An Overview of 10 Years of Activity of a Molecular Laboratory for Buruli Ulcer Diagnosis at a Field Hospital in Benin.

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Early diagnosis is crucial to prevent morbidity. In November 2012, a field laboratory fully equipped for the rapid on-site quantitative PCR (qPCR) diagnosis of M. ulcerans was established at the Buruli ulcer treatment center (CDTLUB) center in Pobè Benin, a region where BU is endemic. We describe its first 10 years of activity and its gradual evolution into an expert laboratory for BU diagnosis. From 2012 to 2022, the laboratory analyzed 3,018 samples from patients attending consultations for suspected BU at the CDTLUB in Pobè. Ziehl-Neelsen staining and qPCR targeting the IS2404 sequence were performed. Since 2019, the laboratory has also received and analyzed 570 samples from other centers. The laboratory confirmed the diagnosis of BU by qPCR for 39.7% samples: M. ulcerans DNA was detected in 34.7% of swabs, 47.2% of all fine needle aspiration samples (FNA) and 44.6% of all skin biopsy specimens. Positive Ziehl-Neelsen staining results were obtained for 19.0% samples. Bacterial load, estimated by qPCR, was significantly greater for the Ziehl-Neelsen-positive samples than for Ziehl-Neelsen-negative samples, and detection rates were highest for FNA samples. Overall, 26.3% of the samples received from other centers were positive for BU. Most of these samples were sent by the CDTLUBs of Lalo, Allada, and Zagnanado, Benin. The establishment of the laboratory in the CDTLUB of Pobè has been a huge success. Optimal patient care depends on the close proximity of a molecular biology structure to BU treatment centers. Finally, FNA should be promoted among caregivers. IMPORTANCE Here, we describe the first 10 years of activity at a field laboratory established at the Buruli ulcer treatment center (CDTLUB) in Pobè, Benin, a country in which Mycobacterium ulcerans is endemic. Between 2012 and 2022, the laboratory analyzed 3,018 samples from patients consulting the CDTLUB of Pobè with a suspected clinical BU. Ziehl-Neelsen staining and qPCR targeting the IS2404 sequence were performed. In total, 39.7% of samples tested positive by qPCR and 19.0% tested positive by Ziehl-Neelsen staining. Detection rates were highest for FNA samples, and the bacterial loads estimated by qPCR were significantly higher for Ziehl-Neelsen-positive samples than for Ziehl-Neelsen-negative samples. Since 2019, the laboratory has also analyzed 570 samples received from outside the CDTLUB of Pobè, 26.3% of which were positive for BU. Most of these samples were sent by the CDTLUBs of Lalo, Allada, and Zagnanado in Benin. The establishment of the laboratory in the CDTLUB of Pobè has been a huge success, with major benefits for both the medical staff and patients. Our findings illustrate that the usefulness and feasibility of having a diagnostic center in rural Africa, where the disease is endemic, is a key part of optimal patient care, and that FNA should be promoted to increase detection rates.

Stable and Local Reservoirs of Mycobacterium ulcerans Inferred from the Nonrandom Distribution of Bacterial Genotypes, Benin.

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease found in rural areas of West and Central Africa. Despite the ongoing efforts to tackle Buruli ulcer epidemics, the environmental reservoir of its pathogen remains elusive, underscoring the need for new approaches to improving disease prevention and management. In our study, we implemented a local-scale spatial clustering model and deciphered the genetic diversity of the bacteria in a small area of Benin where Buruli ulcer is endemic. Using 179 strain samples from West Africa, we conducted a phylogeographic analysis combining whole-genome sequencing with spatial scan statistics. The 8 distinct genotypes we identified were by no means randomly spread over the studied area. Instead, they were divided into 3 different geographic clusters, associated with landscape characteristics. Our results highlight the ability of M. ulcerans to evolve independently and differentially depending on location in a specific ecologic reservoir.

Trends of the leprosy control indicators in Benin from 2006 to 2018.

BACKGROUND: Leprosy, or Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae. The purpose of this study was to describe the epidemiological characteristics of leprosy in Benin from 2006 to 2018. METHODS: This descriptive retrospective study included data from January 2006 to December 2018. The data of all patients treated in the leprosy treatment centres (LTCs) of the Republic of Benin were obtained from the LTC registers and analysed using Stata/SE 11.0 software. Quantum GIS (Geographic Information System) version 2.18.23 software was used for mapping. The main indicators of leprosy were calculated according to the World Health Organization (WHO) recommendations. RESULTS: During the study period, a total of 2785 (annual average of 214) new cases of leprosy were diagnosed. The median age of the patients was 38 years, with extremes ranging from 6 to 88 years. The sex ratio (males/females) was 1.18 (1509/1276). The departments of Plateau, Atacora, and Zou were the most endemic; their leprosy detection rate per 100,000 population during these thirteen years were 6.46 (479/7414297), 5.38 (534/9932880) and 5.19 (526/10134877), respectively. The leprosy detection rate declined from 3.8 to 1.32 per 100,000 inhabitants. The proportion of paediatric cases varied from 8.56 to 2.67% as the proportion of multibacillary forms increased from 72.95 to 90%. From 2006 to 2018, 622 leprosy patients detected had grade 2 disability (G2D) at screening, indicating an average rate of 5.06 (622/122877474) cases with G2D per million population. The proportion of grade 2 disabilities increased from 21.23 to 32% during the study period. The majority of new leprosy cases among foreign-born persons were Nigerian (85.71%). The completion of multidrug therapy (MDT) for paucibacillary (PB) and multibacillary (MB) leprosy cases ranged from 96.36 to 95.65% and from 90.53 to 94.12%, respectively. CONCLUSION: In Benin, leprosy remains a major health challenge; it is important to revitalize the epidemiological surveillance system to achieve its elimination by 2030.

Integrated approach in the control and management of skin neglected tropical diseases in three health districts of Côte d'Ivoire.

BACKGROUND: Neglected tropical diseases (NTDs) comprise 20 communicable diseases that are prevalent in rural poor and remote communities with less access to the health system. For effective and efficient control, the WHO recommends that affected countries implement integrated control interventions that take into account the different co-endemic NTDs in the same community. However, implementing these integrated interventions involving several diseases with different etiologies, requiring different control approaches and driven by different vertical programs, remains a challenge. We report here the results and lessons learned from a pilot test of this integrated approach based on integrated screening of skin diseases in three co-endemic health districts of Côte d'Ivoire, a West African country endemic for Buruli ulcer, leprosy and yaw. METHOD: This cross-sectional study took place from April 2016 to March 2017 in 3 districts of Côte d'Ivoire co-endemic for BU, leprosy and yaws. The study was carried out in 6 stages: identification of potentially co-endemic communities; stakeholder training; social mobilization; mobile medical consultations; case detection and management; and a review meeting. RESULTS: We included in the study all patients with skin signs and symptoms at the screening stage who voluntarily accepted screening. In total, 2310 persons screened had skin lesions at the screening stage. Among them, 07 cases were diagnosed with Buruli ulcer. There were 30 leprosy cases and 15 yaws detected. Other types of ulcerations and skin conditions have been identified and represent the majority of cases detected. We learned from this pilot experience that integration can be successfully implemented in co-endemic communities in Côte d'Ivoire. Health workers are motivated and available to implement integrated interventions instead of interventions focused on a single disease. However, it is essential to provide capacity building, a minimum of drugs and consumables for the care of the patients identified, as well as follow-up of identified patients, including those with other skin conditions. CONCLUSIONS: The results of this study show that the integration of activities can be successfully implemented in co-endemic communities under the condition of staff capacity building and minimal care of identified patients.

Healthcare-associated infections: bacteriological characterization of the hospital surfaces in the University Hospital of Abomey-Calavi/so-ava in South Benin (West Africa).

BACKGROUND: Healthcare-associated infections have become a public health problem, creating a new burden on medical care in hospitals. The emergence of multidrug-resistant bacteria poses a difficult task for physicians, who have limited therapeutic options. The dissemination of pathogens depends on "reservoirs", the different transmission pathways of the infectious agents and the factors favouring them. Contaminated environmental surfaces are an important potential reservoir for the transmission of many healthcare-associated pathogens. Pathogens can survive or persist in the environment for months and be a source of infection transmission when appropriate hygiene and disinfection procedures are inefficient. The aim of this study was to identify bacterial species from hospital surfaces in order to effectively prevent healthcare-associated infections. METHODS: Samples were taken from surfaces at the University Hospital of Abomey-Calavi/So-Ava in South Benin (West Africa). To achieve the objective of this study, 160 swab samples of hospital surfaces were taken as recommended by the International Organization for Standardization (ISO 14698-1). These samples were analysed in the bacteriology section of the National Laboratory for Biomedical Analysis. All statistical analyses were performed using SPSS Statistics 21 software. A Chi Square Test was used to test the association between the Results of culture samples and different care units. RESULTS: Of the 160 surface samples, 65% were positive for bacteria. The frequency of isolation was predominant in Paediatrics (87.5%). The positive samples were 64.2% Gram-positive bacteria and 35.8% of Gram-negative bacteria. Staphylococcus aureus predominated (27.3%), followed by Bacillus spp. (23.3%). The proportion of other microorganisms was negligible. S. aureus and Staphylococcus spp. were present in all care units. There was a statistically significant association between the Results of culture samples and different care units (χ2 = 12.732; p = 0.048). CONCLUSION: The bacteria found on the surfaces of the University Hospital of Abomey-Calavi/So-Ava's care environment suggest a risk of healthcare-associated infections. Adequate hospital hygiene measures are required. Patient safety in this environment must become a training priority for all caregivers.

Decrease in Mycobacterium ulcerans disease (Buruli ulcer) in the Lalo District of Bénin (West Africa).

BACKGROUND: Buruli ulcer (BU) is a chronic, necrotizing infectious skin disease caused by Mycobacterium ulcerans. In recent years, there has been a decrease in the number of new cases detected. This study aimed to show the evolution of its distribution in the Lalo District in Bénin from 2006 to 2017. METHODS: The database of the BU Detection and Treatment Center of Lalo allowed us to identify 1017 new cases in the Lalo District from 2006 to 2017. The annual prevalence was calculated with subdistricts and villages. The trends of the demographic variables and those related to the clinical and treatment features were analysed using Microsoft Excel® 2007 and Epi Info® 7. Arc View version® 3.4 was used for mapping. RESULTS: From 2006 to 2017, the case prevalence of BU in the Lalo District decreased by 95%. The spatial distribution of BU cases confirmed the foci of the distribution, as described in the literature. The most endemic subdistricts were Ahomadégbé, Adoukandji, Gnizounmè and Tchito, with a cumulative prevalence of 315, 225, 215 and 213 cases per 10,000 inhabitants, respectively. The least endemic subdistricts were Zalli, Banigbé, Lalo-Centre and Lokogba, with 16, 16, 10, and 5 cases per 10,000 inhabitants, respectively. A significant decrease in the number of patients with ulcerative lesions (p = 0.002), as well as those with category 3 lesions (p < 0.001) and those treated surgically (p < 0.001), was observed. The patients confirmed by PCR increased (from 40.42% in 2006 to 84.62% in 2017), and joint limitation decreased (from 13.41% in 2006 to 0.0% in 2017). CONCLUSION: This study confirmed the general decrease in BU prevalence rates in Lalo District at the subdistrict and village levels, as also observed at the country level. This decrease is a result of the success of the BU control strategies implemented in Bénin, especially in the Lalo District.

Transmission of Drug-Resistant Leprosy in Guinea-Conakry Detected Using Molecular Epidemiological Approaches.

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.

Assessment of water, sanitation, and hygiene practices and associated factors in a Buruli ulcer endemic district in Benin (West Africa).

BACKGROUND: Control of neglected tropical diseases (NTDs) requires multiple strategic approaches including water, sanitation and hygiene services (WASH). Buruli ulcer (BU), one of the 17 NTDs, remains a public health issue in Benin particularly in the district of Lalo. The availability of water as well as good hygiene are important for the management of Buruli ulcer particularly in the area of wound care one of the main component of the treatment of BU lesions. Given the growing importance of WASH in controlling NTDs and in order to assess the baseline for future cross-cutting interventions, we report here on the first study evaluating the level of WASH and associated factors in Lalo, one of the most BU-endemic districts in Benin. METHOD: A cross-sectional study was carried to assess WASH practices and associated factors in the district of Lalo. Data were collected from 600 heads of household using structured pretested questionnaire and observations triangulated with qualitative information obtained from in-depth interviews of patients, care-givers and community members. Univariate and multivariate analysis were carried to determine the relationships between the potential associated factors and the sanitation as well as hygiene status. RESULTS: BU is an important conditions in the district of Lalo with 917 new cases detected from 2006 to 2012. More than 49 % of the household surveyed used unimproved water sources for their daily needs. Only 8.7 % of the investigated household had improved sanitation facilities at home and 9.7 % had improved hygiene behavior. The type of housing as an indicator of the socioeconomic status, the permanent availability of soap and improved hygiene practices were identified as the main factors positively associated with improved sanitation status. CONCLUSIONS: In the district of Lalo in Benin, one of the most endemic for BU, the WASH indicators are very low. This study provides baseline informations for future cross-cutting interventions in this district.

Wound colonization with methicillin-resistant Staphylococcus aureus and hypotheses about acquisition routes in rural health care settings in Sub-Saharan Africa: Perspective from a center devoted to the treatment of cutaneous neglected tropical diseases.

We identified a high prevalence (46.4%) of wound colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients hospitalized in a center devoted to the treatment of cutaneous tropical diseases in Benin. The proportion of MRSA among S aureus isolates was 54.3%. Thirty percent of these MRSA were identified in outpatients. The analysis of pulsed-field gel electrophoresis demonstrated an important diversity of strains but also identified 8 small clusters containing between 2 and 4 isolates suggesting cross-transmission.

Community based integrated wound care: Results of a pilot formative research conducted in Benin and Côte d'Ivoire, West Africa.

Appropriate treatment of chronic wounds is priority in the management of Neglected Tropical Skin Diseases (NTSDs) and non-communicable diseases. We describe an integrated, community-based wound care pilot project carried out in Benin and Cote d'Ivoire that entailed both outreach education and evidence based wound care training for nurses staffing rural clinics. This research was carried out by a transdisciplinary research. Following the collection of baseline data on wound care at home and in clinics, an innovative pilot project was developed based on a critical assessment of baseline data in three parts: a pragmatic nurse training program; mass community cultural sensitive outreach programs and a mobile consultation. It came out from our investigation that several dangerous homecare and inappropriate wound treatment practices in clinics, gaps in knowledge about Neglected Tropical Skin Diseases (NTSDs), and little health staff communication with patients about appropriate wound care. Nurse training covered 11 modules including general principles of wound management and advice specific to endemic NTSDs. Nurse pre-post training knowledge scores increased substantially. Eight mass community outreach programs were conducted, followed by mobile clinics at which 850 people with skin conditions were screened. Three hundred and three (35.65%) of these people presented with wounds of which 64% were simple, 20% moderate, and 16% severe cases. Patients were followed for ten weeks to assess adherence with wound hygiene messages presented in outreach programs and repeated by nurses during screening. Over 90% of simple and moderate cases were managed appropriately at home and 98% of wounds were healed. Of the 47 cases referred to the health center, 87% came for and adhered to wound care advice. In 90% of cases, wounds healed. This pilot study provides a model for introducing integrated community based wound care in Africa.

Is Benin on track to reach universal household coverage of basic water, sanitation and hygiene services by 2030?

INTRODUCTION: With the end of the Millennium Agenda, the United Nations Member States adopted the Sustainable Development Agenda in 2015. This new agenda identifies 17 Sustainable Development Goals (SDGs) and 169 targets for 2030, including Water, Sanitation and Hygiene (WASH). OBJECTIVE: To study the evolution of household access to WASH services over the last two decades in Benin and make projections for 2030. METHODS: In this study, secondary analyses were performed using the datasets of the Demographic and Health Surveys in Benin from 2001 to 2017-2018. The statistical unit was the household. The achievement of the WASH SDGs targets was monitored through the proportion of households using individual basic WASH services, the proportion of households using surface water for drinking, and the proportion of households practising open defecation. The study generated Annual Percentage Changes (APCs) for outcome variables. Based on the APCs between 2001 and 2017-2018, projections were made for 2030. RESULTS: From 2001 to 2017-2018, household access to individual basic WASH services increased from 50.54% to 63.98% (APC = +1.44%), 5.39% to 13.29% (APC = +5.62%), and 2.12% to 10.11% (APC = +9.92%), respectively. At the same time, the prevalence of surface water consumption and open defecation among households decreased from 10.54% to 5.84% (APC = -3.52%) and 67.03% to 53.91% (APC = -1.31%), respectively. If the trend observed between 2001 and 2017-2018 remains unchanged, the national coverage of households with basic individual WASH services would be 76.50%, 26.33% and 10.51%, respectively, by 2030. The prevalence of surface water consumption and open defecation among households would be 3.73% and 45.71%, respectively, by 2030. CONCLUSION: Benin achieved significant progress in household coverage of adequate WASH services over the last two decades. However, progress appears insufficient to achieve universal coverage of households with basic WASH services, and eliminate surface water consumption and open defecation by 2030. There is a need to strengthen research into the drivers of household access to adequate WASH services.

WASH and NTDs: Outcomes and lessons learned from the implementation of a formative research study in NTD skin co-endemic communities in Benin.

Neglected Tropical Diseases (NTDs) are a diverse group of bacterial, viral, parasitic and fungal diseases affecting people, most of whom live below the poverty threshold. Several control strategies are defined against these diseases, including chemotherapy and Water, Hygiene and Sanitation (WASH). This study assesses the effect of promoting hygiene and sanitation on soil-transmitted helminthiasis s and NTDs of the skin. It took place in the communes of Ze, Lalo, and Zangnanado, three municipalities located in the south of Benin. This is a formative research that took place in three phases. The first phase entailed a baseline informations and situational analysis of the state of hygiene and health, using soil-transmitted helminthiasis and wound hygiene practices as cases studies. In the second phase, interventions to promote improved hygiene and sanitation were implemented. The third phase was devoted to post-intervention evaluation. The situation analysis showed that the prevalence of soil-transmitted helminthiasis was 6.43 and 7.10% in the municipalities of Ze and Lalo, respectively. In the communes of Zangnanado, the most common wound management practices identified were: putting sand or ashes in the wounds to keep flies away, the use of medicinal plants and the application of powder from antibiotic capsules for wound dressing. The post-intervention evaluation showed a decrease in the prevalence of soil-transmitted helminthiasis from 6.43 to 1.19% in the municipality of Lalo and from 7.10 to 1.75% in the municipality of Ze. In the commune of Zangnanado, a significant shift in wound management practices was noted, which led to the healing of several chronic wounds. This research supports the evidence that WASH-based interventions are very important to tackle neglected tropical diseases NTDs in addition to specific diseases based interventions.

Importance of consultations using mobile teams in the screening and treatment of neglected tropical skin diseases in Benin.

CONTEXT: Since 2013, the World Health Organization has recommended integrated control strategies for neglected tropical diseases (NTDs) with skin manifestations. We evaluated the implementation of an integrated approach to the early detection and rapid treatment of skin NTDs based on mobile clinics in the Ouémé and Plateau areas of Benin. METHODS: This descriptive cross-sectional study was performed in Ouémé and Plateau in Benin from 2018 to 2020. Consultations using mobile teams were performed at various sites selected by reasoned choice based on the epidemiological data of the National Program for the Control of Leprosy and Buruli Ulcer. All individuals presenting with a dermatological lesion who voluntarily approached the multidisciplinary management team on the day of consultation were included. The information collected was kept strictly anonymous and was entered into an Excel 2013 spreadsheet and analyzed with Stata 11 software. RESULTS: In total, 5,267 patients with various skin conditions consulted the medical team. The median age of these patients was 14 years (IQR: 7-34 years). We saw 646 (12.3%) patients presenting NTDs with skin manifestations, principally scabies, in 88.4% (571/646), followed by 37 cases of Buruli ulcer (5.8%), 22 cases of leprosy (3.4%), 15 cases of lymphatic filariasis (2.3%) and one case of mycetoma (0.2%). We detected no cases of yaws. CONCLUSION: This sustainable approach could help to decrease the burden of skin NTDs in resource-limited countries.

Apoptosis in Buruli ulcer: a clinicopathological study of 45 cases.

AIMS: To investigate the presence and pathogenetic role of apoptosis in Buruli ulcer (BU), a highly destructive skin disease caused by Mycobacterium ulcerans. METHODS AND RESULTS: Forty-five skin biopsies obtained from 30 Beninese patients affected by BU, in different clinical and therapeutic periods, were analysed for the main histopathological features (inflammatory infiltration, necrosis, sclerosis, oedema, granulomas and nerve damage). Immunofluorescent detection of antigens (anti-Bax, anti-caspases-3 and -8), together with deoxyuridine, 5'-triphosphate (dUTP) nick end labelling (TUNEL) assay, were also performed. A significant decrease in inflammatory infiltration (P = 0.0001) was detected between the beginning and end of antibiotic treatment. Neutrophils predominated in the first phase, while lymphocytes and plasma cells were increased at the end of the therapy. An inverse correlation between tissue necrosis and sclerosis was observed (P = 0.001). In 11 cases, inflammatory and regressive changes involved the nerve bundles with axonal degeneration and disruption of nerve fibres. TUNEL assay detected apoptotic bodies within nerve bundles, and these decreased from beginning to end of therapy. Bax, caspase-3 and -8 were down-regulated over the course of antibiotic therapy. CONCLUSIONS: In BU, apoptosis plays a role in promoting and sustaining the destructive changes and is implicated in the neural pathology that is associated with clinically detected anaesthesia.

Associated factors study into the belated screening for leprosy in Benin.

INTRODUCTION: In the absence of early treatment, leprosy, a neglected tropical disease, due to Mycobacterium leprae or Hansen Bacillus, causes irreversible grade 2 disability (G2D) numerous factors related to the individual, the community and the health care system are believed to be responsible for its late detection and management. This study aims to investigate the factors associated with belated screening for leprosy in Benin. METHODS: This was a cross-sectional, descriptive, and analytical study conducted from January 1 to June 31, 2019, involving all patients and staff in leprosy treatment centers and public peripheral level health structures in Benin. The dependent variable of the study was the presence or not of G2D, reflecting late or early screening. We used a logistic regression model, at the 5% threshold, to find the factors associated with late leprosy screening. The fit of the final model was assessed with the Hosmer-Lemeshow test. RESULTS: A number of 254 leprosy patients were included with a mean age of 48.24 ± 18.37 years. There was a male dominance with a sex ratio of 1.23 (140/114). The proportion of cases with G2D was 58.27%. Associated factors with its belated screening in Benin were (OR; 95%CI; p) the fear of stigma related to leprosy (8.11; 3.3-19.94; <0.001), multiple visits to traditional healers (5.20; 2.73-9.89; <0.001) and multiple visits to hospital practitioners (3.82; 2.01-7.27; <0.001). The unawareness of leprosy by 82.69% of the health workers so as the permanent decrease in material and financial resources allocated to leprosy control were identified as factors in link with the health system that helps explain this late detection. CONCLUSION: This study shows the need to implement strategies in the control programs to strengthen the diagnostic abilities of health workers, to improve the level of knowledge of the population on the early signs and symptoms of leprosy, to reduce stigmatization and to ban all forms of discrimination against leprosy patients.

Comparison of 8 weeks standard treatment (rifampicin plus clarithromycin) vs. 4 weeks standard plus amoxicillin/clavulanate treatment [RC8 vs. RCA4] to shorten Buruli ulcer disease therapy (the BLMs4BU trial): study protocol for a randomized controlled multi-centre trial in Benin.

BACKGROUND: Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans that affects skin, soft tissues, and bones, causing long-term morbidity, stigma, and disability. The recommended treatment for BU requires 8 weeks of daily rifampicin and clarithromycin together with wound care, physiotherapy, and sometimes tissue grafting and surgery. Recovery can take up to 1 year, and it may pose an unbearable financial burden to the household. Recent in vitro studies demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic against M. ulcerans. Consequently, inclusion of amoxicillin/clavulanate in a triple oral therapy may potentially improve and shorten the healing process. The BLMs4BU trial aims to assess whether co-administration of amoxicillin/clavulanate with rifampicin and clarithromycin could reduce BU treatment from 8 to 4 weeks. METHODS: We propose a randomized, controlled, open-label, parallel-group, non-inferiority phase II, multi-centre trial in Benin with participants stratified according to BU category lesions and randomized to two oral regimens: (i) Standard: rifampicin plus clarithromycin therapy for 8 weeks; and (ii) Investigational: standard plus amoxicillin/clavulanate for 4 weeks. The primary efficacy outcome will be lesion healing without recurrence and without excision surgery 12 months after start of treatment (i.e. cure rate). Seventy clinically diagnosed BU patients will be recruited per arm. Patients will be followed up over 12 months and managed according to standard clinical care procedures. Decision for excision surgery will be delayed to 14 weeks after start of treatment. Two sub-studies will also be performed: a pharmacokinetic and a microbiology study. DISCUSSION: If successful, this study will create a new paradigm for BU treatment, which could inform World Health Organization policy and practice. A shortened, highly effective, all-oral regimen will improve care of BU patients and will lead to a decrease in hospitalization-related expenses and indirect and social costs and improve treatment adherence. This trial may also provide information on treatment shortening strategies for other mycobacterial infections (tuberculosis, leprosy, or non-tuberculous mycobacteria infections). TRIAL REGISTRATION: ClinicalTrials.gov NCT05169554 . Registered on 27 December 2021.

Buruli ulcer disease: prospects for a vaccine.

Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, is a neglected bacterial infection of the poor in remote rural areas, mostly affecting children. BUD is a mutilating disease leading to severe disability; it is the third most common mycobacterial infection in immunocompetent people after tuberculosis and leprosy. It is most endemic in West Africa, but cases have been reported from more than 30 countries. Treatment with antibiotics is possible, long-lasting and requires injections; there are cases of treatment failures, and the disease is prone to resistance. A vaccine against M. ulcerans would protect persons at risk in highly endemic areas, and could be used as a therapeutic vaccine to shorten the duration of treatment and prevent relapses. There is considerable evidence supporting the notion that generation of a vaccine is feasible. This article reviews the present state of the art with special emphasis on the immunology of the infection and the prospects for development of a vaccine.

The gendered impact of Buruli ulcer on the household production of health and social support networks: Why decentralization favors women.

BACKGROUND: Buruli ulcer [BU] is a chronic and debilitating neglected tropical skin disease caused by Mycobacterium ulcerans. The treatment of moderate to severe BU affects the well-being of entire households and places a strain on both gender relations within households and social relations with kin asked for various types of support. In this paper, we employ the conceptual lenses provided by the Household Production of Health approach to understanding the impact of illness on the household as a unit of analysis, gender studies, and social support related research to better understand BU health care decision making and the psychosocial experience of BU hospitalization. METHODS: An ethnography attentive to circumstance and the nested contexts within which stakeholders respond to BU was conducted employing semi-structured interviews, illness narratives, and case studies. An iterative process of data collection with preliminary analyses and reflection shaped subsequent interviews. Interviews were conducted with 45 women in households having a member afflicted with BU in two communes of Benin with high prevalence rates for BU. The first commune [ZE] has a well-established decentralized BU treatment program and a well-functioning referral network linked to the Allada reference hospital specializing in the care of BU and other chronic ulcers. The second commune [Ouinhi] is one of the last regions of the country to introduce a decentralized BU treatment program. A maximum variation purposeful sample was selected to identify information-rich health care decision cases for in-depth study. PRINCIPAL FINDINGS: Study results demonstrated that although men are the primary decision makers for healthcare decisions outside the home, women are largely responsible for arranging care for the afflicted in hospital in addition to managing their own households. A woman's agency and ability to influence the decision-making process is largely based on whatever social support and substitute labor she can mobilize from her own network of kin relations. When support wanes, women are placed in a vulnerable position and often end up destitute. Decentralized BU treatment is preferred because it enables a woman to remain in her own household as a patient or caretaker of an ill family member while engaging in child care and petty revenue earing activities. Remaining in the hospital (a liminal space) as either patient or caretaker also renders a woman vulnerable to rumor and innuendo about sexual liaisons and constitutes a form of social risk. Social risk in some cases eclipses the physical risk of the disease in what we would describe as a hierarchy of risks. CONCLUSION: This study illustrates the importance of decentralized treatment programs for NTDs such as BU. Such programs enable patients to remain in their homes while being treated, and do not displace women responsible for the welfare of the entire household. When women are displaced the well-being of the entire household is placed in jeopardy.

Effect of well drilling on Buruli ulcer incidence in Benin: a case-control, quantitative survey.

BACKGROUND: Buruli ulcer is the third most common mycobacterial disease worldwide. The public health burden of this neglected tropical disease is large, particularly in poor areas of west and central Africa. The development of appropriate preventive strategies is hampered by an incomplete understanding of the epidemiology and transmission of the disease. We investigated the effect of the drilling of wells on Buruli ulcer incidence. METHODS: In this case-control, quantitative survey, we obtained field data for Buruli ulcer incidence over a 10-year period from a specialised centre that collected data for the Ouémé and Plateau departments in Benin, and data for well drilling from the Ministry of Energy, Water and Mines in Benin. The coordinates of the wells drilled were obtained during site visits. A case-control study was then done to investigate the role of well water use in protecting against Buruli ulcer. FINDINGS: We found a strong inverse correlation between the incidence of Buruli ulcer and the number of new wells drilled in the Bonou municipality (r2=0·8818). A case-control study (106 cases and 212 controls) showed that regular use of the water from the wells for washing, bathing, drinking, or cooking was protective against Buruli ulcer (adjusted odds ratio 0·1, 95% CI 0·04-0·44; p=0·0012). INTERPRETATION: This study opens up new possibilities for developing an effective yet affordable policy to fight the disease on a substantial geographical scale. Our study shows that providing access to protected water is an efficient and feasable way to reduce the incidence of Buruli ulcer. FUNDING: Fondation Francaise Raoul Follereau, French National Institute of Health and Medical Research, and Région Pays de Loire.