rifampin and Neglected-Diseases

In its 'Road map for neglected tropical diseases 2021-2030', the World Health Organization outlined its targets for control and elimination of neglected tropical diseases (NTDs) and research needed to achieve them. For many NTDs, this includes research for new treatment options for case management and/or preventive chemotherapy. Our review of small-molecule anti-infective drugs recently approved by a stringent regulatory authority (SRA) or in at least Phase 2 clinical development for regulatory approval showed that this pipeline cannot deliver all new treatments needed. WHO guidelines and country policies show that drugs may be recommended for control and elimination for NTDs for which they are not SRA approved (i.e. for 'off-label' use) if efficacy and safety data for the relevant NTD are considered sufficient by WHO and country authorities. Here, we are providing an overview of clinical research in the past 10 years evaluating the anti-infective efficacy of oral small-molecule drugs for NTD(s) for which they are neither SRA approved, nor included in current WHO strategies nor, considering the research sponsors, likely to be registered with a SRA for that NTD, if found to be effective and safe. No such research has been done for yaws, guinea worm, Trypanosoma brucei gambiense human African trypanosomiasis (HAT), rabies, trachoma, visceral leishmaniasis, mycetoma, T. b. rhodesiense HAT, echinococcosis, taeniasis/cysticercosis or scabies. Oral drugs evaluated include sparfloxacin and acedapsone for leprosy; rifampicin, rifapentin and moxifloxacin for onchocerciasis; imatinib and levamisole for loiasis; itraconazole, fluconazole, ketoconazole, posaconazole, ravuconazole and disulfiram for Chagas disease, doxycycline and rifampicin for lymphatic filariasis; arterolane, piperaquine, artesunate, artemether, lumefantrine and mefloquine for schistosomiasis; ivermectin, tribendimidine, pyrantel, oxantel and nitazoxanide for soil-transmitted helminths including strongyloidiasis; chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B, ivermectin and doxycycline for dengue; streptomycin, amoxicillin, clavulanate for Buruli ulcer; fluconazole and isavuconazonium for mycoses; clarithromycin and dapsone for cutaneous leishmaniasis; and tribendimidine, albendazole, mebendazole and nitazoxanide for foodborne trematodiasis. Additional paths to identification of new treatment options are needed. One promising path is exploitation of the worldwide experience wit

Topics: Anti-Infective Agents; Doxycycline; Drug Combinations; Fluconazole; Humans; Ivermectin; Neglected Diseases; Off-Label Use; Rifampin

To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens.. We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI).. We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy.. Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Topics: Adolescent; Adult; Aged; Child; Clinical Protocols; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy, Multibacillary; Leprosy, Paucibacillary; Male; Middle Aged; Minocycline; Mycobacterium leprae; Neglected Diseases; Ofloxacin; Recurrence; Rifampin; Treatment Failure; World Health Organization; Young Adult

Buruli ulcer is caused by

Topics: Africa, Western; Anti-Bacterial Agents; Buruli Ulcer; Clarithromycin; Humans; Macrolides; Mycobacterium Infections; Mycobacterium ulcerans; Neglected Diseases; Polymerase Chain Reaction; Rifampin; Skin Diseases, Bacterial; Streptomycin

Leprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae. Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is found in India, Brazil, and Indonesia. While the exact route of transmission remains unknown, nasal droplet infection is thought to be most likely. The pathogen primarily affects the skin and peripheral nervous system. The disease course is determined by individual host immunity. Clinically, multibacillary lepromatous variants are distinguished from paucibacillary tuberculoid forms. Apart from the various characteristic skin lesions, the condition is marked by damage to the peripheral nervous system. Advanced disease is characterized by disfiguring mutilations. Current treatment options are based on WHO recommendations. Early treatment frequently results in complete remission without sequelae. While paucibacillary forms are treated with rifampicin and dapsone for at least six months, multibacillary leprosy is treated for at least twelve months, additionally requiring clofazimine. Leprosy reactions during therapy may considerably aggravate the disease course. Besides individual treatment, WHO-supported preventive measures and strategies play a key role in endemic areas.

Topics: Adult; Aged; Child; Clofazimine; Cross-Sectional Studies; Dapsone; Disease Progression; Drug Administration Schedule; Female; Guideline Adherence; Humans; Immunity, Cellular; Leprostatic Agents; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Long-Term Care; Male; Neglected Diseases; Rifampin

Topics: Antibiotics, Antitubercular; Arm; Buruli Ulcer; Child; Cote d'Ivoire; Drug Therapy, Combination; Humans; Male; Mass Screening; Mycobacterium ulcerans; Neglected Diseases; Rifampin; School Health Services; Skin; Streptomycin; Treatment Outcome

Topics: Adult; Animals; Clofazimine; Humans; Insecticides; Ivermectin; Leprostatic Agents; Leprosy, Lepromatous; Male; Mycobacterium leprae; Neglected Diseases; Permethrin; Rifampin; Sarcoptes scabiei; Scabies; Skin; Tropical Medicine

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

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical skin disease that is most commonly found in children from West and Central Africa. Despite the severity of the infection, therapeutic options are limited to antibiotics with severe side effects. Here, we show that M. ulcerans is susceptible to the anti-tubercular drug Q203 and related compounds targeting the respiratory cytochrome bc

Topics: Africa; Animals; Antibiotics, Antitubercular; Australia; Buruli Ulcer; Disease Models, Animal; Electron Transport Complex III; Electron Transport Complex IV; Female; Humans; Imidazoles; Inhibitory Concentration 50; Mice; Mice, Inbred BALB C; Mycobacterium ulcerans; Neglected Diseases; Piperidines; Pyridines; Rifampin; Treatment Outcome

Topics: Adult; Biopsy; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Multibacillary; Morocco; Neglected Diseases; Rifampin; Skin

Topics: Adolescent; Adult; Anti-Bacterial Agents; Buruli Ulcer; Child; Child, Preschool; Congo; Epidemiological Monitoring; Female; Humans; Male; Mycobacterium ulcerans; Neglected Diseases; Rifampin; Streptomycin

The neglected tropical disease Buruli ulcer (BU) caused by Mycobacterium ulcerans is an infection of the subcutaneous tissue leading to chronic ulcerative skin lesions. Histopathological features are progressive tissue necrosis, extracellular clusters of acid fast bacilli (AFB) and poor inflammatory responses at the site of infection. After the recommended eight weeks standard treatment with rifampicin and streptomycin, a reversal of the local immunosuppression caused by the macrolide toxin mycolactone of M. ulcerans is observed.. We have conducted a detailed histopathological and immunohistochemical analysis of tissue specimens from two patients developing multiple new skin lesions 12 to 409 days after completion of antibiotic treatment. Lesions exhibited characteristic histopathological hallmarks of Buruli ulcer and AFB with degenerated appearance were found in several of them. However, other than in active disease, lesions contained massive leukocyte infiltrates including large B-cell clusters, as typically found in cured lesions.. Our histopathological findings demonstrate that the skin lesions emerging several months after completion of antibiotic treatment were associated with M. ulcerans infection. During antibiotic therapy of Buruli ulcer development of new skin lesions may be caused by immune response-mediated paradoxical reactions. These seem to be triggered by mycobacterial antigens and immunostimulators released from clinically unrecognized bacterial foci. However, in particular the lesions that appeared more than one year after completion of antibiotic treatment may have been associated with new infection foci resolved by immune responses primed by the successful treatment of the initial lesion.

Topics: Antibiotics, Antitubercular; Antigens, CD; Buruli Ulcer; Child; Humans; Immunohistochemistry; Leukocytes; Male; Mycobacterium ulcerans; Necrosis; Neglected Diseases; Rifampin; Skin; Streptomycin; Treatment Outcome