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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. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium ulcerans infection, commonly known as Buruli ulcer (BU), is a debilitating neglected tropical disease. Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days, wound dressings and skin grafts for large ulcerations, and physical therapy to prevent functional limitations after care. In Benin, BU patient care is being integrated into the government health system. In this paper, we report on an innovative pilot program designed to introduce BU decentralization in Ouinhi district, one of Benin’s most endemic districts previously served by centralized hospital-based care. Methodology/Principal findings: We conducted intervention-oriented research implemented in four steps: baseline study, training of health district clinical staff, outreach education, outcome and impact assessments. Study results demonstrated that early BU lesions (71% of all detected cases) could be treated in the community following outreach education, and that most of the afflicted were willing to accept decentralized treatment. Ninety-three percent were successfully treated with antibiotics alone. The impact evaluation found that community confidence in decentralized BU care was greatly enhanced by clinic staff who came to be seen as having expertise in the care of most chronic wounds. Conclusions/Significance: This study documents a successful BU outreach and decentralized care program reaching early BU cases not previously treated by a proactive centralized BU program. The pilot program further demonstrates the added value of integrated wound management for NTD control. [ABSTRACT FROM AUTHOR]

Background: The control of soil-transmitted helminths (STH) is achieved through mass drug administration (MDA) with deworming medications targeting children and other high-risk groups. Recent evidence suggests that it may be possible to interrupt STH transmission by deworming individuals of all ages via community-wide MDA (cMDA). However, a change in delivery platforms will require altering implementation processes. Methods: We used process mapping, an operational research methodology, to describe the activities required for effective implementation of school-based and cMDA in 18 heterogenous areas and over three years in Benin, India, and Malawi. Planned activities were identified during workshops prior to initiation of a large cMDA trial (the DeWorm3 trial). The process maps were updated annually post-implementation, including adding or removing activities (e.g., adaptations) and determining whether activities occurred according to plan. Descriptive analyses were performed to quantify differences and similarities at baseline and over three implementation years. Comparative analyses were also conducted between study sites and areas implementing school-based vs. cMDA. Digitized process maps were developed to provide a visualization of MDA processes and inspected to identify implementation bottlenecks and inefficient activity flows. Results: Across three years and all clusters, implementation of cMDA required an average of 13 additional distinct activities and was adapted more often (5.2 adaptations per year) than school-based MDA. An average of 41% of activities across both MDA platforms did not occur according to planned timelines; however, deviations were often purposeful to improve implementation efficiency or effectiveness. Visualized process maps demonstrated that receipt of drugs at the local level may be an implementation bottleneck. Many activities rely on the effective setting of MDA dates and estimating quantity of drugs, suggesting that the timing of these activities is important to meet planned programmatic outcomes. Conclusion: Implementation processes were heterogenous across settings, suggesting that MDA is highly context and resource dependent and that there are many viable ways to implement MDA. Process mapping could be deployed to support a transition from a school-based control program to community-wide STH transmission interruption program and potentially to enable integration with other community-based campaigns. Trial registration: NCT03014167. Author summary: Research suggests that many contextual factors affect the success of mass drug administration (MDA) campaigns, yet detailed descriptions of implementation is absent from existing literature. We applied process mapping to describe and compare the flow of activities in MDA programs for soil-transmitted helminths. This represents the first known use of process mapping in community-based campaigns in low resource settings. Process maps were updated annually over three implementation years to identify activities that were added or removed from the MDA process, and whether implementation occurred according to plans. Findings suggest that MDA processes vary widely, are regularly adapted, and deviations from plans often occurred for purposeful reasons. Process mapping may be valuable for microplanning of MDA campaigns because it can generate granular detail about planned activities across national, sub-national and local levels. [ABSTRACT FROM AUTHOR]

Background: The DeWorm3 trial is a multi-country study testing the feasibility of interrupting transmission of soil-transmitted helminths by community-wide mass drug administration (cMDA). Treatment coverage during cMDA delivery was validated by in-person coverage evaluation surveys (CES) after each round of treatment. A mobile phone-based CES was carried out in India when access to households was restricted during the COVID-19 lockdown. Methods: Two focus group discussions were conducted with the survey implementers to document their experiences of conducting phone-based CES via mobile-phone voice calls. Principal findings: In the phone-based CES, only 56% of sampled households were reached compared to 89% during the in-person CES (89%). This was due to phone numbers being wrongly recorded, or calls being unanswered leading to a higher number of households that had to be sampled in order to achieve the sample size of 2,000 households in phone-based CES compared in-person CES (3,600 and 2,352 respectively). Although the phone-based CES took less time to complete than in person coverage evaluations, the surveyors highlighted the lack of gender representation among phone survey participants as it was mostly men who answered calls and were then interviewed. The surveyors also mentioned that eliciting responses to open-ended questions and confirming treatment compliance from every member of the household was challenging during phone based CES. These observations were confirmed by analysing the survey participation data which showed women's participation in CES was significantly lower in phone-based CES (66%) compared to in-person CES (94%) (Z = -22.38; p<0.01) and that a significantly higher proportion of households provided proxy responses in phone-based CES (51%) compared to in-person CES (21%) (Z = 20.23; p<0.01). Conclusions: The phone-based CES may be a viable option to evaluate treatment coverage but issues such as participation bias, gender inclusion, and quality of responses will need to be addressed to optimize this methodology. Author summary: The DeWorm3 Project is a community cluster-randomized trial being conducted in Benin, India, and Malawi to test the feasibility of interrupting STH transmission by six rounds of biannual community-wide MDA (cMDA). As recommended by the World Health Organization, coverage evaluation surveys (CES) among 2,000 households were carried out in the DeWorm3 Project to validate reported treatment coverage of cMDA. During the COVID-19 lockdown in April 2020, the fifth round of CES was conducted using mobile phones instead of in-person survey. In phone-based CES, only 56% of sampled households were reached compared to 89% during the in-person CES. This was due to phone numbers being wrongly recorded, or calls being unanswered leading to a higher number of households that had to be sampled in order to achieve the sample size of 2,000 households in phone-based CES compared in-person CES (3,600 and 2,352 respectively). Focus group discussions conducted with the interviewers showed that phone-based CES took less time to complete than in-person CES; mostly men responded to the interview call; and eliciting responses to open-ended questions and confirming treatment compliance from every member of the household was challenging. These observations were also confirmed by analysing the survey participation data that showed less participation by women and more proxy responses in the phone based CES. Collecting phone numbers of women and avoiding open-ended questions may improve the women's participation and quality of responses. [ABSTRACT FROM AUTHOR]

Background: Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer (BU) and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin. Methods: A six-month pilot project was undertaken with the objectives of establishing a therapeutic community and evaluating its impact on practitioner and patient relations. The project was designed and implemented by a team of social scientists working in concert with the current and previous director of a hospital serving patients suffering from advanced stage BU and other chronic ulcers. Qualitative research initially investigated patients’ understanding of their illness and its treatment, identified questions patients had about their hospitalization, and ascertained their level of social support. Newly designed question–answer health education sessions were developed. Following these hospital wide education sessions, open forums were held each week to provide an opportunity for patients and hospital staff to express concerns and render sources of discontent transparent. Patient group representatives then met with hospital staff to problem solve issues in a non-confrontational manner. Psychosocial support for individual patients was provided in a second intervention which took the form of drop-in counseling sessions with social scientists trained to serve as therapy facilitators and culture brokers. Results: Interviews with patients revealed that most patients had very little information about the identity of their illness and the duration of their treatment. This knowledge gap surprised clinic staff members, who assumed someone had provided this information. Individual counseling and weekly education sessions corrected this information gap and reduced patient concerns about their treatment and the status of their healing process. This led to positive changes in staff–patient interactions. There was widespread consensus among both patients and staff that the quality of communication had increased significantly. Open forums providing an opportunity for patients and staff to air grievances were likewise popular and patient representative meetings resulted in productive problem solving supported by the hospital administration. Some systemic problems, however, remained persistent challenges. Patients with ulcers unrelated to BU questioned why BU patients were receiving preferential treatment, given special medicines, and charged less for their care. The idea of subsidized treatment for one disease and not another was hard to justify, especially given that BU is not contagious. Conclusion: This pilot project illustrates the basic principles necessary for transforming long term residential hospitals into therapeutic communities. Although the focus of this case study was patients suffering from chronic ulcers, the model presented is relevant for other types of patients with cultural adaptation. [ABSTRACT FROM AUTHOR]

Background: Soil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting, resulting in an annual toll of 1.9 million Disability-Adjusted Life Years (DALYs). School-based deworming (SBD), via mass drug administration (MDA) campaigns with albendazole or mebendazole, has been recommended by the World Health Organization to reduce levels of morbidity due to STH in endemic areas. DeWorm3 is a cluster-randomized trial, conducted in three study sites in Benin, India, and Malawi, designed to assess the feasibility of interrupting STH transmission with community-wide MDA as a potential strategy to replace SBD. This analysis examines data from the DeWorm3 trial to quantify discrepancies between school-level reporting of SBD and gold standard individual-level survey reporting of SBD. Methodology/Principal findings: Population-weighted averages of school-level SBD calculated at the cluster level were compared to aggregated individual-level SBD estimates to produce a Mean Squared Error (MSE) estimate for each study site. In order to estimate individual-level SBD coverage, these MSE values were applied to SBD estimates from the control arm of the DeWorm3 trial, where only school-level reporting of SBD coverage had been collected. In each study site, SBD coverage in the school-level datasets was substantially higher than that obtained from individual-level datasets, indicating possible overestimation of school-level SBD coverage. When applying observed MSE to project expected coverages in the control arm, SBD coverage dropped from 89.1% to 70.5% (p-value < 0.001) in Benin, from 97.7% to 84.5% (p-value < 0.001) in India, and from 41.5% to 37.5% (p-value < 0.001) in Malawi. Conclusions/Significance: These estimates indicate that school-level SBD reporting is likely to significantly overestimate program coverage. These findings suggest that current SBD coverage estimates derived from school-based program data may substantially overestimate true pediatric deworming coverage within targeted communities. Trial registration: NCT03014167. Author summary: Soil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting. School-based deworming (SBD) via mass drug administration has been recommended by the World Health Organization to reduce levels of morbidity due to STH in endemic areas. This study examines discrepancies between school-level reporting of SBD and individual-level survey reporting of SBD from the DeWorm3 trial in Benin, India, and Malawi. Study cluster coverages were calculated for both school-level and individual-level data in the intervention arm and the differences between them were used to produce a mean squared error (MSE) statistic for each cluster. These values were then applied to the control arm, where only school-level data had been collected, to estimate individual-level data. In each study site, SBD coverage in the school-level data was substantially higher than in the individual-level data. When applying observed MSE to project individual-level data in the control arm, SBD coverage dropped from 89.1% to 70.5% in Benin, from 97.7% to 84.5% in India, and from 41.5% to 37.5% in Malawi. These estimates indicate that current SBD coverage estimates derived from school-level data may substantially overestimate true pediatric deworming coverage within targeted communities. [ABSTRACT FROM AUTHOR]

Background: Despite the significant success of deworming programs in reducing morbidity due to soil-transmitted helminth (STH) infections globally, efforts to achieve elimination of STH as a public health problem or to potentially interrupt transmission will require improving and intensifying surveillance. However, non-participation in surveillance threatens the ability of programs to adequately monitor program status and limited research has been conducted to investigate drivers of non-participation in stool-based surveillance. Methodology/Principal findings: This mixed-methods exploratory sequential study took place in Comé, Benin in association with the DeWorm3 Project. Six focus group discussions were conducted with individuals invited to participate in annual DeWorm3 stool surveillance. Thematic analysis was used to identify facilitators and barriers to participation and inform the quantitative analysis. A mixed-effects logistic regression model was built using baseline DeWorm3 survey data to identify factors associated with non-participation. Qualitative and quantitative findings were merged for interpretation. Among the 7,039 individuals invited to participate in baseline stool surveillance, the refusal rate was 8.1%. Qualitative themes included: community members weighing community-level benefits against individual-level risks, circulating rumors about misuse of stool samples, interpersonal communication with field agents, and cultural norms around handling adult feces. The quantitative analysis demonstrated that adults were significantly less likely to provide a stool sample than school-aged children (OR:0.69, 95%CI: 0.55–0.88), a finding that converged with the qualitative results. Individuals from areas in the highest quartile of population density were more likely to refuse to participate (OR:1.71, 95%CI:1.16–2.52). Several variables linked to community-affinity aligned with qualitative results; residing mainly in the community (OR:0.36, 95%CI:0.20–0.66) and having lived in the community for more than 10 years (OR:0.82, 95%CI:0.54–1.25) decreased likelihood of refusal. Conclusions/Significance: Optimizing STH surveillance will require that programs reimagine STH surveillance activities to address community concerns and ensure that no subpopulations are inadvertently excluded from surveillance data. Author summary: Soil-transmitted helminths (STH) are a group of intestinal parasites infecting approximately 1.5 billion people globally and resulting in significant adverse health outcomes. STH surveillance is conducted across endemic regions to assess prevalence of infection, to identify areas for mass drug administration implementation, and to monitor progress. The World Health Organization targets the elimination of STH as a public health problem in endemic settings with research currently being conducted to determine the feasibility of interrupting transmission of STH. In order to optimally design and manage programs towards these goals, and to verify whether elimination of STH as a public health problem has occurred, improvements in surveillance are needed. This mixed-methods study took place in Comé, Benin in association with the DeWorm3 Project, to identify drivers of non-participation in stool-based STH surveillance. This study found that certain individuals are more likely to refuse to participate in STH surveillance activities than others, including adults, individuals in urban areas, short-term residents in communities, and those perceiving their families to not be at risk for STH. As STH surveillance is intensified, programs will need to reimagine how surveillance is conducted to address community concerns and ensure that no subpopulations are inadvertently excluded from surveillance data. [ABSTRACT FROM AUTHOR]

Background: Despite several years of school-based MDA implementation, STH infections remain an important public health problem in Benin, with a country-wide prevalence of 20% in 2015. The DeWorm3 study is designed to assess the feasibility of using community-based MDA with albendazole to interrupt the transmission of STH, through a series of cluster-randomized trials in Benin, India and Malawi. We used the pre-treatment baseline survey data to describe and analyze the factors associated with STH infection in Comé, the study site of the DeWorm3 project in Benin. These data will improve understanding of the challenges that need to be addressed in order to eliminate STH as a public health problem in Benin. Methods: Between March and April 2018, the prevalence of STH (hookworm spp., Ascaris and Trichuris trichiura) was assessed by Kato-Katz in stool samples collected from 6,153 residents in the community of Comé, Benin using a stratified random sampling procedure. A standardized survey questionnaire was used to collect information from individual households concerning factors potentially associated with the presence and intensity of STH infections in pre-school (PSAC, aged 1–4), school-aged children (SAC, aged 5–14) and adults (aged 15 and above). Multilevel mixed-effects models were used to assess associations between these factors and STH infection. Results: The overall prevalence of STH infection was 5.3%; 3.2% hookworm spp., 2.1% Ascaris lumbricoides and 0.1% Trichuris. Hookworm spp. were more prevalent in adults than in SAC (4.4% versus 2.0%, respectively; p = 0.0001) and PSAC (4.4% versus 1.0%, respectively; p<0.0001), whilst Ascaris lumbricoides was more prevalent in SAC than in adults (3.0% versus 1.7%, respectively; p = 0.004). Being PSAC (adjusted Odds Ratio (aOR) = 0.2, p< 0.001; adjusted Infection Intensity Ratio (aIIR) = 0.1, p<0.001) or SAC (aOR = 0.5, p = 0.008; aIIR = 0.3, p = 0.01), being a female (aOR = 0.6, p = 0.004; aIIR = 0.3, p = 0.001), and having received deworming treatment the previous year (aOR = 0.4, p< 0.002; aIIR = 0.2, p<0.001) were associated with a lower prevalence and intensity of hookworm infection. Lower income (lowest quintile: aOR = 5.0, p<0.001, 2nd quintile aOR = 3.6, p = 0.001 and 3rd quintile aOR = 2.5, p = 0.02), being a farmer (aOR = 1.8, p = 0.02), medium population density (aOR = 2.6, p = 0.01), and open defecation (aOR = 0.5, p = 0.04) were associated with a higher prevalence of hookworm infection. Lower education—no education, primary or secondary school- (aIIR = 40.1, p = 0.01; aIIR = 30.9, p = 0.02; aIIR = 19.3, p = 0.04, respectively), farming (aIIR = 3.9, p = 0.002), natural flooring (aIIR = 0.2, p = 0.06), peri-urban settings (aIIR = 6.2, 95%CI 1.82–20.90, p = 0.003), and unimproved water source more than 30 minutes from the household (aIIR = 13.5, p = 0.02) were associated with a higher intensity of hookworm infection. Improved and unshared toilet was associated with lower intensity of hookworm infections (aIIR = 0.2, p = 0.01). SAC had a higher odds of Ascaris lumbricoides infection than adults (aOR = 2.0, p = 0.01) and females had a lower odds of infection (aOR = 0.5, p = 0.02). Conclusion: Hookworm spp. are the most prevalent STH in Comé, with a persistent reservoir in adults that is not addressed by current control measures based on school MDA. Expanding MDA to target adults and PSAC is necessary to substantially impact population prevalence, particularly for hookworm. Trial registration: ClinicalTrials.gov NCT03014167. Author summary: Despite several years of deworming campaigns targeting school-aged children, soil-transmitted helminths (STH) remains a public health problem in most developing countries, including Benin. The burden is mostly on children and pregnant women, but also on the whole society. Soil-transmitted helminths are responsible for malnutrition, anemia, low birth weight, cognitive impairment, decrease of school performance, and subsequently economic loss. The current strategy of the Benin National Neglected Tropical Diseases (NTD) Program is to achieve STH control through mass drug administration campaigns targeting school-aged children (SAC). The baseline data of Deworm3 study, implemented in Comé, southern Benin, as part of a multicountry (Benin, Malawi and India) STH elimination trial, shows that previous school deworming campaigns decreased STH prevalence; however there is a persistent reservoir of STH infection in adults and pre-school aged children that should be targeted for a better impact. In order to eliminate STH as a public health problem, Benin National NTD Program would need to increase its target population, from the SAC to the whole community. The future results of Deworm3 trial would demonstrate whether the STH elimination goal STH using community wide mass drug administration would be achievable. [ABSTRACT FROM AUTHOR]

Background: An estimated 30% of women in Sub-Saharan Africa suffer from soil-transmitted helminth infection during pregnancy (SHIP), which has been shown to increase risk of pre-term birth, low birth weight, and maternal anemia. A previous study in Benin found that SHIP was associated with impaired cognitive and gross motor development scores in 635 one-year-old children. The objective of the present study was to follow children prospectively to investigate whether the association between SHIP and child neurocognitive and behavioral development persisted at age six. Principal findings: Our prospective child cohort included 487 live-born singletons of pregnant women enrolled in the Malaria in Pregnancy Preventive Alternative Drugs clinical trial in Allada, Benin. SHIP was assessed at three antenatal visits (ANVs) through collection and testing of stool samples. Neurocognitive and behavioral development was assessed in six-year-old children by trained investigators using the Kaufman Assessment Battery for Children 2nd edition and the parent-reported Strengths and Difficulties Questionnaire (SDQ). Multiple linear regression models generated coefficients and 95% confidence intervals and potential mediating factors were tested. Prevalence of SHIP was 13% at the 1st ANV, 9% at the 2nd ANV, and 1% at delivery. SHIP was not associated with low neurocognitive scores in children at six years. Higher SDQ internalizing scores, indicating increased emotional impairments in children, were associated with helminth infection at the 2nd ANV/delivery 1.07 (95% CI 0.15, 2.00) and at least once during pregnancy 0.79 (95% CI 0.12, 1.46) in adjusted models. Mediation analysis did not reveal significant indirect effects of several mediators on this association. Conclusions: Our study shows that while SHIP is not associated with impaired long-term neurocognitive development, infections may have significant negative impacts on emotional development in six-year-old children. SHIP remains a critical public health issue, and adequate prevention and treatment protocols should be enforced in low- and middle-income countries. Author summary: Soil-transmitted helminth infections impact 1.5 billion individuals, primarily in low- and middle- income countries, each year and contribute to malnutrition, anemia, and impaired neurocognitive development in children. However, these infections in pregnancy and their impact on offspring have been less studied. One previous study found associations between soil-transmitted helminth infection during pregnancy and impaired cognitive functioning in offspring one year after birth. The current study aimed to follow these children prospectively until six years in order to confirm whether these associations persisted or not. Infections during pregnancy were no longer associated with cognitive or motor functioning in children; however, infections were associated with impaired behavioral development. Animal-based models have hypothesized maternal inflammation and poor birth outcomes to be the mechanisms behind this relationship; however, our findings did not support these mechanisms. This is one of very few prospective cohort studies in Sub-Saharan Africa to investigate these associations, and more research is needed to corroborate results. Limitations include limited power and the possibility that results are due to chance from multiple statistical tests. Adequate and accessible prevention and treatment efforts in pregnancy and childhood should be provided to populations in low- and middle- income countries at high risk of infection. [ABSTRACT FROM AUTHOR]

Through international trades, Europe, Africa and South America share a long history of exchanges, potentially of pathogens. We used the worldwide parasite Toxoplasma gondii to test the hypothesis of a historical influence on pathogen genetic diversity in Benin, a West African country with a longstanding sea trade history. In Africa, T. gondii spatial structure is still non-uniformly studied and very few articles have reported strain genetic diversity in fauna and clinical forms of human toxoplasmosis so far, even in African diaspora. Sera from 758 domestic animals (mainly poultry) in two coastal areas (Cotonou and Ouidah) and two inland areas (Parakou and Natitingou) were tested for T. gondii antibodies using a Modified Agglutination Test (MAT). The hearts and brains of 69 seropositive animals were collected for parasite isolation in a mouse bioassay. Forty-five strains were obtained and 39 genotypes could be described via 15-microsatellite genotyping, with a predominance of the autochthonous African lineage Africa 1 (36/39). The remaining genotypes were Africa 4 variant TUB2 (1/39) and two identical isolates (clone) of Type III (2/39). No difference in terms of genotype distribution between inland and coastal sampling sites was found. In particular, contrarily to what has been described in Senegal, no type II (mostly present in Europe) was isolated in poultry from coastal cities. This result seems to refute a possible role of European maritime trade in Benin despite it was one of the most important hubs during the slave trade period. However, the presence of the Africa 1 genotype in Brazil, predominant in Benin, and genetic analyses suggest that the triangular trade was a route for the intercontinental dissemination of genetic strains from Africa to South America. This supports the possibility of contamination in humans and animals with potentially imported virulent strains. Author summary: The parasite Toxoplasma gondii is a worldwide-distributed pathogen, able to infect all warm-blooded animals. There are important differences in the clinical expression of the infection in direct relation with the parasite genetic profile. In some regions, the geographical structuration of its genetic diversity points towards a crucial role of human activities in some lineages introduction or sorting. Benin is a West African country with a history of extensive transcontinental exchanges. Our genetic study of Toxoplasma in Benin shows a surprisingly homogeneous and autochthonous diversity, which contrasts with previous studies from other West and Central African countries. In Benin, the absence of European Toxoplasma lineages may be explained by the extreme rarity of the house mouse (Mus musculus), a host species that was previously described as highly susceptible to the mouse-virulent African strains. Might Benin be the origin region for the Africa 1 lineage, our results suggest that Guinean Gulf coasts may be a starting point of this lineage towards South America, especially Brazil, during the slave trade. As a whole, the present study provides further insights into the recent evolutionary history of Toxoplasma gondii and its consequences on human and animal health. [ABSTRACT FROM AUTHOR]

Global efforts to control morbidity associated with soil-transmitted helminth infections (STH) have focused largely on the targeted treatment of high-risk groups, including children and pregnant women. However, it is not clear when such programs can be discontinued and there are concerns about the sustainability of current STH control programs. The DeWorm3 project is a large multi-country community cluster randomized trial in Benin, India and Malawi designed to determine the feasibility of interrupting the transmission of STH using community-wide delivery of mass drug administration (MDA) with anthelmintics over multiple rounds. Here, we present baseline data and estimate key epidemiological parameters important in determining the likelihood of transmission interruption in the DeWorm3 trial. A baseline census was conducted in October-December 2017 in India, November-December 2017 in Malawi and in January-February 2018 in Benin. The baseline census enumerated all members of each household and collected demographic data and information on occupation, assets, and access to water, sanitation and hygiene (WASH). Each study site was divided into 40 clusters of at least 1,650 individuals per cluster. Clusters were randomized to receive twice yearly community-wide MDA with albendazole (GSK) targeting eligible individuals of all ages (20 clusters), or to receive the standard-of-care deworming program targeting children provided in each country. In each site, a randomly selected group of 150 individuals per cluster (6,000 total per site) was selected from the baseline census using stratified random sampling, and each individual provided a single stool sample for analysis of STH infection using the Kato-Katz technique. Study site, household and individual characteristics were summarized as appropriate. We estimated key epidemiological parameters including the force of infection and the degree of parasite aggregation within the population. The DeWorm3 sites range in population from 94,969 to 140,932. The population age distribution varied significantly by site, with the highest proportion of infants and young children in Malawi and the highest proportion of adults in India. The baseline age- and cluster-weighted prevalence, as measured by Kato-Katz, varied across sites and by species, Baseline hookworm prevalence in India was 21.4% (95% CI: 20.4–22.4%), while prevalence of Ascaris and Trichuris by Kato-Katz was low (0.1% and 0.3% overall). In Malawi, the overall age- and cluster-weighted STH prevalence was 7.7% (95% CI: 7.1–8.4%) predominantly driven by hookworm infections (7.4%) while Ascaris (0.1%) and Trichuris (0.3%) infections were rare. In Benin, the overall age- and cluster-weighted prevalence was significantly lower (5.6%, 95% CI: 5.1–6.2%) and Ascaris (2.0%, 95% CI: 1.6–2.3%) was more common than in other sites. Ascaris infections were more likely to be moderate- or heavy-intensity (43.7%, unweighted) compared to hookworm (5.0%). The force of infection for hookworm was highest in adults in India and Malawi but appeared relatively stable across age groups in Benin. These data demonstrate the significant variability between the sites in terms of demography, socio-economic status and environmental characteristics. In addition, the baseline prevalence and intensity data from DeWorm3 suggest that each site has unique epidemiologic characteristics that will be critical in determining correlates of achieving STH transmission interruption in the DeWorm3 trial. Trial registration: The trial was registered at ClinicalTrials.gov (NCT03014167). Author summary: Intestinal parasitic worms, soil-transmitted helminths, are among the most common infectious organisms of humans. In many low-resource settings, these infections result in considerable morbidity, including reductions in childhood growth and development, increased risk of anemia and reductions in future educational achievement and income earning potential. The current global strategy for controlling these infections is through routine deworming of school and pre-school aged children as well as pregnant women. Since many adults and non-school going children are infected with these parasites, the current strategy does not prevent the rapid reinfection of individuals despite repeated treatment. The DeWorm3 trial is a large multi-country trial being conducted in Benin, India and Malawi to test the feasibility of using mass drug administration of deworming medications to all individuals in a community to interrupt these infections in some geographic areas. Here we present baseline data from these communities and estimate the transmission potential of these infections at each of the sites. [ABSTRACT FROM AUTHOR]

The World Health Organization's Neglected Tropical Disease Roadmap has accelerated progress towards eliminating select neglected tropical diseases (NTDs). This momentum has catalyzed research to determine the feasibility of interrupting transmission of soil-transmitted helminths (STH) using community-wide mass drug administration (MDA). This study aims to identify potential gender-specific facilitators and barriers to accessing and participating in community-wide STH MDA, with the goal of ensuring programs are equitable and maximize the probability of interrupting STH transmission. This research was conducted prior to the launch of community-wide MDA for STH in Comé, Benin. A total of 10 focus group discussions (FGDs) were conducted separately among 40 men, 38 women, and 15 community drug distributors (CDDs). Salient themes included: both men and women believe that community-wide MDA would reduce the financial burden associated with self-treatment, particularly for low income adults. Community members believe MDA should be packaged alongside water, sanitation, and other health services. Women feel past community-wide programs have been disorganized and are concerned these distributions will be similar. Women also expressed interest in increased engagement in the implementation of future community-based public health programs. Men often did not perceive themselves to be at great risk for STH infection and did not express a high demand for treatment. Finally, the barriers discussed by CDDs generally did not align with gender-specific concerns, but rather represented concerns shared by both genders. A door-to-door distribution strategy for STH MDA is preferred by women in this study, as this platform empowers women to participate as health decision makers for their family. In addition, involving women in planning and implementation of community-wide programs may help to increase treatment coverage and compliance. Author summary: Soil-transmitted helminths (STH) affect an estimated 1.5 billion people globally. The DeWorm3 Project is investigating if it is possible to interrupt transmission of STH with community-wide deworming of individuals of all ages. We conducted focus group discussions with adult men, women, and community drug distributors (CDDs) in Comé, Benin to identify gender-specific facilitators and barriers to accessing and participating in community-wide mass drug administration (MDA) programs. Our findings suggest that door-to-door community-wide MDA may not only improve MDA treatment coverage by increasing access but may also empower women by facilitating increased decision making on behalf of their regarding who is treated and where. Additionally, women may be an untapped resource for strategically reaching missed populations and women reported seeking increased involvement within the deworming of their families. Men did not perceive themselves to be at risk and thus did not have high demand for deworming. Both genders reported that they struggle to afford deworming drugs outside of MDA and that MDA coverage would be higher if treatment was integrated with water and sanitation services. Finally, CDDs generally identified only barriers and facilitators to MDA that were shared by both genders and may require more training to ensure MDA programs are equitable and effectively engage all at risk populations. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium ulcerans is the causative agent of the necrotizing skin disease Buruli ulcer (BU), which has been reported from over 30 countries worldwide. The majority of notified patients come from West African countries, such as Côte d'Ivoire, Ghana, Benin and Cameroon. All clinical isolates of M. ulcerans from these countries are closely related and their genomes differ only in a limited number of single nucleotide polymorphisms (SNPs). Methodology/Principal Findings: We performed a molecular epidemiological study with clinical isolates from patients from two distinct BU endemic regions of Cameroon, the Nyong and the Mapé river basins. Whole genome sequencing of the M. ulcerans strains from these two BU endemic areas revealed the presence of two phylogenetically distinct clonal complexes. The strains from the Nyong river basin were genetically more diverse and less closely related to the M. ulcerans strain circulating in Ghana and Benin than the strains causing BU in the Mapé river basin. Conclusions: Our comparative genomic analysis revealed that M. ulcerans clones diversify locally by the accumulation of SNPs. Case isolates coming from more recently emerging BU endemic areas, such as the Mapé river basin, may be less diverse than populations from longer standing disease foci, such as the Nyong river basin. Exchange of strains between distinct endemic areas seems to be rare and local clonal complexes can be easily distinguished by whole genome sequencing. Author Summary: Buruli ulcer (BU) is a progressively necrotizing disease of the skin, caused by infection with Mycobacterium ulcerans. BU occurs very focally with highest incidence in West Africa. The mode of transmission and the nature and role of potential environmental reservoirs are currently not entirely understood. In this study we sequenced whole genomes of sets of M. ulcerans case isolates from two BU endemic regions in Cameroon. We identified two distinct phylogenetic lineages, which directly correlated with the two endemic regions. Furthermore, we showed that the genetic diversity of M. ulcerans is higher in the older endemic region of Cameroon (Nyong river basin) compared to the more recently emerged infection focus in the same country (Mapé river basin). Together, our results demonstrate that M. ulcerans is developing local clonal complexes by the accumulation of single nucleotide polymorphisms (SNPs) and that these complexes often remain confined to individual endemic foci. The gene encoding for rpoB, which is known to harbour drug resistance mutations against rifampicin in M. tuberculosis, was not affected by SNPs in any of the analysed M. ulcerans strains. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of helminth infection during pregnancy on the cognitive and motor functions of one-year-old children. Methods: Six hundred and thirty five singletons born to pregnant women enrolled before 29 weeks of gestation in a trial comparing two intermittent preventive treatments for malaria were assessed for cognitive and motor functions using the Mullen Scales of Early Learning, in the TOVI study, at twelve months of age in the district of Allada in Benin. Stool samples of pregnant women were collected at recruitment, second antenatal care (ANC) visit (at least one month after recruitment) and just before delivery, and were tested for helminths using the Kato-Katz technique. All pregnant women were administered a total of 600 mg of mebendazole (100 mg two times daily for 3 days) to be taken after the first ANC visit. The intake was not directly observed. Results: Prevalence of helminth infection was 11.5%, 7.5% and 3.0% at first ANC visit, second ANC visit and at delivery, respectively. Children of mothers who were infected with hookworms at the first ANC visit had 4.9 (95% CI: 1.3–8.6) lower mean gross motor scores compared to those whose mothers were not infected with hookworms at the first ANC visit, in the adjusted model. Helminth infection at least once during pregnancy was associated with infant cognitive and gross motor functions after adjusting for maternal education, gravidity, child sex, family possessions, and quality of the home stimulation. Conclusion: Helminth infection during pregnancy is associated with poor cognitive and gross motor outcomes in infants. Measures to prevent helminth infection during pregnancy should be reinforced. Author Summary: The WHO recommends anthelmintics for pregnant women after their first trimester but the benefits remain unequivocal. Although the consequences of helminth infection during pregnancy on the health of pregnant women have been well studied, the impact on the early development of offspring has been understudied. Studies suggest that helminth infection in children may be associated with poor cognitive development, but very little is known whether a similar consequence exists for offspring of women infected with helminths during pregnancy. From our study, we found that women who had intestinal worm infection at least once during pregnancy, had children with lower cognitive and motor scores. Moreover, hookworm infection in pregnant women prior to receiving anthelminthic treatment was associated with poor gross motor functions of children at one-year of age. Based on the findings of this study, measures to prevent helminth infections during pregnancy should be reinforced. [ABSTRACT FROM AUTHOR]

Nigeria is known to be endemic to Buruli ulcer, but epidemiological data are remarkably rare. Here, we present a large cohort of 127 PCR-confirmed M. ulcerans infection patients coming from Nigeria and treated in a neighbouring country, Benin. Severe lesions and delay of consultation are factors that should encourage establishment of a treatment centre in South Western Nigeria. Author Summary: Buruli ulcer is known to be endemic to Nigeria since at least 1967, however epidemiological data are rare and incomplete. In total, only 51 Buruli ulcer patients were described in 45 years, all found in Southern Nigeria. This is likely a result of the lack of adequate public health structures dedicated to the diagnosis and treatment of Buruli ulcer in the region. Here, we report a large cohort of 127 PCR-confirmed Nigerian patients treated in neighbouring Benin. Nigerian patients presented mainly severe lesions of Buruli ulcer, and this is linked by the fact that period prior consultation is delayed (24% of the patients waited more than one year between the beginning of the lesion and the consultation in the Buruli ulcer treatment centre in Pobè). We identify South Western Nigeria as an important endemic area for Buruli ulcer, and believe our results will be of importance to Nigerian health authorities, the World Health Organisation and NGO's involved in management of Buruli ulcer. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer may induce severe disabilities impacting on a person's well-being and quality of life. Information about long-term disabilities and participation restrictions is scanty. The objective of this study was to gain insight into participation restrictions among former Buruli ulcer patients in Ghana and Benin. Methods: In this cross-sectional study, former Buruli ulcer patients were interviewed using the Participation Scale, the Buruli Ulcer Functional Limitation Score to measure functional limitations, and the Explanatory Model Interview Catalogue to measure perceived stigma. Healthy community controls were also interviewed using the Participation Scale. Trained native interviewers conducted the interviews. Former Buruli ulcer patients were eligible for inclusion if they had been treated between 2005 and 2011, had ended treatment at least 3 months before the interview, and were at least 15 years of age. Results: In total, 143 former Buruli ulcer patients and 106 community controls from Ghana and Benin were included in the study. Participation restrictions were experienced by 67 former patients (median score, 30, IQR; 23;43) while 76 participated in social life without problems (median score 5, IQR; 2;9). Most restrictions encountered related to employment. Linear regression showed being female, perceived stigma, functional limitations, and larger lesions (category II) as predictors of more participation restrictions. Conclusion: Persisting participation restrictions were experienced by former BU patients in Ghana and Benin. Most important predictors of participation restrictions were being female, perceived stigma, functional limitations and larger lesions. Author Summary: Disabilities among Buruli ulcer patients remain a problem. Previous studies revealed contractures, deformities and functional limitations in daily life after treatment. According to the International Classification of Functioning, Disability and Health, disabilities occur not only at the physical and activity level but at the participation level (participation restrictions) as well. The latter are the social consequences of the disease such as problems in relationships, going to festivals and visiting public places. This study focused on participation restrictions by using the Participation Scale among former Buruli ulcer patients and healthy persons residing in two areas endemic for Buruli ulcer in Ghana and Benin. This study showed that almost half of the former Buruli ulcer patients encountered problems in social life, especially related to employment. In addition, the results suggest that being female, perceived stigma, functional limitations and a larger lesion (category II) predict participation restrictions. These findings indicate that rehabilitation programs should not only focus on physical disabilities but also on participation after completion of medical treatment. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer is a stigmatising disease treated with antibiotics and wound care, and sometimes surgical intervention is necessary. Permanent limitations in daily activities are a common long term consequence. It is unknown to what extent patients perceive problems in participation in social activities. The psychometric properties of the Participation Scale used in other disabling diseases, such as leprosy, was assessed for use in former Buruli ulcer patients. Methods: Former Buruli ulcer patients in Ghana and Benin, their relatives, and healthy community controls were interviewed using the Participation Scale, Buruli Ulcer Functional Limitation Score, and the Explanatory Model Interview Catalogue to measure stigma. The Participation Scale was tested for the following psychometric properties: discrimination, floor and ceiling effects, internal consistency, inter-item correlation, item-total correlation and construct validity. Results: In total 386 participants (143 former Buruli ulcer patients with their relatives (137) and 106 community controls) were included in the study. The Participation Scale displayed good discrimination between former Buruli ulcer patients and healthy community controls. No floor and ceiling effects were found. Internal consistency (Cronbach's alpha) was 0.88. In Ghana, mean inter-item correlation of 0.29 and item-total correlations ranging from 0.10 to 0.69 were found while in Benin, a mean inter-item correlation of 0.28 was reported with item-total correlations ranging from −0.08 to 0.79. With respect to construct validity, 4 out of 6 hypotheses were not rejected, though correlations between various constructs differed between countries. Conclusion: The results indicate the Participation Scale has acceptable psychometric properties and can be used for Buruli ulcer patients in Ghana and Benin. Future studies can use this Participation Scale to evaluate the long term restrictions in participation in daily social activities of former BU patients. Author Summary: Buruli ulcer is a stigmatising condition caused by infection with Mycobacterium ulcerans. Besides the long term medical consequences, Buruli ulcer may lead to participation restrictions in social life. The Participation Scale intends to assess perceived participation restrictions; however, this instrument has been developed in patients affected by leprosy and other disabling conditions, and has never been used before among Buruli ulcer patients. We aimed to analyze the reliability and validity of the Participation Scale among former Buruli ulcer patients in Ghana and Benin. This study included former Buruli ulcer patients from 2 different treatment sites, along with their relatives and healthy community controls residing in similar geographical areas. Former Buruli ulcer patients were interviewed using the Participation Scale, Buruli Ulcer Functional Limitation Score, and the Explanatory Model Interview Catalogue to measure stigma. Relatives and healthy community controls were interviewed using the Participation Scale. We tested the Participation Scale for discrimination, floor and ceiling effects, internal consistency, inter-item correlation, item-total correlation and construct validity. The results of the analysis suggest that the Participation Scale has acceptable psychometric properties. As such, the instrument can be used to assess participation restrictions among former Buruli ulcer patients in Ghana and Benin. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Usually BU begins as a painless nodule, plaque or edema, ultimately developing into an ulcer. The high number of patients presenting with ulcers in an advanced stage is striking. Such late presentation will complicate treatment and have long-term disabilities as a consequence. The disease is mainly endemic in West Africa. The primary strategy for control of this disease is early detection using community village volunteers. Methodology/Principal Findings: In this retrospective, observational study, information regarding Buruli ulcer patients that reported to one of the four BU centers in Bénin between January 2008 and December 2010 was collected using the WHO/BU01 forms. Information used from these forms included general characteristics of the patient, the results of diagnostic tests, the presence of functional limitations at start of treatment, lesion size, patient delay and the referral system. The role of the different referral systems on the stage of disease at presentation in the hospital was analyzed by a logistic regression analysis. About a quarter of the patients (26.5%) were referred to the hospital by the community health volunteers. In our data set, patients referred to the hospital by community health volunteers appeared to be in an earlier stage of disease than patients referred by other methods, but after adjustment by the regression analysis for the health center, this effect could no longer be seen. The Polymerase Chain Reaction (PCR) for IS2404 positivity rate among patients referred by the community health volunteers was not systematically lower than in patients referred by other systems. Conclusions/Significance: This study clarifies the role played by community health volunteers in Bénin, and shows that they play an important role in the control of BU. Author Summary: Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Usually, the number of patients presenting with ulcers in an advanced stage is high. This complicates treatment and increases the risk of disabilities. The disease is endemic mainly in West Africa. The primary strategy for control is early detection using community village volunteers. In Bénin, data was collected to understand the role of the different referral systems on the stage of disease at presentation in the hospital and the diagnostic precision. About a quarter of the patients were referred to the hospital by the community health volunteers. Community health volunteers referred patients more frequently in an earlier stage of disease. The PCR confirmation rate among patients referred by the community health volunteers was not systematically lower than in patients referred by other systems. We found that community health volunteers played an important role in the referral system of BU patients in Bénin. This information is relevant for health care programs attempting to control BU but may also be relevant for health care programs working on other diseases in areas with restricted resources. [ABSTRACT FROM AUTHOR]