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.

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.

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.

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.

A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses.

Buruli ulcer is a neglected tropical disease caused by M. ulcerans, an environmental mycobacterium. This cutaneous infectious disease affects populations with poor access to sanitation, safe water and healthcare living in rural areas of West and Central Africa. Stagnant open bodies of surface water and slow-running streams are the only risk factor identified in Africa, and there is no human-to-human transmission. Appropriate and effective prevention strategies are required for populations living in endemic areas. Based on a multidisciplinary approach in an area in which Buruli ulcer is endemic in South Benin, we investigated the link between all human-environment interactions relating to unprotected water and behaviors associated with Buruli ulcer risk likely to affect incidence rates. We characterised the sources of water as well as water bodies and streams used by communities, by conducting a prospective case-control study directly coupled with geographic field observations, spatial analysis, and the detection of M. ulcerans in the environment. A full list of the free surface waters used for domestic activities was generated for a set of 34 villages, and several types of human behaviour associated with a higher risk of transmission were identified: (i) prolonged walking in water to reach cultivated fields, (ii) collecting water, (iii) and swimming. Combining the results of the different analyses identified the risk factor most strongly associated with Buruli ulcer was the frequency of contact with unprotected and natural water, particularly in regularly flooded or irrigated lowlands. We confirm that the use of clean water from drilled wells confers protection against Buruli ulcer. These specific and refined results provide a broader scope for the design of an appropriate preventive strategy including certain practices or infrastructures observed during our field investigations. This strategy could be improved by the addition of knowledge about irrigation practices and agricultural work in low-lying areas.

Molecular and epidemiological characterization of recurrent Mycobacterium ulcerans infections in Benin.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, an environmental mycobacterium. Although transmission of M. ulcerans remains poorly understood, the main identified risk factor for acquiring Buruli ulcer is living in proximity of potentially contaminated water sources. Knowledge about the clinical features of Buruli ulcer and its physiopathology is increasing, but little is known about recurrence due to reinfection. METHODOLOGY/PRINCIPAL FINDINGS: We describe two patients with Buruli ulcer recurrence due to reinfection with M. ulcerans, as demonstrated by comparisons of DNA from the strains isolated at the time of the first diagnosis and at recurrence. Based on the spatial distribution of M. ulcerans genotypes in this region and a detailed study of the behavior of these two patients with respect to sources of water as well as water bodies and streams, we formulated hypotheses concerning the sites at which they may have been contaminated. CONCLUSIONS/SIGNIFICANCE: Second episodes of Buruli ulcer may occur through reinfection, relapse or a paradoxical reaction. We formally demonstrated that the recurrence in these two patients was due to reinfection. Based on the sites at which the patients reported engaging in activities relating to water, we were able to identify possible sites of contamination. Our findings indicate that the non-random distribution of M. ulcerans genotypes in this region may provide useful information about activities at risk.

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.

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.

Buruli ulcer treatment: Rate of surgical intervention differs highly between treatment centers in West Africa.

BACKGROUND: Antibiotic treatment proved itself as the mainstay of treatment for Buruli ulcer disease. This neglected tropical disease is caused by Mycobacterium ulcerans. Surgery persists as an adjunct therapy intended to reduce the mycobacterial load. In an earlier clinical trial, patients benefited from delaying the decision to operate. Nevertheless, the rate of surgical interventions differs highly per clinic. METHODS: A retrospective study was conducted in six different Buruli ulcer (BU) treatment centers in Benin and Ghana. BU patients clinically diagnosed between January 2012 and December 2016 were included and surgical interventions during the follow-up period, at least one year after diagnosis, were recorded. Logistic regression analysis was carried out to estimate the effect of the treatment center on the decision to perform surgery, while controlling for interaction and confounders. RESULTS: A total of 1193 patients, 612 from Benin and 581 from Ghana, were included. In Benin, lesions were most frequently (42%) categorized as the most severe lesions (WHO criteria, category III), whereas in Ghana lesions were most frequently (44%) categorized as small lesions (WHO criteria, category I). In total 344 (29%) patients received surgical intervention. The percentage of patients receiving surgical intervention varied between hospitals from 1.5% to 72%. Patients treated in one of the centers in Benin were much more likely to have surgery compared to the clinic in Ghana with the lowest rate of surgical intervention (RR = 46.7 CI 95% [17.5-124.8]). Even after adjusting for confounders (severity of disease, age, sex, limitation of movement at joint at time of diagnosis, ulcer and critical sites), rates of surgical interventions varied highly. CONCLUSION: The decision to perform surgery to reduce the mycobacterial load in BU varies highly per clinic. Evidence based guidelines are needed to guide the role of surgery in the treatment of BU.

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.

Ischemic stroke due to embolic heart diseases and associated factors in Benin hospital setting.

INTRODUCTION: Poor access to cardiovascular checkups is a major cause of ignorance of embolic heart diseases as the etiology for ischemic stroke. OBJECTIVE: Study ischemic strokes due to embolic heart diseases and their associated factors. METHOD: It was a cross-sectional, prospective, descriptive and analytical study conducted from November 1, 2014 to August 31, 2015 on 104 patients with ischemic stroke confirmed through brain imaging. Embolic heart diseases included arrhythmia due to atrial fibrillation (AF), atrial flutter, myocardial infarction (MI), heart valve diseases and atrial septal aneurysm (ASA). The dependent variable was embolic heart disease while independent variables encompassed socio-demographic factors, patients' history, and lifestyle. Data analysis was carried out through SAS 9.3. RESULTS: The rate of embolic heart diseases (EHD) as etiology for ischemic stroke was 26% (28/104). AF accounted for 69% of embolic heart diseases and 22.8% of etiologies for ischemic stroke. Ischemic strokes prevalence was 3.5%, 2.5% and 1.2% respectively for heart valve diseases, MI and ASA. The associated factor was age (p=0.000). CONCLUSION: The diagnosis of a potential cardiac source of embolism is essential because of therapeutic and prognostic implications. Wherefore, there is need for cardiovascular examination particularly Holter ECG and cardiac ultrasound examination which are not always accessible to our populations.