minocycline and Leprosy

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

Minocycline belongs to the second generation class of cyclines. It was synthesized in 1967 and marketed in 1972. Minocycline has an antiinfectious activity with a spectrum similar to that of other cyclines, notably against Chlamydias, Treonema and Proprionibacterium acenes. The antiinflammatory activity is associated with this antiinfectious action is greater than that of first generation cyclines with specifically a modulator effect on epidermal cytokines. The pharmokinetics of minocycline is characterized by an excellent absorption, a long half-life and an important lipophilic property inducing good tissue distribution. Clinical trials of minocycline have mainly been performed in sexually transmissible diseases and in acne, a field where randomized studies are the most frequent. These trials show that the effect of minocycline is not stronger than first generation cyclines or doxycycline, but that the action is quicker than that of tetracycline at the dose of 500 mg a day. Minocycline is also efficient in nocardiasis, mycobacteriosis, leprosy, Lyme disease, pyoderma gangrenosum, autoimmune bullous dermatitis, Carteaud disease, and prurigo. However, the effect of minocycline in these different conditions has always been evaluated in open trials with a small number of patients. The usual side effects of cyclines, i.e. digestive problems, fungal infections, are less frequent than with first generation cyclines. No photosensitivity has been demonstrated although pigmentations have been described. Dizziness is a specific side effect of minocycline. Furthermore, rare but severe side effects have been reported, including hypersensitivity syndrome, autoimmune hepatitis, and lupus. Regular indications for minocycline in dermatology are acne and three sexually transmissible diseases (mycoplasm, chlamydia, treponema). Proposed dosage is 100 mg per day in sexually transmissible disease with a reduction to 50 mg per day after 15 days in acne.

Topics: Acne Vulgaris; Anti-Bacterial Agents; Autoimmune Diseases; Cytokines; Drug Administration Schedule; Humans; Leprosy; Lyme Disease; Minocycline; Mycobacterium Infections; Nocardia Infections; Prurigo; Pyoderma Gangrenosum; Research Design; Sexually Transmitted Diseases; Skin Diseases, Vesiculobullous; Treatment Outcome

Clarithromycin(CAM), Roxithromycin(RXM), Minocycline(MINO) and Fosfomycin(FOM) has anti-inflammatory action and immunomodulatory activity, while the anti-mycobacterium leprae activity is shown. CAM and RXM suppress the rat carrageenin edema, and MINO suppresses the rat adjvant arthritis. There is the immunosuppression on adrenocorticosteroid while the inflammatory cytokine is suppressed. CAM, MINO, FOM suppresses the inflammatory cytokine, while it has the immunomodulatory activity. Fusidic acid(FA) suppresses the inflammatory cytokine with the action of being similar to cyclosporin A, and it has the immunomodulatory activity. New macrolides derivatives, CAM and RXM showed the inflammatory regulation, and MINO showed the anti-inflammatory activity with FA. The combination chemotherapy can be enforced, while peripheral neuropathy is prevented by the control of the leprosy reaction.

Topics: Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Clarithromycin; Drug Therapy, Combination; Fosfomycin; Fusidic Acid; Humans; Leprostatic Agents; Leprosy; Minocycline; Peripheral Nervous System Diseases; Protein Synthesis Inhibitors; Rats; Roxithromycin

Nerve function impairment (NFI) in leprosy may occur and progress despite multidrug therapy alone or in combination with corticosteroids. We observed improvement in neuritis when minocycline was administered in patients with type 2 lepra reaction. This prompted us to investigate the role of minocycline in recent onset NFI, especially in corticosteroid unresponsive leprosy patients. Leprosy patients with recent onset clinical NFI (<6 months), as determined by Monofilament Test (MFT) and Voluntary Muscle Test (VMT), were recruited. Minocycline 100mg/day was given for 3 months to these patients. The primary outcome was the proportion of patients with 'restored,' 'improved,' 'stabilized,' or 'deteriorated' NFI. Secondary outcomes included any improvement in nerve tenderness and pain. In this pilot study, 11 patients were recruited. The progression of NFI was halted in all; with 9 out of 11 patients (81.82%) showing ?restored? or ?improved? sensory or motor nerve functions, on assessment with MFT and VMT. No serious adverse effects due to minocycline were observed. Our pilot study demonstrates the efficacy and safety of minocycline in recent onset NFI in leprosy patients. However, larger and long term comparative trials are needed to validate the efficacy of minocycline in leprosy neuropathy.

Topics: Adult; Female; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Minocycline; Motor Activity; Motor Neurons; Neuritis; Neurologic Examination; Peripheral Nervous System Diseases; Pilot Projects; Recovery of Function; Sensory Thresholds; Time Factors; Treatment Outcome; Young Adult

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

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

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

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

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 elimination of leprosy has been possible with the available anti-leprotic drugs. However, the lepra reactions usually occur months or years after multi-drug therapy completion, and continue to be a formidable challenge mainly owing to its role in causing nerve damage and disability. Corticosteroids are commonly used but they lead to systemic complications, and hence require dose reduction and adjunct therapy with a different target. Various drugs with different targets have been identified and are in practice to treat lepra reactions. The newer targets can include genetic and tissue targets in the skin and nerve. Thalidomide treatment reducing pentraxin-3, toll-like receptor antagonists, minocycline, apremilast, immunomodulators, and tenidap can be helpful in lepra reaction. Other modalities to manage lepra reactions include plasma exchange, intravenous immunoglobulins, and immunotherapy. Most of these treatments are based only on the pathological process of the reaction and tend to be incomplete leading to recurrence. Newer multimodal approaches are required based on various biomarkers (genetic, tissue, serological), which can be monitored to prevent the recurrence of reactions. Hence, there is a need for newer targets and drugs to be identified for the management of lepra reactions.

Topics: Humans; Leprosy; Minocycline; Skin

A subset of leprosy patients has clinical and histopathological activity in the form of persistent plaques and granulomas after completion of multidrug therapy (MDT) which can have significant impact on their quality of life. In the absence of clear guidelines regarding management of such patients, majority of the times they are treated either as late reversal reaction with corticosteroids or no active treatment is offered. We observed 11 patients of leprosy with persistent plaques after completing the 6/12-months MDT who were treated favorably with minocycline 100 mg once daily for 16 weeks. Complete clinical resolution was observed in 9/11 patients while two patients had partial improvement. Histopathological improvement in the form of disappearance of granulomas corroborated with the clinical improvement. All the patients tolerated the treatment well and hyperpigmentation was the only adverse effect noted. Minocycline may be considered as a useful and well tolerated therapeutic option for this subset of leprosy patients due to its immune modulatory and anti-inflammatory effects.

Topics: Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Minocycline; Quality of Life

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

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

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

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

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

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

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

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

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 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

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

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

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

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

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

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: 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

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

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

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

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

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

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

Topics: Administration, Oral; Animals; Diet; Female; Leprosy; Mice; Mice, Inbred BALB C; Minocycline; Mycobacterium leprae

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

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