response Relationship, Drug; Female; Fever; Humans; Hypotension; Leprosy; Rifampin; Vomiting

A combination of rifampicin, ofloxacin and minocycline (ROM) is one of the newer recommendations for treatment of leprosy. We performed a systematic review and a meta-analysis of studies that had evaluated the efficacy of ROM therapy in treatment of paucibacillary and multibacillary leprosy patients.. Studies were identified by searching the PubMed, Embase, LILACS and Cochrane databases. Data were abstracted from all relevant studies, and fixed effects models were used to calculate the summary estimate of effect in paucibacillary and multibacillary leprosy patients.. Six studies comparing ROM therapy to multidrug therapy and eight studies that evaluated the effect of ROM therapy alone (no comparison group) were included in the review and meta-analysis. The combined estimate for single dose ROM vs. multidrug therapy in paucibacillary leprosy patients suggested that ROM was less effective than multidrug therapy in these patients [relative risk: 0.91, 95% confidence intervals (CI): 0.86-0.97]. However, the combined estimate for multiple doses of ROM vs. multidrug therapy in multibacillary leprosy patients suggested that ROM was as effective as multidrug therapy in reducing bacillary indices in these patients (proportion change: -4%, 95% CI -31% to 23%). No major side effects were reported in either the ROM or the multidrug treatment groups.. Single-dose ROM therapy was less effective than multidrug therapy in paucibacillary patients. However, there are insufficient data to come to a valid conclusion on the efficacy of multidose ROM therapy in multibacillary leprosy, and additional studies with ROM therapy in multibacillary leprosy are needed. Furthermore, multiple doses may be considered as another alternative even for paucibacillary patients, and randomised controlled trials of this therapy may be useful to understand its contribution in the treatment and control of leprosy.

Topics: Anti-Bacterial Agents; Drug Combinations; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Ofloxacin; Rifampin; Treatment Outcome

Leprosy, a chronic granulomatous infection caused by Mycobacterium leprae, classically presents with cutaneous and neurological manifestations. Musculoskeletal involvement though third most common is underdiagnosed and underreported. It may manifest in the form of Charcot's arthropathy, acute symmetrical polyarthritis or swollen hands and feet syndrome during lepra reactions, insidious-onset chronic symmetrical polyarthritis mimicking RA or as isolated tenosynovitis or tenosynovitis associated with arthritis or neuropathy. At times, articular involvement may be the sole presenting manifestation even without cutaneous lesions. Other rheumatological manifestations occasionally reported are enthesitis, sacroiliitis, cryoglobulinaemic vasculitis and DM. With increasing travel of population between tropical and temperate zones, it is likely that rheumatology clinics in countries free of leprosy may come across cases of leprosy with rheumatological manifestations. Delay in diagnosis and management may be detrimental and may result in deformities and loss of function. Not only this, but recent reports of leprosy being diagnosed in native white populations following anti-TNF-α therapy should alert rheumatologists across the globe to be more familiar with this disease. This review is aimed at presenting a comprehensive clinical scenario of various rheumatological manifestations of leprosy to sensitize rheumatologists and physicians across the continents.

Topics: Arthritis; Clofazimine; Dapsone; Diagnosis, Differential; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin

The World Health Organization field leprosy classification is based on the number of skin lesions: paucibacillary leprosy (1-5 skin lesions), and multibacillary leprosy (more than 5 skin lesions). Worldwide, about 250,000 new cases of leprosy are reported each year, and about 2 million people have leprosy-related disabilities.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent leprosy? What are the effects of treatments for leprosy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: chemoprophylaxis with single-dose rifampicin, Bacillus Calmette-Guerin (BCG) plus killed Mycobacterium leprae vaccine, BCG vaccine, ICRC vaccine, multidrug treatment, multiple-dose treatment, Mycobacterium w vaccine, and single-dose treatment.

Topics: BCG Vaccine; Humans; Leprosy; Leprosy, Lepromatous; Leprosy, Multibacillary; Leprosy, Tuberculoid; Mycobacterium leprae; Rifampin

Leprosy is a granulomatous disease affecting the skin and peripheral nerves caused by Mycobacterium leprae. The range of clinical forms varying from tuberculoid to lepromatous leprosy results from variations in the cellular immune response to the mycobacterium. Despite available combined drug-therapy, it continues to be a significant public health problem, carrying a strong stigma. Although recently there has been no native cases in Chile, a few imported cases have been diagnosed. We present a 56-year-old man who had lived in Paraguay for 8 years, and presented with leprosy 6 years after returning to Chile. The biology of leprosy, clinical features of the disease, current diagnostic criteria and approaches to treatment are discussed.

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Rifampin; Treatment Outcome

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Eye Infections, Bacterial; Global Health; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin

Antibiotic susceptibility test of Mycobacterium leprae still relies on the time consuming methods based on the growth of M. leprae in the mouse footpad. Thus, the establishment of a rapid, simple and reliable method for the detection of drug-resistant M. leprae is one of the most urgent subjects in the treatment of leprosy patients. Recently, many data on the mutation of specific genes correlating with drug resistance have been accumulated. Application of these data permit the establishment of new gene diagnostic methods for drug susceptibility test of leprosy. In this paper, the method using the low density oligonucleotide array that enables the detection of base substitutions involved in resistance against anti-leprosy drugs on a single platform was discussed. The low density oligonucleotide array described in this paper will open the new perspectives in terms of patient management for leprosy with low cost requirement.

Topics: Animals; Dapsone; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Mice; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae; Ofloxacin; Oligonucleotide Array Sequence Analysis; Rifampin

Topics: Adult; Antibiotics, Antitubercular; Child; Drug Interactions; Female; Half-Life; Humans; Intestinal Absorption; Leprosy; Male; Microbial Sensitivity Tests; Middle Aged; Psoriasis; Rifampin; Tuberculosis

Topics: Dapsone; Diagnosis, Differential; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Prognosis; Rifampin; World Health Organization

Topics: Bacterial Vaccines; BCG Vaccine; Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprosy; Mycobacterium leprae; Rifampin

Leprosy, a result of infection by Mycobacterium leprae, is a leading cause of peripheral neuropathy. The World Health Organization aimed to eliminate leprosy as a public health problem by 2000, but this has not been attained. Patients with leprosy continue to present in the UK. The diagnosis of leprosy is frequently not considered, with resultant pathological and psychological problems for patients.

Topics: Clofazimine; Dapsone; Diagnosis, Differential; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Peripheral Nervous System Diseases; Rifampin

Topics: Clofazimine; Cost-Benefit Analysis; Dapsone; Drug Therapy, Combination; Global Health; Humans; International Cooperation; Leprostatic Agents; Leprosy; Mycobacterium Infections; Mycobacterium leprae; Prevalence; Rifampin; World Health Organization

Leprosy is a slowly progressive, chronic infectious disease caused by the bacillus Mycobacterium leprae. It is a very serious, multilating and stigmatizing disease in many parts of the world and early diagnosis and therapy is the most important strategy for its control. The skin and peripheral nerves are the most affected organs. It is highly infective, but has low pathogenicity and low virulence with a long incubation period. The geographical distribution of leprosy has varied greatly with time and it is now endemic only in tropical and subtropical regions such as India and Brazil. The diagnosis of leprosy is made from the clinical picture, but must be complimented by skin bacilloscopy and histopathology. Leprosy has a number of distinct clinical presentations. Indeterminate leprosy is frequently the initial form consisting of a few lesions that either evolves into the other forms or resolves spontaneously. Lepromatous leprosy is the more contagious form and affects mainly the skin. In addition, some peripheral nerves may be thickened and other symptoms maybe present. The tuberculid form affects the skin and nerves, although usually there are few lesions. There is also a form borderline between the lepromatous and tuberculoid forms. Current treatment of leprosy involves use of 3 drugs: rifampicin (rifampin); clofazimine; and dapsone. Multidrug therapy aims to effectively eliminate M. leprae in the shortest possible time to prevent resistance from occurring. The duration of therapy was recently reduced from 24 to 12 months. Other treatment options are under evaluation in both preclinical and clinical trials and a number show promise. The combination of rifampicin, ofloxacin and minocycline given as a single dose has been recommended for the treatment of paucibacillar leprosy. Only when physicians, other health workers, and the population in endemic countries become fully aware of, and able to recognize, the disease in its initial phase, will it be possible for therapy to be instituted at the very beginning with either the standard scheme or the newer ones. Intervention at such an early stage will avoid the onset of the more serious signs and symptoms, meaning that leprosy will eventually become a less important public health problem. Therefore, efforts must be made to alert populations at risk and all health workers of the importance of an early diagnosis and treatment in leprosy infection.

Topics: Adolescent; Adult; Age Factors; Biopsy; Child; Clinical Trials as Topic; Clofazimine; Dapsone; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Male; Multicenter Studies as Topic; Peripheral Nerves; Rifampin; Skin; Time Factors; World Health Organization

To quantify the efficacy of chemoprophylaxis against leprosy.. Literature searching of Medline and Embase databases, hand-searching of references and correspondence with investigators.. published papers relating to the prevention of leprosy and the use of chemotherapy in leprosy were identified for critical appraisal. Trials were selected and grouped into three categories according to study design and control groups.. the relative risks (RR) with 95% confidence intervals were calculated from the original data using a random effects model. To assess the cost-effectiveness of chemoprophylaxis, a further analysis of the rates of disease in the trial and control groups was done based on the numbers needed to be treated (NNT) to prevent one new case of leprosy.. A total of 14 trials were identified from 127 published papers on chemoprophylaxis of leprosy. The trials were categorized into randomized controlled trials, non-randomized controlled trials, and uncontrolled trials. The overall results of the meta-analysis shows that chemoprophylaxis gives around 60% protection against leprosy. The NNT are low in trials of household contacts.. The evidence shows that chemoprophylaxis against leprosy is an effective way to reduce the incidence of leprosy, particularly in household contacts. The role of chemoprophylaxis needs to be re-examined using newer drugs given the continuing case detection rates globally.

Topics: Acedapsone; Clinical Trials as Topic; Cost-Benefit Analysis; Dapsone; Humans; Leprostatic Agents; Leprosy; Rifampin; Risk Factors; Topography, Medical

Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All African Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Paucibacillary (PB) patients are treated with 6 months of MDT. Multibacillary (MB) patients are treated with at least 2 years of MDT and until skin-smear negativity. An analysis was made of the relapses which had been diagnosed among self-reporting patients in four rural districts and Addis Ababa. Among 3065 PB patients, 34 relapses (1.1%) were diagnosed during an average period of 6.1 years after stopping MDT (range 2 1/2 to 7 1/2 years). Among 2379 MB patients, 24 relapses (1.0%) were diagnosed during an average period of 4.7 years after stopping MDT (range 2 1/2 to 6 years). The estimated relapse rate per 1000 patient-years after release from MDT was 2.1 for PB patients and 2.4 for MB patients. From the analysis of the clinical, bacteriological, and histopathological findings, it was concluded that there was strong positive evidence for the diagnosis for 16 of the 34 relapses in the PB patients and for 0 of the 24 relapses in the MB patients. The main cause for overdiagnosis of MB relapses was that too much reliance had been put on skin-smear results, without a careful comparison of the results with those from before, during, and at completion of MDT; the diagnosis was based on the finding of positive smears in one set of smears only; insufficient attention was given to finding solid-staining bacilli; and findings in biopsies, if these were examined, did not confirm the diagnosis. The main cause of overdiagnosis of PB relapses was that too much reliance was put on histological findings, while these are often inconclusive for differentiating between a relapse and late reversal reaction. Recommendations are made on how to limit overdiagnosis of relapses. Operational procedures and criteria for making the diagnosis under conditions where facilities for back-up histological and mouse foot pad investigations are not available are proposed.

Topics: Clofazimine; Dapsone; Epidemiologic Methods; Ethiopia; Humans; Incidence; Leprostatic Agents; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Recurrence; Rifampin

Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Of 6042 paucibacillary patients who were put on MDT during a period of 7 years, 5485 patients (90.8%) completed the course of MDT; 437 patients (7.2%) did not fulfill the requirement for clinic attendance and either discontinued MDT themselves or the treatment was discontinued by the service. The remaining 120 patients (2.0%) either died, were transferred, left the control area or continued MDT after 9 months. The urine spot test for the presence of dapsone showed a significantly higher proportion of positive results for patients on MDT than for patients on dapsone. The analysis of the compliance with the prescribed doses of MDT showed that of 963 patients, 81.9% received six doses of MDT and 18.1%, more than six doses; 82.6% of these 963 patients attended with 100% regularity, 12.7%, 3.6%, and 1.1% missed one, two, or three clinic appointments, respectively, while fulfilling the requirement for overall clinic attendance. Of the 429 patients who had not been treated with dapsone before MDT, the skin lesions were clinically active at the time of stopping MDT in 130 patients (30.3%). In all, except one of the 114 patients (0.9%) who attended for follow-up examinations, the skin lesions had become clinically inactive within 2 years after stopping MDT. The recommended duration of MDT is discussed based on findings in the ALERT leprosy control programs and observations by others.

Topics: Dapsone; Drug Therapy, Combination; Ethiopia; Humans; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Patient Compliance; Rifampin; Time Factors; World Health Organization

From a pharmacochemical point of view the existing anti-leprotics as well as possible innovations in the chemotherapy of leprosy are discussed. Of the main anti-leprotics, which are used nowadays--dapsone, rifampicin, clofazimine, isoniazide, ethionamide and prothionamide--the mechanism of action, the main problems in their application and possibilities to develop improved variants are reviewed. Based on the chemistry of Mycobacterium leprae, the target systems for new anti-leprotics are identified. These systems include the cell wall, the catabolism of reactive oxygen species, the metabolisms of carbon sources, the amino acid metabolism and the uptake of iron. Two possible new lead structures from other fields, 4-quinolones and mycobacterial ribonucleotide reductase inhibitors are presented.

Topics: Dapsone; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin

Topics: Amides; Drug Therapy, Combination; Humans; Leprosy; Recurrence; Rifampin; Thioamides

Cases of leprosy are increasing in the United States because of immigration from countries where the disease is endemic. Infection may not become apparent for several years after immigration. Symptoms related to involvement of peripheral nervous tissue are often the presenting complaint. Prompt treatment can prevent the potentially severe sequelae of this disease. Current regimens utilize rifampin with dapsone to decrease the development of drug resistance.

Topics: Adult; Dapsone; Drug Therapy, Combination; Humans; Leprosy; Male; Peripheral Nervous System Diseases; Rifampin

Topics: Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprosy; Rifampin

Topics: Animals; Clofazimine; Dapsone; Drug Evaluation, Preclinical; Leprostatic Agents; Leprosy; Mice; Mycobacterium leprae; Rifampin; Thioamides

Topics: Animals; Biological Availability; Body Weight; Dapsone; Drug Evaluation, Preclinical; Humans; Leprostatic Agents; Leprosy; Ofloxacin; Oxazines; Rifampin; Species Specificity

Topics: Animals; Clofazimine; Dapsone; Drug Resistance, Microbial; Ethionamide; Humans; Leprosy; Mice; Microbial Sensitivity Tests; Rifampin

Topics: Animals; Clofazimine; Dapsone; Drug Evaluation; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Recurrence; Rifampin

Topics: Bacterial Vaccines; Clofazimine; Dapsone; Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae; Rifampin; World Health Organization

Topics: Antigens, Bacterial; Clofazimine; Dapsone; Erythema Nodosum; Humans; Immune Tolerance; Immunity, Cellular; Leprostatic Agents; Leprosy; Lymphocyte Activation; Mycobacterium leprae; Neutrophils; Rifampin

Topics: Clofazimine; Dapsone; Ear Deformities, Acquired; Humans; Leprosy; Mouth Diseases; Nose Deformities, Acquired; Rifampin; Thalidomide

Topics: Acetamides; Anemia, Hemolytic; Aniline Compounds; Animals; Clofazimine; Dapsone; Disease Models, Animal; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Leprosy; Methimazole; Mice; Mycobacterium leprae; Phenyl Ethers; Rifampin; Sulfonamides; Thiosemicarbazones; Thiourea

Topics: Clofazimine; Dapsone; Ethionamide; Humans; Leprosy; Rifampin; Sulfonamides; Thioacetazone; Thiourea

Topics: Aniline Compounds; Dapsone; Drug Resistance, Microbial; Ethionamide; Humans; Leprosy; Mycobacterium leprae; Phenazines; Rifampin; Sulfonamides; Sulfones; Thioacetazone; Thiosemicarbazones; Thiourea

Topics: Animals; Facial Paralysis; Genetics, Microbial; Hepatitis B Antigens; Humans; Leprosy; Mice; Mycobacterium leprae; Rats; Rifampin; Thalidomide; World Health Organization

Topics: Animals; Antibiotics, Antineoplastic; Antitubercular Agents; Antiviral Agents; Bacteria; Bacterial Infections; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemistry; DNA-Directed RNA Polymerases; Drug Resistance, Microbial; Humans; Leprosy; Microbial Sensitivity Tests; Rifampin; Tuberculosis

Topics: Abnormalities, Drug-Induced; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Chemical and Drug Induced Liver Injury; Drug Interactions; Drug Resistance, Microbial; Endocarditis, Bacterial; Gonorrhea; Humans; Intestinal Absorption; Leprosy; Meningococcal Infections; Mycobacterium; Respiratory Tract Infections; Rifampin; Thrombocytosis; Tuberculosis; Tuberculosis, Pulmonary; Urologic Diseases; Viruses

Considerable developments have occurred in the application of the method for growing Mycobacterium leprae in the mouse foot-pad since it was first described about 10 years ago. The method has been used to study growth curves and histology in normal and in thymectomized irradiated mice, to identify supposed isolates of Myco. leprae that have been made in tissue-culture or in non-living media, to evaluate tests of experimental vaccines, to investigate applications to clinical investigations (the loss of infectivity during chemotherapy as a means of monitoring a drug trial, the demonstration of drug-resistance, and the clinical problem of the patient who responds poorly to therapy), and to study new drugs-e.g., dapsone, acedapsone, clofazimine, and rifampicin.

Topics: Animals; BCG Vaccine; Clofazimine; Dapsone; Disease Models, Animal; Drug Evaluation; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Humans; Leprosy; Mice; Mycobacterium leprae; Radiation Effects; Rifampin; Thymectomy

Leprosy is an ancient infectious disease with an annual global incidence of around 200,000 over the past decade. Since 2018, the World Health Organization (WHO) recommends single-dose rifampicin as post-exposure prophylaxis (SDR-PEP) for contacts of leprosy patients. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial evaluated PEP with a double dose of rifampicin in Comoros and Madagascar. Preliminary results of this trial show some reduction in leprosy incidence in intervention villages but a stronger regimen may be beneficial. The objective of the current Bedaquiline Enhanced ExpOsure Prophylaxis for LEprosy trial (BE-PEOPLE) is to explore effectiveness of a combination of bedaquiline and rifampicin as PEP.. BE-PEOPLE is a cluster-randomized trial in which 44 clusters in Comoros will be randomized to two study arms. Door-to-door screening will be conducted annually during four years, leprosy patients identified will be offered standard of care treatment. Based on study arm, contacts aged five years and above and living within a 100-meter radius of an index case will either receive bedaquiline (400-800 mg) and rifampicin (150-600 mg) or only rifampicin (150-600 mg). Contacts aged two to four years will receive rifampicin only. Household contacts randomized to the bedaquiline plus rifampicin arm will receive a second dose four weeks later. Incidence rate ratios of leprosy comparing contacts who received either of the PEP regimens will be the primary outcome. We will monitor resistance to rifampicin and/or bedaquiline through molecular surveillance in all incident tuberculosis and leprosy patients nationwide. At the end of the study, we will assess anti-M. leprae PGL-I IgM seropositivity as a proxy for the population burden of M. leprae infection in 8 villages (17,000 individuals) that were surveyed earlier as part of the PEOPLE trial.. The COLEP trial on PEP in Bangladesh documented a reduction of 57% in incidence of leprosy among contacts treated with SDR-PEP after two years, which led to the WHO recommendation of SDR-PEP. Preliminary results of the PEOPLE trial show a lesser reduction in incidence. The BE-PEOPLE trial will explore whether reinforcing SDR-PEP with bedaquiline increases effectiveness and more rapidly reduces the incidence of leprosy, compared to SDR-PEP alone.. NCT05597280. Protocol version 5.0 on 28 October 2022.

Topics: Antibodies; Comoros; Humans; Leprosy; Mycobacterium leprae; Post-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Rifampin

Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against. We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts.. A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed.. The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).

Topics: Family Characteristics; Humans; Incidence; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin

To assess the effectiveness of single-dose rifampicin (SDR) after bacillus Calmette-Guérin (BCG) vaccination in preventing leprosy in contacts.. This was a single-centre, cluster-randomized controlled trial at a leprosy control programme in northwest Bangladesh. Participants were the 14988 contacts of 1552 new leprosy patients who were randomized into the SDR-arm (n=7379) and the SDR+arm (n=7609). In the intervention group, BCG vaccination was followed by SDR 8-12 weeks later. In the control group, BCG vaccination only was given. Follow-up was performed at 1year and 2 years after intake. The main outcome measure was the occurrence of leprosy.. The incidence rate per 10000 person-years at risk was 44 in the SDR-arm and 31 in the SDR+arm at 1year; the incidence rate was 34 in the SDR-arm and 41 in the SDR+arm at 2 years. There was a statistically non-significant (p=0.148; 42%) reduction for paucibacillary (PB) leprosy in the SDR+ arm at 1 year. Of all new cases, 33.6% appeared within 8-12 weeks after BCG vaccination.. In the first year, SDR after BCG vaccination reduced the incidence of PB leprosy among contacts by 42%. This was a statistically non-significant reduction due to the limited number of cases after SDR was administered. To what extent SDR suppresses excess leprosy cases after BCG vaccination is difficult to establish because many cases appeared before the SDR intervention.. Netherlands Trial Register: NTR3087.

Topics: Adolescent; Adult; Bangladesh; BCG Vaccine; Child; Child, Preschool; Female; Humans; Incidence; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Rifampin; Vaccination; Young Adult

Leprosy is an ancient infectious disease with a global annual incidence that has plateaued above 200,000 new cases since over a decade. New strategies are required to overcome this stalemate. Post-exposure prophylaxis (PEP) with a single dose of Rifampicin (SDR) has conditionally been recommended by the World Health Organization (WHO), based on a randomized-controlled-trial in Bangladesh. More evidence is required. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial will assess effectiveness of different modalities of PEP on the Comoros and Madagascar.. PEOPLE is a cluster-randomized trial with villages selected on previous leprosy-incidence and randomly allocated to four arms. Four annual door-to-door surveys will be performed in all arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP. Arm-1 is the comparator in which no PEP will be provided. In arms 2, 3 and 4, SDR-PEP will be provided at double the regular dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2 all household-members of incident leprosy patients are eligible. In arm 3 not only household-members but also neighbourhood contacts living within 100-m of an incident case are eligible. In arm 4 such neighbourhood contacts are only eligible if they test positive to anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome.. Different trials on PEP have yielded varying results. The pivotal COLEP trial in Bangladesh showed a 57% reduction in incidence over a two-year period post-intervention without any rebound in the following years. A study in a high-incidence setting in Indonesia showed no effect of PEP provided to close contacts but a major effect of PEP provided as a blanket measure to an entire island population. High background incidence could be the reason of the lack of effect of PEP provided to individual contacts. The PEOPLE trial will assess effectiveness of PEP in a high incidence setting and will compare three different approaches, to identify who benefits most from PEP.. Clinicaltrials.Gov. NCT03662022. Initial Protocol Version 1.2, 27-Aug-2018.

Topics: Child, Preschool; Comoros; Family Characteristics; Female; Humans; Incidence; Leprostatic Agents; Leprosy; Madagascar; Male; Post-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Rifampin

The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs.. Describe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT).. After operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial.. Skin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported.. Loss of some monthly laboratory sample collection.. There was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.

Topics: Adolescent; Adult; Anemia; Brazil; Child; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Hemoglobins; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Rifampin; Risk Factors; Treatment Outcome; Young Adult

Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance.. Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated.. A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable.. We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696].

Topics: Adolescent; Adult; Aged; Child; China; Dapsone; Drug Therapy, Combination; Female; Humans; India; Leprosy; Male; Middle Aged; Rifampin; Treatment Outcome

Despite almost 30 years of effective chemotherapy with MDT, the global new case detection rate of leprosy has remained quite constant over the past years. New tools and methodologies are necessary to interrupt the transmission of M. leprae. Single-dose rifampicin (SDR) has been shown to prevent 57% of incident cases of leprosy in the first two years, when given to contacts of newly diagnosed cases. Immunization of contacts with BCG has been less well documented, but appears to have a preventive effect lasting up to 9 years. However, one major disadvantage is the occurrence of excess cases within the first year after immunization. The objective of this study is to examine the effect of chemoprophylaxis with SDR and immunoprophylaxis with BCG on the clinical outcome as well as on host immune responses and gene expression profiles in contacts of newly diagnosed leprosy patients. We hypothesize that the effects of both interventions may be complementary, causing the combined preventive outcome to be significant and long-lasting.. Through a cluster randomized controlled trial we compare immunization with BCG alone with BCG plus SDR in contacts of new leprosy cases. Contact groups of around 15 persons will be established for each of the 1300 leprosy patients included in the trial, resulting in approximately 20,000 contacts in total. BCG will be administered to the intervention group followed by SDR, 2 months later. The control group will receive BCG only. In total 10,000 contacts will be included in both intervention arms over a 2-year period. Follow-up will take place one year as well as two years after intake. The primary outcome is the occurrence of clinical leprosy within two years. Simultaneously with vaccination and SDR, blood samples for in vitro analyses will be obtained from 300 contacts participating in the trial to determine the effect of these chemo- and immunoprophylactic interventions on immune and genetic host parameters.. Combined chemoprophylaxis and immunoprophylaxis is potentially a very powerful and innovative tool aimed at contacts of leprosy patients that could reduce the transmission of M. leprae markedly. The trial intends to substantiate this potential preventive effect. Evaluation of immune and genetic biomarker profiles will allow identification of pathogenic versus (BCG-induced) protective host biomarkers and could lead to effective prophylactic interventions for leprosy using optimized tools for identification of individuals who are most at risk of developing disease.. Netherlands Trial Register: NTR3087.

Topics: BCG Vaccine; Chemoprevention; Drug Therapy, Combination; Humans; Leprosy; Mycobacterium leprae; Netherlands; Rifampin

The COLEP trial in Bangladesh showed a 57% reduction in leprosy incidence among contacts of newly diagnosed patients in the first 2 years after chemoprophylaxis with single dose rifampicin (SDR). We assessed the impact of this intervention after 6 years and identified characteristics of the leprosy index patients predicting the effectiveness of this intervention.. The cohort of 1037 patients and their 28 092 contacts that participated in the randomised placebo controlled field trial with single dose rifampicin was followed for 6 years. The leprosy status of contacts was established at 2, 4 and 6 years after the intervention. We assessed the association between characteristics of the index leprosy patients and the development of clinical leprosy among their contacts using logistic regression.. The protective effect of SDR was seen only in the first 2 years, with no additional effect after 4 and 6 years. However, the total impact of the intervention was still statistically significant (P = 0.025) after 6 years and no excess cases were observed in the SDR arm at a later stage. The intervention prevented leprosy in contacts that actually received SDR, but did not offer protection to members of the same contact group who did not take chemoprophylaxis. The intervention was most effective in contact groups of female index patients, an enhanced effect was also observed in contact groups of patients belonging to a cluster of two or more leprosy patients at intake as well.. These easy to recognise patient characteristics indicate a possible enhanced risk of transmission of Mycobacterium leprae to contacts in the vicinity of patients and are useful for deciding about preventive measures, such as early detection or chemoprophylaxis.

Topics: Adolescent; Adult; Age Factors; Aged; Bangladesh; Chemoprevention; Contact Tracing; Disease Transmission, Infectious; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Leprosy; Logistic Models; Male; Middle Aged; Mycobacterium leprae; Predictive Value of Tests; Prospective Studies; Rifampin; Risk Assessment; Sex Factors; Treatment Outcome; Young Adult

Leprosy, whose etiologic agent is Mycobacterium leprae, is an illness of ample clinical and immunopathological spectrum. Although chemokines seem to be involved in the immunopathogenesis of leprosis, few studies have been carried out to unveil the potential of chemokines as biological markers of the disease. The purpose of this study was to investigate the value of measuring CCL2, CCL3, CCL11 and CCL24 in plasma of patients with leprosy (LE) at different stages of multi-drug therapy (MDT). Chemokines were measured by ELISA in plasma of 30 non-infected individuals (NI) and 33 LE patients before and at different stages of treatment. The plasma concentration of CCL11 (p<0.01) and CCL24 (p<0.05) was increased in LE patients before treatment when compared to NI individuals. The plasma concentration of CCL24 decreased after MDT (p<0.05). No differences were observed in the concentration of CCL2 and CCL3 in plasma of NI and LE individuals. The elevated levels of CCL11 and CCL24 in plasma of patients with LE suggest that these chemokines may play a role in disease pathogenesis. Moreover, the decrease of CCL24 after treatment suggests that this chemokine might be useful as a biomarker of response to MDT in patients with leprosy.

Topics: Adult; Aged; Chemokine CCL11; Chemokine CCL24; Chemokines; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Laboratories; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Rifampin; Treatment Outcome

With 249,007 new leprosy patients detected globally in 2008, it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy.. We conducted a single centre, double blind, cluster randomised, placebo controlled trial in northwest Bangladesh between 2002 and 2007, including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to close contacts, with follow-up for four years. The main outcome measure was the development of clinical leprosy. We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio (ICER) between the standard multidrug therapy (MDT) program with the additional chemoprophylaxis intervention versus the standard MDT program only. The ICER was expressed in US dollars per prevented leprosy case.. Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total, $6,009 incremental cost was invested and 38 incremental leprosy cases were prevented, resulting in an ICER of $158 per one additional prevented leprosy case. It was the most cost-effective in neighbours of neighbours and social contacts (ICER $214), slightly less cost-effective in next door neighbours (ICER $497) and least cost-effective among household contacts (ICER $856).. Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world.

Topics: Chemoprevention; Cost-Benefit Analysis; Humans; Leprostatic Agents; Leprosy; Rifampin

BCG vaccination and rifampicin chemoprophylaxis are both strategies for leprosy prevention. While the combined effect is unknown, the combination may give the desired push to halt leprosy transmission. Secondary analysis was done on results from a single centre, double blind, cluster randomized, and placebo-controlled trial. Individually, BCG (given at infancy) and rifampicin showed to protect against leprosy (57% [95% CI: 24-75%] and 58% [95% CI: 30-74%], respectively). The combined strategies showed a protective effect of 80% (95% CI: 50-92%). This is the first time that the additive effect of BCG and rifampicin are shown; the combined strategies can possibly lower leprosy incidence.

Topics: Adult; Bangladesh; BCG Vaccine; Chemoprevention; Double-Blind Method; Female; Humans; Leprostatic Agents; Leprosy; Male; Rifampin; Young Adult

To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts.. Single centre, double blind, cluster randomised, placebo controlled trial.. Leprosy control programme in two districts of northwest Bangladesh with a population of more than four million.. 28,092 close contacts of 1037 patients with newly diagnosed leprosy. 21,711 contacts fulfilled the study requirements.. A single dose of rifampicin or placebo given to close contacts in the second month of starting the index patient's treatment, with follow-up for four years.. Development of clinical leprosy.. 18,869 of the 21,711 contacts (86.9%) were followed-up at four years. Ninety one of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had developed leprosy. The overall reduction in incidence of leprosy using a single dose of rifampicin in the first two years was 57% (95% confidence interval 33% to 72%). The groups did not differ between two and four years. The overall number needed to treat (NNT) to prevent a single case of leprosy among contacts was 297 (95% confidence interval 176 to 537). Differences were found between subgroups at two years, both in reduction of incidence and in NNT.. A single dose of rifampicin given to contacts of patients with newly diagnosed leprosy is effective at preventing the development of clinical leprosy at two years. The effect was maintained, but no difference was seen between the placebo and rifampicin groups beyond two years.. Current Controlled Trials ISRCTN61223447 [controlled-trials.com].

Topics: Double-Blind Method; Humans; Leprostatic Agents; Leprosy; Prospective Studies; Rifampin

Chemoprophylaxis was carried out on high risk group of extended contacts of new leprosy cases in Nyaungdon Township, Ayeyarwaddy Division, Myanmar and serological response was followed up for two years. In September 2003, blood samples were collected from 829 contacts after getting informed consent and sera were tested for immunoglobulin M antibodies using NTP-BSA ELISA test. These 300 seropositives were randomized to treated and non-treated groups. In each group 102 each were enrolled in adults and 48 each in children. A single dose of ROM (rifampicin, ofloxacin and minocycline) and RMP (rifampicin) by body weight was administered to treated group of above 15 years and those below 15 years respectively. The vitamins were administered to non-treated group. The blood samples of all contacts were collected again in September 2004 and September 2005 and ELISA was carried out on paired samples on one plate. The mean optical density (OD) titers before vs after chemoprophylaxis were 0.24 vs 0.10 and 0.20 vs 0.09 in treated and non-treated group respectively in adults and 0.25 vs 0.11 and 0.22 vs 0.11 respectively in children after one year. These were 0.24 vs 0.17 and 0.20 vs 0.19 respectively in adults and 0.25 vs 0.19 and 0.22 vs 0.20 respectively in children after two years. The difference of mean antibody titers before and after chemoprophylaxis in treated group was significantly reduced compared to non-treated group in adults but was not significant in children. The findings show that there is a significant role of chemoprophylaxis on serological response in the form of decreasing antibody titer among the adult group of extended contacts.

Topics: Adolescent; Adult; Antibiotic Prophylaxis; Antibodies, Bacterial; Child; Cohort Studies; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Follow-Up Studies; Humans; Immunoglobulin M; Leprostatic Agents; Leprosy; Minocycline; Myanmar; Mycobacterium leprae; Ofloxacin; Rifampin; Risk; Seroepidemiologic Studies; Time Factors

To describe the rationale, design and preliminary results of an open trial of 6 months uniform multi-drug therapy (U-MDT) for all types of leprosy patients assuming a cumulative relapse rate not exceeding 5% over 5 years of follow-up.. We intended to recruit 2500 patients each in multi-bacillary (MB) and pauci-bacillary (PB) groups from India (five centres) and China (two centres). Standardized clinical criteria were used to assess skin lesions in the field.. A total of 2912 patients enrolled from November 2003 to May 2007 (India, 2746; China, 166). MB patients constituted 39% and 3% had grade 2 disability. During follow-up, 27 patients (0.9%) developed new lesions. Of these, 78% were on account of reactions. Six patients had clinically confirmed relapse. Clofazimine-related skin pigmentation was short-lived and was acceptable to patients. We analysed data for clinical status of skin lesions. About 2.9% of patients were lost to follow-up; 85.9% completed treatment, of whom 19% had inactive skin lesions. PB patients responded better than MB patients (27%vs. 6%; P < 0.001). At the end of the first (n = 2013) and second year (n = 807) of follow-up post-U-MDT, in 49% and 46% patients, lesions were inactive, respectively (59% and 57% in PB, 37% and 28% in MB; P < 0.001).. U-MDT appears to be promising with respect to clinical status of skin lesions.

Topics: Adolescent; Adult; Aged; Child; China; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; India; Leprostatic Agents; Leprosy; Male; Middle Aged; Rifampin; Skin Diseases, Bacterial; Treatment Outcome

Monthly doses of rifampin, ofloxacin, and minocycline (ROM) are expected to be effective treatment for multi-bacillary leprosy. Patients with MB leprosy received ROM (n = 10) or World Health Organization multi-drug therapy (MDT) (n = 11). Treatment with ROM was given as 24 consecutive monthly observed doses of rifampin (600 mg), ofloxacin (400 mg), and minocycline (100 mg). Treatment with MDT was given as 24 consecutive monthly observed doses of rifampin (600 mg) and clofazimine (300 mg), and unobserved daily dapsone (100 mg) and clofazimine (50 mg). Twenty patients completed the 24-month regimens with > 99% compliance. Treatments with ROM and MDT were safe, tolerable, and caused similar improvements in lesions, bacterial indices, and histology. All MDT recipients developed clofazimine-induced pigmentation. Six ROM and nine MDT recipients assessed at five or more years after completion of treatment had no evidence of relapse. Twenty-four months of treatment with ROM is a safe, well-tolerated, and convenient regimen that may provide an alternate therapy to MDT for MB leprosy. Larger trials with sufficient follow-up would better define the role of ROM.

Topics: Adolescent; Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Minocycline; Ofloxacin; Rifampin

In this article, we describe the design, methodology and recruitment findings of the COLEP study. The objectives of this study were to determine the effectiveness of chemoprophylaxis with a single dose of rifampicin in the prevention of leprosy among close contacts of leprosy patients, and to find characteristics of contact groups most at risk to develop clinical leprosy. These characteristics should be usable by routine leprosy control programmes. COLEP consists of a cluster randomized, double-blind and placebo-controlled trial, a cohort study to determine risk factors characterizing the sub-groups most at risk within the total contact group of a patient, and a cohort study using a reference group from the general population to determine the prevalence and incidence of leprosy in the total population of the study area. The follow-up period will be 4 years. A coding system was developed describing the physical and genetic distance of the contact person to the patient. This study in Bangladesh includes 1037 newly diagnosed and previously untreated leprosy patients and their 21,867 contacts. The prevalence of leprosy among contacts was 7.3 per 1000. A total of 21,708 contacts without signs and symptoms of clinical leprosy are included in a trial of chemoprophylaxis with single dose rifampicin, and randomized at contact group level in treatment and placebo arms. The results of this large field trial will become available in the years to come.

Topics: Adolescent; Adult; Age Factors; Chemoprevention; Child; Child, Preschool; Contact Tracing; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; India; Leprosy; Male; Middle Aged; Mycobacterium leprae; Pilot Projects; Prevalence; Reference Values; Rifampin; Risk Assessment; Sex Factors; Treatment Outcome

Gastrointestinal toxicity and red skin discoloration were the major side effects observed in leprosy patients undergoing long-term treatment with clofazimine (CFZ). Hematological and biochemical alterations have been cited among other side effects; however, their real magnitude and clinical significance at the doses currently employed in therapy have not been sufficiently documented. We therefore investigated the correlation between CFZ plasma concentration and biochemical (transaminases, bilirubins, alkaline phosphatase, gamma-glutamyltransferase, amylase, urea, creatinine, and potassium plasma levels) as well as hematological changes blood and reticulocyte counts, osmotic fragility, detection of Heinz bodies and methemoglobinemia (MHM), following in two regimes of treatment: CFZ as a single drug and CFZ as part of multidrug (MDT) therapy, in combination with dapsone and rifampicin. MHM and hemolytic anemia were detected in the MDT group only. Eosinophilia was found in patients of either group. Determination of hepatic, pancreatic and renal biochemical parameters showed rare, occasional changes of apparently no clinical significance. We conclude that CFZ is a generally well tolerated and safe drug when given as a daily dose of 50mg, which is currently used in leprosy patients.

Topics: Blood Cell Count; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Rifampin

Topics: Clofazimine; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leprostatic Agents; Leprosy; Male; Minocycline; Mycobacterium leprae; Ofloxacin; Rifampin; Treatment Outcome

Forty-six, newly detected, previously untreated multibacillary (MB) patients with a bacterial index (BI) of > or = 3+ who had received WHO/MDT for 2 years were followed up for a total duration of 424 person-years and a mean duration of 9.26 +/- 2.98 years per patient. The BIs of the patients continued to fall, and all of the patients, except one, reached skin-smear negativity. WHO/MDT was well accepted and well tolerated. Relapse, which was defined as an increase in the BI of 1+ or more with or without clinical evidence of activity, was observed in only one patient, giving a relapse rate of 2.2% or 0.23 per 100 person-years in patients with a BI of > or = 3+ after long-term follow up. This patient was started on a second course of WHO/MDT to which he responded favorably. WHO/MDT for a fixed duration of 2 years for MB patients as recommended by the WHO is vindicated.

Topics: Adult; Clofazimine; Cohort Studies; Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leprostatic Agents; Leprosy; Male; Neuritis; Recurrence; Rifampin; World Health Organization

Treatment for multibacillary leprosy is presently performed with a multidrug therapy (MDT) scheme maintained for 2 years. Leprosy treatment however can benefit from the reduction of length. The lack of interferon-gamma (IFN-gamma) production by lepromatous leprosy (LL) patients' lymphocytes lead us to use this cytokine in the treatment of multibacillary leprosy associated with MDT in the treatment of multibacillary leprosy, and monitor several clinical and immunological parameters during the course of treatment. A total of 20 multibacillary leprosy patients were evaluated, 10 treated with MDT alone, and 10 treated with MDT + 10 daily doses of 2 x 10(6) international units (IU) of recombinant human IFN-gamma/m2 followed by 10 daily doses of 10(7) IU IFN-gamma/m2, intramuscularly, during the first 20 days of MDT. IFN-gamma was well tolerated and did not cause any increase in the rate of leprosy reactions development during treatment. Decrease of bacillary load, fall of anti-Mycobacterium leprae IgG serum antibodies, changes of histological pattern, as well as changes in lymphocyte proliferation assay in response to mitogens (PHA or PWM), M. leprae antigen or PPD was similar in both groups of patients. Among several soluble immunological markers measured before and 30 days after beginning of treatment, levels of soluble IL-2R receptor increased in patients treated with MDT plus IFN-gamma whereas decreased in patients treated with MDT alone. Soluble ICAM-1 levels decreased in the MDT group but did not change in the MDT + IFN-gamma treated patients. Soluble CD4 and soluble CD8 markers did not change significantly in either group of patients. Neopterin, a marker of macrophage activation, increased in all but one patient treated with MDT + IFN-gamma but in none treated with MDT alone, indicating that IFN-gamma was active in vivo. Our findings indicate that despite being able to promote macrophage activation in multibacillary leprosy patients a short course of systemically administered IFN-gamma is not able to change the clinical course of a long standing disease such as leprosy.

Topics: Adolescent; Adult; Antibodies, Bacterial; Child; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Interferon-gamma; Leprostatic Agents; Leprosy; Lymphocyte Activation; Male; Middle Aged; Neopterin; Recombinant Proteins; Rifampin; Skin

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Clofazimine; Cohort Studies; Dapsone; Erythema Nodosum; Female; Humans; Indoles; Leprostatic Agents; Leprosy; Leukotriene Antagonists; Male; Middle Aged; Nerve Degeneration; Phenylcarbamates; Prednisone; Rifampin; Sulfonamides; Thalidomide; Tosyl Compounds

Topics: Adolescent; Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Glucosephosphate Dehydrogenase Deficiency; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Oman; Practice Guidelines as Topic; Rifampin; World Health Organization

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard multidrug therapy (MDT), to 157 bacteriologically positive, lepromin-negative, multibacillary (LL, BL and BB) leprosy patients. The vaccinees were supported by a well-matched control group of 147 patients with similar type of disease who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 2 years and continued until skin-smear negativity, while the vaccine was given at 3-month intervals up to a maximum of 8 doses. The lepromin response evaluated in terms of percentage of subjects converting to positivity status, measurement in millimeters, and duration of lepromin positivity sustained, reflected a statistically significant better outcome in the vaccine group patients (especially LL and BL leprosy) in comparison to those in the placebo group. The data indicate that lepromin-positivity status seems to have an impact on accelerating the bacteriological clearance, as is evident by the statistically significant accelerated decline in the BI of those patients who converted to lepromin positivity as compared to those remaining lepromin negative throughout therapy and post-therapy follow up. To conclude, the addition of the Mycobacterium w vaccine to standard MDT induces a lepromin response of a statistically significant higher magnitude than that observed with MDT alone.

Topics: Bacterial Vaccines; Clofazimine; Dapsone; Double-Blind Method; Drug Therapy, Combination; Humans; Immunotherapy; Lepromin; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin; Single-Blind Method; Skin Tests; Vaccines, Inactivated

To develop a fully supervisable, monthly administered regimen for treatment of leprosy, the bactericidal effect of a single-dose combination of ofloxacin (OFLO) and minocycline (MINO), with or without rifampin (RMP), against Mycobacterium leprae was studied in the mouse footpad system and in previously untreated lepromatous leprosy patients. Bactericidal activity was measured by the proportional bactericidal method. In mouse experiments, the activity of a single dose of the combination OFLO-MINO was dosage related; the higher dosage of the combination displayed bactericidal activity which was significantly inferior to that of a single dose of RMP, whereas the lower dosage did not exhibit a bactericidal effect. In the clinical trial, 20 patients with previously untreated lepromatous leprosy were treated with a single dose consisting of either 600 mg of RMP plus 400 mg of OFLO and 100 mg of MINO or 400 mg of OFLO plus 100 mg of MINO. The OFLO-MINO combination exhibited definite bactericidal activity in 7 of 10 patients but was less bactericidal than the RMP-OFLO-MINO combination. Both combinations were well tolerated. Because of these promising results, a test of the efficacy of multiple doses of ROM in a larger clinical trial appears justified.

Topics: Adolescent; Adult; Animals; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Mice; Mice, Nude; Middle Aged; Minocycline; Mycobacterium leprae; Ofloxacin; Rifampin

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Minocycline; Ofloxacin; Rifampin; Treatment Outcome

In 1995, a field trial was implemented in Senegal in order to evaluate the efficacy of a regimen based on the monthly supervised intake of rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg to treat leprosy. During the first year of the trial, 220 patients with active leprosy (newly detected or relapsing after dapsone monotherapy) were recruited: 102 paucibacillary (PB) (60 males and 42 females) and 118 multibacillary (MB) (71 males and 47 females). All of them accepted the new treatment (none requested to be preferably put under standard WHO/MDT), no clinical sign which could be considered as a toxic effect of the drug was noted, and none of the patients refused to continue treatment because of any clinical trouble. The compliance was excellent: the 113 patients (PB and MB) detected during the first 6 months of the trial have taken six monthly doses in 6 months, as planned. The rate of clearance and the progressive decrease of cutaneous lesions was satisfactory. Although it is too soon to give comprehensive results, it should be noted that no treatment failure was observed in the 56 PB patients who have completed treatment and have been followed up for 6 months. The long-term efficacy of the new regimen is to be evaluated on the rate of relapse during the years following the cessation of treatment. If that relapse rate is acceptable (similar to that observed in patients after treatment with current standard WHO/ MDT), the new regimen could be a solution to treat, for instance, patients very irregular and/or living in remote or inaccessible areas since no selection of rifampin-resistant Mycobacterium leprae should be possible (a monthly dose of ofloxacin and minocycline being as effective as a dose of dapsone and clofazimine taken daily for 1 month). Nevertheless, until longer term results of this and other trials become available, there is no justification for any change in the treatment strategy, and all leprosy patients should be put under standard WHO/MDT.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Child; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Minocycline; Ofloxacin; Rifampin

Methaemoglobinaemia and haemolytic anaemia were the principal side-effects observed in 30 leprosy patients undergoing long-term treatment with dapsone as a single drug or as part of multidrug therapy. Hepatic, pancreatic and renal evaluations showed no relevant clinical changes. Since N-acetylation is a major metabolic pathway for dapsone, slow acetylation phenotype may be a risk factor for the development of these reactions. To confirm this hypothesis we correlated acetylator phenotype and the haematological and biochemical effects induced by dapsone. No excess proportion of slow acetylators was found. We conclude that slow acetylators are not at greater risk of developing haematological side-effects of dapsone than fast acetylators.

Topics: Blood Cell Count; Blood Chemical Analysis; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Glucosephosphate Dehydrogenase; Humans; Leprostatic Agents; Leprosy; Male; Rifampin

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Combinations; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Ofloxacin; Rifampin; Treatment Outcome; World Health Organization

The results of ofloxacin containing combined drug regimens in the treatment of 60 multibacillary leprosy cases from January 1989 to June 1995 are reported. The objective of the trial is to compare the antileprotic property of ofloxacin and rifampicin in multibacillary leprosy patients and to study the killing rate of M. leprae by ofloxacin and rifampicin before mass treatment can be recommended. The complications and side-effects of ofloxacin and rifampicin were of a mild nature and both drugs were well tolerated. Moderate to marked clinical improvement was noticed in a short period with ofloxacin containing regimens in multibacillary leprosy patients. No persisters were detected in any of the 33 specimens (of mouse footpads) that had been obtained after treatment for 6 months. Ofloxacin if added to the currently used WHO recommended MB-MDT regimen may shorten the duration of treatment. Ofloxacin, therefore, may be considered as a suitable alternative in suspected/proven rifampicin resistant cases and where rifampicin is contraindicated. The results were evaluated on the basis of the clinical conditions, mycobactericidal effectiveness, signs of drug toxicity and side effects.

Topics: Adolescent; Adult; Aged; Animals; Child; Dose-Response Relationship, Drug; Female; Humans; Leprostatic Agents; Leprosy; Male; Mice; Mice, Nude; Middle Aged; Ofloxacin; Rifampin; Thailand; Time Factors; Treatment Outcome

The results of combined chemotherapy trials with regimens containing ofloxacin and rifampicin for the treatment of 60 multibacillary leprosy cases from January 1989 to September 1995 was reported. Clinical improvement was achieved by all regimens from the end of the first month. Most patients continued to improve for 3 years. Bacterial indices were gradually reduced during the treatment. Patients on regimens containing rifampicin were clear of M. leprae at the end of the 5th year. The complications and side-effects of ofloxacin and rifampicin were trivial and both drugs were well tolerated. Ofloxacin added to the current WHO recommended M.B.-MDT regimen may shorten the duration of treatment. Ofloxacin may be an alternative in suspected/proven rifampicin resistant cases or rifampicin contraindicated.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Child; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Ofloxacin; Prognosis; Rifampin

Two hundred and fifty paucibacillary (PB) leprosy patients were treated with WHO recommended multidrug therapy (MDT) and followed up them for four years. The paucibacillary MDT regimen (PBR) was well accepted and tolerated by the patients. Clinical regression was attained in 60% patients after 6 doses of PBR. Reversal reaction occurred in 14% cases and relapse were found in 1.6% cases 18-24 months after completing the treatment. The incidence of reversal reaction was high in patients with more than 2 thickened nerve trunks associated with more than 5 patches.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bangladesh; Child; Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leprosy; Male; Middle Aged; Rifampin

A long-term survey of leprosy patients of all clinical types, starting at the time of diagnosis, was carried out to monitor clinical, bacteriological and immunological parameters at regular intervals during multiple drug therapy (MDT). The patients were assigned to two groups for treatment following WHO guidelines: paucibacillary (PB) and multibacillary (MB). Immunoglobulin levels, specific antibodies, skin-test responses to different soluble mycobacterial antigens (new tuberculins), and in vitro proliferative responses to mitogens and to antigens were measured during treatment, as were clinical changes, the bacterial index, and clinical improvement. No exact relations between disease activity and IgM antibody levels, both IgM immunoglobulin and specific IgM antibody to a species-specific antigen (ND-O-BSA), could be seen for MB patients. Changes in in vitro cell-mediated immunity and skin-test response seemed to be more directly related to the bacterial load and could reflect the improvement of bacteriological and clinical parameters during MDT.

Topics: Agglutination Tests; Antibodies, Bacterial; Antigens, Bacterial; Clofazimine; Dapsone; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Humans; Immunity, Cellular; Immunoglobulin M; Immunoglobulins; Leprostatic Agents; Leprosy; Longitudinal Studies; Lymphocyte Activation; Mycobacterium leprae; Rifampin; Skin Tests

We compared 2 single-dose regimens for the treatment of paucibacillary leprosy in a randomized clinical trial in Zaïre. The regimens were: C2 (rifampicin 40 mg/kg and 1200 mg clofazimine once) and C4 (rifampicin 40 mg/kg, clofazimine 100 mg, DDS 100 mg and ethionamide 500 mg once). An analysis of the results of patients enrolled between May 1987 and December 1988, with a maximum follow-up of 4 years, is presented. A total of 622 patients were enrolled and 14 paucibacillary and 1 multibacillary relapses occurred. The overall paucibacillary relapse rate was 2.4 per 100 person years. This relapse rate was higher for older patients as well as for patients with 3 or more lesions. The probability of cure at 3 years is 0.816 for C2 and 0.823 for C4, the difference not being statistically significant. The probability of cure at 3 years with either regimen is higher for patients with 1 or 2 lesions (0.872) than for patients with 3 or more lesions (0.787), and it is higher for patients with a bacterial index of 0 (0.831) than for patients with a bacterial index of 1 (0.699). These results are compared to other studies. We also discuss the potential of single-dose treatment regimens for paucibacillary leprosy.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Ethionamide; Female; Humans; Infant; Leprosy; Male; Middle Aged; Prognosis; Recurrence; Rifampin

Immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium w, was given in addition to standard multidrug therapy (MDT) to 53 multibacillary lepromin negative patients belonging to BB, BL and LL types of leprosy (vaccine group). An equal control group received MDT and injections of micronized starch as placebo. Both the vaccine and placebo were administered intradermally every 3 months. The patients were evaluated at determined intervals by clinical, bacteriological and histopathological parameters and lepromin testing. Reactional episodes were analysed with reference to incidence, onset, frequency and severity during and after release from treatment (RFT). Incidence of reversal reaction (RR) was marginally higher in the vaccine group (22.6% vaccine group vs 15% control group). All cases with a history of downgrading type 1 reaction developed RR during therapy. Most episodes occurred within the 1st year of the commencement of therapy--50% developing within 3 months. Late reversal reaction (after RFT) were observed in 3.8% of cases in both groups, and 50% of the reactors in the control group and 33% in the vaccine group had repeated reactional episodes. Incidence of neuritis associated with RR as well as isolated neuritis was similar in both groups.

Topics: Bacterial Vaccines; Clofazimine; Combined Modality Therapy; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Neuritis; Rifampin; Single-Blind Method

The cure rates of two treatment regimens in PB leprosy were compared in a prospective randomized trial: treatment U consisting of a single dose of rifampicin 40 mg/K bodyweight, and treatment A of rifampicin 1500 mg in a single dose, followed by one year of daily dapsone 100 mg. In patients with a BI = 0, the cure rates evaluated on the basis of histopathology of skin biopsies, were identical for the two regimens but in patients with a BI = 1, cure and relapse rates were unacceptable. For this reason and particularly the need to separate patients on the basis of the BI in skin biopsies, the single dose regimen does not appear to be suited for wide-scale application.

Topics: Dapsone; Democratic Republic of the Congo; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprosy; Prospective Studies; Recurrence; Rifampin; Skin

The objective of the present study was to define short-course treatment regimens for PB leprosy and to compare them with the 'classical' dapsone treatment and the WHO-PB regimen. Five treatment regimens were studied and evaluated by the histologic evolution. The regimens were: (1) dapsone 100 mg daily, non-supervised for 3 years; (2) RMP 900 mg supervised, once weekly, 8 doses; (3) idem 12 doses; (4) RMP 600 mg, once monthly, supervised, 6 doses and during this treatment dapsone 100 mg daily unsupervised; (5) RMP 600 mg together with dapsone 100 mg daily, supervised for 6 days. For each of these regimens there were between 114 and 195 person-years of follow-up. Results are comparable for the 5 treatment regimens, and reach 65-75% cure rates at 36 months and 80-90% at 48 months after the start of therapy. The relapse rate for all groups is about 0.5% per year. The difficulty for the diagnosis of relapse in PB leprosy is discussed. It is concluded that treatment of PB leprosy can be relatively simple but that a relatively long time is needed to evaluate its effect.

Topics: Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprosy; Mycobacterium leprae; Prospective Studies; Random Allocation; Recurrence; Remission Induction; Rifampin

A prospective study is being undertaken in Western Kenya to evaluate the effectiveness and tolerability of WHO-MDT, while at the same time comparing it to a modified multidrug regimen, which is rifampicin 1500mg at the onset supervised, and repeated after 3 months and dapsone 100mg daily for 6 months. Preliminary analysis done on 127 cases admitted into the study are presented. The inactivity index observed between 0-12 weeks was 20% for WHO-MDT and 47% for modified-MDT (p less than 0.01). The inactivity index observed between 0-24 weeks was 63.3% for WHO-MDT and 82.3% for modified-MDT (p less than 0.05). The inactivity index observed between 0-32 weeks was 83% for WHO-MDT, and 88% for modified-MDT. Type 1 reaction was noted in 23.3% on those on WHO-MDT, and 20.3% on those cases on modified-MDT (p greater than 0.1). Compliance rate was 93.8% for those on WHO-MDT and 95.2% on those on modified MDT. All regimens were well tolerated. These preliminary results indicate that MDT is effective in treatment of paucibacillary leprosy, and also that clinical cure can be achieved in much shorter duration, particularly with higher dosage of rifampicin.

Topics: Adolescent; Adult; Child; Child, Preschool; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Kenya; Leprosy; Male; Middle Aged; Prospective Studies; Rifampin; Sex Factors; Time Factors

In 1981, 1982 and 1983, 216 multibacillary patients in Anjouan (Comores) and Burundi were treated for 8 weeks with daily rifampicin (600 mg) ethionamide (500 mg) and dapsone (100 mg) or clofazimine (100 mg) followed for 44 weeks by once weekly rifampicin (600 mg) and daily ethionamide (500 mg) and dapsone (100 mg) or clofazimine (100 mg). There were 109 previously untreated patients and 107 patients who had dapsone monotherapy, 16 of whom were infected with proven dapsone resistant Mycobacterium leprae. Clinical and bacteriological results were excellent but hepatotoxicity of this regimen remains a problem. No relapses were observed during a 2 to 6 years (mean: 4.29 years) follow-up period after the end of treatment (upper 95% confidence limit of 0.40 per 100 persons years). It is concluded that multibacillary leprosy can be successfully treated with a regimen of one year duration, but less toxic regimens, more easily applicable in the field, are necessary.

Topics: Clinical Trials as Topic; Clofazimine; Cohort Studies; Dapsone; Drug Administration Schedule; Ethionamide; Female; Humans; Leprostatic Agents; Leprosy; Male; Rifampin

From 1981 to 1983 all multibacillary patients presenting at the collaborating centres in Zaire and Rwanda were treated with one of the following regimens: 6 months supervised daily RMP 600 mg, ETH 500 mg and DDS 100 mg or CLO 100 mg followed by 6 months unsupervised daily DDS 100 mg or CLO 100 mg with ETH 500 mg added or not. These regimens gave rise to hepatotoxicity, reversal and erythema nodosum leprosum reactions as described previously. Bactericidal activity was excellent. Among the 289 patients in the trial, with a mean follow-up period of 3.88 years, no relapses were observed, with an upper 95% confidence limit of 0.35 per 100 person years. Because of the hepatotoxicity, alternative short-course therapies need to be tested.

Topics: Clinical Trials as Topic; Clofazimine; Cohort Studies; Dapsone; Drug Administration Schedule; Ethionamide; Female; Humans; Leprostatic Agents; Leprosy; Male; Rifampin

Pyrazinamide in a dose of 1500 mg was given to 63 borderline lepromatous (BL) and lepromatous (LL) leprosy patients on different drug regimens for the initial 2 months of therapy. Fifty-one BL and LL patients were put on the same drug regimens without pyrazinamide. There was a rapid and good clinical improvement in the patients in both of the groups. At the end of 2 years, the patients who received pyrazinamide had a morphological index (MI) of zero as compared to those patients who did not receive pyrazinamide, some of whom still had solidly staining bacilli. One out of 20 (5%) scrotal (smooth muscle) biopsies of the patients who received pyrazinamide had growth in the mouse foot pad as compared to 9 out of 38 (23.7%) smooth muscle biopsies of the patients who did not receive pyrazinamide. At the end of 5 years, the patients who received pyrazinamide had slightly better results compared with the non-pyrazinamide group. Pyrazinamide appears to have some effect against persisters in multibacillary leprosy. A well-controlled, randomized trial with longer duration of pyrazinamide therapy in a larger group of patients needs to be carried out to unequivocally determine the exact role of pyrazinamide in leprosy.

Topics: Adolescent; Adult; Animals; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Isoniazid; Leprosy; Male; Mice; Middle Aged; Muscle, Smooth; Pyrazinamide; Rifampin; Scrotum; Skin; Thioacetazone

Topics: Clinical Trials as Topic; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprosy; Prospective Studies; Random Allocation; Rifampin

The ability of the neonatally thymectomized Lewis rat (NTLR) and the congenitally athymic (nude) rat systems to detect low numbers of viable Mycobacterium leprae in tissues from lepromatous leprosy patients undergoing short-course chemotherapy was compared with that of the commonly employed mouse foot pad assay. Fifteen previously untreated lepromatous patients were randomly assigned to treatment regimens of either a single initial 1500 mg dose of rifampin plus daily doses of 100 mg of dapsone, or weekly doses of 900 mg of rifampin plus daily doses of 100 mg of dapsone. Four skin biopsies from each patient taken sequentially up to one month after initiation of therapy were used as the source of the M. leprae inocula. Only 2 of 57 skin biopsies (2%) proved positive for viable M. leprae following direct inoculation into mouse foot pads. However, 30 of 58 patient biopsies (52%) provided positive for viable M. leprae following direct passage into NTLR foot pads or in subsequent mouse subpassage. In contrast, the nude rat was observed to be a poor monitor of such trials. Although not statistically significant, the regimen consisting of a single dose of rifampin plus daily dapsone resulted in a lower percentage of biopsies found to contain viable M. leprae at each of the four sampling intervals.

Topics: Animals; Dapsone; Drug Therapy, Combination; Humans; Immune Tolerance; Immunosuppression Therapy; Leprosy; Mice; Mice, Inbred BALB C; Mycobacterium leprae; Rats; Rats, Inbred Lew; Rifampin; Thymectomy; Thymus Gland

Topics: Clinical Trials as Topic; Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Ethionamide; Humans; Leprosy; Random Allocation; Rifampin

Topics: Adult; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prospective Studies; Prothionamide; Random Allocation; Rifampin

A clinical trial was initiated at ALERT, Addis Ababa, Ethiopia, to study the effect of one-year supplementary treatment on the incidence of dapsone-resistant leprosy in lepromatous patients already on dapsone monotherapy. A total of 806 patients on dapsone therapy were assigned to one of four groups. The first group served as a control group, the second received a combination tablet of thiacetazone and INH (Thiazina) daily for 12 months, the third group received Thiazina daily for 12 months plus rifampin daily during months 1 and 7, and the fourth group received rifampin daily during months 1 and 7 but no Thiazina. Eighty-three percent of the patients were followed for five years after discontinuation of the supplementary treatment. The annual incidence of relapses and dapsone-resistant leprosy in the control group appeared to be 2.3% and 0.7%, respectively. The Thiazina treatment had no significant effect on either the overall relapse rate or the incidence of dapsone-resistant leprosy. The rifampin treatment, on the other hand, did significantly lower the relapse rate and only a single case of dapsone resistance was detected. A high incidence of relapse was found in young female patients. Nineteen of the 45 relapsed patients were bacteriologically negative at the start of the supplementary treatment and six had already been negative for over five years.

Topics: Adolescent; Adult; Dapsone; Drug Combinations; Drug Resistance; Humans; Isoniazid; Leprosy; Recurrence; Rifampin; Sex Factors; Thioacetazone

During treatment of multibacillary leprosy with the combination rifampin (RMP) 600 mg, ethionamide (ETH) 500 mg, and either dapsone (DDS) or clofazimine (CLO) 100 mg, hepatotoxicity was observed in 4.5% of 596 patients. Hepatitis appeared after 5-186 days, with a mean of 93 days and a median of 76 days. Mortality was 26%. ETH and DDS or CLO were administered daily in all regimens in which hepatitis occurred. RMP was given either daily or daily during the first two weeks or eight weeks, followed by a once-weekly dose. It is concluded that the combination RMP + ETH is the toxic component. In some patient groups there was a high correlation of toxicity with age. A regimen in which RMP was administered only twice a week during three months was not accompanied by hepatotoxicity. Future studies should show if reduction of the daily dose of ETH or reduction of the duration of the administration of RMP + ETH might reduce the incidence of hepatotoxicity while conserving the efficacy.

Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Child; Clinical Trials as Topic; Clofazimine; Dapsone; Drug Therapy, Combination; Ethionamide; Female; Humans; Leprosy; Male; Middle Aged; Prospective Studies; Rifampin

Topics: Adolescent; Adult; Clinical Trials as Topic; Dapsone; Female; Humans; Leprosy; Male; Middle Aged; Prospective Studies; Random Allocation; Rifampin; Time Factors

Topics: Acedapsone; Adolescent; Adult; Aged; Child; Child, Preschool; Clinical Trials as Topic; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Infant; Infant, Newborn; Leprosy; Male; Middle Aged; Rifampin; Trinidad and Tobago

Topics: Animals; Clinical Trials as Topic; Clofazimine; Dapsone; Female; Humans; Leprostatic Agents; Leprosy; Male; Mice; Prothionamide; Rifampin

Topics: Clinical Trials as Topic; Clofazimine; Dapsone; Drug Administration Schedule; Humans; Leprostatic Agents; Leprosy; Prospective Studies; Rifampin

In an international multicentre controlled single-blind trial of 93 previously untreated lepromatous leprosy patients the therapeutic effects of adding rifampicin, 450 mg/day orally or 1,200 mg once monthly in a single oral dose, to dapsone (50 mg/day orally) for the first 6 months of treatment were compared. Clinical and histopathological improvements and bacteriological regression, indicated by the decreases in the bacterial and morphological indices of the skin and nose-blow smears, were satisfactory and practically identical after 6 months' treatment. The once-monthly rifampicin schedule was better tolerated than the daily one. In view of the good therapeutic efficacy and tolerability, the much lower cost of treatment (about one-tenth of that of the daily rifampicin regimen) and the possibility of administration under supervision, once-monthly rifampicin given in a single oral 1,200 mg dose should be recommended, along with a standard dapsone regimen, for large-scale, initial, and intensive combination treatment of patients with lepromatous and borderline-lepromatous leprosy, to help prevent an increase in dapsone resistance. A third antileprosy drug (e.g., clofazimine) may be added to this initial dual-treatment regimen.

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Methods; Middle Aged; Random Allocation; Rifampin

Topics: Adult; Clinical Trials as Topic; Clofazimine; Drug Resistance, Microbial; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Rifampin; Sulfones; Thioacetazone

Rifampicin trial in 66 lepromatous cases is reported. Some of these cases were previously treated with Dapsone and some were fresh cases, the main criterion for selection being high BI and MI. The cases were divided into 7 groups depending on the dosage and frequency of administration of RFP. Dapsone was given in all the cases. Whenever MI became zero, Rifampicin was stopped but Dapsone continued. In those cases when MI remained high, RFP was stopped either because of non-improvement or reactions or the patient dropped out. Only 2 groups showed good improvement: RFP 900 mg. once a week and RFP 600 mg. 6 times a week. The latter group is preferable and the average period required to render MI zero was about 45 days.

Topics: Clinical Trials as Topic; Humans; Leprosy; Rifampin

Topics: Adolescent; Adult; Child; Clinical Trials as Topic; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Rifampin

Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Leprosy; Mice; Microbial Sensitivity Tests; Mycobacterium leprae; Rifampin

In this controlled trial in 35 patients with lepromatous leprosy the therapeutic effects of adding rifampin 450 mg daily (Regimen A) or 1200 mg once a month (Regimen B) to a standard dapsone regimen of 50 mg daily were practically identical. Moderate to marked clinical improvement was observed in 88% and 83% of the patients treated with Regimens A and B respectively. The average rates of decrease in the MI of the skin smears and nose-blow smears were similar. The average decreases in the BI of the skin smears were 0.7 and 0.6 in patients on the Regimen A and B respectively. Following 6 months' treatment with Regimens A and B the average decreases in the Logarithmic Bacterial Indexes of Biopsies were 4.7% and 7% respectively. The once-monthly rifampin schedule was well tolerated and did not lead to "flu" syndrome, anuria, oliguria, hemolytic anemia, thrombocytopenia, or anaphylactic shock. This trial revealed the satisfactory efficacy, good tolerability, and practicability of a supervised once-monthly 1200 mg single oral dose rifampin schedule as a component of combination regimes for the initial treatment of patients with lepromatous (LLs and LLp) leprosy.

Topics: Adolescent; Adult; Aged; Biopsy; Child; Clinical Trials as Topic; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Middle Aged; Rifampin; Skin

A double blind trial involving intermittent administration of Rifampicin in addition to daily DDS has been undertaken in order to evaluate the efficacy as also the potential dangers of such a regimen. Twenty untreated LL cases who were otherwise healthy were included in the study. Ten cases received weekly 900 mg Rifampicin for 6 weeks in addition to 100 mg daily DDS, while the rest were treated likewise but were given similar looking placebo capsules instead of RFP. A nine month follow-up, as also mouse foot pad results indicate that the efficacy of this regimen was found to be better than that with DDS alone and this compares favourably with trials involving 600 mg Rifampician administration daily. No major untoward side effects were encountered in the trial group thought the incidence of ENL was slightly higher in the trial group.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Clinical Trials as Topic; Dapsone; Double-Blind Method; Drug Therapy, Combination; Erythema Nodosum; Humans; Leprosy; Mice; Mitotic Index; Mycobacterium leprae; Rifampin; Time Factors

The results of treatment of the group of leprosy patients at the lepromatous side of the leprosy spectrum registered at the Department of Dermatology of the University of Amsterdam in the years 1950-1976 were studied. The average duration of treatment to obtain bacteriologically negative skin biopsies in patients who were untreated at the time of registration, was 5 years. A substantial number of patients suffered a relapse; the main reasons for these relapses were discontinuation of treatment and DDS treatment in low dosage.

Topics: Clinical Trials as Topic; Clofazimine; Dapsone; Drug Evaluation; Humans; Leprostatic Agents; Leprosy; Netherlands; Phenylthiourea; Recurrence; Rifampin; Time Factors

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Middle Aged; Mycobacterium leprae; Nasal Mucosa; Rifampin; Skin

A trial of monthly administration of Rifampicin in 2 doses of 900 mg each on successive days for 3 months along with DDS 100 mg daily has been undertaken. The results have been compared with 2 groups of controls, one, which was administered 300 mg Rifampicin daily for 3 months followed by DDS, and the other which received 100 mg DDS alone. The findings show that the efficacy of this pulsed regimen is almost similar to continuous rifampicin administration and better than DDS alone. No significant adverse effects were encountered in the trial. The regimen thus merits large scale trials in the field.

Topics: Adolescent; Adult; Clinical Trials as Topic; Dapsone; Humans; Leprosy; Nasal Septum; Rifampin; Skin; Time Factors

Topics: Adolescent; Adult; Clinical Trials as Topic; Dapsone; Female; Humans; Leprosy; Male; Rifampin

Over 100 patients with lepromatous leprosy were treated with rifampicin in a series of pilot, uncontrolled, and controlled trials in 1968-77. The rapid bactericidal effect of rifampicin on Mycobacterium leprae was confirmed. Clinical improvement became apparent sometimes as early as 14 days after the start of treatment. Nevertheless, a few persisting viable M leprae were detected as long as five years after the start of treatment with rifampicin either by itself or in combination with the bacteriostatic drug thiambutosine. Treatment with rifampicin and dapsone for six months reduced the number of persisting leprosy bacteria more than treatment with dapsone alone. Although rifampicin proved more effective than dapsone, it is unlikely that used by itself if can significantly shorten the length of treatment in lepromatous leprosy. Therefore initial intensive combined treatment with two or more bactericidal drugs (including rifampicin) warrants further investigation in both untreated leprosy and lepromatous leprosy resistant to dapsone.

Topics: Animals; Clinical Trials as Topic; Dapsone; Drug Combinations; Humans; Leprosy; Mice; Mycobacterium leprae; Phenylthiourea; Rifampin

A double-blind comparative trial of 300 mg of Rifampicin given daily as against 50 mg D.D.S. administered likewise for an initial period of 3 months has been undertaken on 24 untreated cases of lepromatous leprosy. All the patients have been followed up for 6 months. The results revealed that patients in the former group became non-infective, as concluded from M.I. and mouse foot-pad results, within 3-4 weeks and their nasal ulcers healed faster. Clinical improvement was slightly better in the former group while no bacteriological differences were noticed in the two groups. E.N.L. was milder and slightly less common in the Rifampicin group.

Topics: Clinical Trials as Topic; Dapsone; Double-Blind Method; Follow-Up Studies; Humans; Leprosy; Male; Rifampin

Topics: Adolescent; Adult; Aged; Animals; Clinical Trials as Topic; Clofazimine; Dapsone; Female; Humans; Leprosy; Male; Mice; Middle Aged; Mycobacterium leprae; Regression Analysis; Rifampin; Skin

Interrelationships among six patient characteristics recorded upon entry into the trial were analyzed for 67 patients with lepromatous and near-lepromatous leprosy admitted into two chemotherapy trials. Sex was found to be significantly associated with age and with the histopathologic classification; disproportionately large numbers of older patients and of patients classified as borderline-lepromatous (BL) were males. Classifications of the disease process by clinical and histopathologic criteria were closely associated, but many patients classified BL on histopathological grounds were classified fully lepromatous by the clinical criteria. Measurements of the number of Mycobacterium leprae in the patients made by three methods were also significantly correlated. No significant correlations were found between either classification of the disease process on the one hand, and any of the measurements of the numbers of organisms on the other.

Topics: Adolescent; Adult; Age Factors; Aged; Cell Count; Clinical Trials as Topic; Clofazimine; Dapsone; Female; Humans; Leprosy; Male; Middle Aged; Mycobacterium leprae; Rifampin; Sex Factors; Skin; Statistics as Topic

A controlled trial of Rifampicin plus Dapsone had been in progress for two years in the Department of Leprology, School of Tropical Medicine, Calcutta. Interim results of this trial after six months treatment were reported in 1976. The present paper is the final report of the study after two years of treatment. The study reveals that with Rifampicin, MI falls rapidly after six months, but changes in BI are not better than in the DDS group. As a matter of fact, regarding BI, treatment with DDS has given better results as two cases have become negative in the DDS group while no case has become negative in the Rifampicin group. It is, therefore, concluded that clinical improvement with Rifampicin is similar to that with DDS.

Topics: Clinical Trials as Topic; Dapsone; Leprosy; Rifampin; Time Factors

Rusults of treatment with Rifampicin in ten untreated and uncomplicated cases of active lepromatous leprosy are compared with those of D.D.S. in a similar number of cases. Though clinical improvement was similar in both the groups, improvement in B.I. and M.I. appears to be better in the latter group. High price of Rifampicin is its greatest drawback at present.

Topics: Adolescent; Adult; Clinical Trials as Topic; Dapsone; Female; Humans; Leprosy; Male; Middle Aged; Rifampin

Patients with borderline-lepromatous (BL) or fully lepromatous (LL) leprosy were treated in the sanitarium for approximately 1 year with oral rifampin (600 mg daily) or with oral dapsone (100 mg daily). They were then treated as outpatients with intramuscular acedapsone (225 mg every 12 weeks) or oral dapsone (50 mg daily). They have now been followed for a total of 28 to 34 months. Death of Mycobacterium leprae during the initial 24 weeks was monitored by mouse inoculation with M. leprae from skin punch biopsy specimens. With rifampin therapy, death of M.leprae occurred rapidly, and viable M. leprae were nearly undetectable by the time the first specimen was taken after the start of treatment, at 4 weeks. With dapsone therapy, death of M. leprae was slower, and in some cases the inoculation results were still positive at 12 weeks. The therapeutic response during the period of outpatient treatment has been satisfactory. The number of dead M. leprae, as measured by the bacterial index in skin smears and the number of acid-fast bacteria in skin specimens, has continued to decrease, and clinical progress has been satisfactory. The measured drug-induced death of M. leprae occurred at about the same rate in BL patients as in LL patients. Disappearance of dead M. leprae from the tissues was much more rapid in BL patients than in LL patients.

Topics: Acetamides; Animals; Clinical Trials as Topic; Dapsone; Drug Administration Schedule; Erythema Nodosum; Humans; Leprosy; Mice; Microbial Sensitivity Tests; Mycobacterium leprae; Philippines; Recurrence; Rifampin; Sulfones; Time Factors

Acedapsone (DADDS), a repository sulfone given by injection five times a year, has been used since 1967 for the treatment of all leprosy patients in the Karimui, an area of diffic-lt access. More than 460 patients have been treated, 336 beginning in November 1967 and continuing through the latest assessment 6 years later. The injections have been well received and they have been administered very regularly. Clinical observations were begun before 1967, as a base-line of assessments was available for the patients whose disease appeared before that time. The response to DADDS therapy has been satisfactory except in 5 of the 28 multibacillary patients in whose smears solid-staining Mycobacterium leprae have reappeared. M. leprae was isolated in mice from three of these patients; one strain has been proven to be completely susceptible to dapsone (DDS), and the other two very probably are. DDS levels in the plasma of these five patients were normal and well above the minimal inhibitory concentration. The most probable explanation is that a few viable M. leprae survived in the presence of inhibitory concentrations of DDS for the 4 to 6 years during which dead bacilli were disintegrating and disappearing from the tissues. The other 23 multibacillary patients responded satisfactorily. The decrease in the number of M. leprae in the skin smears has been most prompt in patients with low initial bacterial loads and in those with borderline lepromatous diagnoses. A high initial bacterial load and a fully lepromatous diagnosis were associated with a slow initial loss of M. leprae in the 1st year, followed by a more rapid loss the next year. All of the multibacillary patients have now been treated by the addition of a 90-day course of rifampicin.

Topics: Acetamides; Adolescent; Adult; Aged; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Dapsone; Dosage Forms; Female; Humans; Infant; Leprostatic Agents; Leprosy; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium leprae; New Guinea; Recurrence; Remission, Spontaneous; Rifampin; Time Factors

Topics: Animals; Clinical Trials as Topic; Humans; Leprostatic Agents; Leprosy; Mice; Mycobacterium leprae; Rifampin

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Clofazimine; Dapsone; Female; Humans; Leprosy; Male; Middle Aged; Rifampin; Time Factors

Topics: Adult; Clinical Trials as Topic; Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Rifampin

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prothionamide; Rifampin

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Mycobacterium leprae; Prothionamide; Rifampin

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Malta; Prothionamide; Rifampin

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Adolescent; Adult; Child; Child, Preschool; Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Ethiopia; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prothionamide; Rifampin

Topics: Adolescent; Adult; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; India; Leprostatic Agents; Leprosy; Male; Middle Aged; Rifampin

Topics: Animals; Biopsy; Clinical Trials as Topic; Dapsone; Dose-Response Relationship, Drug; Humans; Leprosy; Mice; Mycobacterium leprae; Rifampin; Time Factors

Rifampicin showed high activity against experimental leprosy, inhibiting the multiplication of dapsone-sensitive and dapsone-resistant strains of Mycobacterium leprae in mice fed 5 mg./kg. body weight. In a formal pilot-type trial on six previously untreated patients with active lepromatous leprosy, rifampicin (600 mg. daily by mouth) was as effective as standard treatment with dapsone. Myco. leprae, however, appeared to be killed more rapidly by rifampicin than by dapsone or other antileprosy drugs so far studied. This was confirmed on a further 10 patients, including two with dapsone resistance, and from the infectivity in mice of bacilli recovered from patients during treatment with rifampicin or dapsone. These results are consistent with the bactericidal activity of rifampicin against other micro-organisms, which could be important to the chemotherapy of leprosy, since all antileprosy drugs in current use are bacteriostatic.

Topics: Animals; Clinical Trials as Topic; Dapsone; Drug Resistance, Microbial; Humans; Leprosy; Mice; Mycobacterium leprae; Rifampin

Topics: Case-Control Studies; Dapsone; Drug Therapy, Combination; Humans; Hypersensitivity; Leprostatic Agents; Leprosy; Ofloxacin; Rifampin

Progress towards leprosy elimination is threatened by increasing incidence in 'hot-spot' areas where more effective control strategies are urgently required. In these areas, active case finding and leprosy prevention limited to known contacts is insufficient for control. Population-wide active case-finding together with universal prevention through mass drug administration (MDA) has been shown to be effective in 'hot-spot' areas, but is logistically challenging and expensive. Combining leprosy screening and MDA with other population-wide screening activities such as for tuberculosis may increase programme efficiency. There has been limited evaluation of the feasibility and effectiveness of combined screening and MDA interventions. The COMBINE study aims to bridge this knowledge gap.. This implementation study will assess the feasibility and effectiveness of active leprosy case-finding and treatment, combined with MDA using either single-dose rifampicin or rifamycin-containing tuberculosis preventive or curative treatment, for reducing leprosy incidence in Kiribati. The leprosy programme will run over 2022-2025 in concert with population-wide tuberculosis screening-and-treatment in South Tarawa. The primary research question is to what extent the intervention reduces the annual leprosy new case detection rate (NCDR) in adults and children compared with routine screening and postexposure prophylaxis (PEP) among close contacts (baseline leprosy control activities). Comparisons will be made with (1) the preintervention NCDR separably among adults and children in South Tarawa (before-after study) and (2) the corresponding NCDRs in the rest of the country. Additionally, the postintervention prevalence of leprosy obtained from a survey of a 'hot-spot' sub-population will be compared with prevalence documented during the intervention. The intervention will be implemented in collaboration with the Kiribati National Leprosy Programme.. Approval has been obtained from the Kiribati Ministry of Health and Medical Services (MHMS), the University of Otago (H22/111) and the University of Sydney (2021/127) Human Research Ethics Committees. Findings will be shared with the MHMS, local communities and internationally through publication.

Topics: Adult; Child; Dermatitis; Humans; Leprosy; Mass Drug Administration; Micronesia; Rifampin

Topics: Endemic Diseases; Florida; Humans; Leprosy; Rifampin

Topics: Humans; Leprosy; Rifampin

Topics: Humans; Leprosy; Rifampin

Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India.. Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain.. Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance.. The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.

Topics: Cross-Sectional Studies; Dapsone; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; India; Leprostatic Agents; Leprosy; Mycobacterium leprae; Ofloxacin; Rifampin

Mycobacterium leprae, the causative organism of leprosy, harbors many antigenic proteins, and one such protein is the 18-kDa antigen. This protein belongs to the small heat shock protein family and is commonly known as HSP18. Its chaperone function plays an important role in the growth and survival of M. leprae inside infected hosts. HSP18/18-kDa antigen is often used as a diagnostic marker for determining the efficacy of multidrug therapy (MDT) in leprosy. However, whether MDT drugs (dapsone, clofazimine, and rifampicin) do interact with HSP18 and how these interactions affect its structure and chaperone function is still unclear. Here, we report evidence of HSP18-dapsone/clofazimine/rifampicin interaction and its impact on the structure and chaperone function of HSP18. These three drugs interact efficiently with HSP18 (having submicromolar binding affinity) with 1 : 1 stoichiometry. Binding of these MDT drugs to the 'α-crystallin domain' of HSP18 alters its secondary structure and tryptophan micro-environment. Furthermore, surface hydrophobicity, oligomeric size, and thermostability of the protein are reduced upon interaction with these three drugs. Eventually, all these structural alterations synergistically decrease the chaperone function of HSP18. Interestingly, the effect of rifampicin on the structure, stability, and chaperone function of this mycobacterial small heat shock protein is more pronounced than the other two MDT drugs. This reduction in the chaperone function of HSP18 may additionally abate M. leprae survivability during multidrug treatment. Altogether, this study provides a possible foundation for rational designing and development of suitable HSP18 inhibitors in the context of effective treatment of leprosy.

Topics: Antigens, Bacterial; Bacterial Proteins; Clofazimine; Dapsone; Heat-Shock Proteins; Host-Pathogen Interactions; Humans; Hydrophobic and Hydrophilic Interactions; Leprostatic Agents; Leprosy; Molecular Chaperones; Mycobacterium leprae; Protein Binding; Protein Structure, Secondary; Rifampin

Delay in case detection is a risk factor for developing leprosy-related impairments, leading to disability and stigma. The objective of this study was to develop a questionnaire to determine the leprosy case detection delay, defined as the period between the first signs of the disease and the moment of diagnosis, calculated in total number of months. The instrument was developed as part of the PEP4LEP project, a large-scale intervention study which determines the most effective way to implement integrated skin screening and leprosy post-exposure prophylaxis with a single-dose of rifampicin (SDR-PEP) administration in Ethiopia, Mozambique and Tanzania.. A literature review was conducted and leprosy experts were consulted. The first draft of the questionnaire was developed in Ethiopia by exploring conceptual understanding, item relevance and operational suitability. Then, the first draft of the tool was piloted in Ethiopia, Mozambique and Tanzania. The outcome is a questionnaire comprising nine questions to determine the case detection delay and two annexes for ease of administration: a local calendar to translate the patient's indication of time to number of months and a set of pictures of the signs of leprosy. In addition, a body map was included to locate the signs. A 'Question-by-Question Guide' was added to the package, to provide support in the administration of the questionnaire. The materials will be made available in English, Oromiffa (Afaan Oromo), Portuguese and Swahili via https://www.infolep.org.. It was concluded that the developed case detection delay questionnaire can be administered quickly and easily by health workers, while not inconveniencing the patient. The instrument has promising potential for use in future leprosy research. It is recommended that the tool is further validated, also in other regions or countries, to ensure cultural validity and to examine psychometric properties like test-retest reliability and interrater reliability.

Topics: Adolescent; Adult; Aged; Child; Contact Tracing; Cross-Sectional Studies; Ethiopia; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mozambique; Post-Exposure Prophylaxis; Reproducibility of Results; Rifampin; Surveys and Questionnaires; Tanzania; Young Adult

Leprosy post-exposure prophylaxis (LPEP) with single dose rifampicin (SDR) can be integrated into different leprosy control program set-ups once contact tracing has been established. We analyzed the spatio-temporal changes in the distribution of index cases (IC) and co-prevalent cases among contacts of leprosy patients (CP) over the course of the LPEP program in one of the four study areas in Brazil, namely the municipality of Alta Floresta, state of Mato Grosso, in the Brazilian Amazon basin.. Leprosy cases were mapped, and socioeconomic indicators were evaluated to explain the leprosy distribution of all leprosy cases diagnosed in the period 2016-2018. Data were obtained on new leprosy cases [Notifiable diseases information system (Sinan)], contacts traced by the LPEP program, and socioeconomic variables [Brazilian Institute of Geography and Statistics (IBGE)]. Kernel, SCAN, factor analysis and spatial regression were applied to analyze changes.. Overall, the new case detection rate (NCDR) was 20/10 000 inhabitants or 304 new cases, of which 55 were CP cases among the 2076 examined contacts. Changes over time were observed in the geographic distribution of cases. The highest concentration of cases was observed in the northeast of the study area, including one significant cluster (Relative risk = 2.24; population 27 427, P-value < 0.001) in an area characterized by different indicators associated with poverty as identified through spatial regression (Coefficient 3.34, P-value = 0.01).. The disease distribution was partly explained by poverty indicators. LPEP influences the spatial dynamic of the disease and results highlighted the relevance of systematic contact surveillance for leprosy elimination.

Topics: Brazil; Humans; Leprosy; Post-Exposure Prophylaxis; Rifampin; Spatio-Temporal Analysis

Brazil ranks second among countries for new cases and first for relapse cases of leprosy worldwide. The Mycobacterium leprae Resistance Surveillance Plan was established. We aimed to present the results of a 2-year follow-up of the National Surveillance Plan in Brazil. A cross-sectional study of leprosy cases was performed to investigate antimicrobial resistance (AMR) in Brazil from October 2018 to September 2020. Molecular screening targeting genes related to dapsone (

Topics: Anti-Bacterial Agents; Brazil; Cross-Sectional Studies; Dapsone; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Microbial Sensitivity Tests; Mycobacterium leprae; Recurrence; Rifampin

Purulia is one of the high-endemic districts for leprosy in West Bengal (the eastern part of India). The annual new case detection rate (ANCDR) of leprosy in West Bengal is 6.04/100000 (DGHS 2019-20). Our earlier report provided evidence of secondary drug resistance in relapse cases of leprosy. The aim of the current study was to observe primary drug resistance patterns for dapsone, rifampicin, and ofloxacin amongst new leprosy patients from Purulia, West Bengal in order to better understand the emergence of primary resistance to these drugs.. In the present study, slit-skin smear samples were collected from 145 newly diagnosed leprosy cases from The Leprosy Mission (TLM) Purulia hospital between 2017 and 2018. DNA was extracted from these samples and the Mycobacterium leprae genome was analyzed for genes associated with drug resistance by polymerase chain reaction (PCR), followed by Sanger sequencing. Wild-type strain (Thai-53) and mouse footpad-derived drug-resistant strain (Z-4) were used as reference strains.. Of 145 cases, 25 cases showed mutations in genes associated with resistance to rifampicin, dapsone, and ofloxacin (as described by the World Health Organization, rpoB, folP, and gyrA, respectively) through Sanger sequencing. Of these 25 cases, 16 cases showed mutations in ofloxacin, two cases showed mutations in combinations of ofloxacin and rifampicin, four cases showed a mutation only in rifampicin, one case showed mutations in combinations of rifampicin and dapsone, and two cases showed mutations only in dapsone.. Results from this study indicated the emergence of resistance to antileprosy drugs in new cases of leprosy. As ofloxacin is the alternate drug for the treatment of rifampicin-resistant cases, the emergence of new cases with resistance to ofloxacin indicates that ofloxacin-resistant M. leprae strains are actively circulating in this endemic region (i.e., Purulia, West Bengal), posing challenges for the effective treatment of rifampicin-resistant cases.

Topics: Animals; Dapsone; Drug Resistance, Bacterial; Leprostatic Agents; Leprosy; Mice; Mycobacterium leprae; Ofloxacin; Rifampin

Despite strong leprosy control measures, including effective treatment, leprosy persists in the Comoros. As of May, 2022, no resistance to anti-leprosy drugs had been reported, but there are no nationally representative data. Post-exposure prophylaxis (PEP) with rifampicin is offered to contacts of patients with leprosy. We aimed to conduct a countrywide drug resistance survey and investigate whether PEP led to the emergence of drug resistance in patients with leprosy.. In this observational, deep-sequencing analysis we assessed Mycobacterium leprae genomes from skin biopsies of patients in Anjouan and Mohéli, Comoros, collected as part of the ComLep (NCT03526718) and PEOPLE (NCT03662022) studies. Skin biopsies that had sufficient M leprae DNA (>2000 bacilli in 2 μl of DNA extract) were assessed for the presence of seven drug resistance-associated genes (ie, rpoB, ctpC, ctpI, folP1, gyrA, gyrB, and nth) using Deeplex Myc-Lep (targeted next generation deep sequencing), with a limit of detection of 10% for minority M leprae bacterial populations bearing a polymorphism in these genes. All newly registered patients with leprosy for whom written informed consent was obtained were eligible for inclusion in the survey. Patients younger than 2 years or with a single lesion on the face did not have biopsies taken. The primary outcome of our study was the proportion of patients with leprosy (ie, new cases, patients with relapses or reinfections, patients who received single (double) dose rifampicin-PEP, or patients who lived in villages where PEP was distributed) who were infected with M leprae with a drug-resistant mutation for rifampicin, fluoroquinolone, or dapsone in the Comoros.. Between July 1, 2017, and Dec 31, 2020, 1199 patients with leprosy were identified on the basis of clinical criteria, of whom 1030 provided a skin biopsy. Of these 1030 patients, 755 (73·3%) tested positive for the M leprae-specific repetitive element-quantitative PCR (qPCR) assay. Of these 755 patients, 260 (34·4%) were eligible to be analysed using Deeplex Myc-Lep. 251 (96·5%) were newly diagnosed with leprosy, whereas nine (3·4%) patients had previously received multidrug therapy. 45 (17·3%) patients resided in villages where PEP had been administered in 2015 or 2019, two (4·4%) of whom received PEP. All seven drug resistance-associated targets were successfully sequenced in 216 samples, 39 samples had incomplete results, and five had no results. No mutations were detected in any of the seven drug resistance-related genes for any patient with successfully sequenced results.. This drug resistance survey provides evidence to show that M leprae is fully susceptible to rifampicin, fluoroquinolones, and dapsone in the Comoros. Our results also show, for the first time, the applicability of targeted sequencing directly on skin biopsies from patients with either paucibacillary or multibacillary leprosy. These data suggest that PEP had not selected rifampicin-resistant strains, although further support for this finding should be confirmed with a larger sample size.. Effect:Hope, The Mission To End Leprosy, the Fonds Wetenschappelijk Onderzoek, the EU.

Topics: Comoros; Dapsone; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin

Post-exposure prophylaxis (PEP) with single-dose rifampicin (SDR) reduces the risk of developing leprosy among contacts of leprosy patients. Most evidence for the feasibility of the intervention is from highly endemic settings while low-endemic areas present unique challenges including reduced awareness of the disease among the population and in the health system, and the only sporadic occurrence of cases which together make defining any type of routine process challenging. We complemented the retrospective active case finding (RACF) approach with SDR administration to eligible contacts, and piloted the intervention across 31 operational districts in Cambodia. The aim was to demonstrate the feasibility of improving early case detection and administering SDR in a low endemic setting. The intervention focused on leprosy patients diagnosed since 2011 and was implemented between October 2016 - September 2019. The "drives" approach was employed to trace contacts: a trained team systematically contacted all eligible cases in a district, traced and screened contacts, and administered SDR. A total of 555 index patients were traced by the drive team, and 10,410 contacts in their household and 5 immediate neighbor houses listed. Among these contacts, 72.0% could be screened while most others were absent on the screening day. A total of 33 new leprosy cases were diagnosed and 6189 contacts received SDR (82.6% of the screened contacts). Sixty-one contacts refused SDR administration. We conclude that integrating PEP with SDR in RACF campaigns is feasible, and that this approach is appropriate in low resource and low endemic settings. Over time, evidence on whether or not the approach reduced leprosy transmission in Cambodia, may become clear.

Topics: Cambodia; Humans; Leprosy; Post-Exposure Prophylaxis; Retrospective Studies; Rifampin

Leprosy is a socially stigmatized granulomatous skin disease caused by Mycobacterium leprae. Due to improvements in medicine and hygiene in Taiwan, the incidence is very low, up to one dozen per year; however, leprosy has never been eradicated due to the increased numbers of immigrants from Southeast Asia. This study aimed to characterize the clinical and histopathological features of patients with leprosy in the context of near elimination. Fifteen cases of pathologically proven leprosy were identified from 2000 to 2016 in Kaohsiung Chang Gung Memorial Hospital. The clinical presentations, demographic details, treatment responses, and disease outcomes were reviewed. The mean age was 46 years (range: 26-73 years). Eight cases were native Taiwanese, while 6 cases and 1 case involved foreign workers from Indonesia and Thailand, respectively. The diagnosis was made 3-6 months on average after skin lesions appeared. The most common clinical subtype was lepromatous leprosy (n = 7). Ten patients were multibacillus microscopically. Three cases were deported. The remaining 12 patients received dapsone and rifampicin for 12 months without recurrence to date. In the near leprosy-eradicated country, early diagnosis and physician vigilance are critical in disease control. Immigrants from endemic countries require strict and professional dermatological examinations and regular follow-up.

Topics: Adult; Aged; Dapsone; Disease Eradication; Female; Humans; Leprosy; Leprosy, Lepromatous; Male; Middle Aged; Mycobacterium leprae; Retrospective Studies; Rifampin; Skin; Taiwan

Topics: Feasibility Studies; Humans; Leprosy; Post-Exposure Prophylaxis; Public Health; Rifampin

Topics: Feasibility Studies; Humans; Leprosy; Post-Exposure Prophylaxis; Rifampin

Topics: Feasibility Studies; Humans; Leprosy; Post-Exposure Prophylaxis; Rifampin

The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence.. The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040.. In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme.. The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.

Topics: Brazil; Contact Tracing; Humans; India; Indonesia; Leprostatic Agents; Leprosy; Mass Screening; Myanmar; Nepal; Post-Exposure Prophylaxis; Primary Prevention; Rifampin; Sri Lanka; Tanzania

Topics: Drug Resistance; Erythema Nodosum; Humans; Leprosy; Leprosy, Lepromatous; Rifampin; Steroids

Topics: Contact Tracing; Guideline Adherence; Humans; Leprostatic Agents; Leprosy; National Health Programs; Nepal; Post-Exposure Prophylaxis; Rifampin

Topics: BCG Vaccine; Humans; Leprosy; Rifampin; Vaccination

Topics: BCG Vaccine; Chemoprevention; Humans; Immunization; Leprosy; Rifampin

A case of

Topics: Humans; Leprosy; Mutation; Mycobacterium leprae; Recurrence; Rifampin

India has the highest burden of leprosy in the world. Following a recent WHO guideline, the Indian National Leprosy Programme is introducing post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) in all high-endemic districts of the country. The aim of this study is to estimate the long-term cost-effectiveness of SDR-PEP in different leprosy disability burden situations. We used a stochastic individual-based model (SIMCOLEP) to simulate the leprosy new case detection rate trend and the impact of implementing contact screening and SDR-PEP from 2016 to 2040 (25 years) in the Union Territory of Dadra Nagar Haveli (DNH) in India. Effects of the intervention were expressed as disability adjusted life years (DALY) averted under three assumption of disability prevention: 1) all grade 1 disability (G1D) cases prevented; 2) G1D cases prevented in PB cases only; 3) no disability prevented. Costs were US$ 2.9 per contact. Costs and effects were discounted at 3%. The incremental cost per DALY averted by SDR-PEP was US$ 210, US$ 447, and US$ 5,673 in the 25th year under assumption 1, 2, and 3, respectively. If prevention of G1D was assumed, the probability of cost-effectiveness was 1.0 at the threshold of US$ 2,000, which is equivalent to the GDP per capita of India. The probability of cost-effectiveness was 0.6, if no disability prevention was assumed. The cost per new leprosy case averted was US$ 2,873. Contact listing, screening and the provision of SDR-PEP is a cost-effective strategy in leprosy control in both the short (5 years) and long term (25 years). The cost-effectiveness depends on the extent to which disability can be prevented. As the intervention becomes increasingly cost-effective in the long term, we recommend a long-term commitment for its implementation.

Topics: Chemoprevention; Cost-Benefit Analysis; Government Programs; Humans; India; Leprostatic Agents; Leprosy; Post-Exposure Prophylaxis; Quality-Adjusted Life Years; Rifampin

Topics: Alzheimer Disease; Clofazimine; Cognitive Dysfunction; Coronavirus Infections; COVID-19; Dapsone; Humans; Inflammasomes; Interleukin-1beta; Leprosy; NLR Family, Pyrin Domain-Containing 3 Protein; Pandemics; Parkinsonian Disorders; Pneumonia, Viral; Rifampin; Spike Glycoprotein, Coronavirus; Toll-Like Receptor 2

Subclinical infection with Mycobacterium leprae is one potential source of leprosy transmission, and post-exposure prophylaxis (PEP) regimens have been proposed to control this source. Because PEP trials require considerable investment, we applied a sensitive variation of the kinetic mouse footpad (MFP) screening assay to aid in the choice of drugs and regimens for clinical trials.. Athymic nude mice were inoculated in the footpad (FP) with 6 x 103 viable M. leprae and treated by gastric gavage with a single dose of Rifampin (SDR), Rifampin + Ofloxacin + Minocycline (SD-ROM), or Rifapentine + Minocycline + Moxifloxacin (SD-PMM) or with the proposed PEP++ regimen of three once-monthly doses of Rifampin + Moxifloxacin (RM), Rifampin + Clarithromycin (RC), Rifapentine + Moxifloxacin (PM), or Rifapentine + Clarithromycin (PC). At various times post-treatment, DNA was purified from the FP, and M. leprae were enumerated by RLEP quantitative PCR. A regression analysis was calculated to determine the expected RLEP value if 99.9% of the bacilli were killed after the administration of each regimen. SDR and SD-ROM induced little growth delay in this highly susceptible murine model of subclinical infection. In contrast, SD-PMM delayed measurable M. leprae growth above the inoculum by 8 months. The four multi-dose regimens delayed bacterial growth for >9months post-treatment cessation.. The delay in discernable M. leprae growth post-treatment was an excellent indicator of drug efficacy for both early (3-4 months) and late (8-9 months) drug efficacy. Our data indicates that multi-dose PEP may be required to control infection in highly susceptible individuals with subclinical leprosy to prevent disease and decrease transmission.

Topics: Animals; Asymptomatic Infections; Bacterial Load; Clarithromycin; Drug Combinations; Leprostatic Agents; Leprosy; Mice; Mice, Nude; Minocycline; Moxifloxacin; Mycobacterium leprae; Post-Exposure Prophylaxis; Rifampin

Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13:01, a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10-9, confirming the strong association of HLA-B*13:01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.

Topics: Adolescent; Adult; Alleles; Biomarkers; Case-Control Studies; Clofazimine; Dapsone; Drug Hypersensitivity; Drug Therapy, Combination; Female; HLA-B13 Antigen; Humans; Indonesia; Leprostatic Agents; Leprosy; Logistic Models; Male; Rifampin; Risk Assessment; Syndrome; Young Adult

Topics: Clofazimine; Drug Therapy, Combination; Hospitals; Humans; India; Leprostatic Agents; Leprosy; Minocycline; Ofloxacin; Rifampin; World Health Organization

Rifampicin resistance is a major therapeutic challenge, particularly in tuberculosis, leprosy, P. aeruginosa and S. aureus infections, where it develops via missense mutations in gene rpoB. Previously we have highlighted that these mutations reduce protein affinities within the RNA polymerase complex, subsequently reducing nucleic acid affinity. Here, we have used these insights to develop a computational rifampicin resistance predictor capable of identifying resistant mutations even outside the well-defined rifampicin resistance determining region (RRDR), using clinical M. tuberculosis sequencing information. Our tool successfully identified up to 90.9% of M. tuberculosis rpoB variants correctly, with sensitivity of 92.2%, specificity of 83.6% and MCC of 0.69, outperforming the current gold-standard GeneXpert-MTB/RIF. We show our model can be translated to other clinically relevant organisms: M. leprae, P. aeruginosa and S. aureus, despite weak sequence identity. Our method was implemented as an interactive tool, SUSPECT-RIF (StrUctural Susceptibility PrEdiCTion for RIFampicin), freely available at https://biosig.unimelb.edu.au/suspect_rif/ .

Topics: Antitubercular Agents; Bacterial Proteins; Drug Resistance, Bacterial; Humans; Leprosy; Machine Learning; Mutation, Missense; Mycobacterium leprae; Mycobacterium tuberculosis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tuberculosis

Topics: Anti-Bacterial Agents; Biopsy; Blister; Diagnosis, Differential; DNA, Bacterial; Drug Therapy, Combination; Humans; Leprosy; Male; Middle Aged; Minocycline; Mixed Connective Tissue Disease; Mycobacterium; Pemphigoid, Bullous; Polymerase Chain Reaction; Rifampin; Skin

The country of Kiribati is a small Pacific island nation which had a new case detection rate of 191 per 100,000 in 2016, and is one of the few countries yet to reach the WHO leprosy elimination goal. Chemoprophylaxis of household contacts of new cases, or to the whole population in a highly endemic areas have been found to be effective in reducing new case rates. This study investigated the potential impact of different chemoprophylaxis strategies on future cases in South Tarawa, the main population centre of Kiribati.. The microsimulation model SIMCOLEP was calibrated to simulate the South Tarawa population and past leprosy control activities, and replicate annual new cases from 1989 to 2016. The impact of six different strategies for delivering one round of single dose rifampicin (SDR) chemoprophylaxis to household contacts of new cases and/or one or three rounds of SDR to the whole population was modelled from 2017 to 2030.. Our model predicted that continuing the existing control program of high levels of public awareness, passive case detection, and treatment with multidrug treatment would lead to a substantial reduction in cases but this was less effective than all modelled intervention scenarios. Mass chemoprophylaxis led to a faster initial decline in cases than household contact chemoprophylaxis alone, however the decline under the latter was sustained for longer. The greatest cumulative impact was for household contact chemoprophylaxis with three rounds of mass chemoprophylaxis at one-year intervals.. The results suggest that control of leprosy would be achieved most rapidly with a combination of intensive population-based and household chemoprophylaxis. These findings may be generalisable to other countries where crowding places social contacts as well as household contacts of cases at risk of developing leprosy.

Topics: Adolescent; Adult; Chemoprevention; Child; Contact Tracing; Family Characteristics; Female; Humans; Leprostatic Agents; Leprosy; Male; Micronesia; Models, Theoretical; Rifampin; Young Adult

The WHO recommends inclusion of post-exposure chemoprophylaxis with single-dose rifampicin in national leprosy control programmes. The objective was to estimate the cost of leprosy services at primary care level in two different public-health settings.. Ingredient-based costing was performed in eight primary health centres (PHCs) purposively selected in the Union Territory of Dadra and Nagar Haveli (DNH) and the Umbergaon block of Valsad district, Gujarat, India. All costs were bootstrapped, and to estimate the variation in total cost under uncertainty, a univariate sensitivity analysis was performed.. The mean annual cost of providing leprosy services was USD 29 072 in the DNH PHC (95% CI: 22 125-36 020) and USD 11 082 in Umbergaon (95% CI: 8334-13 830). The single largest cost component was human resources: 79% in DNH and 83% in Umbergaon. The unit cost for screening the contact of a leprosy patient was USD 1 in DNH (95% CI: 0.8-1.2) and USD 0.3 in Umbergaon (95% CI: 0.2-0.4). In DNH, the unit cost of delivering single-dose of rifampicin (SDR) as chemoprophylaxis for contacts was USD 2.9 (95% CI: 2.5-3.7).. The setting with an enhanced public-health financing system invests more in leprosy services than a setting with fewer financial resources. In terms of leprosy visits, the enhanced public-health system is hardly more expensive than the non-enhanced public-health system. The unit cost of contact screening is not high, favouring its sustainability in the programme.

Topics: Costs and Cost Analysis; Female; Health Care Costs; Health Services; Humans; India; Leprosy; Male; Primary Health Care; Public Sector; Rifampin

We report a 46-year-old woman presenting with leprosy, HIV and active pulmonary tuberculosis (TB). It is advisable to screen for each one of TB, HIV and leprosy patients, especially when an extra feature emerges. Particularly in a leprosy case, if TB remains undiagnosed, the development of rifampicin resistance secondary to monotherapy in leprosy is a major concern.

Topics: Antiretroviral Therapy, Highly Active; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Leprostatic Agents; Leprosy; Middle Aged; Rifampin; Tuberculosis, Pulmonary

Topics: Adult; Dapsone; Exanthema; Female; Humans; Leprostatic Agents; Leprosy; Rifampin

Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone.. To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy.. A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events.. Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT.. The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control.. Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10-5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status.. Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.

Topics: Adult; Alleles; China; Clofazimine; Cohort Studies; Dapsone; Drug Hypersensitivity Syndrome; Drug Therapy, Combination; Female; HLA-B13 Antigen; Humans; Incidence; Leprostatic Agents; Leprosy; Male; Middle Aged; Prospective Studies; Rifampin

The island of Anjouan (Comoros) is highly endemic for leprosy with an annual incidence of 5-10/10,000. In May/June, 2015 single-dose Rifampicin post-exposure prophylaxis (SDR-PEP) was administered to 269 close contacts of 70 leprosy-patients in four villages as a pilot programmatic intervention. Two years later we revisited the villages for follow-up investigations. The main aim of our study was to quantify spatial associations between reported leprosy cases before and after PEP implementation. A secondary aim was to assess the effect of this single round of SDR-PEP at the individual level.. We conducted door-to-door leprosy screening in all four villages in August/September, 2017. We screened all consenting individuals for leprosy and recorded geographic coordinates of their household. We also recorded whether they had received SDR-PEP and whether they had been diagnosed with leprosy, before or after the 2015 intervention. We fitted a Poisson model with leprosy as outcome and distance to the nearest pre-intervention case and SDR-PEP as predictors.. During the survey we found 114 new cases among 5760 contacts screened (2.0% prevalence), in addition to the 39 cases detected in the two preceding years. We found statistically significant associations of incident leprosy with physical distance to index cases ranging from 2.4 (95% confidence interval (95% CI) 1.5-3.6) for household contacts to 1.8 (95% CI 1.3-2.5) for those living at 1-25 m, compared to individuals living at ≥75 m. The effect of SDR-PEP appeared protective but did not reach statistical significance due to the low numbers, with an incidence rate ratio (IRR) of 0.6 (95% CI 0.3-1.2) overall, and 0.5 (95% CI 0.2-1.3) when considering only household contacts.. This pilot demonstrated an increased risk of leprosy in contacts beyond the household, therefore a wider circle should be considered for chemoprophylaxis. Baseline surveys and extended contact definitions are essential for improving SDR-PEP effectiveness.

Topics: Antibiotics, Antitubercular; Cluster Analysis; Comoros; Humans; Leprosy; Post-Exposure Prophylaxis; Prevalence; Rifampin

In Canada, Hansen disease (leprosy) is rare and not considered in diagnoses for nonimmigrant patients. We report Mycobacterium leprae infection in a Canadian man whose sole travel was to Florida, USA. The M. leprae isolate was identified as armadillo-associated genotype 3I-2-v1. Travelers to the southern United States should avoid contact with armadillos.

Topics: Aged; Anti-Bacterial Agents; Canada; Dapsone; Drug Therapy, Combination; Florida; Humans; Leprostatic Agents; Leprosy; Male; Mycobacterium leprae; Ofloxacin; Rifampin; Travel

Topics: Adult; Cranial Nerve Diseases; Dapsone; Diagnosis, Differential; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Male; Positron Emission Tomography Computed Tomography; Prednisolone; Recurrence; Rifampin

Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network.. From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA.. Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases.. This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Biopsy, Needle; Brazil; Colombia; Dapsone; DNA Gyrase; Drug Resistance, Bacterial; Endemic Diseases; Epidemiological Monitoring; Global Health; Humans; India; Leprosy; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae; Ofloxacin; Polymerase Chain Reaction; Prospective Studies; Recurrence; Rifampin; Sentinel Surveillance; Skin; Surveys and Questionnaires; World Health Organization

The rpoB gene encodes the β subunit of RNA polymerase holoenzyme in Mycobacterium leprae (M. leprae). Missense mutations in the rpoB gene were identified as etiological factors for rifampin resistance in leprosy. In the present study, we identified mutations corresponding to rifampin resistance in relapsed leprosy cases from three hospitals in southern India which treat leprosy patients. DNA was extracted from skin biopsies of 35 relapse/multidrug therapy non-respondent leprosy cases, and PCR was performed to amplify the 276 bp rifampin resistance-determining region of the rpoB gene. PCR products were sequenced, and mutations were identified in four out of the 35 cases at codon positions D441Y, D441V, S437L and H476R. The structural and functional effects of these mutations were assessed in the context of three-dimensional comparative models of wild-type and mutant M. leprae RNA polymerase holoenzyme (RNAP), based on the recently solved crystal structures of RNAP of Mycobacterium tuberculosis, containing a synthetic nucleic acid scaffold and rifampin. The resistance mutations were observed to alter the hydrogen-bonding and hydrophobic interactions of rifampin and the 5' ribonucleotide of the growing RNA transcript. This study demonstrates that rifampin-resistant strains of M. leprae among leprosy patients in southern India are likely to arise from mutations that affect the drug-binding site and stability of RNAP.

Topics: Adolescent; Adult; Bacterial Proteins; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Female; Humans; India; Leprostatic Agents; Leprosy; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Mycobacterium leprae; Protein Binding; Protein Stability; Recurrence; Rifampin; Sequence Analysis, DNA; Structure-Activity Relationship; Treatment Outcome; Young Adult

Indonesia ranking third in the world, regarding leprosy burden. Chemoprophylaxis is effective in reducing risk of developing leprosy among contacts. 'Blanket approach' is an operational strategy for leprosy post-exposure prophylaxis in which all members of an isolated community, high endemic for leprosy are screened and given a single dose of rifampicin (SDR) in the absence of signs and symptoms of leprosy. The objective is to assess the operational feasibility of a population-wide 'blanket' administration of SDR for leprosy prevention in isolated communities in a remote island.. A prospective follow-up study was conducted in the year 2014, 2015 and 2016 in Lingat village of Selaru Island, Indonesia. During the first two visits, screening and SDR were provided, whereas only screening was conducted during the third visit. The demographic and clinical data were used for a descriptive analysis of the project coverage and leprosy epidemiology.. During the first two visits, 1671 persons (88%) were screened, 1499 (79%) received SDR, and 213 (11%) were excluded based on the exclusion criteria. During the first two visits, 43 (2.6%) cases were diagnosed with leprosy with a rate of 2263 per 100,000 population. The prevalence was highest in the age groups 15-24 and 25-49 years. Total, 14 (33%) cases had MB and 29 (67%) PB leprosy. Two cases (5%) had grade 2 disability. During the third visit, 10 new leprosy cases, with no grade 2 disability, were detected out of 1481 screened persons at the rate of 484 cases per 100,000 population (n = 2065 population in 2016). Among those screened during the third visit, there was a 50% reduction of leprosy among those who had previously received SDR compared to those who had not.. With adequate planning and some additional investment, it is feasible to implement a blanket approach of chemoprophylaxis in a remote island of Indonesia, although effort needs to be made to cover as many people as possible in the first visit. Contingency plans need to be made to actively follow this village closely in the coming years and continue leprosy elimination efforts until no new cases are found any more.

Topics: Adolescent; Adult; Feasibility Studies; Female; Humans; Indonesia; Leprosy; Male; Middle Aged; Post-Exposure Prophylaxis; Prevalence; Rifampin; Young Adult

Skin biopsies from US leprosy patients were tested for mutations associated with drug resistance. Dapsone resistance was found in 4 of 6 biopsies from American Samoa patients. No resistance was observed in patients from other origins. The high rate of dapsone resistance in patients from American Samoa warrants further investigation.

Topics: American Samoa; Biopsy; Clofazimine; Dapsone; Drug Administration Schedule; Drug Resistance, Bacterial; Genes, Bacterial; Humans; Leprostatic Agents; Leprosy; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae; Rifampin; Skin

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).

Topics: Anti-Bacterial Agents; Clarithromycin; Fluoroquinolones; Humans; Leprosy; Moxifloxacin; Netherlands; Post-Exposure Prophylaxis; Rifampin

Topics: Adjuvants, Immunologic; Adult; Animals; Bacterial Vaccines; Child; Communicable Diseases, Emerging; Disease Models, Animal; Humans; Immunotherapy; Leprostatic Agents; Leprosy; Mycobacterium leprae; Neglected Diseases; Post-Exposure Prophylaxis; Rifampin; Vaccines, Synthetic

Morocco has achieved the goal of leprosy elimination as a public health problem several years ago (less than 1 case/ 10 000 habitant). The aim of this study was to analyze trends of leprosy detection during the last 17 years taking into consideration the implementation of single dose rifampicin chemoprophylaxis (SDRC) started in 2012.. Time series of leprosy cases detected at national level between 2000 and 2017. Variable collected for each year were leprosy per 100000 H, age category, gender, origin, regions, grade of disabilities and clinical forms. The detection time series was assessed by Joinpoint Regression Analysis. Annual percentage changes (APCs) were estimated to identify the years (joinpoint) when significant changes occurred in the trend. We therefore examined trends in leprosy detection according to epidemiological variables.. Joinpoint regression showed a reduction in the detection rate between 2000 and 2017. The APC for the period 2012-2017 (-16.83, 95% CI: -29.2 to -2.3, p <0.05) was more pronounced than that of the previous period 2000-2012 (- 4.68, 95% CI: -7.3 to -2.0, p <0.05); with a significant break in the same joinpoint year SDRC implementation. In stratified analysis, case detection decreased, but not significantly, after the joinpoint years in men, children, multi-bacillary cases, grade 0-1 disabilities, rural and urban cases and in ten regions.. Leprosy detection was declining over years with a significant reduction by 16% per year from 2012 to 2017. SDRC may reduce leprosy detection over the years following its administration.

Topics: Adult; Chemoprevention; Child; Female; Humans; Leprosy; Male; Morocco; Rifampin; Rural Population; Urban Population

This paper, the first in a series of three on 'feline leprosy', provides a detailed description of disease referable to Candidatus 'Mycobacterium tarwinense', the most common cause of feline leprosy in Victoria, Australia.. Cases were sourced retrospectively and prospectively for this observational study, describing clinical, geographical and molecular microbiological data for cats definitively diagnosed with Candidatus 'M tarwinense' infection.. A total of 145 cases of feline leprosy were scrutinised; 114 'new' cases were sourced from the Victorian Infectious Diseases Reference Laboratory records, veterinary pathology laboratories or veterinarians, and 31 cases were derived from six published studies. Forty-two cats were definitively diagnosed with Candidatus 'M tarwinense' infection. Typically, cats were between 3 and 11 years of age, with no gender predilection, and were generally systemically well. All had outdoor access. Most cats underwent surgical resection of lesions with adjunctive medical therapy, often utilising a combination of oral clarithromycin and rifampicin for at least 3 months. Prognosis for recovery was generally good. Resolution of lesions was not observed in the absence of treatment, but a number of untreated cats continued to enjoy an acceptable quality of life despite persistence of the disease, which extended locally but did not appear to disseminate to internal organs. Preliminary results of draft genome sequencing confirmed that the species is a member of the Mycobacterium simiae complex.. Candidatus 'M tarwinense', a fastidious member of the M simiae complex, is capable of causing feline leprosy with a tendency to produce lesions on the head, particularly involving the eyes and periocular skin. The disease has an indolent clinical course and generally responds favourably to therapy despite lesions often containing large numbers of organisms. Detailed genomic analysis may yield clues as to the environmental niche and culture requirement of this elusive organism. Prospective treatment trials and/or drug susceptibility testing in specialised systems would further inform treatment recommendations.

Topics: Animals; Cat Diseases; Cats; Clarithromycin; Female; Leprostatic Agents; Leprosy; Male; Mycobacterium; Prospective Studies; Retrospective Studies; Rifampin; Victoria

Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient.. A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression.. Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R.

Topics: Antigens, Bacterial; Dapsone; Drug Therapy, Combination; Graft Rejection; Humans; Immune Reconstitution Inflammatory Syndrome; Immunosuppression Therapy; Kidney Transplantation; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Prednisone; Rifampin; Skin; T-Lymphocytes, Regulatory; Treatment Outcome

Topics: BCG Vaccine; Global Health; Humans; Leprostatic Agents; Leprosy; Practice Guidelines as Topic; Rifampin; Surveys and Questionnaires; World Health Organization

Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens.. The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite's stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite's stained slides (n = 3) were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able to identify mixed infections of susceptible and resistant M. leprae. However, to avoid false positives we recommend that clinical specimens be tested for the presence of the M. leprae using the qPCR-RLEP assay prior to being tested in the qPCR-HRM DST and that all specimens demonstrating drug resistant profiles in this assay be subjected to DNA sequencing.. Taken together these results further demonstrate the utility of qPCR-HRM DST as an inexpensive screening tool for large-scale drug resistance surveillance in leprosy.

Topics: Bacterial Proteins; Dapsone; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Leprostatic Agents; Leprosy; Microbial Sensitivity Tests; Mycobacterium leprae; Ofloxacin; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Rifampin; Sensitivity and Specificity; Sequence Analysis, DNA; Skin

Topics: Adult; Clofazimine; Dapsone; Diagnosis, Differential; Exanthema; Humans; Leprostatic Agents; Leprosy; Male; Mycobacterium leprae; Patient Care Management; Rifampin; Skin

Leprosy has a wide range of clinical and socio-economic consequences. India, Indonesia and Nepal contribute significantly to the global leprosy burden. After integration, the health systems are pivotal in leprosy service delivery. The Leprosy Post Exposure Prophylaxis (LPEP) program is ongoing to investigate the feasibility of providing single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) to the contacts of leprosy cases in various health systems. We aim to compare national leprosy control programs, and adapted LPEP strategies in India, Nepal and Indonesia. The purpose is to establish a baseline of the health system's situation and document the subsequent adjustment of LPEP, which will provide the context for interpreting the LPEP results in future.. The study followed the multiple-case study design with single units of analysis. The data collection methods were direct observation, in-depth interviews and desk review. The study was divided into two phases, i.e. review of national leprosy programs and description of the LPEP program. The comparative analysis was performed using the WHO health system frameworks (2007).. In all countries leprosy services including contact tracing is integrated into the health systems. The LPEP program is fully integrated into the established national leprosy programs, with SDR and increased documentation, which need major additions to standard procedures. PEP administration was widely perceived as well manageable, but the additional LPEP data collection was reported to increase workload in the first year.. The findings of our study led to the recommendation that field-based leprosy research programs should keep health systems in focus. The national leprosy programs are diverse in terms of organizational hierarchy, human resource quantity and capacity. We conclude that PEP can be integrated into different health systems without major structural and personal changes, but provisions are necessary for the additional monitoring requirements.

Topics: Adult; Child; Delivery of Health Care, Integrated; Feasibility Studies; Female; Government Programs; Humans; India; Indonesia; Leprostatic Agents; Leprosy; Male; Nepal; Post-Exposure Prophylaxis; Program Evaluation; Rifampin

Hansen's Disease (HD) is a rare, chronic granulomatous infection of the skin and peripheral nerves caused by the noncultivable organism

Topics: Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Clofazimine; Cross-Over Studies; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Methotrexate; Mycobacterium leprae; Retrospective Studies; Rifampin; Skin; Steroids; Thalidomide; United States

Hansen disease, also known as leprosy, is a chronic granulomatous infectious disease that is caused by

Topics: Aged; Biopsy; Dapsone; Diagnosis, Differential; Florida; Humans; Leprostatic Agents; Leprosy; Male; Mandatory Reporting; Mycobacterium leprae; Rifampin; Skin; Treatment Outcome

Topics: Dapsone; Drug Therapy, Combination; Humans; Leprosy; Mycobacterium leprae; Rifampin

Molecular drug susceptibility testing was performed on skin biopsies from 24 leprosy patients from Guinea-Conakry for the first time. We identified primary drug resistance in 4 cases and a dapsone-resistant cluster caused by the same strain. Primary transmission of drug-resistant Mycobacterium leprae, including a rifampicin-resistant strain, is reported.

Topics: Antibiotics, Antitubercular; Antitubercular Agents; Biopsy; Dapsone; DNA, Bacterial; Drug Resistance, Microbial; Female; Genome, Bacterial; Guinea; Humans; Leprosy; Male; Mycobacterium leprae; Rifampin; Sequence Analysis, DNA; Skin

An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, where Colombia is a sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively. Three isolates exhibited mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu, Ser458Met), two in the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate exhibited mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu), suggesting multidrug resistance. One isolate had a double mutation in folP1 (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR that required in vivo evaluation of their association or not with drug resistance: rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and gyrA Ala107Leu. Seventy percent of M. leprae mutations were related to drug resistance and were isolated from relapsed patients; the likelihood of relapse was significantly associated with the presence of confirmed resistance mutations (OR range 20.1-88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as a primary treatment. In summary, the current study calls attention to M. leprae resistance in Colombia, especially the significant association between confirmed resistance mutations and relapse in leprosy patients. A high frequency of DRDR mutations for rifampicin was seen in a region where dapsone monotherapy was used extensively.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Proteins; Child; Colombia; Dapsone; DNA, Bacterial; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Humans; Leprostatic Agents; Leprosy; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Mycobacterium leprae; Ofloxacin; Polymerase Chain Reaction; Recurrence; Rifampin; Sentinel Surveillance; Skin; Young Adult

Topics: Clofazimine; Dapsone; Humans; Leprostatic Agents; Leprosy; Peripheral Nervous System Diseases; Rifampin; United Kingdom

The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50-60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data.. The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented.. Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for national and global policymakers to strengthen current leprosy elimination strategies.

Topics: Contact Tracing; Female; Humans; India; Indonesia; Leprostatic Agents; Leprosy; Male; Myanmar; Nepal; Post-Exposure Prophylaxis; Research Design; Rifampin; Sri Lanka; Tanzania

Presence of point mutations within the drug resistance determining regions of Mycobacterium leprae (M. leprae) genome confers molecular basis of drug resistance to dapsone, rifampin and ofloxacin in leprosy. This study is focused on the identification of mutations within the rpoB gene region of M. leprae that are specific for rifampin interaction, and further in silico analysis was carried out to determine the variations in the interactions. DNA and RNA were isolated from slit skin scrapings of 60 relapsed leprosy patients. PCR targeting rpoB gene region and amplicon sequencing was performed to determine point mutations. mRNA expression levels of rpoB and high-resolution melt analysis of mutants were performed using Rotor Gene Q Realtime PCR. Molecular docking was performed using LigandFit Software. Ten cases having point mutations within the rpoB gene region were identified and were clinically confirmed to be resistant to rifampin. A new mutation at codon position Gln442His has been identified. There is a 9.44-fold upregulation in the mRNA expression of rpoB gene in mutant/resistant samples when compared with the wild/sensitive samples. In silico docking analysis of rifampin with wild-type and Gln442His mutant RpoB proteins revealed a variation in the hydrogen-bonding pattern leading to a difference in the total interaction energy and conformational change at position Asp441. These preliminary downstream functional observations revealed that the presence of point mutations within the rifampin resistance determining regions of rpoB gene plays a vital role in conferring genetic and molecular basis of resistance to rifampin in leprosy.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Computational Biology; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Female; Gene Expression Profiling; Humans; India; Leprosy; Male; Middle Aged; Molecular Docking Simulation; Molecular Sequence Data; Mycobacterium leprae; Point Mutation; Polymerase Chain Reaction; Rifampin; RNA, Messenger; Sequence Analysis, DNA; Young Adult

Previous studies of drug resistance have shown that mutations in the drug resistance-determining region (DRDR) in the Folp1, RpoB and GyrA genes of Mycobacterium leprae are responsible for resistance to dapsone, rifampin and ofloxacin, respectively.. To investigate the prevalence of mutations in genes associated with drug resistance in M. leprae isolates from patients with leprosy in Shandong Province.. The DRDR in the FolP1, RpoB and GyrA genes was analysed by direct sequencing of the PCR product from 85 isolates of M. leprae sampled from patients with leprosy in Shandong, China.. Sequencing results were obtained for FolP1, RpoB and GyrA in 67, 57 and 81 of the 85 samples, with mutation rates of 1.5% (1/67), 8.8% 5/57 and 25.9% (21/81). Three multidrug-resistant samples were found among the new cases: one had a mutation in both Folp1 and RpoB, while the other two had a mutation in both RpoB and GyrA.. Primary resistance appears to be to either single drugs or combinations of two drugs. The resistance rate to dapsone seems to be low. To our knowledge, this is the first case of multidrug-resistant M. leprae from China.

Topics: Adult; Bacterial Proteins; China; Dapsone; DNA, Bacterial; Drug Resistance, Bacterial; Female; Humans; Leprostatic Agents; Leprosy; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Mycobacterium leprae; Ofloxacin; Polymerase Chain Reaction; Prevalence; Rifampin

Topics: Dapsone; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Myositis; Rifampin; Treatment Outcome

Topics: Adult; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Genes, Bacterial; Humans; India; Leprosy; Male; Middle Aged; Mutation; Mycobacterium leprae; Rifampin

Topics: Antibiotics, Antitubercular; Communicable Disease Control; Humans; Leprosy; Rifampin; Systematic Reviews as Topic

Molecular drug susceptibility testing was performed on 39 US patients with leprosy. Of these, 2 had dapsone-resistant Mycobacterium leprae and 1 of these patients also had rifampin-resistant M. leprae. Even though antileprosy drug resistance occurs in this leprosy population, resistance does not appear to be a major problem.

Topics: Anti-Bacterial Agents; Dapsone; DNA, Bacterial; Drug Resistance, Bacterial; Genes, Bacterial; Humans; Leprosy; Mycobacterium leprae; Polymerase Chain Reaction; Rifampin; Sequence Analysis, DNA; United States

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software.

Topics: Adult; Analysis of Variance; Catalase; Clofazimine; Cytochrome P-450 CYP2C19; Dapsone; Drug Therapy, Combination; Female; Glutathione; Heinz Bodies; Humans; Leprostatic Agents; Leprosy; Male; Methemoglobin; Middle Aged; Oxidation-Reduction; Oxidative Stress; Protein Binding; Reactive Oxygen Species; Rifampin; Time Factors; Treatment Outcome; Young Adult

Mycobacterium leprae and Mycobacterium tuberculosis antimicrobial resistance has been followed with great concern during the last years, while the need for new drugs able to control leprosy and tuberculosis, mainly due to extensively drug-resistant tuberculosis (XDR-TB), is pressing. Our group recently showed that M. leprae is able to induce lipid body biogenesis and cholesterol accumulation in macrophages and Schwann cells, facilitating its viability and replication. Considering these previous results, we investigated the efficacies of two statins on the intracellular viability of mycobacteria within the macrophage, as well as the effect of atorvastatin on M. leprae infections in BALB/c mice. We observed that intracellular mycobacteria viability decreased markedly after incubation with both statins, but atorvastatin showed the best inhibitory effect when combined with rifampin. Using Shepard's model, we observed with atorvastatin an efficacy in controlling M. leprae and inflammatory infiltrate in the BALB/c footpad, in a serum cholesterol level-dependent way. We conclude that statins contribute to macrophage-bactericidal activity against Mycobacterium bovis, M. leprae, and M. tuberculosis. It is likely that the association of statins with the actual multidrug therapy effectively reduces mycobacterial viability and tissue lesion in leprosy and tuberculosis patients, although epidemiological studies are still needed for confirmation.

Topics: Animals; Antitubercular Agents; Atorvastatin; Cell Line; Drug Synergism; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leprosy; Macrophages; Mice; Mice, Inbred BALB C; Mycobacterium leprae; Mycobacterium tuberculosis; Pyrroles; Rifampin; Simvastatin

Topics: Aged, 80 and over; Clofazimine; Dapsone; Humans; Leprostatic Agents; Leprosy; Male; Mycobacterium leprae; Rifampin; Skin; Treatment Outcome

The aim of this study was to identify polymorphisms in the folp1, gyrA, and rpoB genes in leprosy patients treated in Amazonas State, Brazil. Among 197 slit-skin smear samples from untreated or relapsed patients, we found three cases of primary resistance to rifampin and one confirmed case of multidrug resistance.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Brazil; Drug Resistance, Bacterial; Female; Humans; Leprosy; Male; Mycobacterium leprae; Polymorphism, Genetic; Rifampin

Topics: Anti-Bacterial Agents; Humans; Hyperpigmentation; Leprostatic Agents; Leprosy; Male; Middle Aged; Minocycline; Rifampin; Staining and Labeling

Topics: Anti-Inflammatory Agents; Arthritis; Arthritis, Rheumatoid; Clofazimine; Dapsone; Delayed Diagnosis; Diagnosis, Differential; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Prednisolone; Rifampin; Treatment Outcome

Topics: Adult; Aged; Dapsone; Drug Resistance, Bacterial; Female; Humans; Japan; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Polymerase Chain Reaction; Recurrence; Registries; Rifampin

Histoid leprosy is a rare but well-defined entity with specific clinical, histopathologic, and bacteriologic features. We present a case of histoid leprosy in an 84-year-old Egyptian male in view of the rarity of this condition. The patient presented with erythematous itchy discrete and coalescent papules that were distributed bilaterally and symmetrically on the front and back of the trunk. Before approaching us, he was initially misdiagnosed as a case of pityriasis rosea. There was no mucosal or facial affection and the patient's general examination was normal. Routine hematologic investigations, urine analysis, liver and renal function tests were all normal. Slit skin smear revealed acid-fast bacilli of BI - 6+ and MI - 50-60%. Histopathologic examination of hematoxylin and eosin-stained section revealed atrophic epidermis with flattened rete ridges and dermal infiltration by nodular granulomata formed of spindle shaped histiocytes with pyknotic nuclei oriented in a storiform pattern. Fite's stain for lepra bacilli showed plenty of acid fast bacilli. So, the diagnosis of histoid leprosy was made. Therefore, ROM therapy (rifampicin 600 mg, ofloxacin 400 mg, minocycline 200 mg) was started and followed by multi-drug therapy for 2 years.

Topics: Aged; Atrophy; Dermis; Epidermis; Humans; Leprostatic Agents; Leprosy; Male; Minocycline; Ofloxacin; Rifampin

Topics: Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Mycobacterium leprae; Ofloxacin; Patient Compliance; Rifampin; World Health Organization

Multidrug therapy for leprosy is currently done with dapsone, clofazimine and rifampicin. Dapsone is known to cause hemolytic anemia (HA) and this adverse event during MDT seems to be more frequent than reported. The aim of this report is to discuss and grade HA due to dapsone during MDT treatment for leprosy.. This is a retrospective study of 194 leprosy patients from a Leprosy Control Programme Unit in Vit6ria-ES, Brazil.. HA was observed in 48 (24.7%) patients and occurred within the first 3 months in 51% of these. Mean hematocrit levels fell from 38.5 to 31.5 and hemoglobin from 12.8 to 10.3.. Dapsone used in the MDT regime for leprosy decreases the hematocrit and hemoglobin levels due to a low grade hemolysis, which can result in significant anemia.

Topics: Adolescent; Adult; Aged; Anemia, Hemolytic; Brazil; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Hematocrit; Hematologic Tests; Hemoglobins; Hemolysis; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Retrospective Studies; Rifampin; Treatment Outcome; World Health Organization; Young Adult

The autosomal recessive disorder, because of a single mutation in interferon-γ receptor-1(IFNGR1) at position -56, was found to be associated with susceptibility to leprosy in children of the same family. The existence of such heterozygous carriers might explain the crucial role of IFNGR1 in the host defense against intracellular pathogens such as Mycobacterium leprae. The single nucleotide polymorphisms (SNPs) in major candidate genes, i.e., natural resistance-associated macrophage protein 1 (NRAMP1), vitamin D receptor (VDR), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-12-receptor 1 (IL-12R1), were not found to be associated with this disease.

Topics: Child; Clofazimine; Family; Genetic Predisposition to Disease; Humans; Interferon gamma Receptor; Leprostatic Agents; Leprosy; Male; Polymorphism, Genetic; Promoter Regions, Genetic; Receptors, Interferon; Rifampin

Topics: Adult; Antibiotics, Antitubercular; Comorbidity; Dapsone; Drug Therapy, Combination; Humans; Leprosy; Male; Rifampin; Tuberculosis, Pulmonary

Leprosy remains an important public health and social issue in South Asia, particularly in India. Its presence in childhood is an immense social burden because of the associated disabilities and widely prevalent misconceptions regarding communicability and treatment potential. The prevalence of leprosy among children suggests a possible gap in the national programmes aimed at leprosy elimination. This article reports a 10-year retrospective study of childhood leprosy in a tertiary care hospital setting (2000-2009) along with an analysis of selected socio-epidemiologic correlates. We stress the importance of early detection and the application of appropriate prophylactic measures in susceptible children.

Topics: Adolescent; Chemoprevention; Child; Child Welfare; Dapsone; Female; Humans; India; Leprostatic Agents; Leprosy; Male; Prevalence; Retrospective Studies; Rifampin

To assess the adverse effects of multi drug therapy (MDT) in leprosy patients.. A prospective and descriptive study carried out in Department of Dermatology, Government Medical College, Jagdalpur. The adverse effects were recorded on the personal record of every individual patient, filled during the course of treatment.. 176 patient's records were analysed, looking for adverse effects. Among the 176 patients, 79 had adverse effects due to one or more components of MDT, 73 had adverse effects due to dapsone, eight due to rifampicin and 16 due to clofazimine. Mean (+/- SD) duration for the development of adverse effects from the start of therapy was 1.99 (+/- 0.69) months for dapsone, 36 (+/- 0.68) months for rifampicin and 7.13 (+/- 0.79) months for clofazimine. There was a significant (P < 0.05) correlation between adverse effects and low Body Mass Index (BMI). The suspected drug was stopped and an alternative regime started in nine patients; six had dapsone stopped, two had rifampicin stopped and one had clofazimine stopped.. Adverse effects attributed to MDT are comparable to previous studies and we found that ADR due to Dapsone was very high but most of the ADR were managed by supportive treatment without replacing the suspected drug.

Topics: Adolescent; Adult; Body Mass Index; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; India; Leprostatic Agents; Leprosy; Male; Prospective Studies; Rifampin; Risk Factors

Conventional Mouse foot-pad (MFP) assay for screening drug resistance in M. leprae is cumbersome and time-consuming (approximately 6 to 12 months). Molecular targets for different anti-leprosy drugs have been well defined. Molecular tools for rapid detection of drug resistance in M. leprae have been standardised. A study to compare molecular methods with MFP assay in determining the drug susceptibility of M. leprae was carried out.. Forty Bacteriological Index (BI) positive patients of leprosy with clinical features of relapse (25), new cases (11) and defaulters (4) were included in the study. A skin biopsy was done and the samples were processed using both MFP assay and Molecular method. PCR assays were carried out to amplify, 388 bp of folP1 gene for dapsone resistance, 305 bp of rpoB gene for rifampicin resistance and 342 bp of gyrA gene for ofloxacin resistance, followed by direct DNA sequencing.. Significant growth in the MFP test was obtained in only 28 out of 40 biopsies processed (70%). Ten of these isolates were dapsone resistant; one isolate showed combined resistance against dapsone, rifampicin and clofazimine. Amplification for all three genes was successful in all the 40 (100%) samples. Among folP1 products sequenced, six isolates showed mutations at 53 (or) 55 amino acid positions. Those strains which showed high-level resistance with two log growth in MFP test, and/or showed growth in passage had mutations in folp1 gene. No mutation was detected in rpoB and gyrA products. Thus no molecular evidence of Rifampicin resistance was found in the DNA isolated from biopsies.. Thus PCR-direct sequencing--the rapid and high sensitive molecular technique can be applied for detection of resistance against dapsone, rifampicin and ofloxacin in M. leprae, to over come the limitations of the conventional MFP assay.

Topics: Animals; Bacterial Proteins; Biopsy; Clofazimine; Cross-Sectional Studies; Dapsone; Dihydropteroate Synthase; DNA Gyrase; Drug Resistance, Bacterial; Genetic Predisposition to Disease; Humans; Leprostatic Agents; Leprosy; Mice; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae; Ofloxacin; Polymerase Chain Reaction; Rifampin

Drug resistance surveillance identified six untreated leprosy patients in the Philippines with Mycobacterium leprae folP1 mutations which confer dapsone resistance. Five patients share a village of residence; four who carried the mutation, Thr53Val, were also linked by M. leprae variable-number tandem repeat (VNTR) strain types. In India, folP1 mutations were detected in two relapse patients with a history of dapsone treatment. Mutations were not found in the rifampin target gene rpoB. These findings indicate that dapsone resistance is being transmitted.

Topics: Bacterial Proteins; Dapsone; Humans; India; Leprostatic Agents; Leprosy; Molecular Epidemiology; Mutation; Mycobacterium leprae; Philippines; Rifampin

Chemoprophylaxis with single dose rifampicin is a promising intervention to prevent leprosy in close contacts of patients. However, application in control programmes often requires disclosure of the leprosy diagnosis, which is still a stigmatised disease in many countries. Promoting control and treatment of stigmatised diseases without contributing towards stigma of the individuals involved can be very difficult. The objective of this study was to assess the social acceptability of disclosure of the diagnosis and the attitude towards taking prophylactic medicines in a leprosy endemic area in Bangladesh.. Qualitative study through focus group discussions with 136 healthy men and women from different age groups and religions, coming from two rural villages and an urban area in northwest Bangladesh, and 14 health workers with extensive experience with leprosy patients.. The participants would not object to disclosure of the diagnosis to household members and nearby family if they were diagnosed with leprosy. However, many participants were not willing to share this information with their neighbours and other social contacts due to stigma of the disease. All healthy participants were willing to take chemoprophylaxis if any of their close contacts were diagnosed with leprosy, even after explaining that full protection against leprosy was not guaranteed.. It can be concluded that chemoprophylaxis for household contacts of leprosy patients is an effective and socially acceptable addition to the current leprosy control programme. Chemoprophylaxis for other categories of contacts likely to benefit would only be feasible, without disclosure of patient information, if given in the form of mass campaigns for the whole population in the area.

Topics: Adolescent; Adult; Bangladesh; Family Characteristics; Female; Focus Groups; Health Knowledge, Attitudes, Practice; Humans; Leprostatic Agents; Leprosy; Male; Patient Acceptance of Health Care; Prejudice; Qualitative Research; Rifampin; Stereotyping; Truth Disclosure; Young Adult

To evaluate the occurrence of relapse of multibacillary leprosy after multi-drug treatment including daily rifampin.. A retrospective review was performed utilizing data from the National Hansen's Disease Program (NHDP) on patients with leprosy treated and followed from 1988-1997 who received multi-drug therapy including daily rifampin. The occurrence of relapse in this cohort was measured, and demographic data and various clinical variables were also gathered.. Ultimately, 158 cases fulfilled the eligibility criteria. 77% of cases were multibacillary patients and were treated with 2 or 3 drug protocols at rates of 36% and 35% before and after 1992, respectively. Only one case of relapse was found, and this patient underwent 2-drug therapy versus 3-drug therapy.. These data are remarkable for the absence of relapse with daily rifampin, as contrasted with the published experience using the WHO protocol with monthly rifampin.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Biopsy; Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Health Surveys; Humans; Leprostatic Agents; Leprosy; Male; Medical Records; Middle Aged; Retrospective Studies; Rifampin; Secondary Prevention; Treatment Outcome; United States

Sixty two patients with relapsed leprosy seen between Jan 2004 and Dec 2009 were studied using clinical, bacteriological and histopathological parameters. The findings thus obtained were correlated to parameters such as trend and source of referral, clinical characteristics at diagnosis, treatment received, other events during or after RFT and duration between cessation of treatment and relapse.. Referrals per year have doubled since 2006. Most patients were referred by NGOs (58%), followed by Govt. hospitals (16%) and then by GPs (25%); 76% had received one of the WHO - MDT regimens including 16 treated with 24 months or more MB - MDT, 23 with 12 months MB - MDT and eight with 6 months PB - MDT. Of the remaining 14 cases, four had received DDS mono-therapy, seven had single dose of Rifampicin, Ofloxacin and Minocycline (ROM) and four Rifampicin and Ofloxacin (RO) daily for 28 days. The average incubation time of relapse, defined as duration between cessation of treatment and relapse was (SD) + 6-4 years. 59% of patients had positive slit skin smears on relapse. Relapse for the second time occurred in six BL cases including five from group 2 and one RO treated patient and 11/23 cases from group 2 conferred to BT-BB leprosy. Clinical features at diagnosis and on relapse were comparable in 47% of cases.. All leprosy patients, regardless of their type and MDT regime, carry 'risk of relapse'. A shorter treatment duration reduces the incubation time to relapse. In group 2 (treated with 12 months MB-MDT regime) 11/23 were BT-BB cases and 5/23 (21%) were relapse for the second time, which further supports our earlier documented findings and maybe the efficacy of WHO-MDT regime is poor in a small subset of patients.

Topics: Academies and Institutes; Adult; Aged; Biomedical Research; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; India; Leprostatic Agents; Leprosy; Male; Middle Aged; Minocycline; Ofloxacin; Recurrence; Referral and Consultation; Rifampin; Risk Factors; Skin; Time Factors; Treatment Outcome; Young Adult

Topics: China; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Prevalence; Rifampin

With 254,525 new cases reported in 2007, leprosy is the worlds' second most widespread form of mycobacteriosis. According to the WHO, eradication of leprosy as a public health problem (defined by less than one case per 10,000 people) has been globally achieved. High endemic zones, however, still subsist. Leprosy rates among children, which reflect a country's endemic level, ranged from 0.55 to 19.2 % in 2006. Due to world population migrations, cases of leprosy are now seen in mainland France, in both children and adults.. We describe three leprosy patients aged under 15 years treated at the Dermatology Unit of Saint Louis Hospital between 1st January 2002 and 31st December 2008. The three cases described account for 3 % of new patients treated for leprosy at Saint Louis Hospital over this 7-year period. All were born in an endemic country. Lesions appeared 18 months after arrival in France in two cases and clinical diagnosis was made in only one case. Due to absence of sensory loss in the lesions, diagnosis was reliant upon histopathological examination in two cases.. Leprosy should be suspected in children from endemic countries presenting skin lesions, particularly hypochromic lesions, even if there is no sensory loss, regardless of how long they have been living in France.

Topics: Adolescent; Adrenal Cortex Hormones; Age of Onset; Biopsy; Brazil; Child; Drug Therapy, Combination; Endemic Diseases; Female; France; Guinea; Humans; India; Leprosy; Male; Retrospective Studies; Rifampin; Skin

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Hyperpigmentation; Leprostatic Agents; Leprosy; Minocycline; New York; Patient Preference; Rifampin

The simple method to detect mutations conferring resistant to dapsone, rifampicin, and quinolone was exploited in Mycobacterium. leprae on the basis of reverse DNA hybridization with capture probe fixed to the glass slide. Mutations were discriminated by a series of oligonucleotide probes corresponding to each mutation in the folP1, rpoB, and gyrA genes of M. leprae. The method was transferred to two laboratories in developing countries. The results obtained with the kit at those laboratories were highly concordant with results of sequencing. The method is feasible for the testing by local person in areas with high prevalence of leprosy.

Topics: Developing Countries; Drug Resistance, Bacterial; Humans; Leprostatic Agents; Leprosy; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae; Oligonucleotide Array Sequence Analysis; Quinolones; Rifampin

Mexico is a country with sporadic leprosy cases, and the reemergence of drug resistance is a concern. In this study, molecular analysis of Mycobacterium leprae was employed to clarify the spread of drug-resistant leprosy. Thus, drug resistance-determining regions in the folP1, rpoB, and gyrA genes, which are associated with resistance to dapsone, rifampicin, and ofloxacin, respectively, were analyzed by direct sequencing of the PCR product. No mutations in the folP1 gene were observed in any of the 72 slit skin samples obtained from 38 patients, although two samples carrying a mutation at codon 425 in the rpoB gene, which confers resistance to rifampicin, a key component of multidrug therapy, were identified. In addition, a mutation at codon 91 in the gyrA gene, which correlates with ofloxacin resistance, was found in one sample. These results demonstrate the existence of rifampicin- and ofloxacin-resistant leprosy. Interestingly, wild-type and mutant sequences in the gyrA gene were found to coexist in one clinical sample. In addition, all three drug resistance-related mutations were found in only one of the two earlobes of the patients concerned, suggesting a possible pathway for the spread of drug-resistant M. leprae.

Topics: Bacterial Proteins; Dapsone; DNA Gyrase; DNA, Bacterial; Drug Resistance, Bacterial; Drug Therapy, Combination; Ear, External; Humans; Leprostatic Agents; Leprosy; Mexico; Mutation; Mycobacterium leprae; Ofloxacin; Polymerase Chain Reaction; Prevalence; Rifampin; Sequence Analysis, DNA

There is an estimate low incidence of patients with Hansen's disease in Portugal. Following the 1982 World Health Organization (WHO) recommendations, extended multidrug therapy (MDT) was started for multibacillary (MB) patients. Patients were then treated with rifampicine (RFP), clofazimine (CLF) and dapsone (DDS) for a minimum of 2 years or until smear negativity. The aim of this study was to evaluate MDT efficacy in our patient population.. Retrospective and descriptive study of 102 MB patients who underwent MDT from 1988 to 2003.. The number of new MB patients has gradually increased since 1960, the first year of our consultation, due mostly to a rise in imported cases. Overall, 34% of the subjects were immigrants, mainly from former Portuguese Colonies. Forty-six patients had previously received monotherapy with DDS (mean duration of this treatment, 22 years). Relapse after MDT occurred in 9 cases (8.8%), but importantly, all relapsed cases were smear negative at least on one occasion after the end of treatment, suggesting these were true relapses rather than treatment failures.. Despite the 2-year WHO-MDT regimen, patients with MB disease clearly face the possibility of relapse. We propose that any reduction in the duration of therapy such as the recently proposed 6-month standard MDT is likely to increase the relapse rate even further. Important issues for future consideration are the needs to identify those at risk of relapse and in need of alternative antimicrobial treatment with a prolonged clinical follow-up.

Topics: Aged; Anti-Bacterial Agents; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Middle Aged; Portugal; Prevalence; Retrospective Studies; Rifampin

Topics: Dapsone; Humans; Japan; Leprosy; Minocycline; Plant Oils; Quinolones; Rifampin

Topics: Adult; Female; Humans; Leprostatic Agents; Leprosy; Rifampin; Treatment Outcome; Zambia

Topics: Dapsone; Female; Humans; Leprostatic Agents; Leprosy; Middle Aged; Rifampin; Tattooing

Multidrug therapy (WHO/MDT) in multibacillary leprosy consists of treatment with rifampicin, dapsone and clofazimine. However, adverse effects can cause the patient to abandon treatment. We report on a patient who presented agranulocytosis and hemolytic anemia associated with this treatment regime. We also examined the importance of laboratory exams for diagnosis and follow-up of the patient, and for early detection of adverse effects,with a view to improving adhesion to treatment and contributing to the eradication of Hansen's disease as a public health issue.

Topics: Adult; Agranulocytosis; Anemia, Hemolytic; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Rifampin

Several forms of arthritis and rheumatism can sometimes complicate leprosy. However, its presentation as an acute onset arthritis is unusual. We report two adult male naïve patients who presented to our rheumatology outpatient clinic with acute onset inflammatory polyarthritis, skin rash and mild sensory neurodeficit. Borderline lepromatous leprosy (in type I lepra reaction) was diagnosed. We also refer to 19 case records of Hansen arthritis in the clinic database (1998-2007) from approximately 35,000 patients and a community study to highlight the missed diagnosis of Hansen's disease and its unusual association with rheumatoid arthritis. In countries like India where leprosy is endemic, this disease also merits attention in rheumatology clinics.

Topics: Acute Disease; Aged; Arthritis; Clofazimine; Dapsone; Diagnosis, Differential; Drug Therapy, Combination; Exanthema; Glucocorticoids; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Peripheral Nerves; Peripheral Nervous System Diseases; Rifampin; Treatment Outcome

The diagnostic process of sensory-motor neuropathies is difficult. Atypical variants and rare etiologies also contribute to delay the diagnosis. We report the case of a 70-year-old woman with slowly progressive asymmetric axonal sensory-motor neuropathy. Leprosy was identified after an eight-year delay. Nerve biopsy was required to establish the diagnosis: electron microscopy revealed debris of Hansen's bacillus in the nerve. Treatment was fully curative after several months. Leprosy is a rare cause of neuropathy in Europeans. Systematic inquiry about travel to endemic areas would be helpful in establishing the diagnosis. In such cases, nerve biopsy is crucial.

Topics: Adrenal Cortex Hormones; Aged; Aspirin; Clofazimine; Dapsone; Diagnosis, Differential; Female; Humans; Leprostatic Agents; Leprosy; Macrophages, Peritoneal; Mycobacterium lepraemurium; Rifampin

The Malta Leprosy Eradication Project (MLEP) was proposed in 1971 by Freerksen with the aim of eradicating leprosy in Malta. The project involved re-treatment of all known cases in Malta as of 1972 and all new cases thereafter with a regimen consisting of Isoprodian (a combination of dapsone, prothionamide and isoniazid) and rifampicin for varying intervals depending on the severity of their disease and their response to treatment. Overall the response to therapy was excellent with an extremely low relapse rate. During the 30 years of the project the incidence of leprosy steadily decreased continuing a decline that had started at least two decades earlier and Freerksen declared the disease eradicated from Malta in 2001. Although given the long incubation period of leprosy cases may still be occasionally detected in the future, the disease has been basically eradicated at this time and there are no patients currently receiving treatment. This work was done at the leprosy clinic, Boffa Hospital, Floriana, Malta.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Leprostatic Agents; Leprosy; Male; Malta; Program Evaluation; Prothionamide; Rifampin; Treatment Outcome

Dapsone Hypersensitivity Syndrome (DHS) occurs in approximately 2% of leprosy patients in Nepal. DHS and other adverse effects of dapsone lead to withdrawal of the drug.. We reviewed the notes of patients who had dapsone withdrawn from their multi-drug therapy (MDT) following an adverse reaction to the drug between 1990 and 2007.. 105 patients were identified from the database and 67 had a documented completion of a modified course of MDT. The majority were treated with rifampicin and clofazimine. All 36 individuals who were slit-skin smear positive had a satisfactory fall in their mean bacterial index. There were no cases of relapse.. Rifampicin and clofazimine appear to be satisfactory treatment for both paucibacillary and multibacillary patients who have to have dapsone stopped because of severe adverse effects.

Topics: Adolescent; Adult; Aged; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Nepal; Retrospective Studies; Rifampin; Treatment Outcome

Rifampicin-resistant Mycobacterium leprae is regularly reported and drug resistance is a major threat for the elimination of leprosy. There is an urgent need for a simple method that can detect rifampicin resistance in clinical isolates. This study developed a multiple-primer PCR amplification refractory mutation system, a simple, reliable and economical method for clinical specimens that allowed the rapid detection of mutations in the nucleotides of the codon for Ser425 of the M. leprae rpoB gene, mutation of which to Leu, Met or Phe is associated with rifampicin resistance. The approach involved a multiple-primer PCR in which both mutant-specific and normal sets of primers were included in the reaction. The mutant-specific primer was complementary to the corresponding sequence of the wild-type gene except for one additional deliberate mismatch at the fourth nucleotide from the 3'-OH terminus. A single mismatch has little influence on the yield of PCR products, but if there are two mismatches as a result of mutation at the position being tested, the mutant-specific primer will not function in PCR under appropriate conditions, leading to no yield of PCR product from the mutant allele. The assay was evaluated successfully using a panel of plasmids and M. leprae reference strains carrying the wild-type or known rpoB mutations. The assay was subsequently applied to M. leprae DNA extracts from skin biopsies taken from patients. In all biopsy samples, the wild-type allele was detected for Ser425. The PCR results correlated with rifampicin susceptibility, as also measured by the traditional in vivo mouse footpad technique.

Topics: Anti-Bacterial Agents; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Humans; Leprosy; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae; Polymerase Chain Reaction; Rifampin; Sensitivity and Specificity; Statistics as Topic

To detect the presence of rifampin- and dapsone-resistant strains of Mycobacterium leprae in three patients with recurring leprosy and clinically-suspected antimicrobial resistance through molecular techniques.. A retrospective, descriptive study was conducted of three multibacillary patients at the "Agua de Dios" Sanitarium in Cundinamarca, Colombia, that presented leprosy relapses that were documented by medical history, bacilloscopy, and biopsy. Biopsies were taken of the skin lesions and the bacteria were subject to DNA extraction and purification. Regions of the rpoB and folP1 genes associated with antimicrobial resistance were amplified and subjected to touch-down polymerase chain reaction and the amplified products were sequenced using the Sanger method.. A punctual mutation was identified in nucleotide 1367 of the rpoB gene in two of the samples studied. This mutation was not found in the folP1 gene of any of the three patients.. The mutation identified showed strains of rifampin-resistant M. leprae in two of the three patients with recurring leprosy. Mutations that indicate dapsone-resistance were not detected in any of the three patients.

Topics: Aged; Dapsone; DNA, Bacterial; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Recurrence; Retrospective Studies; Rifampin

Topics: Health Policy; Humans; Leprostatic Agents; Leprosy; Rifampin

Topics: Humans; Leprostatic Agents; Leprosy; Rifampin

Three native-born patients from the Mississippi Delta presented with leprosy over a 13-month period. None had a history of foreign travel, contact with each other, or known leprosy patients. Two patients' lesions lacked anesthesia, and all had a history of armadillo exposure. These cases add to the association of armadillo exposure and the subsequent development of leprosy.

Topics: Aged; Aged, 80 and over; Animals; Armadillos; Biopsy; Clofazimine; Dapsone; Diagnosis, Differential; Disease Reservoirs; Drug Therapy, Combination; Endemic Diseases; Female; Humans; Leprostatic Agents; Leprosy; Male; Mississippi; Mycobacterium leprae; Polymerase Chain Reaction; Rifampin; Skin; Zoonoses

Topics: Age Factors; Aged, 80 and over; Clofazimine; Dapsone; Diagnosis, Differential; Exanthema; Humans; Leprostatic Agents; Leprosy; Male; Rifampin

A model of leprosy was used to study the therapeutic effect of horse-radish root (HRR) containing peroxidase in combination with rifampicin (RFP) and potassium iodide (PI) as compared to routine combined therapy with RFP and diaminodiphenylsulfonum. Therapy with HRR and iodide showed the best antimicrobial effect than the routine combined therapy. A combination of RFP, HRR, and PI increased the activity of neutrophilic myeliperoxidase produced an anti-inflammatory activity and caused no persistent anemia or toxic effect on the murine liver.

Topics: Animals; Armoracia; Disease Models, Animal; Drug Therapy, Combination; Horseradish Peroxidase; Leprosy; Mice; Mice, Inbred CBA; Neutrophils; Peroxidase; Plant Roots; Potassium Iodide; Rifampin; Treatment Outcome

This reports a long-term follow-up study on clinical effects of ofloxacin (OFLX)-combined therapy to 14 leprosy patients with various types and stages. Combined drugs were diaminodiphenyl sulfone (DDS), rifampicin (RFP) and clofazimine. Clinical evaluation of the treatment after OFLX-combined therapy was remarkable improvement 10 cases, improvement 3 and re-exacerbated after improvement 1 to whom clofazimine and minocycline were prescribed. The evaluation during the follow-up was remarkable improvement 10, improvement 1; three cases died of traffic accident or complications not related to chemotherapy and none of them showed relapse of leprosy. Bacterial negativity after onset of OFLX-combined therapy was achieved in about the same periods as RFP-combined therapy. OFLX-combined therapy was effective and safe. This follow-up study supports the efficacy of clinical guideline for the use of new quinolones published by Japanese leprosy Association.

Topics: Aged; Anti-Bacterial Agents; Clofazimine; Cystamine; Drug Therapy, Combination; Follow-Up Studies; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Minocycline; Ofloxacin; Rifampin; Time Factors; Treatment Outcome

Topics: Diagnosis, Differential; Drug Therapy, Combination; Granuloma; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Ofloxacin; Rifampin; Skin Diseases

Leprosy affects skin and peripheral nerves, and acute inflammatory type 1 reactions (reversal reaction) can cause neurologic impairment and disabilities. Single skin lesion paucibacillary leprosy volunteers (N = 135) recruited in three Brazilian endemic regions, treated with single-dose rifampin, ofloxacin, and minocycline (ROM), were monitored for 3 years. Poor outcome was defined as type 1 reactions with or without neuritis. IgM anti-phenolic glycolipid I, histopathology, Mitsuda test, and Mycobacterium leprae DNA polymerase chain reaction (ML-PCR) were performed at baseline. chi(2) test, Kaplan-Meir curves, and Cox proportional hazards were applied. The majority of volunteers were adults with a mean age of 30.5 +/- 15.4 years; 44.4% were ML-PCR positive. During follow-up, 14.8% of the patients had a poor clinical outcome, classified as a type 1 reaction. Older age (> or = 40 years), ML-PCR positivity, and lesion size > 5 cm were associated with increased risk. In multivariate analysis, age (> or = 40 years) and ML-PCR positivity remained baseline predictors of type 1 reaction among monolesion leprosy patients.

Topics: Adolescent; Adult; Aging; Cohort Studies; DNA, Bacterial; Erythema Nodosum; Female; Humans; Leprosy; Male; Middle Aged; Minocycline; Mycobacterium leprae; Ofloxacin; Polymerase Chain Reaction; Rifampin; Risk Factors; Time Factors

The WHO MDT for leprosy treatment was officially introduced in Brazil in 1991 and comprises three drugs: dapsone, rifampicin and clofazimine. There are few good studies on the frequency of side-effects attributable to MDT in Brazil.. A retrospective and descriptive study carried out in a LCP in Vitória, State of Espirito Santo, Brazil. A specific and detailed protocol about side-effects was prepared and filled in from the patient records.. One hundred ninety four patients' records were analysed looking for side-effects attributable to MDT. Side-effects were attributed to at least one MDT component in 88 (45%) patients and 85 had side-effects due to dapsone, 24 due to rifampicin and 18 due to clofazimine. 185 episodes were identified. The suspected drug was stopped in 47 out of 88 episodes (24% patients); 46 had dapsone stopped, 5 had rifampicin stopped and no-one had clofazimine stopped.. Side-effects attributed to MDT is more frequent than previously described, resulting in interruption of treatment in many patients.

Topics: Adult; Brazil; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Retrospective Studies; Rifampin; Treatment Outcome

Topics: Drug Resistance, Bacterial; Global Health; India; Leprostatic Agents; Leprosy; Rifampin

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Dapsone; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Leprostatic Agents; Leprosy; Male; Middle Aged; Rifampin

A 67-year-old man, who had widespread and well-defined erythematous violaceous hyperkeratotic plaques on his skin, was diagnosed with borderline tuberculoid leprosy. The patient began treatment with clofazimine, rifampicin, and dapsone, but 15 days afterwards he complained of acral edema with godet sign. Magnetic resonance imaging was done, and the case was interpreted as remitting seronegative symmetrical synovitis with pitting edema. About 8 mg/day of methylprednisolone were started with excellent response.

Topics: Aged; Clofazimine; Dapsone; Drug Therapy, Combination; Edema; Foot; Humans; Leprostatic Agents; Leprosy; Magnetic Resonance Imaging; Male; Methylprednisolone; Rifampin; Synovitis; Treatment Outcome

To review the reported trend of leprosy in Hong Kong.. Retrospective study.. Three major leprosy clinics in Hong Kong.. Leprosy patients registered between 1970 and 2004.. Incidence, rate of deformities, distribution of leprosy subtypes, age distribution, and relapses after therapy.. The incidence of leprosy has decreased from 3.2 per 100,000 population in 1970 to 0.088 per 100,000 population in 2004. The proportion of the three subtypes of leprosy has remained roughly equal. There have been 87 relapses within this period with 54 (62%) cases of lepromatous leprosy, 22 (25%) borderline leprosy, and 11 (13%) tuberculoid leprosy. The overall relapse rate was 6.7% (0.2 per 100 person-years); this can be subdivided as a relapse rate for multidrug therapy of 3.2% (0.33 per 100 person-years) and for dapsone monotherapy of 8.3% (0.2 per 100 person-years). The mean interval to relapse for multidrug therapy and dapsone monotherapy was 1.83 and 5.8 years, respectively. The mean duration till relapse for patients on dapsone monotherapy was 15.6 years.. Treatment with recommended WHO-multidrug therapy is effective and well tolerated. Dapsone monotherapy is no longer effective. Leprosy is well controlled in Hong Kong but continued surveillance is required to detect relapses and to ensure good patient compliance with treatment.

Topics: Clofazimine; Dapsone; Drug Resistance, Bacterial; Drug Therapy, Combination; Hong Kong; Humans; Incidence; Leprostatic Agents; Leprosy; Practice Guidelines as Topic; Recurrence; Retrospective Studies; Rifampin; Steroids; World Health Organization

Nucleic acid sequences of Mycobacterium leprae were detected using gene probes hybridizing with targeting ribosomal RNA (16S rRNA), ribosomal DNA (16S rDNA) and gene amplification techniques (PCR) in skin lesion of paediatric leprosy patients and the effect of treatment on the by these methods. Eighty paediatric leprosy patients were included in the study. Most cases (79%) were between 9 and 16 years of age. Cases were divided into three groups according to treatment status, viz. untreated (30), undergoing treatment (30), and at the end of treatment (20). Clinical and slit smear examination for acid fast bacilli (AFB) was performed and nucleic acids were extracted and fractionated from skin biopsies. M. leprae specific 16S rRNA and 16S rDNA was detected by hybridization with gene probes whereas the 36 kDa gene sequence was detected by a gene amplification assay (PCR). The cases were classified as paucibacillary (PB) and multibacillary (MB) by the standard criteria of WHO (1988). Positivity of 16S rRNA in PB cases decreased from 60% in untreated to 10.5% after 4-8 months of treatment whereas for 16S r DNA, it decreased from 50% to 21%, for PCR from 70% to 36.8% for the same specimen, and all became negative at 1 year. Similar trends were seen in MB cases where positivity in smear positive untreated cases decreased from 100% to 56.2% with 16S rRNA and 42.8% with 16S rDNA and PCR, respectively, after 9-12 months of treatment and all became negative at 2 years, except one case which remained positive with PCR. Similar results were observed in smear negative MB cases, 100% positivity detected by 16S r RNA and PCR, 75% detected by 16S rDNA decreased to zero after 9-12 months of therapy. This study suggests the potential usefulness of gene probes targeting 16S rRNA and 16S rDNA and PCR as supportive molecular tools for diagnosis of smear negative evolving MB disease and also monitoring the response to treatment, these observations however, needs to be validated in prospective follow up studies.

Topics: Adolescent; Child; Child Welfare; Dapsone; DNA Probes; DNA, Bacterial; Female; Humans; Leprostatic Agents; Leprosy; Male; Mycobacterium leprae; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction; Predictive Value of Tests; Rifampin; RNA, Ribosomal, 16S

Mutations in the rpoB gene of 40 biopsy isolates of Mycobacterium leprae were analyzed by reverse hybridization-based line probe assay after PCR, and nine distinct single-nucleotide substitutions were found. Among them, a 3-nucleotide substitution was found in two, and 2-nucleotide substitutions were found in seven isolates. This is a new finding of multiple mutations in a single point of the rpoB gene for rifampicin resistance. This investigation demonstrates that the pattern of mutations in the rpoB gene for rifampicin resistance in Nepal involves more variety.

Topics: Biological Assay; Biopsy; Drug Resistance, Bacterial; Genes, Bacterial; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Polymerase Chain Reaction; Rifampin

ad hoc committee of Japanese Leprosy Association recommends revised standard treatment protocol of leprosy in Japan, which is a modification of World Health Organization's multidrug therapy (WHO/MDT, 1997). For paucibacillary (PB) leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough. However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment seems insufficient. Thus, (A) For MB with bacterial index (BI) > or = 3 before treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is necessary. When BI become negative and active lesion is lost within 2 years, no maintenance therapy is necessary. When BI is still positive, one year of MDT/MB is added (3 years in total), followed by maintenance therapy by dapsone and clofazimine until BI negativity and loss of active lesions. (B) For MB with BI < 3 or fresh MB (less than 6 months after the onset of the disease) with BI > or = 3, 1 year treatment by MDT/MB is necessary. When BI become negative and active lesion is lost within one year, no maintenance therapy is necessary. When BI is still positive or active lesion is remaining, additional therapy with MDT/MB for one more year is recommended. This is a simplification of first version in 2000. Brief summary of diagnosis, purpose of therapy, character of drugs, and prevention of deformity is also described.

Topics: Clofazimine; Congenital Abnormalities; Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Japan; Leprostatic Agents; Leprosy; Rifampin; Surgical Procedures, Operative

Antimicrobial susceptibility testing of Mycobacterium leprae by non-radioactive bioluminescence assay was developed. Optimization of the assay conditions such as temperature and time for ATP extraction, bacteria dose, preparation of bacteria suspension and pH of culture medium was carried out using M. leprae Thai 53 strain. Samples of bacterial suspension of M. leprae were first treated with filamentous cell treatment reagent at room temperature for 30 minutes and ATP was extracted from the leprosy bacilli by heating at 60 degrees for five minutes. Luciferin luciferase was added to the extract after cooling to room temperature followed by measurement of relative light units (RLU) of each sample using a luminometer. The concentrations of the drugs used for the evaluation of antimicrobial activities of rifampin (RFP), clofazimine (CLF), ofloxacin (OFLX) and clarithromycin (CAM) were 0.125, 0.50, 2.0 and 8.0 microg/ml respectively. Middlebrook 7H9 broth medium was used (pH6.6) as the basal medium and the bacilli were cultivated at 32 C for 0-14 days. ATP was extracted from 0.1 ml of culture suspension and inhibition of the luminescent activity was calculated. The results were compared to that obtained by radio-active CO2 detection system, Buddemeyer method which is commonly used for measuring anti-M. leprae activity. There was a good correlation between the results obtained by ATP method on the tenth day of culture and the results obtained by Buddemeyer method on the seventh day of culture. ATP method may be useful for the determination of drug susceptibility ofM. leprae.

Topics: Animals; Clarithromycin; Clofazimine; Drug Resistance, Bacterial; Leprostatic Agents; Leprosy; Luciferases; Luminescent Agents; Mice; Mice, Nude; Microbial Sensitivity Tests; Mycobacterium leprae; Ofloxacin; Rifampin

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Practice Guidelines as Topic; Rifampin; World Health Organization

Leprosy is an ancient disease, which was treated by local application of chaulmoogra/hydnocarpus oil during prechemotherapeutic era. Since 1940, dapsone was the only chemotherapeutic agent used for treatment of leprosy for about three decades. Prolonged, interrupted and inadequate use of dapsone monotherapy, leads to development of dapsone-resistant cases. Usefulness of clofazimine was known in 1962. Introduction of rifampicin--a powerful bactericidal drug in 1970 has opened the avenues of multidrug therapy to treat leprosy. Multidrug therapy recommended by World Health Organisation came into practice after 1982. The regimen followed now is for duration of 6 months in paucibacillary and for the duration of 12 months in multibacillary cases. It is proven to be safe and effective. Multidrug therapy for leprosy cases is available in the form of blister calender packs and is available free of cost at all government health facilities. Although more new drugs such as ofloxacin, minocyclin, clarithromycin, etc, are known now but they are used as alternative drugs if a component of combination in multidrug therapy becomes contra-indicated. This article brings the details of various drugs used under multidrug therapy, their characteristics, side-effects, regimens and alternative drugs available for treating leprosy.

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin; World Health Organization

Most of the research in clinical trials is based on longitudinal designs, which involve repeated measurements of a variable of interest. Such designs are very powerful, both statistically and scientifically. Recent advances in statistical theory and software development incorporate the covariance structures such as unstructured, compound symmetry, auto-regressive and random effects, etc., for analysing longitudinal data. Hathaway et al. propose a technique for summarizing longitudinal data using linear growth curve model and establish that the number of summary statistics is fixed as four irrespective of the length of study. In this paper, we develop a procedure for analysing the longitudinal data through a piecewise linear growth curve model on the lines of Hathaway et al. Under different covariance structures, the linear model is fitted for Leprosy data and the residual sum of squares computed. Goodness of fit has also been considered for various models. In order to prove that the proposed method is robust and better than the others in terms of goodness of fit, simulation studies are carried out and the results presented.

Topics: Biometry; Clinical Trials as Topic; Data Interpretation, Statistical; Humans; Leprostatic Agents; Leprosy; Linear Models; Longitudinal Studies; Mycobacterium leprae; Randomized Controlled Trials as Topic; Rifampin

An intervention study was implemented on five Indonesian islands highly endemic for leprosy to determine whether rifampicin can be used as chemoprophylaxis to prevent leprosy. The population was actively screened before the intervention and subsequently once a year for three years. In the control group, no chemoprophylaxis was given. In the contact group, chemoprophylaxis was only given to contacts of leprosy patients and in the blanket group to all eligible persons. The cohort consisted of 3,965 persons. The yearly incidence rate in the control group was 39/10,000; the cumulative incidence after three years was significantly lower in the blanket group (P = 0.031). No difference was found between the contact and the control groups (P = 0.93). Whether this apparent reduced leprosy incidence in the first three years in the blanket group is due to a delayed development of leprosy or a complete clearance of infection needs to be determined.

Topics: Case-Control Studies; Cohort Studies; Humans; Incidence; Indonesia; Leprostatic Agents; Leprosy; Rifampin

Dapsone syndrome is a rare hypersensitivity reaction to dapsone and is characterized by high fever, papular or exfoliative dermatitis, progressing to liver toxicity and generalized lymphadenopathy, resembling a mononucleosis infection. We report a patient who developed acute renal failure, as well as other complications characteristic of dapsone syndrome, during leprosy treatment. Renal involvement had not been previously described as a dapsone syndrome feature.

Topics: Acute Kidney Injury; Adult; Clofazimine; Dapsone; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Rifampin; Syndrome

We describe clinical and pathological features of kidney and skin involvement in a patient with hypersensitivity vasculitis associated with dapsone. Although visceral damage occurs rarely, similar skin and kidney histopathologic and immunohistochemical findings indicate that this organ is a target for type IV cell-mediated dapsone reaction. To our knowledge, this is the first reported case of renal hypersensitivity vasculitis associated with dapsone.

Topics: Adult; Anti-Bacterial Agents; Antitubercular Agents; Clofazimine; Cyclophosphamide; Dapsone; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Kidney Diseases; Leprostatic Agents; Leprosy; Methylprednisolone; Rifampin; Tuberculosis, Pulmonary; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Aged; Clofazimine; Dapsone; Exanthema; Humans; Hypesthesia; Leprostatic Agents; Leprosy; Male; Rifampin; Spain; Venezuela

Topics: Adult; Clofazimine; Dapsone; Diagnosis, Differential; Drug Therapy, Combination; Face; Humans; Leprostatic Agents; Leprosy; Male; Rifampin; Skin Diseases; Thalidomide

For advanced control of leprosy in Pakistan where the World Health Organization leprosy elimination goal was achieved in 1996, we conducted surveillance of Mycobacterium leprae-seropositive patients and their contacts and drug resistant strains of M. leprae. We measured anti-PGL-I antibody level in sera from leprosy patients and their contacts for early detection of M. leprae infection. Out of 34 leprosy patients undergoing treatment, 4 lepromatous leprosy patients were antibody positive, and 6.8 to 23.7 percent of occupational or household contacts were seropositive. Furthermore, three cases (1.2%) had a high antibody titer. For surveillance of drug resistant strains of M. leprae, dapsone and rifampin were targeted. Four out of 18 polymerase chain reaction (PCR) positive samples had mutation in folP gene, and among 10 PCR positive samples, one had a mutation in the rpoB gene. These results indicate that serological analysis of patient contacts might be useful to find out high risk individuals, and there are M. leprae strains resistant to chemotherapeutic agents in Pakistan.

Topics: Adult; Antibodies, Bacterial; Antigens, Bacterial; Child; Dapsone; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Family Characteristics; Glycolipids; Humans; Leprostatic Agents; Leprosy; Leprosy, Lepromatous; Mycobacterium leprae; Occupational Exposure; Pakistan; Population Surveillance; Prevalence; Rifampin

Topics: Dapsone; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin; World Health Organization

DNA sequences of Mycobacterium leprae in particular regions of the gyrA, rpoB, and folP genes responsible for resistance to new quinolones, rifampicin and dapsone, respectively, were analyzed. Among 88 isolates of M. leprae from leprosy patients in Japan, Haiti, Indonesia, Pakistan, and the Philippines, eleven isolates had mutational changes in 2 genes (resistance to 2 drugs), and 2 isolates (Shinsei-1 and Zensho-4) showed mutations in 3 genes (resistance to 3 drugs). These findings are suggesting emergence of multi-drug resistant M. leprae.

Topics: Animals; Base Sequence; Dapsone; DNA Gyrase; DNA-Directed RNA Polymerases; Drug Resistance, Multiple; Humans; Leprostatic Agents; Leprosy; Mutation; Mycobacterium leprae; Ofloxacin; Rifampin

The alkaline single cell gel electrophoresis assay was performed on peripheral blood lymphocytes of lepromatous and tubercloid leprosy patients (untreated and those undergoing treatment) in order to ascertain whether differential damage to DNA occurs. The study group included 28 male and 2 female patients and 15 healthy males who were matched for age and socio-economic status. The results revealed DNA damage in all patients, with a mean DNA migration length of 29.88 +/- 3.39 microm and 38% of their cells damaged when compared with the respective values obtained in healthy controls (1.28 +/- 0.40 microm, 5%). Multiple regression analysis for effects of confounding factors revealed antibiotic treatment in patients and alcohol consumption in controls as the only variables influencing DNA damage. In lepromatous and tubercloid patients, both untreated and those undergoing treatment, DNA damage increased significantly from that observed in control individuals, with greater increased damage in lepromatous patients. An increase in treatment time increased DNA damage linearly. Furthermore, an arbitrary classification of damaged cells (categories I-IV) was made based on observed tail lengths in leprosy patients (5.00-225.00 microm). The number of damaged cells in untreated patients was lower than in those undergoing treatment; the latter also had more cells with greater DNA migration lengths. There were no category III or IV cells in the control group. The results of the study therefore reveal that patients undergoing therapy had significantly greater DNA damage than untreated patients, indicating bacterial infection and drug therapy as the causal factors, since lepromatous-type disease is the more severe form with the patients having lower resistance to Mycobacterium leprae and requiring heavier and prolonged dosage of antibiotics. The study also corroborates that the assay offers an opportunity for correlating levels of therapy-induced DNA damage with administered dose and for modulating the dose-schedule so as to achieve lower levels of genotoxic damage.

Topics: Adolescent; Adult; Aged; Clofazimine; Dapsone; DNA Damage; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Rifampin

The WHO MDT regimens have proved highly successful in preventing relapse of leprosy cases. It has indirectly lad to marked reduction in prevalence of disabilities. For PB leprosy, rifampicin 600 mg monthly and 100 mg dapsone daily for a total of 6 months therapy is required. For MB leprosy clofazimine 300 mg once monthly, supervised and 50 mg daily self administered is added. For single skin lesion the current WHO recommendation is 600 mg rifampicin + 400 mg ofloxacin + 100 mg minocycline given as a single dose for adults. Dose adjustment for children and clinical information have been discussed in a nutshell. A number of trials are going on, some are yet to be completed which do offer the prospect of perhaps simplifying therapy and improving with shorter duration.

Topics: Anti-Bacterial Agents; Clofazimine; Dapsone; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans; Hypersensitivity; India; Leprosy; Minocycline; Nausea; Ofloxacin; Rifampin; Secondary Prevention; Tuberculosis; World Health Organization

The antimicrobial effects of sitafloxacin (DU-6859a) against Mycobacterium leprae, either singly or in combination with either rifampicin, rifabutin or KRM-1648, were studied using a mouse footpad assay technique and the results were compared with those obtained with ofloxacin. When used singly, the minimum concentrations of sitafloxacin and ofloxacin needed to inhibit completely the growth of M. leprae were 25 and 100 mg per kg body weight per day, respectively, and the effects were bactericidal. Both sitafloxacin and ofloxacin exhibited excellent synergistic effects when combined with either rifabutin or KRM-1648, but not with rifampicin. Thus, incorporation of sitafloxacin and rifabutin (or KRM-1648) in the multidrug regimen for treating leprosy patients is suggested.

Topics: Animals; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fluoroquinolones; Leprostatic Agents; Leprosy; Mice; Mice, Inbred BALB C; Mycobacterium leprae; Ofloxacin; Rifampin

Areas of low endemicity of Hansen's disease, such as Texas, California, and Hawaii, exist due to immigration and rare autochthonous infections. Managing this disease in these areas of low endemicity is difficult, especially in observing for relapse. The accurate diagnosis of relapse is imperative so that appropriate therapy can be promptly reinstituted and unnecessary treatment can be avoided. To assess treatment failures in an area of low endemicity, we retrospectively evaluated 113 patients with Hansen's disease treated in southern Texas. Of 57 patients who completed therapy, 11 were later restarted on medications for this disease for presumed relapse. However, nine of the 11 were found not to have true relapses of Hansen's disease. The accurate diagnosis of relapse of this disease is essential not only in the individual patient but also for prospective treatment trials to establish best practices.

Topics: Adolescent; Adult; Aged; Child; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Medical Records; Middle Aged; Recurrence; Retrospective Studies; Rifampin; Texas; Treatment Failure; Treatment Refusal

The World Health Organization (WHO) Field Trials of multidrug therapy (MDT) started at Schieffelin Leprosy Research and Training Centre (SLR & IC), Karigiri, India in December 1981. The patients were treated with two MDT regimens. The first (regimen A) consisted of 600mg rifampicin and 300mg of clofazimine given under supervision on 2 consecutive days monthly, 225mg injection of acedapsone bimonthly and dapsone 100mg daily. The second regimen (regimen B) was the conventional MDT (WHO/MDT), rifampicin 600mg and clofazimine 300mg supervised once a month, dapsone 100mg and clofazimine 50mg daily, unsupervised. Both the regimens were administered for a minimum period of 2 years or until skin smear negativity, whichever occurred later. Thirty-four newly detected previously untreated MB patients, 16 of whom received regimen A and 18 regimen B, were reassessed. Both regimens were well accepted and well tolerated by the patients. Clofazimine discolouration was the only adverse effect of MDT seen in these patients. After completion of treatment with MDT, the patients were followed up for a total duration of 466 person-years with a mean of 13.7 +/- 1.4 years per patient. No relapse was seen.

Topics: Acedapsone; Adult; Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leprostatic Agents; Leprosy; Male; Rifampin; Skin; Treatment Outcome; World Health Organization

This is the first report of secondary resistance to rifampin following MDT in a patient with prolonged, but irregular treatment. Repeated mouse foot-pad studies demonstrated resistance to dapsone after several years of monotherapy, and following subsequent MDT the studies demonstrated the development of resistance to rifampin.

Topics: Dapsone; Drug Resistance, Bacterial; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Rifampin

We explored the prognostic value of in situ cytokine patterns in 39 patients with single-skin-lesion paucibacillary leprosy before single-dose therapy, with 3 years of follow-up. Interferon (IFN)-gamma, interleukin (IL)-12, IL-10, IL-4, tumor necrosis factor (TNF)-alpha, and macrophage inflammatory protein (MIP)-1alpha mRNA was quantified in skin biopsy samples at diagnosis, and Mycobacterium leprae DNA was detected in 51.4% of cases. Type 1 immunity predominance with measurable IFN-gamma and undetectable IL-4, which is indicative of effective cell-mediated immunity, is compatible with both the reversal reactions (33.3%) and the resolution of lesions (64.1%) observed. A positive correlation between IL-12 and IFN-gamma indicated type 1 polarization via IL-12. The TNF-alpha/MIP-1alpha correlation implied the TNF-alpha induction of chemokines, which is important for granuloma formation. Positive correlations between key regulatory cytokines-IL-10 and IFN-gamma, IL-10 and IL-12, and IL-10 and TNF-alpha-suggests that there may be some level of an intralesional pro- or anti-inflammatory mechanism essential in avoiding immunopathology.

Topics: Adolescent; Adult; Antibodies, Bacterial; Biopsy; Child; Cohort Studies; Cytokines; Female; Gene Expression Regulation, Bacterial; Humans; Leprosy; Male; Minocycline; Mycobacterium leprae; Ofloxacin; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; RNA, Messenger; RNA, Viral; Th1 Cells

We report two cases of Hansen's disease. Case 1 was 71-year old Japanese man who developed left ulnar nerve palsy since 7 years ago, multiple erythema on his body since 2-3 years ago, and erythematous nodules on his face since 3 months ago. He had no history of living outside Ibaraki prefecture. The clinical feature, the skin biopsy, laboratory data showed that he had borderline lepromatous leprosy. He was treated with multi-drug therapy which was effective and was stopped 3 years after the bacterial index showed negative. Ten months later, erythema on his body and face appeared and the therapy was restarted. Case 2 was 68-year old Japanese man who developed 5 cm of nummular erythema with slight numbness on his right forearm since 3 months ago. He had lived in Brazil since he was 24 to 64 years old. The skin biopsy showed epithelioid cell granuloma in the dermis involving vessels and nerves. Polymerase chain reaction test showed the M.leprae DNA, and he was diagnosed as indeterminate leprosy. He was treated with dapson and rifampicin and 2 months later, erythema and numbness disappeared.

Topics: Aged; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Male; Recurrence; Rifampin; Treatment Outcome

Topics: Clinical Trials as Topic; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Ofloxacin; Recurrence; Rifampin

Acute renal failure (ARF) caused by rifampicin typically occurs on intermittent administration. There are isolated case reports and only one series reported in the literature. Systematic data, especially from countries endemic for tuberculosis and leprosy, are sparse.. We studied demographic, clinical, biochemical, and histopathologic features and prognosis of 25 consecutive patients with rifampicin-associated ARF admitted from July 1990 to June 2000.. Rifampicin-associated ARF constituted 2.5% of all cases of ARF seen during the study period. The most common pattern of drug intake resulting in ARF (40%) was ingestion of a single dose preceded by a drug-free period (range, 10 days to 6 years) after a course of daily rifampicin (range, 8 days to 18 months). Onset was with gastrointestinal and flu-like symptoms 4 hours (median) after drug intake. All patients were oliguric. Anemia and thrombocytopenia each occurred in 60% of patients. Acute hepatitis was present in 32%. Among 12 patients who underwent kidney biopsy, 7 patients (58%) had acute interstitial nephritis (AIN). Crescentic glomerulonephritis was seen in 1 patient, and mesangial proliferation, in 3 patients. No single feature at presentation predicted the severity of renal failure. There were no deaths, and all patients recovered renal function.. Patients with rifampicin-associated ARF were oliguric and presented with gastrointestinal and flu-like symptoms, typically after reintroduction of the drug after a drug-free period. Anemia and thrombocytopenia were common. AIN was the most common biopsy finding. No factor predicted severity, but the renal prognosis was good.

Topics: Acute Kidney Injury; Adult; Aged; Antibiotics, Antitubercular; Drug Administration Schedule; Female; Humans; Leprosy; Male; Middle Aged; Oliguria; Prognosis; Rifampin; Tuberculosis, Lymph Node

Between 1989 and 1993, 136 multibacillary leprosy patients received a 6-week treatment regimen consisting of daily rifampicin 600 mg, ofloxacin 400 mg, clofazimine 100 mg and a weekly dose of 100 mg minocycline. A previous analysis after a mean follow-up of 4-7 years revealed a relapse rate of 2%, involving six late (after more than 5 years of follow-up) relapses. During the following years, 12 more relapses appeared during years 8-9 of follow-up. A mean follow-up period of 5 years is insufficient to evaluate treatment regimens in multibacillary leprosy. The present regimen cannot be recommended.

Topics: Belgium; Clofazimine; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Humans; Leprostatic Agents; Leprosy; Ofloxacin; Recurrence; Rifampin

A 25-year-old man with a history of mid-borderline (BB) Hansen's disease developing a reversal reaction after starting dapsone and rifampin therapy is presented. His clinical features included erythematous, edematous plaques and peripheral neuropathy. Reversal reactions are caused immunologically by enhanced cell-mediated (Th-1) immunity to Mycobacterium leprae, resulting in inflammation of infected tissues, such as skin and nerves. Acute neuritis can lead to permanent nerve damage and necessitate prompt treatment with prednisone and/or clofazamine.

Topics: Adult; Humans; Leprosy; Male; Prednisone; Rifampin; Severity of Illness Index

Molecular detection of rifampin resistance (rpoB analysis) in Mycobacterium leprae was determined for 49 patients who experienced relapse of multibacillary leprosy and for 34 untreated patients. Molecular detection of ofloxacin resistance (gyrA analysis) was determined for the 12 patients who experienced relapse and who had received ofloxacin. Results of molecular tests were compared with the reference susceptibility test in the mouse footpad. Overall, the efficiency of molecular detection--that is, positive DNA amplification--was 95%, whereas that of the in vivo test was 55% (P<.001). Results of molecular detection and in vivo test were fully concordant when both were available--that is, for 35 rifampin--sensitive cases of leprosy (no rpoB mutation), 4 ofloxacin-sensitive cases (no gyrA mutation), 11 rifampin-resistant cases (rpoB missense mutations), and 1 ofloxacin-resistant case (gyrA mutation). rpoB and gyrA analysis appears to be an effective method for detection of rifampin and ofloxacin resistance in patients with leprosy.

Topics: Adult; Aged; Antibiotics, Antitubercular; Disease Models, Animal; DNA Gyrase; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Leprosy; Microbial Sensitivity Tests; Middle Aged; Mutation; Mycobacterium leprae; Ofloxacin; Plant Proteins; Recurrence; Rifampin

Topics: Animals; Drug Resistance, Microbial; Female; Humans; Leprostatic Agents; Leprosy; Male; Mice; Microbial Sensitivity Tests; Mycobacterium leprae; Pilot Projects; Research; Rifampin

Topics: Clofazimine; Dapsone; Dermatomycoses; Diagnosis, Differential; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin; World Health Organization

Topics: Aftercare; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin

Topics: Aged; Cell Count; China; Clofazimine; Dapsone; Diabetes Mellitus, Type 1; Emigration and Immigration; Female; Hawaii; Humans; Leprosy; Mycobacterium leprae; Rifampin; United States

Topics: Adult; Animals; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Mice; Middle Aged; Minocycline; Ofloxacin; Recurrence; Rifampin

Sequences of the folP1, rpoB, and gyrA genes were analyzed for 88 isolates of Mycobacterium leprae from leprosy patients in Japan, Haiti, Indonesia, Pakistan, and the Philippines. Thirteen isolates (14.8%) showed representative mutations in more than two genes, suggesting the emergence of multidrug-resistant M. leprae.

Topics: Animals; Anti-Infective Agents; Antibiotics, Antitubercular; Base Sequence; DNA Primers; DNA, Bacterial; Drug Resistance, Microbial; Drug Resistance, Multiple; Genes, Bacterial; Humans; Leprostatic Agents; Leprosy; Mice; Molecular Sequence Data; Mycobacterium leprae; Ofloxacin; Reverse Transcriptase Polymerase Chain Reaction; Rifampin

A genotypic method for predicting rifampicin resistance in Mycobacterium leprae has been developed and rigorously tested on mouse footpad-derived and clinical specimens. A series of immobilized oligonucleotide capture probes can discriminate between wild type and mutant rpoB alleles, and positive controls are available for the most frequent mutation affecting Ser425. Two different non-radioactive detection formats have been tested with comparable success in both an industrialized and a developing country. The standardized procedure could now be used in a prospective study of potential rifampicin resistance among multibacillary patients.

Topics: Animals; Base Sequence; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Mice; Molecular Sequence Data; Mycobacterium leprae; Oligonucleotide Probes; Polymerase Chain Reaction; Predictive Value of Tests; Rifampin

Therapeutic effect of lyophilized horseradish peroxidase in complex with the basic antileprosy drugs diaminodiphenylsulfone and rifampicin was studied in experimental leprosy. Oral therapy with drug complexes was more effective than monotherapy. Treatment with drug combinations activated myeloperoxidase in blood neutrophil, produced an antiinflammatory effect, stimulated cell immunity, and had no toxic effect on mouse liver.

Topics: Animals; Anti-Inflammatory Agents; Dapsone; Drug Combinations; Horseradish Peroxidase; Leprostatic Agents; Leprosy; Liver; Mice; Mice, Inbred CBA; Neutrophils; Peroxidase; Phagocytes; Rifampin; Time Factors

Topics: Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Leprosy, Tuberculoid; Male; Rifampin; United States; Vietnam

Topics: Clofazimine; Drug Therapy, Combination; Global Health; Humans; Hypersensitivity, Delayed; Leprostatic Agents; Leprosy; Prevalence; Public Health; Rifampin; Skin

Bactericidal activities of HMR 3647 (HMR), moxifloxacin (MXFX), and rifapentine (RPT) against Mycobacterium leprae, measured by the proportional bactericidal technique in the mouse footpad system, were compared with those of the established antileprosy drugs clarithromycin (CLARI), ofloxacin (OFLO), and rifampin (RMP). Administered in five daily doses of 100 mg/kg of body weight, HMR appeared slightly more bactericidal than CLARI. In a single dose, MXFX at 150 mg/kg was more active than the same dose of OFLO and displayed exactly the same level of activity as RMP at 10 mg/kg; the combination MXFX-minocycline (MINO) (MM) was more bactericidal than the combination OFLO-MINO (OM); RPT at 10 mg/kg was more bactericidal than the same dose of RMP and even more active than the combination RMP-OFLO-MINO (ROM); the combination RPT-MXFX-MINO (PMM) killed 99.9% of viable M. leprae and was slightly more bactericidal than RPT alone, indicating that the combination PMM showed an additive effect against M. leprae.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Female; Fluoroquinolones; Foot; Ketolides; Leprostatic Agents; Leprosy; Macrolides; Mice; Microbial Sensitivity Tests; Moxifloxacin; Mycobacterium leprae; Quinolines; Rifampin; Skin

A programme of chemoprophylaxis was introduced as a component of the leprosy control programme in the Federated States of Micronesia (FSM), beginning in 1996. The entire population of the country was to be screened, and a single dose of 600 mg rifampicin, 400 mg ofloxacin and 100 mg minocycline (ROM) was to be administered to the entire population. Two rounds of screening the entire population were carried out, approximately 1 year apart, and chemoprophylaxis was administered at the time of each screening. Ninety percent of the population were screened at least once, and 55% were screened in both rounds; 87% of the population received at least one dose, and 54% received two doses. In the course of the first round, 322 new cases were detected, whereas only 80 new cases were detected during the second round, of whom only 12 had received chemoprophylaxis in the course of the first round. A third round of screening, confined to a small number of villages in both Chuuk and Pohnpei, in which states leprosy endemicity was high, was carried out approximately 2 years after the second. Only 16 new cases were detected during the third round of screening, whereas 102 new cases had been detected in this same population during the first round of screening, and 32 new cases during the second. Six of the 16 newly detected cases stated that they had been administered chemoprophylaxis at least once; however, this information may not be reliable.

Topics: Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Incidence; Leprostatic Agents; Leprosy; Male; Mass Screening; Micronesia; Minocycline; Ofloxacin; Rifampin; Treatment Outcome

In 1988, a programme of leprosy chemoprophylaxis, employing a supervised, single 25 mg/kg dose of rifampicin, was implemented in the Southern Marquesas Islands. Of the 2786 inhabitants, 2751 (98.7%) were treated. In addition, 3144 South Marquesans living elsewhere in French Polynesia were administered the same chemoprophylaxis. During the following 10 years, seven leprosy patients were detected among those who had been administered chemoprophylaxis. Of these, two were very likely missed cases of leprosy, and cannot be considered a failure of chemoprophylaxis. The epidemiometric projection model, based on cases of leprosy observed in the Southern Marquesas during the 20 years preceding implementation of the programme, predicted that 17 leprosy cases could be expected in the South Marquesan population if no chemoprophylaxis were given. In fact, only five cases were detected in the treated population, a number significantly smaller than 17, suggesting that the chemoprophylaxis was 70% effective, assuming that no change of detection rate would have occurred without chemoprophylaxis. However, during the 10 years following implementation of the chemoprophylaxis programme, the detection rate in the Polynesian population that was not administered chemoprophylaxis declined by about 50%. Therefore, the effectiveness of the chemoprophylaxis was only 35-40%.

Topics: Adolescent; Adult; Child; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Incidence; Leprostatic Agents; Leprosy; Male; Middle Aged; Polynesia; Retrospective Studies; Rifampin; Risk Factors; Treatment Outcome

Topics: Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; India; Leprostatic Agents; Leprosy; Minocycline; Ofloxacin; Prognosis; Rifampin; Treatment Outcome

To further the development of a multidrug regimen for treatment of leprosy that is suitable for monthly administration and fully supervisable, the bactericidal activities against Mycobacterium leprae of HMR 3647 (HMR), moxifloxacin (MXFX) and rifapentine (RPT) were measured by the proportional bactericide technique in the mouse footpad system, and compared with those of the established antileprosy drugs clarithromycin (CLARI), ofloxacin (OFLO) and rifampicin (RMP). Administered in five daily doses of 100 mg per kg body weight, HMR appeared slightly more bactericidal than CLARI, but the difference did not attain statistical significance. Administered as single doses, MXFX in a dosage of 150 mg per kg was more active than OFLO in the same dosage, and displayed the same level of activity as RMP in a dosage of 10 mg per kg; the combination MXFX-minocycline (MINO) (MM) was more bactericidal than the combination OFLO-MINO (OM); RPT in a dosage of 10 mg per kg was more bactericidal than RMP administered in the same dosage, and even more active than the combination RMP-OFLO-MINO (ROM); the combination RPT-MXFX-MINO (PMM) killed 99.9% of viable M. leprae, and was slightly more bactericidal than was RPT alone, indicating that the combination PMM showed an additive effect against M. leprae. These promising results justify a clinical trial among lepromatous patients, in which MM is being compared with OM, and PMM with ROM, in terms of efficacy and tolerance.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fluoroquinolones; Leprostatic Agents; Leprosy; Mice; Mice, Inbred Strains; Minocycline; Moxifloxacin; Probability; Quinolines; Rifampin; Treatment Outcome

Topics: Clofazimine; Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Nepal; Prevalence; Rifampin

Topics: Anti-Infective Agents; Drug Therapy, Combination; Granuloma; Humans; Leprostatic Agents; Leprosy; Minocycline; Ofloxacin; Rifampin; Tetracycline

A new finding is reported of multiple mutations in the rpoB gene of 9 Mycobacterium leprae strains from leprosy patients in Thailand, who did not respond to therapy even when rifampicin, the main drug in multi-drug therapy was used. By means of sequence analysis of 9 Thai M. leprae strains, various mutations in 289 bps of the rpoB gene revealed forms of mutation never before described, such as multiple mutations (ie, mutation at two, three, six, seven, eight and nine positions in the rpoB gene), most of which were point-mutation substitutions (a few of which were silent), and some insertions. This investigation demonstrates that mutation in the rpoB gene of M. leprae strains from Thailand involves more variety than previously reported for rpoB mutation patterns in rifampicin resistance M. leprae strains.

Topics: Codon; DNA-Directed RNA Polymerases; DNA, Bacterial; Humans; Leprostatic Agents; Leprosy; Mutation; Mycobacterium leprae; Plant Proteins; Polymerase Chain Reaction; Rifampin; Sequence Analysis, DNA; Thailand

Mycobacterium leprae were isolated from a Japanese patient, and susceptibility to antileprosy drugs was examined by the mouse foot pad method. The isolate was susceptible to clofazimine and clarithromycin, and resistant to dapsone, rifampin, ofloxacin and sparfloxacin. Mutations were identified in the genes associated with resistance to these drugs. The risk of the emergence of leprosy with multidrug resistance is emphasized.

Topics: Animals; Anti-Infective Agents; Antitubercular Agents; Clarithromycin; Clofazimine; Colony Count, Microbial; Dapsone; Drug Resistance, Microbial; Drug Resistance, Multiple; Fluoroquinolones; Humans; Leprostatic Agents; Leprosy; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Mycobacterium leprae; Ofloxacin; Rifampin

Intercellular adhesion molecule-1 (ICAM-1) and E-selectin and other variables were evaluated as possible markers of the success of multidrug therapy (MDT) in leprosy. Multibacillary (MB, N = 45) and paucibacillary (PB, N = 29) leprosy patients were examined during MDT, which typically lasted 12 months for MB and 6 months for PB patients. Serum values for total protein, albumin, immunoglobulin gamma (IgG), ICAM-1, and E-selectin (selectin) were recorded, as were lesion type, number, and distribution. Response at the end of therapy was assessed as good, fair, or poor. The bacterial index (BI) of lesions was measured at the beginning and end of therapy. The earlier reported findings of this investigation are herein re-examined.. age and lowered serum albumin correlated with the poorer condition of the patients, as did elevated selectin. Albumin was inversely correlated with the BI (p = 0.008) in MB patients, and IgG was positively correlated (p = 0.009). ICAM and E-selectin alone were not useful markers of individual patient condition. A regression combining serum albumin under 41 g/l, age and E-selectin was able to identify 85% of the patients in poorer condition.. serum albumin was a useful nonspecific marker of both patient condition and infection. Age is an important negative factor in patient response. Albumin and IgG correlate with the BI and with each other (p = 0.011) in MB patients, but not in PB patients.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Child; Clofazimine; Dapsone; Drug Therapy, Combination; E-Selectin; Female; Humans; Immunoglobulin G; Intercellular Adhesion Molecule-1; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Rifampin; Serum Albumin; Treatment Outcome

SIMLEP is a computer program for modeling the transmission and control of leprosy which can be used to project epidemiologic trends over time, producing output on indicators such as prevalence, incidence and case-detection rates of leprosy. In SIMLEP, health states have been defined that represent immunologic conditions and stages of leprosy infection and disease. Three types of interventions are incorporated: vaccination, case detection and chemotherapy treatment. Uncertainties about leprosy have led to a flexible design in which the user chooses which of many aspects should be included in the model. These aspects include natural immunity, asymptomatic infection, type distribution of new cases, delay between onset of disease and start of chemotherapy, and mechanisms for leprosy transmission. An example run illustrates input and output of the program. The output produced by SIMLEP can be readily compared with observed data, which allows for validation studies. The support that SIMLEP can give to health policy research and actual decision making will depend upon the extent of validation that has been achieved. SIMLEP can be used to improve the understanding of observed leprosy trends, for example, in relation to early detection campaigns and the use of multidrug therapy, by exploring which combinations of assumptions can explain these trends. In addition, SIMLEP allows for scenario analysis in which the effects of control strategies combining different interventions can be simulated and evaluated.

Topics: BCG Vaccine; Computer Simulation; Dapsone; Drug Therapy, Combination; Humans; Incidence; Leprostatic Agents; Leprosy; Models, Biological; Mycobacterium leprae; Prevalence; Rifampin

The skin and nasal mucosa of 10 lepromatous leprosy patients who had completed 24 doses of fixed duration multidrug therapy (MDT) but who continued to be skin-smear positive for acid-fast bacilli (AFB) were examined histopathologically. The nasal mucosa showed granuloma fractions that exceeded those seen in the skin specimens, signifying that activity in this region subsides much more gradually than the activity in the skin. Mouse foot pad studies done using T900r mice with an inoculum from the nasal mucosa biopsy specimens of these patients did not demonstrate any growth of Mycobacterium leprae, indicating that these bacilli were not viable. A skin specimen from one patient grew significant amounts of bacteria in the T900r mouse foot pad. These results show that 2 years of treatment with MDT would prevent dissemination of M. leprae from the nasal mucosa and, therefore, should preclude further transmission of the disease. It also indicates that viable bacteria might persist in the skin of patients, especially those with an initial bacterial index of > or = 4+ who have completed 24 doses of regular MDT. Therefore, a more cautious approach to administering only 12 doses of MDT to highly positive multibacillary patients is suggested.

Topics: Adult; Animals; Biological Assay; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Histocytochemistry; Humans; Leprostatic Agents; Leprosy; Male; Mice; Middle Aged; Mycobacterium leprae; Nasal Mucosa; Rifampin; Skin

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Community Health Workers; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Mycobacterium leprae; Ofloxacin; Rifampin

Topics: Adolescent; Anti-Bacterial Agents; Anti-Infective Agents; Child; Clofazimine; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Mycobacterium leprae; Ofloxacin; Prednisolone; Rifampin; Secondary Prevention

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Cohort Studies; Confidence Intervals; Drug Therapy, Combination; Follow-Up Studies; Humans; Leprostatic Agents; Leprosy; Minocycline; Mycobacterium leprae; Ofloxacin; Rifampin; Secondary Prevention

Topics: Acedapsone; Chemoprevention; Clinical Trials as Topic; Dapsone; Humans; India; Leprostatic Agents; Leprosy; Pacific Islands; Rifampin

Topics: Adolescent; Adult; Chemoprevention; Humans; Leprostatic Agents; Leprosy; Micronesia; Minocycline; Ofloxacin; Rifampin; World Health Organization

Topics: Adolescent; Chemoprevention; Child; Child, Preschool; Communicable Disease Control; Humans; Leprostatic Agents; Leprosy; Mass Screening; Micronesia; Minocycline; Ofloxacin; Patient Care Team; Rifampin

Topics: Chemoprevention; Contact Tracing; Drug Therapy, Combination; Leprostatic Agents; Leprosy; Mass Screening; Micronesia; Minocycline; Ofloxacin; Prevalence; Rifampin

(1) Clinical trials have shown that clofazimine monotherapy is effective. To avoid the emergence of resistance, however, the WHO reference treatment since 1982 has been the rifampicin + dapsone + clofazimine combination. (2) Epidemiological studies show that this polychemotherapy regimen is effective, but we do not yet know if treatment should be continued until skin smears become negative, or whether a 2-year course suffices. (3) Adding clofazimine to the polychemotherapy regimen partly prevents and also lessens the intensity of lepra reactions. However, in the absence of comparative trials, we do not know the part played by clofazimine in the efficacy of the WHO-recommended three-drug regimen. (4) The main adverse effects of clofazimine arise from its accumulation in the skin and eyes, where it frequently causes hyperpigmentation that resolves very slowly on treatment cessation.

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin; Treatment Outcome; World Health Organization

In order to develop objective criteria to monitor trends of therapeutic responses positivity of PCR signals and ATP assay methods has been compared in multibacillary (MB) leprosy patients. Biopsies from lesions of 95 BL/LL patients before and after one year of treatment with a new drug regimen comprising of conventional and newer drugs ofloxacin and minocycline have been studied. These biopsies were processed for bacillary ATP assay and PCR positivity for a 36 kDa gene target by earlier published methods. In the untreated patients bacillary ATP levels were detectable in all specimens and ranged from 0.02 to more than 36 pg/millions organisms. After one year of treatment ATP levels were not detectable in any of the 57 biopsies specimens available for analysis. However, PCR signals were detectable in 3 out of 57 biopsies. In two specimens signals were very weak detectable only by hybridization. It may be concluded that DNA based PCR assay may be useful in monitoring the trends of therapeutic responses in MB patients under treatment.

Topics: Adenosine Triphosphate; Biopsy; Clofazimine; Dapsone; DNA, Bacterial; Drug Evaluation; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Mycobacterium leprae; Ofloxacin; Polymerase Chain Reaction; Rifampin; Sensitivity and Specificity; Treatment Outcome

Topics: Adult; Drug Therapy, Combination; Humans; Leprosy; Male; Ofloxacin; Recurrence; Rifampin

Topics: Clofazimine; Dapsone; Drug Administration Schedule; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin; Time Factors; World Health Organization

Topics: Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Leprosy, Lepromatous; Leprosy, Tuberculoid; Mycobacterium leprae; Rifampin; World Health Organization

Topics: Anti-Infective Agents; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Ofloxacin; Recurrence; Rifampin

Topics: Animals; Anti-Bacterial Agents; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mice; Minocycline; Rifampin

Topics: Antibodies, Bacterial; Antibodies, Monoclonal; Antigens, Bacterial; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Nasal Mucosa; Rifampin; Serologic Tests; Skin Tests

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Ofloxacin; Rifampin; World Health Organization

Groups of nude mice, with both hind footpads infected with 10(8) Mycobacterium leprae organisms, were treated with 4-week courses of different drug combinations. The effect treatment on each group was evaluated by subinoculating footpad homogenates from the treated mice into groups of normal and nude mice for subsequent regrowth, assessed 1 year later. A combination of rifampin (RMP) with clarithromycin (CLARI), minocycline (MINO), and ofloxacin (OFLO) resulted in the complete killing of M. leprae after 3 weeks of treatment. A combination of sparfloxacin (SPAR) and RMP also resulted in a similar bactericidal effect after 3 weeks of treatment. Other drug combinations showed variable effects. Very little or no effect was observed with any regimen if the treatment was given for less than 2 weeks. World Health Organization (WHO) multidrug therapy (MDT) given for 8 weeks was as effective as the two combinations described above. The results suggest that multidrug combinations consisting of RMP-OFLO (or SPAR)-CLARI (and/or MINO) are as effective as the WHO MDT for the treatment of experimental leprosy. Moreover, they imply that these combinations, which were found to be active in a 4-week experimental treatment protocol, could be administered as treatment to patients for a period of time shorter than the present 2-year regimen without a loss of effectiveness.

Topics: Animals; Clarithromycin; Drug Therapy, Combination; Leprostatic Agents; Leprosy; Mice; Mice, Nude; Mycobacterium leprae; Ofloxacin; Rifampin

Topics: Adult; Aged; Aged, 80 and over; Dapsone; Diagnosis, Differential; Female; Humans; Leprostatic Agents; Leprosy; Leprosy, Lepromatous; Leprosy, Tuberculoid; Male; Rifampin; Spain; Thalidomide

Topics: Animals; Armadillos; Host-Parasite Interactions; Humans; Leprostatic Agents; Leprosy; Peripheral Nervous System; Rifampin

Dapsone (DDS) is useful in the treatment of a number of inflammatory conditions which are characterized by neutrophil infiltration. It is the drug of choice for the treatment of leprosy and prophylaxis of malaria. Haematological side effects of methaemoglobinaemia and haemolysis have been long recognized. However, the frequency and severity of these side effects in patients already treated with DDS as a single drug or as part of a multidrug therapy (MDT) have not been well documented. We report herein an investigation of the effect of dapsone long-term treatment on the haematological and biochemical alterations in leprosy patients undergoing dapsone as a single drug (DDS group) or as part of a multidrug therapy in combination with rifampin and clofazimine (MDT group). Methaemoglobinaemia and haemolytic anaemia were the principal side effects observed. Reticulocytes were found to be elevated (> 1.5%) in 90% of the patients. Heinz bodies were also detected (6.6% of the patients). The osmotic fragility test showed a reduction in cell resistance and in the evaluation of white cells a severe eosinophilia was found. Hepatic, pancreatic and renal evaluation by the determination of biochemical parameters showed rare and occasional changes of no apparent clinical significance. We conclude that haematological side effects of dapsone are significant even at doses currently used to treat leprosy (100 mg/day) and that rifampin and clofazimine do not increase the incidence of these effects during long-term treatment.

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Methemoglobinemia; Rifampin

Leprosy in Federated States of Micronesia is still endemic with incidence rate 221/100,000 and prevalence 33/10,000 in 1996. The disease was introduced by the patients from Nauru. Epidemic of the disease was observed in Pingelap during the 1960's and Kpingamarangi since 1966. Special project for the elimination of the disease by the chemoprophylaxis was launched in 1996. The preventive therapy is consist of one dose of an association of 3 antibiotics (rifampicin, ofloxacine and minocyclin) for adults and rifampicin alone for children. The project is completed for two years and followed by evaluation for 6 years. It is expected to reach the elimination level before year 2000.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Child; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Micronesia; Minocycline; Ofloxacin; Rifampin

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Mycobacterium leprae; Ofloxacin; Rifampin; Skin

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin

Renal function at the brush border membrane level has been studied using characteristic enzymes, such as alkaline phosphatase, leucine-aminopeptidase and gamma-glutamyl transpeptidase. Urinary enzyme studies were performed using leprosy patients, classified on the basis of bacteriological index (BI>3; n=20, BI<3; n=12, BI-ve; n=10) and compared with control subjects (n=10). The role of enzymuria in monitoring WHO-recommended multidrug therapy (MDT) has been evaluated in these patients. A significant increase in the enzyme activities (p<0.01), as well as significant (p<0.01) proteinurea in 24-hour urine samples of both the smear positive groups (BI>3, BI<3) prior to therapy compared to control subjects, indicates proximal tubular functional impairment at brush border membrane level. In the smear negative (BI-ve) group, no significant difference was observed in enzyme activities as compared with the control group. In a follow-up study (BI>3;n=13, BI<3; n=4) the activities of all the enzymes decreased significantly in all the groups when compared to a corresponding untreated group. The follow-up study was not carried out on the smear negative group. The surprising finding was the differential behaviour of r-glutamyl transpeptidase, whose activity increased significantly (p<0.01) even after therapy in BI>3 group when compared with untreated patients. However in a detailed work-up including hepatic and renal function tests, the serum biochemistry was found to be normal both before and after therapy. Urinary excretion of brush border enzymes seems to be related to bacterial load, and their potential in studying the effect of MDT remains unclear.

Topics: Alkaline Phosphatase; Biomarkers; Clofazimine; Dapsone; Drug Monitoring; Drug Therapy, Combination; Follow-Up Studies; gamma-Glutamyltransferase; Humans; Kidney; Leprostatic Agents; Leprosy; Leucyl Aminopeptidase; Microvilli; Rifampin

Although multidrug therapy (MDT) was introduced into Nepal in 1983, the MDT coverage only recently exceeded 67%. In view of the large number of patients who were still receiving dapsone monotherapy, it is relevant to investigate the current levels of dapsone and rifampin resistance. The study was undertaken at a leprosy referral hospital near Kathmandu. Over a 5 1/2-year period, 157 leprosy patients with a bacterial index (BI) > or = 2.0 were investigated for drug resistance according to the method of Rees. Among previously untreated cases, 6% of 88 isolates showed low-dose dapsone resistance; among previously treated patients with a presumed relapse, 47% of 34 isolates demonstrated dapsone resistance. In the remaining 35 cases there was no growth in control mice. Rifampin resistance was not confirmed in any case.

Topics: Adolescent; Adult; Aged; Animals; Dapsone; Drug Resistance; Female; Humans; Leprosy; Male; Mice; Middle Aged; Rifampin

The bactericidal activities of 12 regimens with various combinations of new drugs (clarithromycin [CLARI], minocycline [MINO], and ofloxacin [OFLO]) and the standard antileprosy drugs, especially rifampin (RMP), were compared in nude mice with established Mycobacterium leprae infection. The longest duration of treatment was 24 weeks for intermittent (once every 4 weeks) therapy and 8 weeks for daily therapy. Bactericidal effects were monitored by titrating the proportion of viable M. leprae isolates by subinoculating the organisms into the footpads of immunocompetent and nude mice. The results indicate that RMP was more bactericidal than any combination of the new drugs. A single dose of CLARI-MINO, with or without OFLO, displayed bactericidal activity as great as that of 4 weeks of daily treatment with dapsone (DDS) plus clofazimine (CLO); thus, intermittent CLARI-MINO, with or without OFLO, may replace DDS and CLO of the standard multidrug regimen, and these will become regimens that can be administered monthly and under full supervision. Additional evidence that this may be the case is provided by the finding that intermittent RMP-CLARI-MINO or RMP-CLARI-MINO-OFLO administered for 12 or 24 weeks was as active as the standard multidrug regimen. While the intermittent treatment always displayed significantly greater bactericidal activity than the same number of doses of daily treatment, daily treatment with CLARI-MINO and CLARI-MINO-OFLO were more active than the drugs given as intermittent treatment for the same duration; therefore, unless these combinations are to be administered together with intermittent RMP, they should be given daily, especially for the treatment of RMP-resistant cases of infection. Finally, 12 weeks of daily treatment with DDS-CLO was more bactericidal than had been expected, suggesting that it may not be necessary to administer the standard multidrug regimen for multibacillary leprosy for as long as 24 months in order to minimize the risk of developing RMP resistance.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Clarithromycin; Colony Count, Microbial; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Leprostatic Agents; Leprosy; Mice; Mice, Nude; Minocycline; Mycobacterium leprae; Ofloxacin; Rifampin

Topics: Drug Hypersensitivity; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Rifampin

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Animals; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Leprostatic Agents; Leprosy; Mice; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Rats; Retrospective Studies; Rifampin

Rifampin in picogram quantities inhibited the ability of Mycobacterium bovis 44 BCG P3 to release 14CO2 from the oxidation of [14C]palmitic acid. By using these mycobacteria in a bioassay, samples of serum and posterior tibial nerve were assayed for inhibitory concentrations of rifampin. Within 8 to 12 h after ingestion of 600 mg of rifampin, the drug was detected in eight patients in concentrations ranging from 0.52 to 4.1 micrograms/ml in serum and in concentrations ranging from 0.6 to 6.3 ng/mg in posterior tibial nerve fiber tissue.

Topics: Adolescent; Adult; Aged; Biological Assay; Humans; Leprostatic Agents; Leprosy; Middle Aged; Mycobacterium bovis; Nerve Tissue; Oxidation-Reduction; Palmitic Acids; Rifampin; Tibial Nerve

Many leprosy patients treated with multidrug therapy (MDT) had previously received dapsone (DDS) monotherapy for many years. We report here 2 such patients treated with modified paucibacillary MDT composed of rifampicin and DDS who subsequently relapsed with multibacillary leprosy 5 and 6 years after release from treatment. Isolates of Mycobacterium leprae from both patients were resistant to DDS but sensitive to rifampicin, suggesting that the relapses were caused by rifampicin sensitive 'persister' organisms. The implications of this for surveillance of patients released from treatment (RFT) and the management of relapsed patients is discussed.

Topics: Adult; Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Mycobacterium leprae; Recurrence; Rifampin

The long-term effect of leprosy control was studied in two prefectures of different geographical conditions and socio-economic status. During 1955-1985, the incidence rate in Weifang of Shandong decreased by 94.5% (9.1-0.5/10,000) and became evident after the introduction of MDT in 1986 (0.04/10,000, 1993). In Wenshan of Yunnan, however, it remained at about 20/10,000 before 1980. After the introduction of rifampin plus dapsone in 1979 and fixed duration MDT in 1986, it decreased by 94% (20-1.2/10,000), whereas the detection rate remained constant (+5/100,000). In comparison with the features of new patients detected since 1980, we noted a steady increase of MB rate and voluntary reporting, and a decrease of deformity rate, in the last 8 years in Weifang. It is estimated that by the year 2000 Weifang may have the detection rate of 0.001260/10 thousand and the incidence rate of 0/00757/10 thousand in contrast to the detection rate of 0.2980/10 thousand and the incidence rate of 0.316/10 thousand in Wenshan.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; China; Dapsone; Drug Therapy, Combination; Female; Humans; Incidence; Leprostatic Agents; Leprosy; Male; Middle Aged; Prevalence; Rifampin

In these studies we evaluated the activity of low levels of five antimicrobials against Mycobacterium leprae-infected mice when administered singly and in all possible two- and three-drug combinations. Antibiotics studied were: dapsone (D) 0.0001% in the diet, rifampin (R) 20 mg/kg by gavage once monthly, minocycline (M) 0.004% in the diet, clarithromycin (C) 0.001% in the diet, and sparfloxacin (S) 5 mg/kg by gavage five times weekly. Singly each agent was found bacteriostatic (D + R) or partially bactericidal (M, C, and S) but not fully bactericidal. All 10 two-drug regimens were found at least bacteriostatic, 2 being "partially bactericidal" and 4 being "fully bactericidal." Of the 10 three-drug regimens, 9 were found "fully bactericidal" and the other "partially bactericidal." We conclude that combinations of antibiotics active against M. leprae are generally additive in combination.

Topics: Animals; Anti-Infective Agents; Clarithromycin; Dapsone; Drug Therapy, Combination; Female; Fluoroquinolones; Leprosy; Mice; Mice, Inbred BALB C; Minocycline; Quinolones; Rifampin

Topics: Clofazimine; Dapsone; Drug Administration Schedule; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Rifampin

Topics: Adult; Antigen-Antibody Complex; Drug Hypersensitivity; Female; Fever; Headache; Humans; Leprosy; Male; Nausea; Rifampin; Syndrome; Vomiting

An elderly patient with borderline tuberculoid Hansen's disease (leprosy) developed the diaminodiphenylsulphone syndrome after approximately 8 weeks of multi-drug therapy comprising dapsone and rifampicin. Postmortem histological examination, following autopsy, demonstrated features consistent with drug-induced hepatitis, tubulo-interstitial nephritis and myocarditis. Although these could have been engendered by dapsone toxicity, it was thought that a concommitant adverse reaction to rifampicin, which is known to be hepatotoxic, nephrotoxic and possibly capable of predisposing to the dapsone syndrome, could not be excluded.

Topics: Acute Kidney Injury; Aged; Chemical and Drug Induced Liver Injury; Dapsone; Diagnosis, Differential; Drug Therapy, Combination; Fatal Outcome; Humans; Kidney; Leprosy; Liver; Male; Myocarditis; Myocardium; Nephritis, Interstitial; Rifampin

The antimicrobial effects of ofloxacin against Mycobacterium leprae, either alone or in combination with rifampicin and rifabutin, were studied using mouse foot pad assay technique. When used singly, the minimum concentrations of the drugs needed to completely inhibit the growth of Mycobacterium leprae in foot pads of mice were 50 mg/kg body weight for ofloxacin and 0.003% and 0.0001%, respectively, for rifampicin and rifabutin. However, excellent synergistic effects were observed when mice were fed with 25 mg/kg body weight of ofloxacin along with 0.00003% rifabutin, but not rifampicin. Thus, incorporation of ofloxacin and rifabutin in the multiple drug therapy of leprosy patients is suggested.

Topics: Animals; Armadillos; Drug Synergism; Female; Foot; Leprostatic Agents; Leprosy; Liver; Mice; Mice, Inbred BALB C; Mycobacterium leprae; Ofloxacin; Rifabutin; Rifampin

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprosy; Rifampin

When multidrug therapy was implemented in Senegal, 406 multibacillary (MB) patients who had been treated for more than 10 years by dapsone alone, and who had become clinically inactive and skin-smear negative, were released from treatment. Of these 406 patients, 298 were given a supervised single dose of 1500 mg of rifampin. Subsequently, 302 of them (229 who had been given rifampin and 73 who had not) were followed up by means of annual clinical and bacteriological examinations. Of the former 229 followed up for a mean period of 4.9 years, 34 patients relapsed (22 males and 12 females), giving a crude relapse rate of 15% and an overall risk of relapse of 3.1 per 100 patient-years. Of the latter 73 followed up for a mean period of 2.4 years, 5 relapsed (4 males and 1 female), giving a crude relapse rate of 6.8% and an overall risk of relapse of 2.9 per 100 patient-years. Such results, which are in agreement with those of a similar study conducted recently in Mali, indicate that the intake of a single dose of 1500 mg of rifampin by MB patients when they are released from long-course dapsone monotherapy does not result in a decrease of the relapse rate. Therefore, MB patients who have been treated with dapsone alone, even for long periods, should be put under multidrug therapy prior to their release from control.

Topics: Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leprosy; Male; Recurrence; Rifampin; Risk Factors; Senegal; Skin

Topics: Humans; Leprosy; Rifampin

To investigate whether drug treatment improves the electroneurological measures of affected peripheral nerve function in leprosy patients.. Clinical status of patients determined on the first visit by an investigator administered, pre-designed questionnaire, followed by measurement of motor conduction velocity (MCV) and distal latency (DL) of ulnar, median, common peroneal and posterior tibial nerves bilaterally in patients referred consecutively from the dermatology unit and leprosy clinic, Teaching Hospital, Galle. MCV and DL measurements were repeated after 6 to 12 months of treatment.. Department of Physiology, Faculty of Medicine, University of Ruhuna, Galle.. 24 diagnosed leprosy patients; tuberculoid, lepromatous and borderline in clinical type.. Based on clinical typing. Tuberculoid (paucibacillary) type rifampicin 600 mg monthly and dapsone 100 mg daily for six months. Lepromatous and borderline (multibacillary) type rifampicin 600 mg and clofazimine 300 mg monthly and dapsone 100 mg and clofazimine 50 mg daily for 24 months.. DL in all 4 nerves and MCV in 3 nerves tested were significantly different (p > 0.001) to those for the normal population and remained so after 6 to 12 months of treatment. The DL in the ulnar nerve showed significant improvement (p < 0.05) after treatment. When analysed in each patient individually, before and after treatment, the MCV showed an improvement in 48 to 72% of patients and the DL in 41 to 59%, but differences were not significant.. Electroneurological recovery (return to normal state) of the affected peripheral nerves of leprosy patients does not occur after 6 to 12 months of drug treatment. The significant (p < 0.05) improvement (becoming better) of ulnar nerve DL indicates that, if at all, electroneurologically detectable improvement of nerve function occurs in the early stages of nerve damage, and that it may take longer than one year after starting treatment.

Topics: Adolescent; Adult; Aged; Child; Clofazimine; Dapsone; Drug Therapy, Combination; Electrophysiology; Female; Humans; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Male; Middle Aged; Neural Conduction; Peripheral Nerves; Reaction Time; Rifampin

Topics: Animals; Drug Administration Schedule; Humans; Leprosy; Mice; Rifampin

To describe the role of the clinical pharmacist in a Hansen's disease (HD, leprosy) clinic and to describe the development, validation, and operation of a dapsone compliance monitoring program.. HD remains a major, worldwide healthcare problem. Dapsone is the drug of choice for treatment of HD; however, high rates of noncompliance with this agent have been reported by many treatment centers. The assessment of compliance in HD patients is important to help distinguish between treatment failure secondary to noncompliance or to the development of resistance.. In the US, the Chicago Regional Hansen's Disease Center at the University of Illinois at Chicago is one of ten centers that provide comprehensive care to patients diagnosed with this condition. This article reviews the clinical pharmacy services and dapsone compliance program in the clinic encompassing the years 1983-93.. The clinical pharmacist provides a variety of clinical services in the clinic as well as coordinating the clinical research program. A pharmacist-generated dapsone compliance program led to improvement in compliance rates and clinical outcome. This improvement in compliance has been sustained over an extended period of time.. The clinical pharmacy services performed in the HD clinic provide a model for pharmacy involvement in other chronic disease states. The dapsone compliance program has been successful in improving patient care and obtaining reimbursement for clinical pharmacy services.

Topics: Academic Medical Centers; Chicago; Clofazimine; Dapsone; Drug Monitoring; Humans; Leprosy; Patient Care Team; Patient Compliance; Pharmacy Service, Hospital; Rifampin

The proportion of relapses among all patients detected each year increased steadily since the initiation of the national leprosy control program in China with dapsone monotherapy in 1955, reaching 18%-24% in the more leprosy-endemic provinces along the coast. Relapses were also reported in the formerly rifampin-plus-dapsone-treated patients. So far, only three paucibacillary relapses after 6 months of multidrug therapy (MDT) have been reported, and these were due to misclassification at the time of diagnosis. A short course of MDT should be given to all formerly dapsone- and/or rifampin-plus-dapsone-cured patients for the prevention of relapse. If not, they should be screened every 1 to 2 years for any possible signs of relapse, and MDT given when needed.

Topics: China; Clofazimine; Dapsone; Drug Therapy, Combination; Follow-Up Studies; Humans; Leprosy; Recurrence; Retrospective Studies; Rifampin; Risk Factors

The anti-Mycobacterium leprae activity of clarithromycin when administered alone and in combination with rifampin and dapsone in the diet was determined using the kinetic method of drug evaluation in mice. Clarithromycin when administered at a concentration of 0.1% (w/w) in the diet completely prevented growth of 2 pan-susceptible, 3 dapsone-resistant, 2 rifampin-resistant, and 2 rifampin and dapsone double resistant strains of M. leprae. A 0.03% (w/w) concentration also completely prevented growth of M. leprae in all mice infected with 2 of 7 strains tested, but in only some of the mice infected with the remaining 5 strains. No antagonistic drug interactions were observed between clarithromycin and dapsone or rifampin. The addition of clarithromycin to the currently recommended multidrug regimen should improve the rate of killing of M. leprae and help to prevent the growth of dapsone-resistant and rifampin-resistant strains.

Topics: Administration, Oral; Animals; Clarithromycin; Dapsone; Drug Interactions; Drug Resistance, Microbial; Female; Leprosy; Mice; Mycobacterium leprae; Rifampin

A total of 1211 Cuban multibacillary leprosy patients treated for at least 5 years were clinically and bacteriologically examined. They were being treated according to a 2-phase monotherapy regimen with RMP first and DADDS afterwards. On skin-smear examination 50 patients were found positive, of which 9 showed a BI of 3+ or higher at any site. With regard to the clinical status the only cases found with clinical signs of relapse were 5 out of 7 long-standing patients with BI of 4+ and 5+. A 6th patient of this high BI group who showed a good clinical condition, except for a heavy infiltration of both earlobes, was receiving a second RMP course when examined and biopsied for this research. These 9 patients were biopsied and susceptibility tests to RMP and DDS performed. The results showed that in 1 case the Mycobacterium leprae were resistant to both drugs; the organisms from 2 other patients were susceptible to RMP but low-grade resistant to DDS. Those from another patient were susceptible to RMP and fully resistant to DDS. In 3 other cases the bacilli did not multiply in any of the mice but 1 of these strains was from the patient taking a second RMP course, therefore this strain might also be susceptible to RMP and resistant to DDS. In the last 2 cases multiplication was only observed in 2 of the controls and in 1 of the 0.0001% DDS treated mice; therefore, these experiments were not conclusive, and the AFB recovered were inoculated into fresh mice to repeat the tests but these failed to multiply.

Topics: Animals; Dapsone; Drug Resistance, Microbial; Female; Humans; Leprosy; Male; Mice; Mice, Inbred BALB C; Mycobacterium leprae; Rifampin

A total of 49 patients with paucibacillary leprosy (PB) who completed multidrug therapy (MDT) between 1985 and 1990 were analysed retrospectively for efficacy and complications; 20 (40.8%) patients had borderline-tuberculoid (BT), 13 (26.5%) had tuberculoid (TT), 1 (2.1%) had indeterminate (I) and 15 (30.0%) had pure neural (N) leprosy; 26 patients (76.5% of 34 non-neural leprosy) were skin biopsied for histological cure before MDT was stopped. Of these 26 patients, 19 had histological clearance at 6 months while the remaining 7 cleared beyond 1 year (18-36 months). The remaining 8 non-neural patients who refused rebiopsy had MDT for 6-8 months and the MDT was stopped when there was clinical clearance. Of the 15 neural (N) leprosy patients, 11 were given MDT for 6 months while the rest had 12-18 months of treatment; 1 patient with neural leprosy, who was treated for 6 months, relapsed with BT leprosy 18 months post-treatment. There were few complications among the 49 patients-4 (8.2%) patients developed reaction to dapsone, 1 (2.0%) had the dapsone syndrome, 2 (4.1%) had haemolytic anaemia and 1 (2.0%) had dapsone hepatitis; 7 (14.3%) patients had type I reaction.

Topics: Adult; Aged; Aged, 80 and over; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Rifampin

The in vivo anti-Mycobacterium leprae activity of the newly synthesized benzoxazinorifamycin, KRM-1648, was studied. KRM-1648 was given orally to athymic nude mice, infected subcutaneously with M. leprae in the hindfoot pad, at doses between 0.001 and 0.01 mg of the drug/mouse/day six times per week, from day 31 to day 80. KRM-1648 administration markedly suppressed bacterial growth in the foot pads for 360 days. KRM-1648 given daily at the dose of 0.01 mg/mouse elicited a 2-4-log decrease in the number of acid-fast bacilli. The therapeutic effects of KRM-1648 were significantly higher than that of rifampin when both drugs were given in the same dosage. Moreover, when mice were fed a KRM-1648-containing diet (0.00004%-0.0004%), the drug displayed an even higher efficacy against M. leprae infection, causing an almost 4-log decrease in the number of leprosy bacilli in the infected foot pad compared to untreated controls.

Topics: Administration, Oral; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Leprostatic Agents; Leprosy; Mice; Mice, Inbred BALB C; Mice, Nude; Mycobacterium leprae; Rifampin; Rifamycins

Ofloxacin (OFLX), having superior antileprosy activity among the various quinolones, was studied for its combined therapeutic efficacy with rifampin (RMP) against Mycobacterium leprae infection induced in nude mice. When OFLX (3 mg/mouse) was given to infected mice in combination with RMP (0.01 mg/mouse) by gavage once daily six times per week, from day 31 to day 80 postinfection, a significant combined effect was observed. This study demonstrates the possibility of using OFLX in multidrug regimens for the clinical control of bacilliferous leprosy patients.

Topics: Animals; Disease Models, Animal; Drug Therapy, Combination; Female; Leprosy; Mice; Mice, Inbred BALB C; Mice, Nude; Ofloxacin; Quinolones; Rifampin

Rifampin is currently the most potent drug used in leprosy control programs. We show that the rifampin resistance which emerged in nine patients with lepromatous leprosy, who had received rifampin monotherapy, stemmed from mutations in the rpoB gene, which encodes the beta subunit of RNA polymerase of Mycobacterium leprae. In eight cases missense mutations were found to affect a serine residue, Ser-425, while in the remaining mutant a small insertion was found close to this site. These findings will be of use for the development of a rapid screening procedure, involving the polymerase chain reaction, for monitoring the emergence of rifampin-resistant M. leprae strains.

Topics: Amino Acid Sequence; Animals; Base Sequence; Conserved Sequence; Drug Resistance, Microbial; Genes, Bacterial; Humans; Leprosy; Mice; Molecular Sequence Data; Mutation; Mycobacterium leprae; Rifampin

The bactericidal activities against Mycobacterium leprae of single or multiple doses of various combinations of new antileprosy drugs [minocycline (MINO), clarithromycin (CLARI), ofloxacin (OFLO), and sparfloxacin (SPFX)] and/or rifampin (RMP) were titrated in immunocompetent mice by the proportional bactericidal method. Drugs were administered by gavage at the following dosages (mg/kg) per dose: RMP 10, MINO 25, CLARI 100, OFLO 150, and SPFX 50. All 15 regimens exerted significant bactericidal activities, at least 96% of viables were killed. The activity of a single dose MINO + CLARI was only slightly inferior to that of RMP, and the activities of a single dose OFLO/SPFX + MINO + CLARI were similar to that of RMP. This suggests that either MINO + CLARI or OFLO/SPFX + MINO + CLARI may be administered once monthly together with RMP 600 mg for the treatment of multibacillary (MB) leprosy, and monthly administration of MINO + CLARI or OFLO/SPFX + MINO + CLARI may also be employed for the treatment of RMP-resistant MB leprosy. Because the killing effects of multiple doses of the combinations were so powerful, comparison of the bactericidal activities of these regimens was beyond the sensitivity of the immunocompetent mouse model, and are being tested in the nude mouse model. Although SPFX is more active against M. leprae than OFLO on a weight-to-weight basis, when both drugs were administered in mice at dosages equivalent to clinically tolerated dosages in humans, SPFX did not show more superiority than OFLO, and its real advantage over OFLO in the treatment of leprosy remains unclear.

Topics: Animals; Clarithromycin; Disease Models, Animal; Female; Fluoroquinolones; Foot; Hindlimb; Immunocompetence; Leprostatic Agents; Leprosy; Mice; Microbial Sensitivity Tests; Minocycline; Mycobacterium leprae; Ofloxacin; Quinolones; Rifampin

Side-effects of leprosy treatment with dapsone are said to be uncommon, with drug allergy occurring in only one of every several hundred patients treated with dapsone. The dapsone or sulphone syndrome (DDS) has been recognized since the earliest days of sulphone therapy but until recently its incidence had been decreasing. In Vanuatu, during the years 1988-1991, nine leprosy patients have developed the dapsone syndrome, four of whom have died. During the last 4 years only 37 patients were started on treatment, which is an incidence of the dapsone syndrome of 24% with a fatality rate of 11%. All the patients were being given multi-drug treatment (MDT) of daily dapsone (100 mg) and clofazimine (50 mg) and monthly rifampicin (600 mg) and clofazimine (300 mg). There has been speculation that the increased incidence of what was previously described as a rare reaction is due to the use of MDT, and the reasons for this are discussed. We feel the increase in the number of reactions in Vanuatu since starting MDT is probably due to the high starting dose of 100 mg of dapsone, possibly enhanced by the combination with clofazimine and rifampicin and a genetic susceptibility of the Melanesian population.

Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Clofazimine; Dapsone; Drug Eruptions; Drug Synergism; Drug Therapy, Combination; Female; Humans; Incidence; Leprosy; Male; Middle Aged; Rifampin; Syndrome; Vanuatu

In 1982, following the recommendations of a WHO study group, multidrug therapy (MDT) was introduced into French Polynesia to treat all patients suffering from active leprosy, and--only on request--those still on dapsone monotherapy. After 5 years, a clear-cut decrease of prevalence and mean annual detection rates for leprosy (except for detection rates among children aged less than 15 years, many of such cases being detected early by increased household contact training) has been observed. There was also a decrease in the proportion of newly detected cases with disabilities. During the 21-year period preceding the introduction of MDT into the control programme, mean annual detection rates for leprosy had remained stable, and this led to the consideration that such a decrease was due neither to the natural decline of the disease nor to the economic improvement of the country. Our results, together with the fact that, to date, the relapse rate was nil in the Polynesian patients put on MDT, strongly suggest that the implementation of MDT has resulted in a decrease of detection rates for leprosy which may be a consequence of a decrease in the transmission of the disease.

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Ethionamide; Humans; Leprosy; Polynesia; Rifampin

The objective of the present study was to assess renal damage, if any, by non-invasive technique, viz NAG activity in urine and GFR in patients on continuous and intermittent rifampicin therapy. Eighty-four tuberculosis patients for cross-sectional study and six subjects for longitudinal study on antitubercular therapy and ten patients on withdrawal of rifampicin participated in the investigation; 13 leprosy patients intermittently treated with rifampicin were also included. Twenty-seven normal subjects served as controls. Rifampicin on continuous use resulted in a progressive increase in enzymuria with no change in GFR. An additive toxic effect was obvious in patients receiving streptomycin; when the treatment was withdrawn the urinary NAG activity stabilized within 15-21 days. However, patients receiving rifampicin intermittently did not show any evidence of renal damage. The results suggest that there is a need for monitoring renal damage, particularly on antitubercular therapy, when nephrotoxic agents are administered together.

Topics: Acetylglucosaminidase; Adult; Cross-Sectional Studies; Drug Synergism; Drug Therapy, Combination; Glomerular Filtration Rate; Humans; Kidney; Leprosy; Middle Aged; Prospective Studies; Rifampin; Streptomycin; Tuberculosis, Pulmonary

The bactericidal effect of a new quinolone, ofloxacin (OFLO), was determined on an established Mycobacterium leprae infection in nude mice. Various drug regimens, including combinations of drugs, were examined for different treatment periods. OFLO and rifampin (RMP) individually failed to produce significant killing after treatment with a single large dose. However, when single large doses of OFLO and RMP were given in combination, a 100-fold reduction in viability was achieved. For a longer period of treatment both of these drugs, at lower doses, produced a moderate reduction in viability. The addition of dapsone to the lower dose of OFLO resulted in a significant reduction in viability, while lower doses of RMP and OFLO together produced a moderate reduction in viability.

Topics: Animals; Dapsone; Disease Models, Animal; Drug Therapy, Combination; Leprosy; Mice; Mice, Nude; Mycobacterium leprae; Ofloxacin; Rifampin; Serum Bactericidal Test

In January-February 1988, a program of chemoprophylaxis for leprosy, using a single 25 mg/kg dose of rifampin, was conducted among 2786 (98.7%) inhabitants of the Southern Marquesas and 3144 South Marquesan "emigrants" and their families. Among the treated population, during the 4 years which followed the implementation of the program, two leprosy patients were detected, one of whom can be considered as a failure of chemoprophylaxis because she was not known by the leprosy control unit. During the same period (1988-1991), a decrease in detection rates for leprosy in the entire French Polynesian population has been observed, an event which makes the interpretation of these findings very difficult. Nevertheless, according to presently available data, the effectiveness of chemoprophylaxis with a single dose of 25 mg/kg rifampin is estimated to be about 40% to 50%. When considering not only the results of the present study but also the financial and logistic constraints raised by such a program, one is led to the conclusion that chemoprophylaxis, even with a single dose of rifampin, is not likely to become an effective component of leprosy control programs.

Topics: Adolescent; Adult; Child; Dosage Forms; Female; Humans; Incidence; Leprosy; Male; Polynesia; Premedication; Rifampin; Treatment Outcome

An improved protocol for PCR analysis of Mycobacterium leprae-infected tissues, based on enzymatic lysis, has been developed and used to demonstrate the feasibility of using PCR for detecting M. leprae in routine skin biopsies taken from leprosy patients throughout the clinical spectrum. Of 92 multibacillary patients tested, 99% were PCR-positive using gel electrophoresis or DNA hybridization to detect the amplified product. Similar analysis of paucibacillary patients, in which only one of 27 biopsies had demonstrable AFB microscopically, gave a positivity rate of 74%. No PCR signals were demonstrated from skin biopsies from seven patients with non-leprosy dermatoses and one AIDS patient with a disseminated atypical mycobacteriosis. Evaluation of leprosy patients with antileprosy drug therapy prior to biopsy demonstrated that PCR signals were either greatly diminished or absent after 2 months of continuous antibiotic therapy. PCR was also able to detect the presence of M. leprae in tissues of patients receiving antibacterial therapy when patients were suspected of harbouring drug-resistant M. leprae.

Topics: Anti-Bacterial Agents; Biopsy; Clofazimine; Dapsone; DNA Probes; DNA, Bacterial; Drug Therapy, Combination; Electrophoresis, Agar Gel; Feasibility Studies; Humans; Leprosy; Mycobacterium leprae; Nucleic Acid Hybridization; Polymerase Chain Reaction; Rifampin; Sensitivity and Specificity; Skin

Renal failure is a rare complication associated with the use of rifampin. Intravascular hemolysis leading to acute renal failure following rifampin therapy is extremely rare. Two patients with leprosy who developed hemolysis and acute renal failure following rifampin are reported.

Topics: Acute Kidney Injury; Adult; Anemia, Hemolytic; Hemolysis; Humans; Leprosy; Leprosy, Borderline; Leprosy, Tuberculoid; Male; Rifampin

Topics: Adult; Epistaxis; Humans; Leprosy; Male; Rifampin; Thrombocytopenia

Topics: Bacterial Vaccines; Global Health; Humans; Leprosy; Mycobacterium leprae; Ofloxacin; Prevalence; Rifampin

Topics: Dapsone; Drug Therapy, Combination; Follow-Up Studies; Humans; Leprosy; Recurrence; Rifampin

The introduction briefly describes the pathogenesis, classification, diagnosis and modern treatment possibilities. In Africa leprosy is considered endemic. The World Health Organization estimates the total number of cases at 3.5 million. Over the last 20 years, however, the recorded number of cases has decreased dramatically. Increasing mobility on the part of the population, relocation from countryside to the cities, and a tendency towards urbanization are introducing a new dimension to leprosy distribution and the fight against the disease in Africa. Despite the not-inconsiderable financial, material and human resources that have so far been made available--mostly from outside the country--only a small percentage of the presumptive number of leprosy sufferers are receiving an adequate, modern combination therapy. This means that leprosy continues to represent a serious public and individual health problem in Africa.

Topics: Adolescent; Adult; Africa; Child; Cross-Sectional Studies; Drug Therapy, Combination; Humans; Isoniazid; Leprosy; Leprosy, Lepromatous; Leprosy, Tuberculoid; Prothionamide; Rifampin; Trimethoprim

Topics: Humans; Leprosy; Patient Compliance; Rifampin

Minimal effective doses of rifabutin and rifampicin were determined in Mycobacterium leprae isolated from skin biopsies of newly diagnosed, previously untreated lepromatous leprosy patients. Rifabutin was more potent than rifampicin. Our previous report that rifabutin was fully active against rifampicin-resistant M. leprae could not be confirmed. Examination of two strains of rifampicin-resistant M. leprae from elsewhere, and a repeat experiment on our original strain of rifampicin-resistant bacilli, showed full cross-resistance between rifampicin and rifabutin. A clinical trial in three newly diagnosed, previously untreated lepromatous patients showed that rifabutin has rapid bactericidal activity.

Topics: Adult; Animals; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Male; Mice; Middle Aged; Mycobacterium leprae; Rifabutin; Rifampin; Rifamycins

The effect of tuftsin was studied in vivo using CBA mice infected with M. leprae by Shepard's technique and in vitro using macrophage-like cell line P. 388 (Co-cultivated with M. leprae) and the cultivated leproma tissue. It was found out that tuftsin acted as a stimulator of M. leprae multiplication in foot-pads of mice and as a prolongator of M. leprae survival in the cells of macrophage-like cell line P .388. It is concluded that using tuftsin might be useful in view of studying different aspects of experimental leprosy.

Topics: Animals; Cell Line; Dapsone; Leprosy; Mice; Mice, Inbred CBA; Mycobacterium leprae; Rifampin; Tuftsin

As determined by the proportional bactericide method, clarithromycin had strong bactericidal activity against Mycobacterium leprae. Clarithromycin was administered to mice by gavage as 20 daily doses at dosages of 12.5 to 50 mg/kg of body weight. At a dosage of 25 mg/kg, minocycline was more active than clarithromycin at a dosage of 50 mg/kg. Additive effects were displayed with the combination of clarithromycin (50 mg/kg) and minocycline (25 mg/kg), both of which were administered daily by gavage, and of clarithromycin and minocycline, both of which were administered daily by gavage at dosages of 25 mg/kg each, with rifampin at a single oral dose of 10 mg/kg.

Topics: Animals; Clarithromycin; Drug Therapy, Combination; Erythromycin; Leprosy; Mice; Minocycline; Mycobacterium leprae; Rifampin

We have examined the Mycobacterium leprae phenolic glycolipid-I (PG-I) antigen levels in the sera of 45 multibacillary leprosy patients commencing chemotherapy. The PG-I antigen levels correlated with the bacterial and morphological indices, but not with the serum IgM anti-PG-I antibody levels. Antigen levels were significantly higher in patients with diffuse skin infiltration, but did not vary significantly with other parameters reflecting the duration and extent of untreated disease. The PG-I antigen levels in 27 patients examined serially decreased consistently over the first year of multidrug therapy.

Topics: Antibodies, Bacterial; Antigens, Bacterial; Carbohydrate Sequence; Clofazimine; Dapsone; Drug Therapy, Combination; Glycolipids; Humans; Immunoglobulin M; Leprostatic Agents; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Molecular Sequence Data; Mycobacterium leprae; Rifampin; Skin; Time Factors

The antimicrobial effects of a new benzylamine, ME-93 (N-methyl-3,5-dichloro-benzylamine hydrochloride), alone and in combination with dapsone and rifampicin, have been evaluated in vitro in cell-free culture system and in vivo in mouse foot pad system. Even at 50 micrograms/ml, ME-93 did not completely inhibit the in vitro growth of M. leprae, and the effects were bacteriostatic. However, there was a synergism when ME-93 was combined with rifampicin, and the effects were bactericidal. Similar findings were also obtained in the mouse foot pad system. Thus, there is a new drug that needs further attention in the chemotherapy of leprosy.

Topics: Animals; Armadillos; Benzylamines; Dapsone; Leprostatic Agents; Leprosy; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mycobacterium leprae; Rifampin

In Bauchi State, Nigeria, a retrospective study was carried out among 973 patients on multidrug therapy (MDT), multibacillary (MB) and paucibacillary (PB), and 118 patients on a dapsone-clofazimine therapy. These patients were registered between January 1983 and September 1989. Clinical results and the problem of defaulting were investigated. The most important conclusions drawn are: although relapses occur, MDT-PB can be a valuable treatment; health education, shorter duration of treatment and permission to come less often lower the default rate, but in spite of this, the distance between home and clinic remains a problem.

Topics: Adolescent; Adult; Clofazimine; Dapsone; Drug Administration Schedule; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Health Services Accessibility; Hospitals, General; Humans; Leprostatic Agents; Leprosy; Male; Nigeria; Patient Compliance; Recurrence; Retrospective Studies; Rifampin; Sex Factors

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Global Health; Humans; Leprosy; Patient Compliance; Rifampin

The frequencies of chromosome aberrations and sister chromatid exchanges (SCEs), cell proliferation kinetics and mitotic indices were studied in peripheral blood lymphocyte cultures of leprosy patients both before and after chemotherapy. The differences in the frequencies of chromosome aberrations and SCEs between controls, paucibacillary and multibacillary patients were found to be statistically highly significant (P less than 0.001). The extent of cytogenetic damage seemed to depend on the severity of the disease. Lymphocytes of untreated leprosy patients showed a low mitotic index and a slow rate of cell proliferation. Following combined treatment with dapsone and rifampicin there was an increase, but to a lesser degree (P less than 0.01), in the frequency of SCEs and chromosome aberrations while the drug combination of dapsone, rifampicin and clofazamine had a nonmutagenic effect on chromosomes of the patient. Furthermore, after drug treatment, the cell proliferation rate and mitotic indices in paucibacillary patients were comparable to that of controls. These results indicate the clastogenic potency of Mycobacterium leprae and the remedial effects that follow therapeutic drug treatment.

Topics: Adult; Aged; Cell Cycle; Cells, Cultured; Chromosome Aberrations; Dapsone; Female; Follow-Up Studies; Humans; Karyotyping; Leprosy; Male; Middle Aged; Mitotic Index; Rifampin; Sister Chromatid Exchange

The activity of amoxicillin plus clavulanic acid against logarithmically multiplying Mycobacterium leprae was evaluated by treating mice by gavage five times weekly with various amounts of the compound from day 60 to day 150 after footpad infection. At 25, 50, and 100 mg/kg, it was inactive; at 200-600 mg/kg, multiplication of M. leprae was entirely prevented for 6-11 months after drug discontinuation, consistent with observations of bactericidal activity for M. leprae. In a confirmatory study in mice, five-times-weekly intraperitoneal ticarcillin plus clavulanic acid, 1000 mg/kg, was not bactericidal for M. leprae, while amoxicillin plus clavulanic acid, 400 mg/kg five times weekly, was weakly bactericidal (80% +/- 14%). In addition, activity of amoxicillin plus clavulanic acid, 400 mg/kg, was evaluated in combination with previously established active drugs dapsone, 0.0001% (in diet), rifampin, 20 mg/kg monthly (by gavage), and kanamycin, 25 mg/kg five times weekly (intraperitoneally). All three combinations were active, and the combination with kanamycin was more active than either drug alone.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; Clavulanic Acids; Dapsone; Drug Therapy, Combination; Kanamycin; Kinetics; Leprosy; Mice; Mycobacterium leprae; Rifampin

The World Health Organization (WHO) has recommended a fixed duration of multidrug therapy (MDT) for paucibacillary leprosy which is currently widely implemented in India. A clinico-pathological study was initiated in 1984 to assess the efficacy of this regimen. The clinical and histological responses of the patients to MDT were assessed at the end of 6 months, when their treatment was stopped, and at 2 1/2 years, when they were released from surveillance, and compared with the responses of a matched patient group to conventional dapsone (DDS) monotherapy during the same period. Of 28 patients who completed the MDT schedule, there was less than 60% improvement in 33% of them when treatment was stopped at the end of 6 months and in 20% of them at the end of 2 1/2 years. Of 26 patients receiving DDS monotherapy, 37% showed less than 60% improvement at the end of 6 months but only 8.8% had less than 60% improvement at 2 1/2 years. It is concluded that MDT for paucibacillary leprosy as recommended by WHO may not have a major advantage over DDS monotherapy, since about 20% of those patients on MDT continue to have evidence of active disease when discharged from surveillance.

Topics: Adolescent; Adult; Aged; Child; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Leprosy, Borderline; Leprosy, Tuberculoid; Male; Middle Aged; Rifampin; Time Factors

Topics: Humans; Kidney Diseases; Kidney Transplantation; Leprosy; Male; Middle Aged; Rifampin

The possibility of synergy between immunotherapy with recombinant interferon-gamma (IFN-gamma) and chemotherapy with rifampin (RMP) and dapsone (DDS) against Mycobacterium leprae was examined in nude mice. IFN-gamma alone failed to show any effect on the growth of M. leprae in the nude mouse foot pad. No synergy was demonstrable between DDS, either at 0.0001% or at 0.001%, and IFN-gamma. A subinhibitory level of RMP with IFN-gamma was also ineffective, but RMP at 0.006% with IFN-gamma produced a statistically significant enhancement of killing (26-fold) when compared with RMP at 0.006% only. It should be emphasized, however, that results obtained in the immunodeficient nude mouse model may not be comparable to those which might have been given by lepromatous leprosy patients.

Topics: Animals; Combined Modality Therapy; Dapsone; Drug Therapy, Combination; Interferon-gamma; Leprosy; Mice; Mice, Nude; Recombinant Proteins; Rifampin

Since the application of short duration multidrug therapy (MDT) in leprosy, it has been reported that reversal reactions (RR) may occur after withdrawal of treatment. Surprisingly, such "late reversal reactions" have quite never been described after monosulphonotherapy. Such RR, especially in endemic areas, may represent diagnostic and therapeutic difficult problems. We report 5 cases of late RR. In 4 cases (1 BT patient and 3 BL-LLs patients), the RR occurred 1 month 1/2 to 3 years after cessation of MDT. In the last case (form LLs), the RR happened 6 months after that a 14 years monosulphonotherapy has been stopped. These observations strengthen the need of a complete clinical, bacteriological and immunological evaluation at the time of the diagnostic, more useful than a single bacteriological study, to differentiate late RR from relapses. Moreover, the last case confirms that late RR may occur after monosulphonotherapy.

Topics: Clofazimine; Dapsone; Drug Combinations; Ethionamide; Female; Humans; Leprosy; Male; Recurrence; Rifampin

Topics: Animals; Clofazimine; Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Ethionamide; Humans; Leprosy; Mycobacterium leprae; Prothionamide; Rifampin

Topics: Administration, Oral; Antibiotics, Antitubercular; Clofazimine; Dapsone; Humans; Injections, Intramuscular; Isoniazid; Leprostatic Agents; Leprosy; Rifampin; Streptomycin; Tuberculosis

The feasibility and effects of a 3-year treatment using rifampicin (RFP), clofazimine (B663) and dapsone (DDS) in multibacillary leprosy patients in Yangzhou Prefecture and Dongtai County (1983-1986) are reported. Among 591 active multibacillary leprosy patients in the two areas, 569 (96.30%) were treated with this regimen. Of 303 cases available for analysis, 196 (64.7%) cases showed negative skin smears and clinical inactivity. The rest showed different degrees of improvement. The average reduction of BI was 0.78. The intensity and frequency of ENL and neuritis decreased markedly with treatment. The main side-effects were pigmentation and ichthyosiform changes of the skin, but these did not influence treatment.

Topics: Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Male; Middle Aged; Rifampin

The efficaciousness evaluation of the polychemotherapics regimens recommended by WHO to the hansenian paucibacillary patients, is carried out mainly by the suitable follow up of patients after therapeutic discharge. The criterion for inclusion of patients as paucibacillary ones is another point of importance. The authors based on the follow up of 66 patients that completed treatment and in the absence of relapses until the moment, advise that together with the clinical classification it should be considered factors like: the Mitsuda test, the number of lesions and the bacilloscopy result.

Topics: Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Humans; Lepromin; Leprosy; Recurrence; Rifampin; Sulfones

'Flu' syndrome as a complication of intermittent weekly administration of rifampicin is well documented. The rare occurrence of 'flu' syndrome on once monthly rifampicin is reported in this paper.

Topics: Antigen-Antibody Complex; Drug Administration Schedule; Drug Hypersensitivity; Humans; Leprosy; Male; Middle Aged; Rifampin; Syndrome

Topics: Drug Administration Schedule; Humans; India; Leprosy; Mycobacterium leprae; Rifampin

Topics: Antibodies, Monoclonal; Antigens, Bacterial; Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae; Recurrence; Rifampin

A study was undertaken to evaluate the efficacy of multidrug therapy (MDT) in paucibacillary leprosy. Out of 155 fresh cases studied 48 had indeterminate, 38 tuberculoid and 69 had borderline tuberculoid leprosy. Out of 155 cases, 64 patients in the first group were treated with dapsone 100 mg daily for 12 months. In the second group, 91 patients were given MDT, consisting of rifampicin 600 mg once a month and dapsone 100 mg daily for consecutive 12 months. The cases receiving dapsone and the cases having MDT remained clinically active at the end of 6 months in 56.1% and 37.2% respectively; 13.1% of cases having single lesion and 66.3% of patients with multiple lesions were found to be active after 6 months of MDT. At the end of one year 79.6% cases receiving dapsone and 91.2% cases having MDT became inactive.

Topics: Administration, Oral; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprosy; Mycobacterium leprae; Rifampin

Among 39 strains of Mycobacterium leprae isolated from patients with multibacillary leprosy who relapsed after treatment with rifampin (RMP), 22 strains were resistant to RMP and 17 were susceptible. All of the RMP-resistant strains were recovered from patients who had been treated with more than 50 doses of RMP, usually given as monotherapy. RMP-susceptible strains were recovered from only six patients who had received more than 50 doses of RMP, and from 11 patients who had received no more than seven doses. The median time to relapse after the beginning of RMP therapy was 9 years (range 1-12 years) among the patients harboring RMP-resistant strains of M. leprae, and the median time to relapse after discontinuation of RMP treatment was 7 years (range 1-11 years) among the patients harboring RMP-susceptible strains. These data suggest that monotherapy with more than a few doses of RMP can be responsible for the emergence of RMP-resistant strains of M. leprae, thus emphasizing the need to employ RMP only in combination with other effective drugs in the chemotherapy of multibacillary leprosy.

Topics: Animals; Drug Resistance, Microbial; Female; Humans; Leprosy; Male; Mice; Mycobacterium leprae; Recurrence; Rifampin; Time Factors

In Paraguay, the National Leprosy/Tuberculosis Program is based on a combined chemotherapy with isoprodian and rifampicin. The aim of this descriptive study was to investigate the therapy durations used so far in the treatment of 475 leprosy patients and to analyze the criteria responsible for the wide-ranging differences in therapy durations. As initial criteria, the following parameters were identified to have a significant influence on the therapy duration: Patients never treated before or pretreated, clinical classification and initial bacteriological index (BI) value. During therapy, conditions like the attendance and BI decrease/year showed a significant correlation with the therapy duration. Even though the studied criteria did not allow to draw a definite conclusion with regard to an 'ideal' therapy duration, they proved to be reliable, as only 2 patients have relapsed so far.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Mycobacterium leprae; Paraguay; Patient Compliance; Prothionamide; Rifampin; Time Factors

In experimental infections of normal mice with Mycobacterium leprae, the bactericidal activity of four consecutive weekly doses of rifampicin (RMP) was suppressed when this treatment was preceded, for one month, by daily administration of dapsone (DDS), and then the latter. Up until now, it has been impossible to detect this antagonism between the action of RMP and DDS, since all studies involved the simultaneous administration of these two drugs, and such a phenomenon would therefore have been masked by the rapid and potent action of RMP. Previous clinical observations suggest that such a delayed antagonistic effect may also occur in humans. The demonstration of this antagonism between RMP and DDS raises the problem of the long-term efficacy of therapeutic regimens currently used in leprosy and that of the role of DDS in induction of bacillary persistence. It is suggested that this particular methodology, the delayed combination of RMP with a less active drug, should be applied to the study of other drug combinations recommended in the treatment of leprosy.

Topics: Animals; Dapsone; Drug Interactions; Drug Therapy, Combination; Female; Leprosy; Mice; Mycobacterium leprae; Rifampin

Twenty-five patients of bacilliferous leprosy (17 LL, 8 BL) were studied by the modified haemolysis method for occurrence of bacillaemia and its clearance after two multidrug therapy regimens. Acid-fast bacilli were found in 76% of all patients and in 88.2% LL and 50% BL patients. Bacillaemia occurred with significantly reduced frequency in patients with type II reaction. Acid-fast bacilli were demonstrable in peripheral blood after 1 month in one patient on MDT of an Indian Working Group and 3 lepromatous patients on WHO multidrug therapy. However, bacillaemia could not be demonstrated in any patients after 2 and 3 months of treatment with both regimens.

Topics: Adolescent; Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Male; Middle Aged; Mycobacterium leprae; Rifampin; Sepsis; Skin

Though much information is available on MDT organising, it poses a challenge to the field staff due to limited field trials conducted and varied field conditions. The MDT project was begun on 11th June, 1984 in Baroda by the Govt. of India, with active assistance of State Government, the World Health Organisation and the Swedish International Development Agency. The Drug combinations for MB cases were Rifampicin 600 mg, Clofazamine 300 mg and dapsone 100 mg daily for 14 days intensive supervised therapy followed by once a month (Pulse) supervised dose of Rifampicin 100 mg, Clof. 300 mg and dapsone 100 mg for minimum period of 2 years or more if indicated and Clof 50 mg daily with dapsone 100 mg daily unsupervised for minimum period of 2 years or more if indicated, for PB cases, dapsone 100 mg daily for 6 months along with Rifampicin 600 mg supervised (Pulse) once a month for minimum period of 6 months or more if indicated. Total number of active cases at commencement of MDT was 10706, out of these 10348 (96.37%) brought under MDT till Dec. 1987. Amongst 10348, old active cases 9112 (88.05%) are cured with MDT, (3110 MB + 6002 PB) 180 old MB cases BI is still positive inspite of completed 24 pulse. The rest 1056 (10.23%) stopped the treatment for various reasons. 790 (74.81%) cases have left the villages to earn their livelihood, 30 (2.86%) were being treated by skin specialist, 86 (7.19%) refuse to continue the treatment inspite of best efforts of field staff. New cases detected since June 1984 till Dec. 1987 are 7628, out of which 7549 (96.28%) brought under treatment. Now cases cured till Dec. 1987 are 4640 (1120 MB + 3520 PB) 17 cases relapsed after MDT (15 PB + 2 MB). 280 (1.56%) cases got complications, 250 developed reactions, 3 cases Jaundice, 15 cases Gastritis and rest 12 got moderate to severe anaemia. The prevalence rate came down from 5.81 to 1.01% per thousand population till Dec., 1987. The deformity rate came down amongst new cases from 6.15 to 1.50% till Dec. 1987. regularity of treatment among PB cases is 90.84% as compared to 90.48% for MB cases. The study showed that MDT can be implemented in tribal, rural and urban populations with high rate of compliance.

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; India; Leprosy; National Health Programs; Patient Compliance; Rifampin

Fifty three multibacillary leprosy cases were treated with two regimens of MDT L1 consisting of Rifampicin, Dapsone and Ethionamide and L2 consisting of Rifampicin, Dapsone and clofazimine. The results were compared at regular intervals and at the end of the study (24 months). Clinical inactivity, bacteriological negativity, ENL reactions, upgrading reactions were seen in L1 group in 65%, 4.54%, 50% and 41% of cases respectively while 65%, 25.8%, 30% and 45% respectively in L2 regimen group. Zero percent morphological Index was achieved in all cases in L1 regimen 90% in L2 regimen cases. No viability was found on mouse foot pad inoculation after 6 months in L1 while after 18 months in L2 cases.

Topics: Clofazimine; Dapsone; Drug Evaluation; Drug Resistance, Microbial; Drug Therapy, Combination; Hospitalization; Humans; Leprosy; Rifampin

Flu like syndrome was found in a patient of BT leprosy taking Rifampicin in pulse therapy. This side effect was absent when the dose of Rifampicin was decreased. Details of this case is given with a review of literature.

Topics: Adult; Humans; Leprosy; Male; Rifampin

Three multidrug regimens all containing rifampin and dapsone have been tried for the treatment of 278 cases of paucibacillary leprosy. Regimen I was the one recommended by the WHO Study Group. Regimen II was the same as Regimen I with depsone alone continued for a further 6 months. Regimen III was the same as Regimen II but rifampin was given daily for the first 7 days. The patients were comparable with regard to disease classification, lepromin status, bacteriological status, and number of lesions. As reported earlier, the disease inactivity rates by 1 year of treatment were much greater with Regimens II and III than with Regimen I (94% and 97% vs 76%). Early reaction was seen in 6% of those in Regimen III and in none in Regimens I and II. Late reaction was observed in 9% of those in Regimen I and none in Regimens II and III. During 3 1/2 years of follow up, 13% of the cases in Regimen I, 1% in Regimen II, and 2% in Regimen III relapsed. Since the patients in the three regimens were otherwise comparable, it is concluded that the high inactivity rate, low relapse rate (1%-2%), and no early or late reaction as observed in Regimen II patients were because of adequate treatment.

Topics: Adult; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lepromin; Leprosy; Male; Recurrence; Rifampin

Two infants, one 4 months old and the other 2 months old, having histologically confirmed indeterminate leprosy are reported. The route of infection, mode of transmission, and incubation period are discussed with reference to these two cases of infantile leprosy.

Topics: Dapsone; Female; Humans; Infant; Leprosy; Rifampin

Topics: Animals; Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isonicotinic Acids; Leprosy; Mice; Prothionamide; Rifampin

Topics: Animals; Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprosy; Mice; Rifampin

Thirty-three active multibacillary patients from nine counties of Weifang Prefecture, Shandong Province, and 47 active cases from Menla County, Yunnan Province, People's Republic of China, were treated with 24 and 27 months of multidrug therapy (MDT), respectively, in 1983. Clinical assessments, smears, and histopathologic examinations were carried out independently by study teams from the Institutes of Dermatology of these two provinces. Reexaminations at 12-14 months and at termination of therapy showed marked improvement, and there was continued improvement at 12-18 and 33 months on follow up. Conversion of the bacterial index to negativity was 0/33, 5/47 for the patients from Shandong and Yunnan provinces, respectively, at the end of MDT and 2/33 at 12 months' and 17/47 at 18 months' follow up, which increased to 21/33 and 26/44 at 33 months' follow up. Regression of specific infiltration was about 21%-100% after 24-27 months of MDT; further regression to 95%-100% occurred at 33 months' follow up.

Topics: Adult; China; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Male; Middle Aged; Retrospective Studies; Rifampin; Skin

Between 1967 and 1987 in the Southern Marquesas, a remote archipelago in French Polynesia, the detection rate of leprosy was 48.9 per 100,000 when it was 8.6 per 100,000 for French Polynesia as a whole. In 1988, a program of chemoprophylaxis of leprosy with a single dose of 25 mg/kg rifampin was implemented, and 2751 persons (98.7% of the population) were treated in the Southern Marquesas. In addition, 678 South Marquesans and 2466 members of their families living in the Northern Marquesas and in the Society Archipelago, received the same chemoprophylaxis. Among 2676 persons studied in the Southern Marquesas (97.4% of the treated population), 130 had elevated IgM anti-phenolic glycolipid-I antibodies by ELISA without any evidence of leprosy. The onset of a skin lesion of borderline leprosy in a boy 3 months after chemoprophylaxis raises the question of the nature of such a skin lesion and, indirectly, of the effectiveness of the chemoprophylaxis.

Topics: Antibodies, Bacterial; Antigens, Bacterial; Child; Glycolipids; Humans; Immunoglobulin M; Leprosy; Male; Polynesia; Rifampin

Topics: Adult; Aged; Animals; Female; Humans; Leprostatic Agents; Leprosy; Male; Mice; Middle Aged; Mycobacterium leprae; Rifampin

Topics: Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae; Rifampin

Serum LDH (total) and LDH isoenzymes were studied in leprosy patients undergoing multidrug treatment. Serum LDH (total) did not show any significant difference between normal human subjects and patients but LDH isoenzymes have shown elevated levels in LDH4 and LDH5 in leprosy patients. The M/H ratios were high in leprosy patients and they exhibited a further rise in patients on treatment.

Topics: Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isoenzymes; L-Lactate Dehydrogenase; Leprosy; Rifampin

Preliminary results of a clinical trial in one hundred untreated paucibacillary leprosy cases with multidrug therapy (MDT) as per WHO recommendation are presented. Out of 100 fresh cases studied 18 had indeterminate, 35 tuberculoid and 47 cases had borderline tuberculoid leprosy. All were given MDT consisting of rifampicin 600 mg once a month and dapsone 100 mg daily for six months. At the end of six months all the cases were evaluated clinically and histopathological examination of lesions were studied. The lesions were still active in 35% of patient clinically and 47% histologically. Complete histological resolution have come across only in 4 cases suffering from indeterminate leprosy. Altogether 65% cases receiving MDT have shown marked improvement to total inactivation. Histologically, lymphocytic infiltration still persisted in 90% of slides examined and nerve infiltration were still present in 64% of cases at the end of six months receiving MDT.

Topics: Adolescent; Adult; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Middle Aged; Remission Induction; Rifampin

Topics: Allied Health Personnel; Clofazimine; Dapsone; Data Collection; Drug Administration Schedule; Drug Therapy, Combination; Humans; India; Leprosy; National Health Programs; Patient Compliance; Recurrence; Rifampin

Two cases of tuberculoid leprosy with primary hyperpigmented anaesthetic lesions are reported and subject is reviewed.

Topics: Adult; Dapsone; Drug Therapy, Combination; Humans; Leprosy; Leprosy, Tuberculoid; Male; Pigmentation Disorders; Rifampin

Fifty eight cases including 44 paucibacillary and 14 multibacillary leprosy diagnosed at Command Hospital SC Pune were hospitalised for the entire period of multidrug therapy. 76% cases belonged to high endemic states of India. Reactions occurred in 13 cases during treatment, type I in 10 and type II in three. 7 Multibacillary cases experienced reaction. 69% reaction patients developed reaction within two months of starting MDT and all of them were multibacillary. Usually it took 3-6 months for majority (61.5%) of reactions subside completely. In 65.5% paucibacillary patients activity subsided within twelve months, however 70.5% paucibacillary cases took more than six months to exhibit subsidence of activity. In 13 multibacillary cases activity subsided by 18 months though bacteriological negativity was obtained from fourth to twelve months.

Topics: Adult; Clofazimine; Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Rifampin

Since a year, the implementation of multidrug therapy on leprosy control in Guinea has been needing a good cooperation between Department of Leprosy Control and local nurses. The known prevalence, in the area of Pita is 1.23%. 246 patients has been detected: 36 multibacillary and 210 paucibacillary. The sex-ratio of the patients has changed, during one year, toward the men. With the sensitivity of the local population, number of detected cases is increasing and the rate of regular attendance at treatment is correct in 87.6% of cases.

Topics: Africa, Western; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Rifampin

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Ethionamide; Humans; Leprosy; Rifampin

The study was undertaken to evaluate the efficacy of various multidrug regimens (MDT). Three groups of 10 cases each of Paucibacillary cases were given different schedule of multidrug therapy. First group (T-0) was administered modified WHO regimen consisting of Rifampicin 600 mg once a month, Clofazimine 100 mg alternate days and Dapsone 100 mg daily for 6 months. In second group (T-1) Rifampicin 600 mg was given daily for 6 weeks and in third group (T-2) Rifampicin 600 mg was given daily for 6 months. In both the latter groups Clofazimine 100 mg on alternate days and Dapsone 100 mg daily was also administered for 6 months. Objective clinical scoring was done at the time of admission, three months and six months after treatment in all three groups. The best results were obtained by T-2 followed by T-1; and least effective was T-0 regimen. Pinkish colour of urine and skin was observed in 26 cases and icthyosis in all the cases. All the patients remain under treatment. The work is in progress and subsequent results will be published later.

Topics: Adult; Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprosy; Male; Rifampin

Out of 92 Pauci-bacillary leprosy patients treated with MDT (WHO 1982), two patients developed indisputable clinical signs of relapse during 10th and 26th month of observation period. Two more patients developed reversal reaction during 8th and 12th month of observation period, which we presume to be early manifestation of relapse. Addition of a more bactericidal drug, rifampicin, appear to have a bearing on the incidence of relapse, though not on it's incubation period. No change of classification was noticed at the time of relapse. Incidence of relapse in female patients was much higher than in male patients.

Topics: Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Recurrence; Rifampin; Sex Factors

736 paucibacillary (PB) patients were given multidrug therapy (MDT) for at least 6 months. Overall, 44% became inactive after 6 doses, and 69% after 12 doses. However, 27% remained active at the time of analysis. It is recommended that at least 12 doses of MDT be given to PB patients irrespective of the type.

Topics: Adolescent; Adult; Child; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Prospective Studies; Rifampin

A strain of Mycobacterium leprae resistant to rifampicin (RMP) failed to infect normal mice when injected into the foot pads (FP) at a dose of 10 or 100 bacilli/FP, although it could be maintained by serial passage in mice by the use of inocula of 10(4) bacilli/FP; normal mice can be infected by RMP-sensitive M. leprae at a dose of 10 bacilli/FP. By contrast, nude (athymic) mice could be infected with an inoculum of 10 bacilli/FP of the RMP-resistant strain. It is suggested that the strain concerned possessed reduced virulence for normal mice, and the implications of this for the probability of occurrence of human disease caused by RMP-resistant strains of M. leprae are discussed.

Topics: Animals; Drug Resistance, Microbial; Germ-Free Life; Leprosy; Male; Mice; Mice, Nude; Mycobacterium leprae; Rifampin; Virulence

In leprosy patients in Nigeria the influence of daily clofazimine and of once-monthly rifampicin on the pharmacokinetics of dapsone has been investigated. Three days after rifampicin the elimination half-life of dapsone was reduced from 40.4 to 25.3 h (n = 23). Correspondingly, the plasma dapsone 24 h after the last dose had fallen significantly from 2.63 to 2.02 mg/l. Clofazimine did not cause change in the pharmacokinetics of dapsone. It was concluded that, although rifampicin had a considerable influence on the pharmacokinetics of dapsone, there is no reason to adjust the dose of dapsone during multidrug therapy of leprosy.

Topics: Adolescent; Adult; Aged; Clofazimine; Dapsone; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Half-Life; Humans; Leprosy; Male; Middle Aged; Nigeria; Patient Compliance; Rifampin

Topics: Clofazimine; Dapsone; Diagnosis, Differential; Drug Combinations; Humans; Leprosy; Rifampin

Topics: Clofazimine; Dapsone; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Humans; Leprosy; Rifampin

Topics: Dapsone; Female; Humans; Leprosy; Middle Aged; Mouth Mucosa; Palate; Prednisolone; Rifampin

In order to determine the duration of follow-up needed to evaluate the efficacy of short-course bactericidal regimens for multibacillary leprosy, information is needed on the incubation time of relapses after stopping treatment. Several groups of patients, who had been on rifampicin-containing regimens, were followed up for periods ranging from 4 to 10 years. Two groups of relapses were observed: early relapses occurring within 3.5 years after stopping treatment, with a median incubation time of 1 year and 10 months (upper limit of 95% confidence interval: 2 years); and late relapses occurring more than 3.5 years after stopping treatment, with a median incubation of 5 years. Early relapses are probably due to insufficient treatment, and late relapses to persisting bacilli or to reinfection. It is concluded that the efficacy of short-course RMP-containing therapeutic regimens can be evaluated by observing the occurrence of early relapses, 50% of which occur before 2 years after the end of therapy.

Topics: Drug Therapy, Combination; Follow-Up Studies; Humans; Leprosy; Recurrence; Rifampin

A study was undertaken within the framework of the LEPRA Evaluation Project and the LEPRA Control Project in Malawi (Central Africa) to study the incidence rates of type 1 reactions and of relapses in paucibacillary leprosy patients treated with the current World Health Organization-recommended multiple drug regimen (WHO/MDT). Of 503 patients recruited into the study, 488 were reviewed at the end of treatment and 480 have now been followed for 1 year after completion of treatment. At the end of treatment the skin lesions had completely disappeared in 27.4%, but were judged to be still active in 4.3%. During the follow-up period two patients were found with new active skin lesions, giving a relapse rate of 4.17 (2 of 480) per 1000 person years during the first year after completion of WHO/MDT (95% confidence interval 1.14 to 15.06 per 1000 person years). The incidence rate of marked type 1 reaction (renewed inflammation in previously inactive lesions) during the first year after completion of WHO/MDT was 47.8 per 1000 person years in self-reporting patients but zero in patients identified by active case finding. Data are presented which suggest that the incidence rate of late type 1 reactions is closely related to the classification and stage of the disease at detection.

Topics: Adolescent; Adult; Age Factors; Aged; Child; Child, Preschool; Dapsone; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Humans; Leprosy; Malawi; Male; Middle Aged; Patient Compliance; Rifampin; Sex Factors

Topics: Adult; Drug Administration Schedule; Drug Eruptions; Humans; Leprosy; Male; Respiration Disorders; Rifampin; Urticaria

Topics: Animals; Leprosy; Mice; Mycobacterium leprae; Rifabutin; Rifampin; Rifamycins

Topics: Adolescent; Adult; Aged; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Middle Aged; Rifampin

Topics: Dapsone; Drug Resistance, Microbial; Humans; Isoniazid; Leprosy; Mycobacterium leprae; Mycobacterium tuberculosis; Rifampin; Streptomycin; Tuberculosis

Topics: Animals; Leprosy; Mice; Minocycline; Mycobacterium leprae; Rifampin; Tetracyclines

Topics: Animals; Animals, Newborn; Dapsone; Humans; Leprosy; Mice; Mice, Inbred BALB C; Mycobacterium leprae; Rats; Rifampin; Thymectomy

Two aspects of the immune deficiency of nude mice make these animals particularly useful tools for leprosy research. Nude mice are capable of supporting multiplication of M. leprae to levels approaching 10(10) per g in peripheral body tissues. In addition, nude mice may be inoculated with greater than 10(4) (in fact, with as many as 10(8) organisms per foot pad, without provoking an immune response that prevents multiplication of the organisms. Thus, the nude mouse should be particularly suitable for detecting persisting M. leprae in treated patients, and as a model of the patient for evaluating chemotherapeutic regimens.

Topics: Animals; Leprosy; Mice; Mice, Nude; Mycobacterium leprae; Rifampin

Topics: Animals; Drug Administration Schedule; Drug Therapy, Combination; Female; Leprostatic Agents; Leprosy; Mice; Rifampin

Topics: Adolescent; Adult; Child; Dapsone; Drug Combinations; Female; Humans; Leprosy; Male; Middle Aged; Rifampin; World Health Organization

The bactericidal activity of the aminoglycoside antibiotics streptomycin and kanamycin for Mycobacterium leprae in mice was assessed, both alone and in combination with rifampin, utilizing various dosage schedules. As in previous studies, 100 mg/kg five times weekly of streptomycin and kanamycin resulted, respectively, in 96% +/- 2% and 89% +/- 6% bactericide. Reducing the dosage of streptomycin to 50 mg/kg, 25 mg/kg, and even 12.5 mg/kg resulted in less but significant bactericidal activity. Such a reduction of kanamycin dosage resulted in no significant bactericidal activity. Reducing the frequency of administration of streptomycin (100 mg/kg) to twice weekly and once weekly resulted in a decreased but still significant killing of M. leprae; for kanamycin such a reduction in frequency of administration resulted in loss of bactericidal activity. Streptomycin when combined with rifampin was found more bactericidal than either drug alone, even when each was administered only once monthly.

Topics: Animals; Drug Therapy, Combination; Kanamycin; Leprosy; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mycobacterium leprae; Rifampin; Streptomycin; Time Factors

The rise in the incidence of dapsone-resistant leprosy requires new therapeutic approaches. Based on the recommendations of the WHO and the experiences from many countries where leprosy is endemic, a standardized treatment regimen is presented. It is based on the combination of three chemotherapeutically active substances.

Topics: Clofazimine; Dapsone; Drug Resistance; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin

Three regimens containing rifampin have been tried in paucibacillary leprosy patients. The patients were selected according to the criteria laid down by the World Health Organization (WHO). In Regimen I, rifampin 600 mg is given once a month for 6 months with dapsone 100 mg daily. Treatment is stopped at the end of 6 months. Regimen II is the same as Regimen I, and is supplemented with an additional 6 months' treatment with dapsone 100 mg daily. Regimen III is the same as Regimen II, except that rifampin is administered daily for the first 7 days. At the end of the scheduled treatment period, 72.2% of the patients in Regimen I, 94.9% of the patients in Regimen II, and 97.1% in Regimen III became inactive. Eighteen out of the 25 active cases at the time Regimen I treatment was stopped had to be restarted on drug therapy since they showed a worsening of their disease, as indicated by an increase in their bacterial index, the appearance of new lesions, renewed activity in old lesions, an increase in the size of old lesions, or development of nerve abscesses. The remaining seven cases regressed without further treatment. All four Regimen II patients and two Regimen III patients who had evidence of activity at the time treatment was stopped did not require any further treatment. On follow-up for 1 1/2 years, three Regimen I patients and none of the Regimen II or Regimen III patients showed relapses. It is thus apparent that rifampin helps to shorten the time duration and to increase the cost effectiveness of treatment of paucibacillary leprosy cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leprosy; Male; Middle Aged; Rifampin; Time Factors

The acceptance of the WHO regimen in a group of 220 patients was approximately 84.5%. Only 11% abandoned the treatment, and the substitution of ethionamide or prothionamide for clofazimine due to excessive hyperpigmentation was necessary in only eight cases. The WHO regimens adopted provided a more frequent (monthly) relationship between the patients and their health service. It was necessary to: a) reorganize the technical-administrative infrastructure, with the intention of providing an improved service to the patients for treatment and control; and b) pay more attention to the problem of deformities and health education activities. As for the side effects of the drugs, 54 patients showed alterations in their liver function tests, which were usually mild and which resolved despite continuation of the treatment. Of the reactional episodes observed during MDT, it would not appear that the therapeutic regimens contributed to their occurrence or aggravation.

Topics: Adolescent; Adult; Brazil; Clofazimine; Dapsone; Drug Therapy, Combination; Ethionamide; Female; Humans; Leprostatic Agents; Leprosy; Male; Patient Acceptance of Health Care; Patient Compliance; Prednisolone; Prothionamide; Rifampin; Urban Population

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Middle Aged; Pilot Projects; Prospective Studies; Rifampin

Topics: Accidents, Occupational; Dapsone; Humans; Laboratories; Leprosy; Personnel, Hospital; Punctures; Rifampin

Topics: Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprosy; Rifampin; World Health Organization

Topics: Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin

Topics: Drug Resistance, Microbial; Female; Humans; Leprosy; Male; Rifampin; Tuberculosis

Topics: Adult; Dapsone; Female; Humans; Leprosy; Patient Education as Topic; Physician-Patient Relations; Radio; Rifampin

Melanesian leprosy patients from New Caledonia were studied for the following parameters during the course of polychemotherapy: peripheral blood T-cell subsets, as identified in an immunofluorescence assay with monoclonal antibodies OKT3 ("pan-T"), OKT4 ("helper/inducer"), and OKT8 ("cytotoxic-suppressor"), and anti-Mycobacterium leprae antibodies in the serum, as measured by the fluorescent leprosy antibody absorption test. A group of Melanesian healthy subjects with no known exposure to M. leprae served as controls. Healthy contacts of leprosy patients were also studied for the presence of anti-M. leprae antibodies. Untreated, nonreactional lepromatous patients displayed moderate but significant T-cell abnormalities, consisting of a decrease in the percentage of OKT3+ and OKT4+ cells with a decrease in the OKT4:OKT8 ratio. These abnormalities disappeared within nine months of treatment. A transient decrease in the percentage of OKT8+ cells with an increase in the OKT4:OKT8 ratio was seen in patients suffering erythema nodosum leprosum (ENL). Tuberculoid patients, whether treated or not, did not show any T-cell marker disturbances. Positive serological tests for anti-M. leprae antibodies were found in 100% of lepromatous patients, 92% of tuberculoid patients, and 56% of healthy contacts. No significant decline in the antibody titer was observed with treatment during the survey period.

Topics: Adolescent; Adult; Antibodies, Bacterial; Child; Clofazimine; Dapsone; Drug Therapy, Combination; Erythema Nodosum; Ethionamide; Fluorescent Antibody Technique; Humans; Leprosy; Middle Aged; Mycobacterium leprae; New Caledonia; Rifampin; T-Lymphocytes; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Topics: Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin

While the emergence of drug resistance in Mycobacterium leprae was foreseen and known for a long time, it is now presented as a tragedy jeopardizing leprosy control through monotherapy. This resistance has been mainly reported in the United States. It is not observed in other parts of the world. In our opinion, the unfavorable observations made at present result from an incorrect implementation of dapsone (DDS) therapy in the patients, resulting in low sulfone blood levels, as a consequence of the use of complex disubstituted sulfones, insufficient daily dapsone dosages, irregular or noncompliance to treatment, premature interruption of treatment, etc. Two measures are required in order to prevent the emergence of primary or secondary resistance to dapsone in M. leprae. First, it is necessary to go back to the previous regimen of 200 mg dapsone daily in an adult. It yields the "maximum tolerated effective dosage." It should never have been rejected in favor of 100 mg daily as currently recommended at the moment. The second measure is the implementation of multiple drug therapy (MDT), using concurrently DDS in association with rifampin and clofazimine. This is a logical and rational approach, at least from a theoretical point of view. However, MDT is most unfortunately quite expensive and therefore inapplicable in most countries with high prevalence, since they are poor and underdeveloped. Implementation of MDT also raises great problems, since dosages have to be strictly adhered to in order to prevent a potentially catastrophic emergence of multiple drug resistance in M. leprae.

Topics: Clofazimine; Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Leprosy; Mycobacterium leprae; Rifampin

Sera from 92 patients were tested by the ELISA method for the presence of IgM antibodies to phenolic glycolipid-1 (PGL-1) of Mycobacterium leprae, and of both IgM and IgG antibodies to the whole M. leprae bacillus. All untreated lepromatous patients exhibited high antibody levels in all three assays. A sharp decline of IgM antibodies to PGL-1 and whole M. leprae was observed during the first two years of therapy, while IgG antibodies to whole M. leprae showed a progressive decrease only over a number of years. Low titers of IgM antibodies to PGL-1 and IgG antibodies to whole M. leprae could be detected in about 50% and 75% of patients, respectively, after more than ten years of treatment, with only 15% showing persisting IgM antibodies to the whole bacillus. Antibody levels as measured by the three assays used were correlated with the bacterial index in patients treated for less than four years. In patients treated longer than four years, only IgM antibodies, whether directed to PGL-1 or to whole M. leprae, remained correlated to the bacillary load. Tuberculoid patients exhibited a different antibody pattern, showing a lower frequency (and lower levels) of antibodies of PGL-1 and of IgG antibodies to whole M. leprae than lepromatous patients, and no detectable IgM antibodies to the whole bacillus. IgG antibodies to whole M. leprae were more frequently noted than antibodies to PGL-1, the latter declining more rapidly during therapy.

Topics: Antibodies, Bacterial; Antigens, Bacterial; Clofazimine; Dapsone; Drug Therapy, Combination; Ethionamide; Glycolipids; Humans; Immunoglobulin G; Immunoglobulin M; Leprostatic Agents; Leprosy; Longitudinal Studies; Mycobacterium leprae; Rifampin; Time Factors

The antimycobacterial activities of two newer ansamycins, isobutylpiperazinylrifamycin SV (R-76-1) and cyclopentylrifamycin SV (DL 473), were compared with those of rifampin (RMP) both in vitro and in vivo. In terms of minimal inhibitory concentrations against a number of cultivable mycobacteria, R-76-1 was about eight times more active in vitro than RMP; whereas DL 473 was only slightly more active than RMP. Therapeutic activities of R-76-1 versus RMP and DL 473 versus RMP were compared, respectively, in the experimental infection of mice with Mycobacterium lepraemurium by different treatment schedules (immediate and delayed) and dosage regimens. R-76-1 appeared to have been three times more effective than RMP; DL 473 was also more effective than RMP in that an equivalent therapeutic effect could be obtained by fewer doses of DL 473 than of RMP, and in that DL 473 exerted a more prolonged activity than RMP. With the kinetic method and a dosage of 0.001% in the diet, R-76-1 demonstrated a bactericidal-type effect against M. leprae whereas RMP did not; with the proportional bactericidal method, R-76-1 possessed about three times the bactericidal activity of RMP against M. leprae. When drugs were administered once in 4 weeks, the RMP dose required to prevent multiplication of M. leprae in the foot pads of half of the mice was in the range of 1.25 to 2.5 mg/kg; whereas that of DL 473 was less than 0.625 mg/kg. With the proportional bactericidal method, even a single dose of 1.25 mg DL 473 per kg was active against M. leprae; whereas the smallest single active dose of RMP was 10 mg/kg. DL 473 in single doses of 5 mg/kg and 10 mg/kg was significantly more effective than RMP in equal doses and, among the intermittent regimens administered four times, once every 4 weeks, no significant differences of bactericidal activity were observed between RMP at 20 mg/kg and DL 473 at 0.625 mg/kg. A preliminary clinical trial of R-76-1 in 20 patients with lepromatous leprosy showed that the compound, administered in a dosage of 150 mg daily, was very effective.

Topics: Animals; Humans; Leprostatic Agents; Leprosy; Mice; Microbial Sensitivity Tests; Mycobacterium Infections; Mycobacterium leprae; Mycobacterium lepraemurium; Rifampin; Rifamycins

Topics: Dapsone; Drug Therapy, Combination; Humans; Leprosy; Malawi; Rifampin

Topics: Adolescent; Adult; Child; Child, Preschool; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Recurrence; Rifampin

Topics: Adolescent; Child; Child, Preschool; Clofazimine; Dapsone; Dominican Republic; Drug Therapy, Combination; Female; Humans; Infant; Leprostatic Agents; Leprosy; Male; Rifampin

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprosy; Netherlands; Recurrence; Rifampin

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Evaluation Studies as Topic; Follow-Up Studies; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Malta; Prothionamide; Recurrence; Rifampin

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Leprostatic Agents; Leprosy; Paraguay; Prothionamide; Rifampin; Tuberculosis

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prothionamide; Rifampin; Tanzania

Topics: Adolescent; Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Kinetics; Leprosy; Male; Middle Aged; Rifampin

Topics: Dapsone; Drug Interactions; Humans; Isonicotinic Acids; Kinetics; Leprosy; Prothionamide; Rifampin

A systematic study was performed on the reactions occurring during several short-course therapy regimens for the treatment of paucibacillary and multibacillary patients. Most type 1 upgrading reactions in paucibacillary (PB) leprosy were mild to moderate and of short duration, while the time of onset was extremely variable. Their incidence was higher in the regimen rifampin (RMP) 900 mg once weekly for ten weeks than when a single dose of RMP 40 mg/kg body weight was given or 1500 mg in one dose followed by one year of dapsone (DDS) 100 mg daily. In multibacillary (MB) leprosy, three regimens were compared: MB-WHO regimen; regimen C, consisting of daily RMP 600 mg, ethionamide (ETH) 500 mg, and DDS or clofazimine (CLO) 100 mg for six months, followed by six months of daily DDS or CLO; and regimen D, identical to regimen C but comprising daily DDS or CLO plus ETH 500 mg during the second semester. Type 1 upgrading reactions occurred more frequently in MB patients and were more severe than in PB patients. They occurred more frequently and were more severe in regimens C and D than in the MB-WHO regimen. CLO 100 mg daily prevented type 1 reactions in MB patients and rendered them less severe. ENL was also more frequent in regimens C and D and was not prevented by CLO in the dosage used. Although there is some correlation between type 1 reactions and the total amount of RMP administered, other aspects of RMP administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Child; Clofazimine; Dapsone; Drug Therapy, Combination; Edema; Erythema Nodosum; Ethionamide; Female; Humans; Leprostatic Agents; Leprosy; Male; Neuritis; Prospective Studies; Rifampin

An electrogustometric study of 225 cases of Hansen's disease revealed impairment of taste in 55.1% of the cases. It was related to the duration of the disease, and was seen in 74.6% of the cases of lepromatous leprosy, 49.3% of the cases of borderline leprosy, and 41.3% of tuberculoid leprosy cases. Only in lepromatous cases was complete ageusia seen (9.39% of cases). All of the cases having lesions in the oropharynx and those with facial nerve palsy revealed impairment of taste, but it was not related to the type of antileprosy drug used or to the development of ENL reaction.

Topics: Adolescent; Adult; Ageusia; Clofazimine; Dapsone; Erythema Nodosum; Facial Paralysis; Female; Humans; Leprosy; Male; Rifampin; Taste Disorders

A leprosy patient who developed acute renal failure on multidrug therapy is reported. The patient had initially received a once-weekly dose of rifampin and after he had stopped taking the drug for a time, was given rifampin on a once-monthly dose schedule. He recovered completely from his acute renal failure. Kidney biopsy showed interstitial nephritis with mononuclear and eosinophilic cellular infiltrates.

Topics: Acute Kidney Injury; Adult; Dapsone; Drug Hypersensitivity; Drug Therapy, Combination; Humans; Leprosy; Male; Nephritis, Interstitial; Rifampin

Topics: Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Ethiopia; Humans; Leprosy; Rifampin

Topics: Adolescent; Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Ethiopia; Female; Humans; Leprosy; Male; Middle Aged; Patient Compliance; Rifampin; Self Administration

Topics: Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin

Topics: Female; Humans; Leprosy; Middle Aged; Rifampin

Topics: Abnormalities, Drug-Induced; Female; Humans; Infant, Newborn; Lactation; Leprosy; Pregnancy; Pregnancy Complications, Infectious; Rifampin

Fifteen untreated leprosy patients were given rifampicin and dapsone for seven days, and then rifampicin, dapsone and clofazimine for seven days. Concentrations of rifampicin and dapsone were estimated in timed plasma specimens and in 24 h urine specimens on days 7 and 14. No significant differences in the pharmacokinetics of rifampicin and dapsone were observed between the two occasions of sampling.

Topics: Clofazimine; Dapsone; Half-Life; Humans; Kinetics; Leprosy; Rifampin

Topics: Animals; Leprosy; Muridae; Mycobacterium leprae; Peripheral Nervous System Diseases; Rifampin

Topics: Bacterial Vaccines; Clofazimine; Dapsone; Drug Therapy, Combination; Eye Diseases; Humans; Leprosy; Mycobacterium leprae; Rifampin

Topics: Antibodies, Bacterial; Antigens, Bacterial; Dapsone; Glycolipids; Humans; Leprosy; Mycobacterium leprae; Rifampin

Topics: Clofazimine; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Leprostatic Agents; Leprosy; Mycobacterium leprae; Prothionamide; Rifampin

Because a 13% incidence of hepatotoxicity was observed in a first study of multibacillary leprosy patients treated daily with dapsone, rifampin, and 10 mg/kg thioamide, the patients were treated in a second study with 5 mg/kg thioamide in daily combination with dapsone and rifampin. In this study, monthly assessments of liver function were performed in order to detect early hepatic disturbances. Despite the reduced dosage of thioamide, a 16.5% incidence of hepatotoxicity was observed among 110 multibacillary patients. However, jaundice was observed in only 2 out of 18 cases of hepatotoxicity (11%); whereas it was observed in 5 out of the 7 cases of hepatotoxicity (71%) in the first study (p less than 0.05). The decrease in the thioamide dosage and the performance of monthly assessments of liver function did not decrease the incidence of hepatotoxicity but did decrease its severity. It is concluded that thioamide should not be used in daily combination with rifampin unless the daily dose is 5 mg/kg and monthly assessments of liver function are routinely performed.

Topics: Adolescent; Adult; Aged; Body Weight; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isonicotinic Acids; Leprosy; Liver; Male; Middle Aged; Prothionamide; Rifampin

It has been reported that normal individuals have precipitating antibody which binds to rifamycin-conjugated proteins. An enzyme-linked immunosorbent assay has failed to confirm this claim, although antibodies demonstrable in a solid-phase binding assay are easily raised in mice if complete adjuvant is used. Moreover, no antibodies to rifamycin-protein conjugates were found in sera from the patients included in THELEP trials of six rifampin-containing regimens. Similarly, there was no antibody by the indirect Coombs test performed in another laboratory. Further studies using rifamycin-membrane conjugates regarded as more likely to be immunogenic in vivo also failed to reveal antibody in patients' sera, although this technique revealed an interesting antibody in one of four control sera known to be positive by the indirect Coombs test.

Topics: Animals; Antibodies, Bacterial; Clofazimine; Coombs Test; Dapsone; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Erythrocyte Membrane; Humans; Immunoglobulin G; Immunoglobulin M; Leprosy; Lymphocytes; Mice; Rifampin; Rifamycins; Serum Albumin

Topics: Bacterial Infections; Humans; Kinetics; Leprosy; Mycobacterium Infections; Rifampin; Tuberculosis, Pulmonary

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy; Male; Prothionamide; Rifampin; Sex Ratio; Time Factors

A 24 year old man admitted to hospital with borderline lepromatous leprosy was treated with rifampicin, dapsone, and clofazimine. After four months he developed a reversal reaction and the diagnosis was modified to borderline tuberculoid leprosy. The dose of clofazimine was raised and prednisolone added to the regimen without any symptomatic response. His condition improved dramatically after five plasma exchanges on five successive days.

Topics: Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprosy; Leukocyte Count; Male; Plasma Exchange; Rifampin; T-Lymphocytes

Topics: Adult; Aged; Chemical and Drug Induced Liver Injury; China; Drug Therapy, Combination; Female; Humans; Isonicotinic Acids; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Recurrence; Rifampin

Topics: Clofazimine; Dapsone; Developing Countries; Drug Therapy, Combination; Humans; India; Leprosy; Patient Compliance; Rifampin; Rural Population

Topics: Adult; Aged; Drug Resistance; Female; Humans; Leprosy; Male; Middle Aged; Rifampin

As part of a larger study of nerve biopsies from leprosy patients in Ethiopia for the presence of muramidase (lysozyme), sections were also examined by light microscopy after staining with hematoxylin and eosin for cellular infiltrate and a modification of the Ziehl-Neelsen stain for leprosy bacilli. The muramidase findings will be reported separately. This paper describes the infiltrative and bacterial findings in a group of 18 patients, including four with nonlepromatous forms of leprosy who were suffering from delayed hypersensitivity reaction at the time of biopsy. The findings were unexpectedly interesting and revealing. Lepromatous and borderline-lepromatous patients all showed endoneurial and perineurial infiltration of considerable extent and, in several instances, bacilli were wide-spread from one end of the biopsy to the other; in two patients, solid-staining bacilli and globi were found, indicating relapse. In all except two of the nonlepromatous patients (mainly borderline-tuberculoid) there was an extensive and severe granulomatous infiltration, and in one case there was marked caseation in the endoneurial zone. Within the limits of the present study, the findings indicate that biopsy of a peripheral nerve, even when it is not obviously associated with a skin lesion, may reveal pathological changes which are greater in degree than those suggested by skin biopsy or clinical examination. These observations in a somewhat heterogeneous group of patients treated for varying periods of time, and in a study which was not prospectively planned, suggest that similar observations in a larger group of untreated and treated patients, including those who have relapsed, may be of value.

Topics: Adolescent; Adult; Biopsy; Child; Dapsone; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Prednisolone; Rifampin; Skin; Spinal Nerves; Sural Nerve

Two therapeutic regimens of one-year duration were administered to two groups of 20 previously untreated multibacillary leprosy patients. Regimen A was rifampin 600 mg twice weekly, prothionamide 500 mg, and dapsone (DDS) 100 mg daily for six months, followed by 100 mg DDS daily for another six months. Regimen B was identical to Regimen A but without prothionamide. Follow-up was for 4 1/2 and 5 years in 15 and 14 patients, respectively. Clinical improvement was rapid, and the bacterial index (BI) of the patients diminished by one unit per year after stopping treatment. Five patients were skin-smear negative at 54 months. The BI in the nasal mucosa became negative after 48 months. There were many attacks of erythema nodosum leprosum between month 3 of treatment until 13 and 21 months. Up to now no relapses have been observed. These results have confidence limits of 20% and 23%, respectively. However, when the results of the two regimens are added, the confidence limit for six months' twice weekly rifampin together with DDS and followed by six months of DDS and 4 1/2 years follow-up is 12%.

Topics: Adolescent; Adult; Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Isonicotinic Acids; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Dapsone; Drug Therapy, Combination; Humans; Leprosy; Rifampin

A 2 year follow-up study of 4 drug regimen in 45 cases is reported; whereas the combination of Rifampicin and Dapsone had been found to effect clearance of bacteraemia within a week and effect negativity of nasal smears in a shorter period of time, at 2 years the clinical and bacteriological results in the DDS, DDS + Rifampicin, DDS + Thiacetazone + INH, and DDS + Clofazimine regimen were similar. However, on inoculating bacilli obtained from the dartos muscle into the foot-pads of mice, multiplication was found in 1 out of 11 cases on Rifampicin and DDS, whereas 2 out of 9 cases on DDS + Thiacetazone + INH; 2 out of 10 cases on DDS + Clofazimine and 4 out of 8 cases on DDS alone showed multiplication. Therefore at the end of 2 years there was no significant difference in the results of treatment with any of the drug combinations used in the trial. However, the drug combinations have been found to be better than monotherapy with dapsone alone.

Topics: Adult; Animals; Clofazimine; Dapsone; Drug Administration Schedule; Drug Resistance, Microbial; Humans; Isoniazid; Leprostatic Agents; Leprosy; Male; Mice; Middle Aged; Rifampin; Thioacetazone

Topics: Clofazimine; Dapsone; Drug Hypersensitivity; Ethionamide; Humans; Leprostatic Agents; Leprosy; Rifampin; Thioacetazone

Macrophage cultures pulsed with viable Mycobacterium leprae were assessed for erythrocyte rosetting in three groups of individuals, i.e., normal subjects, and tuberculoid and lepromatous patients. Of these, only the lepromatous group showed a reduction in rosetting ability after infection with M. leprae. The specificity of such a reduction pattern was confirmed by using various mycobacteria to infect the macrophages. A threshold effect was noted in all three groups. Although a reduction was obtained in the amount of rosetting of macrophages from lepromatous patients with 10(4) acid-fast bacilli per culture, tuberculoid and normal macrophages resisted such an effect with as large a dose as 20 X 10(6) to 30 X 10(6) and 30 X 10(6) bacilli per culture, respectively. The M. leprae-caused alterations in macrophages from lepromatous patients were reversible by treatment with trypsin and colchicine. Cytochalasin B and Tween 80 were unable to alter the pattern. Treatment of cells with neuraminidase was inconclusive since it enhanced rosetting values of both control and infected cultures. These manipulations were significant in elucidating the target point of the host (macrophage) and parasite (M. leprae) interaction and in delineation of the external and internal effects upon the macrophages. Both M. leprae and macrophages were participants in Fc reduction, as treatment of the former with rifampicin and of the latter with cyclocheximide significantly augmented the rosetting ability. In conclusion, it appears that M. leprae, upon entering a lepromatous macrophage, initiates the production of a protein which acts via the microtubules to alter membrane topography. It is possible that the altered membrane prevents effective macrophage-lymphocyte interaction. This could be one of the mechanisms by which cell-mediated immunity is suppressed in lepromatous leprosy.

Topics: Animals; Cells, Cultured; Colchicine; Cycloheximide; Cytochalasin B; Humans; Leprosy; Macrophages; Mycobacterium leprae; Neuraminidase; Polysorbates; Receptors, Fc; Rifampin; Rosette Formation; Trypsin

Topics: Adult; Animals; Clofazimine; Dapsone; Drug Resistance, Microbial; Erythema Nodosum; Ethionamide; Humans; Leprosy; Mycobacterium leprae; Patient Compliance; Prothionamide; Rifampin

Soon after more than 10(6) Mycobacterium leprae, freshly harvested from armadillo liver or harvested and 60CO irradiated, were inoculated into the hind footpads of either normal or thymectomized and irradiated (T900R) mice, the organisms were found to reside within phagosomes of polymorphonuclear and mononuclear cells. On the other hand, 7 and 8 months after 10(4) freshly harvested M. leprae were inoculated into the footpads of normal or T900R mice and the organisms had multiplied to their maximum in the normal mice, many organisms, largely intact by electron-microscopic criteria, were found to reside free in the cytoplasm of the footpad macrophages, whereas damaged organisms were contained within phagosomes. After 11 months, many intact organisms were found to lie free in the cytoplasm of the macrophages of T900R mice, whereas only damaged intraphagosomal M. leprae cells were observed in the macrophages of normal mice. Finally, a remarkably large proportion of damaged extraphagosomal M. leprae was found in T900R mice administered rifampin for 2 days in a bactericidal dosage. It appears that M. leprae multiplies free in the cytoplasm of the footpad macrophages of infected mice, whereas the M. leprae cells resident within the phagosomes of the macrophages are dead. As the result of treatment with rifampin, the organisms appeared to have been killed in their extraphagosomal location, only afterwards being incorporated into phagosomes. However, the intracellular site in which M. leprae is killed in the course of an effective immune response remains unclear.

Topics: Animals; Female; Immunologic Deficiency Syndromes; Leprosy; Macrophages; Mice; Mice, Inbred Strains; Microscopy, Electron; Mycobacterium leprae; Phagocytosis; Rifampin; Thymectomy

Nose forms an important site at which the M. leprae in lepromatous leprosy (LL) patients lodge and multiply. Nose forms an important reservoir for M. leprae, from where they may be transmitted to healthy contacts. Inspite of realizing the above fact, nose does not normally receive due importance during the chemotherapy of leprosy. LL patients, after regular treatment with dapsone or rifampin for about 20 wks and 3 wks respectively are normally considered non-infectious. From the present investigation it is clear that local treatment of the ones with a bactericidal agent should perhaps be necessary during chemotherapy of LL patients to make them non-infectious and to control the transmission of the disease.

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprosy; Mycobacterium leprae; Nose; Rifampin

Topics: Clofazimine; Dapsone; Disease Models, Animal; Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae; Rifampin; Syndrome; T-Lymphocytes

Topics: Aged; Dapsone; Humans; Laryngeal Diseases; Leprosy; Male; Rifampin

Topics: Clofazimine; Female; Humans; Leprostatic Agents; Leprosy; Male; Rifampin; Vietnam

Topics: Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Rifampin

The practical problems related to dapsone monotherapy for a prolonged period to infectious leprosy patients are well known to the scientific community and combined treatment of dapsone with clofazimine, rifampicin or prothionamide has been successfully carried out by several workers in hospitalised leprosy patients. The application of polytherapy in field condition was hindered by the cost of the drugs and fear of side effects. 42 infectious leprosy patients attending 5 field leprosy clinics in the slums of Bombay city were put on combined drug schedule. The drug compliance of these patients was judged along with their regularity in attendance at clinics by the persons in charge and periodic and frequent check up of urines. 27 (65%) were regular in treatment from the beginning, 8(19%) who were initially irregular after motivation and 7(17%) remained irregular through out the period. The urine samples collected from leprosy patients on monotherapy and attending the same centres revealed 31% irregularity in drug consumption. The study indicates that advocating combined therapy in field conditions by paramedical workers is quite feasible. The patients on multiple drugs are more regular in drug consumption as compared to monotherapy group. The frequent check up of urine for drug content and advice to patients who are irregular in treatment improve their regularity in drug consumption.

Topics: Adolescent; Adult; Clofazimine; Dapsone; Drug Evaluation; Drug Therapy, Combination; Humans; India; Leprosy; Middle Aged; Patient Compliance; Rifampin

Topics: Adrenal Cortex Hormones; Adrenal Gland Diseases; Humans; Leprosy; Rifampin

Topics: Adult; Aged; Drug Resistance, Microbial; Female; Humans; Leprosy; Male; Recurrence; Rifampin

A 13% incidence of hepatitis was observed among 54 cases of multibacillary leprosy treated daily with the three-drug combination of dapsone, rifampin, and a thioamide (ethionamide or prothionamide). No hepatitis was observed among 109 cases of paucibacillary leprosy treated daily with the two-drug combination of dapsone and rifampin. Symptoms were jaundice in five cases and nausea plus vomiting associated with a significant increase of transaminase levels in two cases. In five cases, the symptoms appeared during the first two months of therapy and in two cases, later. Discontinuing treatment with rifampin and the thioamide but not dapsone resulted in recovery. When rifampin was resumed without the thioamide, the hepatitis did not recur. Viral etiology could be eliminated in six cases. Neither sex, age, weight nor the fact that the patient was a new case or a relapse case appeared to be a contributing factor. Hepatotoxicity caused by administration of a thioamide might have been potentiated by the concurrent administration of rifampin.

Topics: Adolescent; Adult; Aging; Amides; Chemical and Drug Induced Liver Injury; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Middle Aged; Rifampin; Sex Factors; Thioamides

Topics: Clofazimine; Dapsone; Drug Packaging; Ethionamide; Humans; Leprostatic Agents; Leprosy; Prothionamide; Rifampin; Tablets

Topics: Adolescent; Adult; BCG Vaccine; Child; Child, Preschool; Developing Countries; Drug Resistance, Microbial; Humans; Infant; Isoniazid; Leprosy; Middle Aged; Rifampin; Tuberculosis, Pulmonary

Topics: Clofazimine; Costs and Cost Analysis; Dapsone; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Prothionamide; Rifampin

Topics: Clofazimine; Dapsone; Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae; Rifampin

The basis of the immunological unresponsiveness seen in leprosy patients is unknown. Untreated lepromatous leprosy patients display an unspecific cellular anergy which disappears with treatment, leaving an anergy specific for Mycobacterium leprae. These patients suffer from a complication, erythema nodosum leprosum, characterized by a recurrent eruption of tender skin nodules disappearing in 2 to 3 days. These nodules show a histological picture reminiscent of an Arthus reaction. Erythema nodosum leprosum can occur in untreated patients but it is more frequent in those receiving effective chemotherapy, and this has been thought to be due to massive release of antigen from the bacilli. By using monoclonal antibodies detecting different subpopulations of human peripheral blood T lymphocytes, we have shown that both borderline lepromatous leprosy patients had increased circulating suppressor cells (P less than 0.001) while the total number of T cells was within the normal range. The suppressor-cell population decreased with the duration of treatment, the change being evident at as early as 21 days. Five patients developed erythema nodosum leprosum during the study period. In all these patients the number of suppressor cells was decreased prior to the complication, increasing to original values with clinical recovery from this syndrome. There was no significant effect on T-lymphocyte subpopulations during chemotherapy of borderline tuberculoid leprosy patients. It seems that antileprosy chemotherapy precipitates erythema nodosum leprosum by interfering with immunoregulatory T cells.

Topics: Antibodies, Monoclonal; Dapsone; Erythema Nodosum; Humans; Leprosy; Lymphocyte Activation; Mycobacterium leprae; Rifampin; T-Lymphocytes; Thalidomide

Topics: Dapsone; Follow-Up Studies; Humans; Leprosy; Rifampin

Topics: Dapsone; Humans; Leprosy; Macrophages; Microscopy, Electron; Rifampin; Skin

Assessment of bacteraemia has been made at weekly intervals in 36 lepromatous leprosy patients who were put on different antileprosy drug under four regimens, viz., DDS alone, DDS in combination with rifampicin (DDS + RIF), clofazimine (DDS + CLF) and thiacetazone (DDS + TCT). In general, with the continuation of treatment the bacillary load in the blood decreased considerably while bacteriological index (BI) of the skin remained constant during the study. No significant difference was noted in M. leprae clearance from blood between the groups treated with DDS alone and groups treated in combination with CLF and TCT. However, DDS + RIF treatment was most efficient in clearing acid-fast bacilli (AFB) from blood as compared to those noted with other drug regimens.

Topics: Clofazimine; Dapsone; Drug Evaluation; Drug Therapy, Combination; Humans; Leprosy; Male; Rifampin; Sepsis; Thioacetazone

A comparative study with 2 tier and 3 tier combination of Rifampicin, Clofazimine, DDS, INAH and Thiacetazone was conducted on fifty lepromatous leprosy cases for varying periods. Assessment showed that 2 tier combination of clofazimine and DDS produced good results but the cost stood in the way; whereas 3 tier combination of DDS, thiacetazone and INAH also yielded good results with much less expenses to be incurred by the patients. Whether therapy with this 3 tier combination could be continued for a longer period with sustained improvement is yet to be assessed by further studies for a considerable period.

Topics: Adolescent; Adult; Child; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Isoniazid; Leprosy; Male; Middle Aged; Rifampin; Thioacetazone

A 33 year old male Nigerian presented with widespread involvement of peripheral nerves, several of which were tender and painful. Nerve biopsies confirmed the presence of Mycobacterium leprae in both endoneurial and perineurial areas, mainly in foamy macrophages (Virchow cells), but there were also large accumulations of an amorphous, acid-fast and alcohol-fast material which was not obviously of bacterial origin. Appropriate stains indicated that this had many characteristics of lipofuscin. Although not previously known, it was at this stage discovered that the patient had received treatment with anti-leprosy drugs nearly three years before presentation in this country. One of these was clofazimine, an aniline aposafranine derivative known to produce a ceroid-like pigment in the tissues of patients treated with this drug or lepromatous leprosy.

Topics: Adult; Ceroid; Clofazimine; Dapsone; Drug Therapy, Combination; Histocytochemistry; Humans; Leprosy; Macrophages; Male; Peripheral Nerves; Peripheral Nervous System Diseases; Pigmentation Disorders; Pigments, Biological; Rifampin

Topics: Adult; Animals; Dapsone; Drug Administration Schedule; Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae; Rifampin; Time Factors

Topics: Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Leprosy; Rifampin; Tuberculosis

Topics: Adolescent; Adult; Clofazimine; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Middle Aged; Rifampin

Indication of an enhancing effect of Rifampicin on the urinary excretion of DDs has already been reported from this institution. Further observations on this aspect in 25 cases of lepromatous leprosy treated with a 15 day schedule of Rifampicin at a dose of 600 mg daily along with DDS are presented. The earlier findings that Rifampicin in the initial phase of administration enhance the urinary output of DDS are confirmed. An estimation of Rifampicin Creatinine levels in urine done concurrently also showed a quicker elimination of the drug in the earlier phase compared to later phases of the drug administration. As part of the study of drug interactions, the influence of Clofazimine administration on DDS metabolism was also studied. The findings indicate that Clofazimine does not exert any influence on DDs excretion by leprosy patients. The findings and their implications are discussed.

Topics: Clofazimine; Creatinine; Dapsone; Drug Interactions; Humans; Leprosy; Rifampin

Lepromatous patients of "Introductory Rifampicin therapy' (Lepr. India, 50: 1978) who received 300 mg Rifampicin daily for 3 months followed by 50-100 mg DDS daily for another 21 months are investigated for persisters in the skin. Mouse foot pad results revealed that at the end of 2 years of treatment viable M. leprae are still persisting in 3 out of 6 patients.

Topics: Animals; Dapsone; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Leprosy; Mice; Rifampin

Topics: Adult; Eosinophilia; Female; Humans; Leprosy; Male; Rifampin; Tuberculosis, Pulmonary

Topics: Acedapsone; Animals; Dapsone; Drug Therapy, Combination; Ethionamide; Humans; Leprostatic Agents; Leprosy; Mice; Prothionamide; Rifampin; Thioacetazone

The purpose of this paper is to alert practitioners to the possibility of leprosy by giving practical points from local experience together with a modicum of background information. Local experience of 45 patients is described in the form of a recent survey done in 1979 in Auckland together with illustrative records.

Topics: Adult; Clofazimine; Dapsone; Female; Fiji; Humans; Independent State of Samoa; Leprosy; Male; New Zealand; Patient Compliance; Rifampin

Neonatally thymectomized Lewis rats (NTLR) were shown to be highly susceptible to infection with Mycobacterium leprae. We have used them in chemotherapeutic studies as models of human lepromatous leprosy. NTLR chronically infected with M. leprae were treated with various regimens combining a background of the minimal effective dose (MED) of dapsone (4,4'-diaminodiphenylsulfone, DDS) or 100 times this dose in the diet with one to ten doses of rifampin (RMP) of 10 mg/kg. To test for persisting viable M. leprae passage of 5 X 19(3) organisms was made to intact mice, and 10(5) to 10(7) acid-fast bacilli were passaged to NTLR. The only regimen that appeared to be completely effective in eliminating infectivity for intact mice was ten doses of RMP given on the background of the MED of DDS. No viable organisms were detected in any passage mice, but multiplication of M. leprae was detected in 12 of 16 passage NTLR, representing three of the four groups in which passage was made. In no instance did we fail to detect organisms in passage of NTLR when we detected them in passage mice, and multiplication was demonstrated in passage NTLR in 14 instances in which M. leprae failed to multiply in passage mice. Because of its high degree of immunosuppression, the NTLR was able to detect a small population of viable M. leprae in inocula containing up to 5000 times the number of organisms that can be inoculated into intact mice. The NTLR appears to provide a model for the study of microbial persistence in leprosy.

Topics: Animals; Dapsone; Drug Therapy, Combination; Female; Leprosy; Male; Mice; Mice, Inbred BALB C; Models, Biological; Mycobacterium leprae; Pregnancy; Rats; Rats, Inbred Strains; Rifampin; Thymectomy

The effect of treatment with a single dose of Rifampicin (1500 mg) has been investigated in previously untreated lepromatous leprosy patients. A group of 14 cases were administered 1500 mg of Rifampicin in a single dose along with 100 mg Dapsone (DDS) daily. A control group received only 100 mg DDS daily. The patients were followed up for a period of 24 weeks. The clinical, bacteriological and results of mouse foot-pad inoculations do not indicate a significant advantage of the addition of a single dose of Rifampicin to the conventional therapy with DDA.

Topics: Animals; Dapsone; Follow-Up Studies; Humans; Leprosy; Mice; Rifampin

Topics: Drug Administration Schedule; Ethionamide; Follow-Up Studies; Humans; Leprosy; Rifampin

Topics: Clofazimine; Drug Resistance, Microbial; Ethionamide; Humans; Leprostatic Agents; Leprosy; Prothionamide; Rifampin

Studies on the interactions of the drugs used in combination therapy of leprosy were attempted at this Institute. INH supplementation with clofazimine, therapy appeared to lower the skin levels of clofazimine, raising the plasma and urinary content of clofazimine. Concurrent administration of clofazimine with DDS does not appear to exert any influence on the excretion of DDS. The plasma DDS lowering effect of Rifampicin does not vary between fast and slow acetylators for DDS.

Topics: Adult; Clofazimine; Dapsone; Drug Interactions; Drug Therapy, Combination; Humans; Isoniazid; Leprosy; Male; Middle Aged; Rifampin

Topics: Animals; Dapsone; Drug Resistance; Humans; Leprosy; Mice; Rifampin

Topics: Adult; Antibody Formation; Central Nervous System Diseases; Clofazimine; Dapsone; Diagnosis, Differential; Female; Humans; Leprosy; Male; Motor Neurons; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Rifampin

Topics: Animals; Antitubercular Agents; Clofazimine; Dapsone; Drug Resistance, Microbial; Leprostatic Agents; Leprosy; Mice; Mycobacterium leprae; Rifampin; Sulfamethoxypyridazine

Topics: Dapsone; Humans; Leprosy; Mycobacterium leprae; Rifampin

Topics: Clofazimine; Dapsone; Humans; India; Leprosy; Recurrence; Rifampin; Thalidomide

The plasma half-lives and urinary excretion levels of DDS were compared before and during concurrent administration of Rifampicin in 23 cases of active lepromatous leprosy. The plasma half-life of DDS was found to be slightly less during Rifampicin administration. The urinary excretion of DDS was found to be consistently enhanced in all the cases, particularly duotal duration of Rifampicin therapy. The findings are discussed.

Topics: Adult; Dapsone; Female; Humans; Leprosy; Male; Rifampin

A case of Erythema Multiforme Bullosum in patient of lepromatous leprosy with pulmonary tuberculosis due to Rifampicin is described. It is stressed that ethambutol may act as a trigger factor to the toxic effects of Rifampicin.

Topics: Adult; Erythema Multiforme; Humans; Leprosy; Male; Rifampin; Tuberculosis, Pulmonary

Topics: Adult; Eosinophilia; Female; Humans; Leprosy; Male; Rifampin; Tuberculosis, Pulmonary

A 34-year-old man with a three-month history of intraocular inflammation after ocular trauma with a fir branch, had an acute unilateral fulminant iridocyclitis. The iris had a thick, gray, cheesy membrane composed of nodular lepromata. The patient denied a history of Hansen's disease, despite the dermatologic and facial features that suggested the diagnosis. Anterior chamber paracentesis and scleral nodule biopsy demonstrated Mycobacterium lepra. The iridocyclitis resolved after treatment with dapsone, corticosteroids, and rifampin.

Topics: Adult; Anterior Chamber; Atropine; Biopsy; Dapsone; Humans; Leprosy; Male; Prednisone; Punctures; Rifampin; Sclera; Triamcinolone; Uveitis, Anterior

In this work are presented results obtained in the treament of thirty patients suffering of lepromatous leprosy. In a group of fifteen patients L-tetramisol was administrated in association to antimocrobian drugs. The control group received only the last medication. Immunological modifications were not observed in any case. However, in six patients treated with L-tetramisol associated to rifampicin during three months it was possible to observe a notable improvement of the clinical state. In the patients that received L-tetramisol associated to other drugs or in those that received only antimicrobian drugs the clinical improvement was very low or null.

Topics: Adolescent; Adult; Drug Therapy, Combination; Humans; Leprosy; Middle Aged; Rifampin; Tetramisole

This report is based on data obtained from 64 lepromatous cases. Despite many years of DDS monotherapy, the homogenates from biopsies of these patients revealed 10(4) or more bacteria. From the beginning of combination therapy with synergistic-acting substances (rifampicin + isoprodian (INH + PTH + DDS) the logarithms of the number of bacteria in the homogenates decreased, both during treatment period and during treatment-free observation period (Figs. 3--8). During the whole time biopsies were taken almost monthly. A considerable regression of the bacterial mass or even "negativity" could be observed within a relatively short time. Once started, the process of reduction of bacteria continued also after termination of therapy. To be able to evaluate a medication, therapy-free observation periods (for a minimum of 5 years) are indispensable.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Leprostatic Agents; Leprosy; Prothionamide; Rifampin

Topics: Dapsone; Dihydroxyphenylalanine; Drug Resistance, Microbial; Humans; In Vitro Techniques; Isotope Labeling; Leprosy; Microbial Sensitivity Tests; Mycobacterium leprae; Rifampin; Thymidine

We tested the corneal penetration of rifampin in four vehicles: dimethylsulfoxide, polyethylene glycol, an ocular lubricant, and as rifampin ointment. We measured drug concentrations in the aqueous humor in rabbits after topical instillation of 1 and 2.5% rifampin according to two dosage schedules. Drug concentrations in the aqueous humor were bactericidal to Mycobacterium leprae. Since leprosy of the cornea, iris, and ciliary body may develop despite standard systemic bacteriostatic treatment, treatment of leprotic involvement of the anterior eye may be enhanced by intensive topical application of rifampin.

Topics: Administration, Topical; Animals; Aqueous Humor; Chlorobutanol; Ciliary Body; Cornea; Dimethyl Sulfoxide; Drug Administration Schedule; Drug Combinations; Iris; Keratitis; Lanolin; Leprosy; Mineral Oil; Mycobacterium leprae; Ointments; Petrolatum; Pharmaceutical Vehicles; Polyethylene Glycols; Rabbits; Rifampin; Uveal Diseases

Topics: Clofazimine; Dapsone; Diagnosis, Differential; Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae; Rifampin

Topics: Adolescent; Adult; Aged; Bacteriological Techniques; Child; Dapsone; Drug Therapy, Combination; Female; Humans; Isoniazid; Leprosy; Male; Malta; Middle Aged; Prothionamide; Rifampin; Time Factors

Sensitivity to anti-leprous drugs of M. leprae isolated from an L-type leprosy patient was tested using M--Y 14b liquid medium by direct and indirect methods. The results revealed that the strain, SR61-L74, was almost completely resistant to DDS, and responded only to the long-term administration of Streptomycin and Isoniazid. However, the strain was completely sensitive to rifampicin which had never been administered previously. The subsequent administration of rifampicin resulted in a rapid improvement of the patient's clinical symptoms. It can be concluded that the in vitro method, both direct and indirect, to test the sensitivity of M. leprae to anti-leprous drugs is economic, and accordingly available practically as one of the routine examinations in the laboratory of ordinary leprosaria. This must be very beneficial to the treatment of leprosy patients.

Topics: Dapsone; Drug Resistance, Microbial; Humans; Isoniazid; Leprostatic Agents; Leprosy; Microbial Sensitivity Tests; Mycobacterium leprae; Rifampin; Streptomycin

Topics: Dapsone; Drug Therapy, Combination; Erythema Nodosum; Female; Humans; Leprosy; Malaysia; Male; Mycobacterium leprae; Rifampin

Topics: Clofazimine; Dapsone; Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae; Patient Compliance; Rifampin

"Leprosy Relief through Leprosy Research" means that the results of research are made available for curing and eradicating the disease. The "Marinum Model" and the "planter test in mice" are, along with determination of serum activity in healthy test subjects, part of a complex of experiments for the assessment of the therapeutic value of an antimycobacterial substance. This replaces the "controlled studies" which, in their proper form, are scarcely possible for leprosy. With the recently developed forms of combination therapy, the duration of leprosy treatment is reduced to a few years. Because of the relationship of Mycobacterium leprae to Mycobacterium tuberculosis, certain types of combination therapy can be used in both diseases at the same time.

Topics: Animals; Armadillos; Dapsone; Drug Therapy, Combination; Humans; Isoniazid; Leprosy; Mice; Models, Biological; Mycobacterium; Prothionamide; Rifampin

Topics: Attitude to Health; Bacterial Vaccines; BCG Vaccine; Dapsone; Humans; India; Leprosy; Patient Compliance; Physical Therapy Modalities; Rehabilitation, Vocational; Rifampin; Surgery, Plastic; World Health Organization

Topics: Animals; Drug Resistance, Microbial; Humans; Leprosy; Male; Mice; Microbial Sensitivity Tests; Middle Aged; Mycobacterium leprae; Rifampin

Continuous dietary administration of rifampin to mice with an established Mycobacterium leprae footpad infection reduced the bacillary solid ratio, with an estimated survival half-life of 5-6 days. In rifampin-treated immunosuppressed animals the survival half-life of solid bacilli, in the absence of host immunity, was 12-13 days. Clofazimine and B1912 produced a significant effect on solid ratio only after a lag period of apparently 100 days. The rate of action was considerably slower than that of rifampin. Intermittent (once monthly) administration of both drugs produced effects similar to those of continuous administration.

Topics: Animals; Antibodies, Bacterial; Clofazimine; Immunosuppression Therapy; Leprosy; Mice; Mycobacterium leprae; Rifampin; Time Factors

In 1971, rifampin was approved for treatment of pulmonary tuberculosis and asymptomatic carriers of Neisseria meningitidis. At present, the approved indications remain the same. However, rifampin in conjunction with at least one other antituberculous drug may be of great value in therapy of extrapulmonary tuberculosis and infections due to other susceptible mycobacteria. In addition, results of clinical trials in leprosy have been highly encouraging. Rifampin appears to induce light chain proteinuria in a majority of patients and has been implicated in suppression of both humoral and cell-mediated immune responses. However, these effects appear to have been of little consequence to treated patients. A variety of possibly immunologically mediated reactions to rifampin has been closely associated with irregular administration of the drug. These reactions and hepatic toxcity may be preventable in many patients. Rifampin or one of its congeners, alone or in combination with other antibiotics, may prove useful in treatment of various infectious, and possibly malignant, diseases.

Topics: Animals; Antibody Formation; Antineoplastic Agents; Antiviral Agents; Chemical and Drug Induced Liver Injury; Drug Interactions; Drug Resistance, Microbial; Drug Therapy, Combination; Forecasting; Humans; Immunity, Cellular; Immunosuppressive Agents; Leprosy; Liver; Meningococcal Infections; Mycobacterium Infections; Rifampin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aged; Humans; Leprosy; Male; Rifampin

Leprosy is a complex disease, but recent research and the Ridley-Jopling classification which emphasize its immunologic aspects have greatly aided our understanding of and approach to the problem. The diagnosis should be considered whenever skin lesions and sensory loss occur. Dapsone remains the treatment of choice, but several newer drugs show great promise, especially in those cases whose bacilli have become sulfone resistant. Immunotherapy may play an increasingly prominent role in the future. Reactive episodes continue to be a serious complication, but the availability of thalidomide to control erythema nodosum leprosum has markedly improved the prognosis. Physicians of the US Public Health Service Hospital at Carville, Louisiana, are available at all times for consultation on these and other matters related to leprosy.

Topics: Biopsy; Clofazimine; Dapsone; Erythema Nodosum; Humans; Immunotherapy; Leprosy; Recurrence; Rifampin; Sensation; Skin; Thalidomide; United States

The clinical features and management of a case of major tuberculoid leprosy presenting in the United Kindom are described. The possibility of encountering tropical disease in one's practice should be remembered.

Topics: Adult; Dapsone; Diagnosis, Differential; Female; Humans; Leprosy; Rifampin; Skin Manifestations; Tuberculosis, Cutaneous; United Kingdom

Topics: Chloroquine; Clofazimine; Dapsone; Drug Resistance, Microbial; Erythema Nodosum; Humans; Leprosy; Prednisone; Rifampin; Thalidomide

A single dose of 1500 mg. of rifampicin failed to make the lepromatous leprosy patients non-infective by using mouse foot-pad technique. It is essential to extend the trial further.

Topics: Humans; Leprosy; Male; Rifampin

Two groups of patients were chosen for this treatment; the first group of 14 patients was treated with a daily dose of 600 mg. of Rifampicine and the second group with Rifampicine associated with Isoprodian (1-2 tablets). In the first group clinical and bacteriological improvement was apparent. This was parallel in bacteriological and morphological index. Two patients became negative in nasal mucous. Tolerance was good and number of leprosy reactions 65%. In the second group clinical improvement was good in general but one case that presented a continuous polyneuritis and hepatic intolerance. Bacteriological results were lightly lower than the first group and the number of leprosy reactions 85%. This treatment is considered inferior to the sulfons, which is very expensive. A longer period of time will be needed to appriase results.

Topics: Dapsone; Drug Combinations; Drug Evaluation; Humans; Isoniazid; Isonicotinic Acids; Leprosy; Prothionamide; Rifampin; Tablets

Topics: Humans; Leprosy; Rifampin

In the course fo evaluating the effect of different drugs on the morphology of Mycobacterium leprae (Edwards, Draper & Draper, 1972) and on the phagocytic cells containing these organisms (Edwards, 1973), an unusual feature was observed in the dermal connective tissue of skin biopsies obtained from some of the patients. Variable amounts of an extracellular, cross-striated osmiophilic material were present in the dermis. The purpose of this communication is to describe the banded substance observed in the extracellular space of the lepromatous skin and to compare it briefly with similar substances and structures reported to occur elsewhere.

Topics: Animals; Collagen; Connective Tissue; Dapsone; Extracellular Space; Granuloma; Humans; Leprosy; Microscopy, Electron; Mycobacterium leprae; Rifampin; Skin; Staining and Labeling; Streptomycin

The authors describe an eruption of cutaneons nodules after a BCG vaccination. Investigation demonstrated that the lesions were caused by Lepromata. An increased number of B lymphocytes was observed in the bloodstream. Ryphampycin was used with good results.

Topics: Adolescent; BCG Vaccine; Female; Humans; Leprosy; Rifampin; T-Lymphocytes; Tuberculosis

Topics: Humans; Leprosy; Mycobacterium leprae; Rifampin

Topics: Clofazimine; Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae; Rifampin; Sulfameter; Sulfanilamides

The total minimal inhibitory dose of rifampicin determined in the experimental mouse model, was found to be 10 mg/kg body weight, administered once a week for 6 weeks or once every 2 weeks for 12 weeks. From these and other results it is suggested that administration of RMP in human treatment can be reduced to a total amount of 7.2 either as a 600 mg dose once a week for 12 weeks or as a 900 mg dose once a week for 8 weeks. At present these regimens can only be used as an introductory treatment for multibacillary cases and are still too expensive for developing countries, but their efficacy should be evaluated in the field as sole treatments in tuberculoid cases, since they could signify a substantial economy for the management of the majority of leprosy infections.

Topics: Animals; Body Weight; Disease Models, Animal; Humans; Leprosy; Mice; Mice, Inbred Strains; Mycobacterium leprae; Rifampin; Time Factors

Topics: Antitubercular Agents; Drug Administration Schedule; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Rifampin; Tuberculosis, Pulmonary

Topics: Acetylation; Dapsone; Drug Resistance; Female; Humans; Leprosy; Male; Metabolic Clearance Rate; Mycobacterium leprae; Phenotype; Rifampin; Sulfamethazine

There are some 20 million people in the world with leprosy. In the lepromatous form of the illness the nose becomes infected very early in the disease process. The nasal discharge which occurs is heavily bacillated and is the most potent source of exit of Mycobacterium leprae from the body. The necessity for early diagnosis and treatment of leprosy in the absence of an effective vaccine is discussed and the pathological changes that occur in the nose are outlined. The roles which the leprologist and the rhinologist are able to play are mentioned.

Topics: Dapsone; Humans; Leprosy; Mycobacterium leprae; Nasal Mucosa; Nose Diseases; Rifampin

Topics: Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy; Male; Neuritis; Pilot Projects; Prednisone; Rifampin

Topics: Anti-Bacterial Agents; Humans; Leprosy; Male; Rifampin

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Prothionamide; Rifampin

Topics: Adolescent; Adult; Child; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; India; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Acetylation; Dapsone; Half-Life; Humans; Leprosy; Protein Binding; Rifampin; Sulfamethazine

Topics: Acute Disease; Adrenal Cortex Hormones; Aniline Compounds; Clofazimine; Dapsone; Drug Therapy, Combination; Humans; Leprosy; Rifampin; Thalidomide; Thiourea

Topics: Clofazimine; Dapsone; Drug Resistance, Microbial; Humans; Leprostatic Agents; Leprosy; Rifampin

Topics: Acute Kidney Injury; Amebiasis; Antimalarials; Cholera; Drug Resistance, Microbial; Encephalitis; Glomerulonephritis; Helminthiasis; Hepatitis B Antigens; Humans; Leprosy; Malaria; Neurologic Manifestations; Parasitic Diseases; Pyrimethamine; Rifampin; Sulfonamides; Thiabendazole; Tropical Medicine; Trypanosomiasis, African

Topics: Adult; Aged; Animals; Dapsone; Female; Humans; Leprosy; Male; Mice; Middle Aged; Mycobacterium leprae; Rifampin; Sepsis; Skin

Topics: Complement System Proteins; Cryoglobulins; Dapsone; Humans; Leprosy; Precipitin Tests; Precipitins; Prednisone; Rifampin

Topics: Dapsone; Drug Resistance, Microbial; Humans; Leprosy; Male; Middle Aged; Mycobacterium leprae; Rifampin; Skin Ulcer

Topics: Drug Therapy, Combination; Humans; Isoniazid; Leprosy; Microbial Sensitivity Tests; Muscle, Smooth; Mycobacterium leprae; Pyrazines; Rifampin; Skin; Sulfanilamides; Time Factors

Topics: Animals; Animals, Laboratory; Antitubercular Agents; Clofazimine; Dapsone; Ethionamide; Humans; In Vitro Techniques; Isoniazid; Leprosy; Mice; Mycobacterium lepraemurium; Rifampin; Sulfonamides; Trimethoprim

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Child; Dapsone; Drug Therapy, Combination; Ethiopia; Female; Histocytochemistry; Humans; Leprosy; Male; Middle Aged; Mycobacterium leprae; Rifampin; Skin; Sulfonamides; Thalidomide; Time Factors; Trimethoprim

Topics: Animals; Clofazimine; Dapsone; Drug Resistance, Microbial; Leprosy; Mice; Mycobacterium leprae; Rifampin

Topics: Adult; Animals; Biopharmaceutics; Dapsone; Humans; Leprosy; Mice; Phenazines; Rifampin; Thiourea

Topics: Dapsone; Drug Resistance, Microbial; Humans; Leprosy; Male; Middle Aged; Rifampin

Topics: Antitubercular Agents; Drug Therapy, Combination; Humans; Leprosy; Mycobacterium Infections; Rifampin; Time Factors; Tuberculosis

Topics: Adult; Antitubercular Agents; Drug Therapy, Combination; Humans; Isoniazid; Leprosy; Male; Pilot Projects; Pyrazines; Rifampin; Sulfanilamides; Sulfonamides; Time Factors; Trimethoprim; Uganda

Topics: Africa, Eastern; Antitubercular Agents; Dapsone; Drug Therapy, Combination; Female; Humans; Isoniazid; Leprosy; Male; Prognosis; Pyrazines; Rifampin; Sulfanilamides; Time Factors

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Ethionamide; Female; Humans; Infant; Infant, Newborn; Isoniazid; Leprosy; Male; Mediterranean Islands; Middle Aged; Public Health; Rifampin; Sulfonamides

Topics: Administration, Oral; Animal Feed; Animals; Dapsone; Drug Resistance, Microbial; Kinetics; Leprosy; Mice; Microbial Sensitivity Tests; Mycobacterium leprae; Rifampin; Time Factors

Topics: Animals; Biopsy; Dapsone; Humans; Leprosy; Mice; Mycobacterium leprae; Rifampin; Skin

Topics: Animals; Biopsy; Dapsone; Humans; Leprosy; Mice; Mycobacterium leprae; Rifampin; Skin

Topics: Aniline Compounds; Animals; Antimalarials; Dapsone; Drug Resistance, Microbial; Humans; Imines; Leprosy; Male; Mice; Mycobacterium leprae; Phenazines; Pigmentation Disorders; Rifampin; Sulfonamides

Topics: Anti-Bacterial Agents; Dapsone; Humans; Leprosy; Microscopy, Electron; Mycobacterium leprae; Rifampin; Skin; Streptomycin

Topics: Glucocorticoids; Humans; Kanamycin; Leprosy; Rifampin; Sulfonamides; Sulfones; Thalidomide; Thiourea

Topics: Aniline Compounds; Animals; Dapsone; Disease Models, Animal; Drug Combinations; Ethionamide; Humans; Isoniazid; Leprosy; Mice; Models, Biological; Mycobacterium Infections; Phenazines; Pyrazines; Rabbits; Rifampin; Sulfonamides; Trimethoprim

Topics: Adult; Blindness; Conjunctiva; Cornea; Eye Manifestations; Female; Fundus Oculi; Humans; Inflammation; Injections; Leprosy; Malaysia; Male; Middle Aged; Racial Groups; Rifampin; Sclera; Sex Factors; Sulfones; Uvea

Topics: Anemia, Hemolytic; Aniline Compounds; Anti-Bacterial Agents; Dapsone; Drug Resistance, Microbial; Humans; Injections, Intramuscular; Leprosy; Mycobacterium leprae; Phenazines; Rifampin; Sulfonamides; Sulfones; Thioacetazone; Thiourea

Topics: Animals; Antimalarials; Cephaloridine; Dapsone; Diet; Evaluation Studies as Topic; Injections, Subcutaneous; Kinetics; Leprosy; Malaria; Methods; Mice; Mycobacterium leprae; Oxadiazoles; Pyridines; Rifampin; Salicylates; Streptovaricin; Viomycin

Topics: Adult; Humans; Leprosy; Male; Rifampin

Topics: Adolescent; Adult; Child; Follow-Up Studies; Humans; Leprosy; Male; Polyneuropathies; Quadriplegia; Recurrence; Rifampin; Sulfamethoxypyridazine; Sulfones; Thalidomide

Topics: Animals; Communicable Diseases; Dapsone; Disease Models, Animal; Drug Resistance, Microbial; Hindlimb; Humans; Leprosy; Mice; Microscopy, Electron; Muscles; Mycobacterium leprae; Rifampin; Sciatic Nerve

Topics: Female; Humans; Leprosy; Pregnancy; Rifampin; Tuberculosis

Topics: Adult; Female; Humans; Leprosy; Male; Middle Aged; Rifampin

Topics: Adult; Humans; Leprosy; Male; Rifampin; Tuberculosis

Topics: Humans; Injections, Intramuscular; Leprosy; Male; Rifampin