Drugs for treating Buruli ulcer (Mycobacterium ulcerans disease)

Background Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The infection progresses from nodules under the skin to deep ulcers, often on the upper and lower limbs or on the face. If left undiagnosed and untreated, it can lead to lifelong disfigurement and disabilities. It is often treated with drugs and surgery. Objectives To summarize the evidence of drug treatments for treating Buruli ulcer. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (Ovid); and LILACS (Latin American and Caribbean Health Sciences Literature; BIREME). We also searched the US National Institutes of Health Ongoing Trials Register (clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en/). All searches were run up to 19 December 2017. We also checked the reference lists of articles identified by the literature search, and contacted leading researchers in this topic area to identify any unpublished data. Selection criteria We included randomized controlled trials (RCTs) that compared antibiotic therapy to placebo or alternative therapy such as surgery, or that compared different antibiotic regimens. We also included prospective observational studies that evaluated different antibiotic regimens with or without surgery. Data collection and analysis Two review authors independently applied the inclusion criteria, extracted the data, and assessed methodological quality. We calculated the risk ratio (RR) for dichotomous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach. Main results We included a total of 18 studies: five RCTs involving a total of 319 participants, ranging from 12 participants to 151 participants, and 13 prospective observational studies, with 1665 participants. Studies evaluated various drugs usually in addition to surgery, and were carried out across eight countries in areas with high Buruli ulcer endemicity in West Africa and Australia. Only one RCT reported adequate methods to minimize bias. Regarding monotherapy, one RCT and one observational study evaluated clofazimine, and one RCT evaluated sulfamethoxazole/trimethoprim. All three studies had small sample sizes, and no treatment effect was demonstrated. The remaining studies examined combination therapy. Rifampicin combined with streptomycin We found one RCT and six observational studies which evaluated rifampicin combined with streptomycin for different lengths of treatment (2, 4, 8, or 12 weeks) (941 participants). The RCT did not demonstrate a difference between the drugs added to surgery compared with surgery alone for recurrence at 12 months, but was underpowered (RR 0.12, 95% CI 0.01 to 2.51; 21 participants; very low‐certainty evidence). An additional five single‐arm observational studies with 828 participants using this regimen for eight weeks with surgery (given to either all participants or to a select group) reported healing rates ranging from 84.5% to 100%, assessed between six weeks and one year. Four observational studies reported healing rates for participants who received the regimen alone without surgery, reporting healing rates ranging from 48% to 95% assessed between eight weeks and one year. Rifampicin combined with clarithromycin Two observational studies administered combined rifampicin and clarithromycin. One study evaluated the regimen alone (no surgery) for eight weeks and reported a healing rate of 50% at 12 months (30 participants). Another study evaluated the regimen administered for various durations (as determined by the clinicians, durations unspecified) with surgery and reported a healing rate of 100% at 12 months (21 participants). Rifampicin with streptomycin initially, changing to rifampicin with clarithromycin in consolidation phase One RCT evaluated this regimen (four weeks in each phase) against continuing with rifampicin and streptomycin in the consolidation phase (total eight weeks). All included participants had small lesions, and healing rates were above 90% in both groups without surgery (healing rate at 12 months RR 0.94, 95% CI 0.87 to 1.03; 151 participants; low‐certainty evidence). One single‐arm observational study evaluating the substitution of streptomycin with clarithromycin in the consolidation phase (6 weeks, total 8 weeks) without surgery given to a select group showed a healing rate of 98% at 12 months (41 participants). Novel combination therapy Two large prospective studies in Australia evaluated some novel regimens. One study evaluating rifampicin combined with either ciprofloxacin, clarithromycin, or moxifloxacin without surgery reported a healing rate of 76.5% at 12 months (132 participants). Another study evaluating combinations of two to three drugs from rifampicin, ciprofloxacin, clarithromycin, ethambutol, moxifloxacin, or amikacin with surgery reported a healing rate of 100% (90 participants). Adverse effects were reported in only three RCTs (158 participants) and eight prospective observational studies (878 participants), and were consistent with what is already known about the adverse effect profile of these drugs. Paradoxical reactions (clinical deterioration after treatment caused by enhanced immune response to M ulcerans) were evaluated in six prospective observational studies (822 participants), and the incidence of paradoxical reactions ranged from 1.9% to 26%. Authors' conclusions While the antibiotic combination treatments evaluated appear to be effective, we found insufficient evidence showing that any particular drug is more effective than another. How different sizes, lesions, and stages of the disease may contribute to healing and which kind of lesions are in need of surgery are unclear based on the included studies. Guideline development needs to consider these factors in designing practical treatment regimens. Forthcoming trials using clarithromycin with rifampicin and other trials of new regimens that also address these factors will help to identify the best regimens

Hansen\u27s disease (leprosy) in Japan, 1947-2020: an epidemiologic study during the declining phase to elimination

Objectives: Leprosy, or Hansen’s disease was a major public health problem in Japan in the early 20th century. Today, the number of new cases has decreased significantly. We aimed to investigate the trends of leprosy in Japan over the past 73 years and the challenges faced in recent years. Methods: We assessed the data on newly registered cases of leprosy from 1947 to 2020. Results: A total of 10,796 newly registered cases of leprosy were reported during the study period, of which 7573 were registered in mainland Japan, 2962 in Okinawa, and 250 were of foreign origin. Most autochthonous cases were born before 1950 in mainland Japan and before 1975 in Okinawa. The number of nonautochthonous cases surpassed that of autochthonous cases in 1992. Nonautochthonous cases orig- inated from 26 countries, particularly Brazil and the Philippines. Three cases of antimicrobial resistance have been detected among nonautochthonous cases since 2004. Conclusion: Our data suggest that ongoing transmission of leprosy likely ceased in the 1940s in mainland Japan and in the 1970s in Okinawa. With the recent rise of nonautochthonous cases with globalization, continuous surveillance and effort s to maint ain leprosy services within the country are necessary even after reaching the state of elimination

The Early Detection and Case Management of Skin Diseases With an mHealth App (eSkinHealth): Protocol for a Mixed Methods Pilot Study in Côte d’Ivoire

Background: There is a high prevalence of skin diseases sub-Saharan Africa, including skin neglected tropical diseases (NTDs) that could lead to lifelong disabilities and deformities if not diagnosed and treated early. To achieve early detection and early treatment of these skin diseases, we developed a mobile health app, eSkinHealth.Objective: This paper outlines a protocol for evaluating the effect of our eSkinHealth app in the early detection and effective management of skin diseases in Côte d’Ivoire.Methods: A mixed methods pilot trial will be conducted in Côte d’Ivoire and will consist of 3 phases: (1) the development and improvement of the eSkinHealth app, (2) a pilot trial to evaluate the usability of the eSkinHealth app for local medical staff in Côte d’Ivoire, and (3) a pilot trial to evaluate the effectiveness of early detection and case management of targeted skin NTDs (Buruli ulcer, leprosy, yaws, and lymphatic filariasis) with the eSkinHealth app in Côte d’Ivoire. The pilot study will be implemented as a 2-arm trial with local health care providers and patients with skin NTDs over a 3-month follow-up period. The local health care providers will be assigned to an intervention group receiving the eSkinHealth app to be used in their daily practices or a control group. Training will be provided on the use and implementation of the app and the diagnostic pipeline to the intervention group only, while both groups will receive training on skin diseases. Our primary outcome is to evaluate the early detection and effective management of skin diseases using the eSkinHealth app in Côte d’Ivoire by the number of cases diagnosed and managed. Additionally, we will evaluate the eSkinHealth app with validated questionnaires and in-depth interviews. Procedures of our methods have been reviewed and approved by the Institutional Review Board of the Ministry of Health, Côte d’Ivoire and by Tulane University in 2021.Results: This study was funded in 2021. We started the enrollment of patients in February 2022, and data collection is currently underway. We expect the first results to be submitted for publication in 2023.Conclusions: Our eSkinHealth app is a field-adapted platform that could provide both direct diagnostic and management assistance to health workers in remote settings. The study will provide evidence for the usability and the effectiveness of the eSkinHealth app to improve the early detection and case management of skin NTDs in Côte d’Ivoire and, furthermore, is expected to contribute to knowledge on mobile health approaches in the control of skin NTDs

Support for children identified with acute flaccid paralysis under the global polio eradication programme in Uttar Pradesh, India: a qualitative study

Background Cases of polio in India declined after the implementation of the polio eradication programme especially in these recent years. The programme includes surveillance of acute flaccid paralysis (AFP) to detect and diagnose cases of polio at early stage. Under this surveillance, over 40,000 cases of AFP are reported annually since 2007 regardless of the number of actual polio cases. Yet, not much is known about these children. We conducted a qualitative research to explore care and support for children with AFP after their diagnosis. Methods The research was conducted in a district of western Uttar Pradesh classified as high-risk area for polio. In-depth interviews with parents of children with polio (17), with non-polio AFP (9), healthcare providers (40), and key informants from community including international and government officers, religious leaders, community leaders, journalists, and academics (21) were performed. Results Minimal medicine and attention were provided at government hospitals. Therefore, most parents preferred private-practice doctors for their children with AFP. Many were visited at homes to have stool samples collected by authorities. Some were visited repetitively following the sample collection, but had difficulty in understanding the reasons for these visits that pertained no treatment. Financial burden was a common concern among all families. Many parents expressed resentment for their children's disease, notably have been affected despite receiving multiple doses of polio vaccine. Both parents and healthcare providers lacked information and knowledge, furthermore poverty minimised the access to available healthcare services. Medicines, education, and transportation means were identified as foremost needs for children with AFP and residual paralysis. Conclusions Despite the high number of children diagnosed with AFP as part of the global polio eradication programme, we found they were not provided with sufficient medical support following their diagnosis. Improvement in the quality and sufficiency of the healthcare system together with integration of AFP surveillance with other services in these underprivileged areas may serve as a key solution

Integrated Management of Skin NTDs—Lessons Learned from Existing Practice and Field Research

Integration of neglected tropical diseases (NTDs) into the public health agenda has been a priority in global health for the last decade. Because a number of these diseases share not only the geographical distribution, but also a common feature which is skin involvement, bringing together a sub-group of ‘skin NTDs’ is one way forward to promote further integration among NTDs. With these diseases, which include leprosy, Buruli ulcer, yaws, mycetoma, lymphatic filariasis, and leishmaniasis, patients may be left with life-long deformities and disabilities when diagnosis and treatment are delayed. Stigma is another serious consequence of skin NTDs as it places a large barrier on the economic activities and social life of a patient. As a result, this creates a vicious cycle and obstructs a key goal of society, the elimination of poverty. Enhancement in surveillance systems as well as the further development of diagnostic methods, improvement in treatment and management, and identification of preventative measures for skin NTDs are therefore urgently needed. This article summarizes the existing practices and field research on skin NTDs and identifies potential synergies that could be achieved by adopting this integrated approach

Methods and Approaches for Buruli Ulcer Surveillance in Africa: Lessons Learnt and Future Directions.

Over 95% of the global burden of Buruli ulcer disease (BU) caused by Mycobacterium ulcerans occurs in equatorial Africa. National and sub-national programs have implemented various approaches to improve detection and reporting of incident cases over recent decades. Regional incidence rates are currently in decline; however, surveillance targets outlined in 2012 by WHO have been missed and detection bias may contribute to these trends. In light of the new 2030 NTD roadmap and disease-specific targets, BU programs are required to strengthen case detection and begin a transition towards integration with other skin-NTDs. This transition comes with new opportunities to enhance existing BU surveillance systems and develop novel approaches for implementation and evaluation.In this review, we present a breakdown and assessment of the methods and approaches that have been the pillars of BU surveillance systems in Africa: (1) Passive case detection, (2) Data systems, (3) Clinical training, (4) Active case finding, (5) Burden estimation, and (6) Laboratory confirmation pathways. We discuss successes, challenges, and relevant case studies before highlighting opportunities for future development and evaluation including novel data collection tools, risk-based surveillance, and integrated skin-NTD surveillance. We draw on both experience and available literature to critically evaluate methods of BU surveillance in Africa and highlight new approaches to help achieve 2030 roadmap targets

Hansen's disease (leprosy) in Japan, 1947-2020: an epidemiologic study during the declining phase to elimination

Objectives: Leprosy, or Hansen's disease was a major public health problem in Japan in the early 20th century. Today, the number of new cases has decreased significantly. We aimed to investigate the trends of leprosy in Japan over the past 73 years and the challenges faced in recent years. Methods: We assessed the data on newly registered cases of leprosy from 1947 to 2020. Results: A total of 10,796 newly registered cases of leprosy were reported during the study period, of which 7573 were registered in mainland Japan, 2962 in Okinawa, and 250 were of foreign origin. Most autochthonous cases were born before 1950 in mainland Japan and before 1975 in Okinawa. The number of nonautochthonous cases surpassed that of autochthonous cases in 1992. Nonautochthonous cases originated from 26 countries, particularly Brazil and the Philippines. Three cases of antimicrobial resistance have been detected among nonautochthonous cases since 2004. Conclusion: Our data suggest that ongoing transmission of leprosy likely ceased in the 1940s in mainland Japan and in the 1970s in Okinawa. With the recent rise of nonautochthonous cases with globalization, continuous surveillance and efforts to maintain leprosy services within the country are necessary even after reaching the state of elimination

The Early Detection and Case Management of Skin Diseases With an mHealth App (eSkinHealth): Protocol for a Mixed Methods Pilot Study in Côte d’Ivoire

BackgroundThere is a high prevalence of skin diseases sub-Saharan Africa, including skin neglected tropical diseases (NTDs) that could lead to lifelong disabilities and deformities if not diagnosed and treated early. To achieve early detection and early treatment of these skin diseases, we developed a mobile health app, eSkinHealth. ObjectiveThis paper outlines a protocol for evaluating the effect of our eSkinHealth app in the early detection and effective management of skin diseases in Côte d’Ivoire. MethodsA mixed methods pilot trial will be conducted in Côte d’Ivoire and will consist of 3 phases: (1) the development and improvement of the eSkinHealth app, (2) a pilot trial to evaluate the usability of the eSkinHealth app for local medical staff in Côte d’Ivoire, and (3) a pilot trial to evaluate the effectiveness of early detection and case management of targeted skin NTDs (Buruli ulcer, leprosy, yaws, and lymphatic filariasis) with the eSkinHealth app in Côte d’Ivoire. The pilot study will be implemented as a 2-arm trial with local health care providers and patients with skin NTDs over a 3-month follow-up period. The local health care providers will be assigned to an intervention group receiving the eSkinHealth app to be used in their daily practices or a control group. Training will be provided on the use and implementation of the app and the diagnostic pipeline to the intervention group only, while both groups will receive training on skin diseases. Our primary outcome is to evaluate the early detection and effective management of skin diseases using the eSkinHealth app in Côte d’Ivoire by the number of cases diagnosed and managed. Additionally, we will evaluate the eSkinHealth app with validated questionnaires and in-depth interviews. Procedures of our methods have been reviewed and approved by the Institutional Review Board of the Ministry of Health, Côte d’Ivoire and by Tulane University in 2021. ResultsThis study was funded in 2021. We started the enrollment of patients in February 2022, and data collection is currently underway. We expect the first results to be submitted for publication in 2023. ConclusionsOur eSkinHealth app is a field-adapted platform that could provide both direct diagnostic and management assistance to health workers in remote settings. The study will provide evidence for the usability and the effectiveness of the eSkinHealth app to improve the early detection and case management of skin NTDs in Côte d’Ivoire and, furthermore, is expected to contribute to knowledge on mobile health approaches in the control of skin NTDs. Trial RegistrationClinicalTrials.gov NCT05300399; https://clinicaltrials.gov/ct2/show/study/NCT05300399 International Registered Report Identifier (IRRID)DERR1-10.2196/3986