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Morbidity burden of lymphatic filariasis (LF) relies on the information from the Mass Drug Administration (MDA) programme where Community Health Volunteers (CHVs) passively report cases identified. Consequently, the exact prevalence of morbidity cases is not always accurate. The use of mobile phone technology to report morbidity cases was piloted in Ghana using a text-based short messaging service (SMS) tool by CHVs. Though successful, illiterate CHVs could not effectively use the SMS tool. The aim of this study was to evaluate the use of a mobile phone-based Interactive Voice Response System (mIVRS) by CHVs in reporting LF morbidity cases and acute dermatolymphangioadenitis (ADLA) attacks in Ghana. The mIVRS was designed as a surveillance tool to capture LF data in Kassena Nankana Districts of Ghana. One hundred CHVs were trained to identify and report lymphedema and hydrocele cases as well as ADLA attacks by calling a hotline linked to the mIVRS. The system asked a series of questions about the disease condition. The ability of the CHV to report accurately was assessed and the data from the mIVRS were compared with the paper records from the CHVs and existing MDA programme records from the same communities and period. Higher numbers of lymphedema and hydrocele cases were recorded by the CHVs using the mIVRS (n = 590 and n = 103) compared to the paper-based reporting (n = 417 and n = 76) and the MDA records (n = 154 and n = 84). Female CHVs, CHVs above 40 years, and CHVs with higher educational levels were better at paper-based reporting (P = 0.007, P = 0.001, P = 0.049 respectively). The system, when fully developed and linked to national databases, may help to overcome underreporting of morbidity cases and ADLA attacks in endemic communities. The system has the potential to be further expanded to other diseases. Author summary: The goal towards the elimination of lymphatic filariasis as indicated by Global Programme to Eliminate Lymphatic Filariasis (GPELF) is to identify persons with morbidity such as lymphedema and hydrocele and manage their condition to make their lives better. Patients who experience acute attacks also need to be identified and given help or treatment. The number of lymphedema and hydrocele patients in lymphatic filariasis endemic communities are usually underreported. This consequently affects their management. Therefore, an innovative tool such as a mobile phone-based interactive voice response system (mIVRS) that can give accurate information on morbidity cases in real time and also reduce the underreporting of cases is needed. In this study, more morbidity cases and more acute attacks were reported using mIVRS than with the traditional methods. If implemented, this innovative method of reporting cases and acute attacks may help programme managers to ensure that the patients are identified to receive care. It can also be extended to other infectious and non-infectious diseases. [ABSTRACT FROM AUTHOR]

Background: Snake bite envenoming (SBE) is one neglected tropical disease that has not received the needed attention. The sequelae of burdensome disability and mortality impact the socioeconomic life of communities adversely with little documentation of SBE in health facility records in Ghana. This study details SBE and snake distribution, habits/habitats, type of venom expressed and clinical manifestations. Methodology: We conducted a structured thematic desk review of peer reviewed papers, books and reports from repositories including PubMed, WHO and WCH using bibliographic software EndNote and search engine Google Scholar with the following key words; snakes, medical importance, snake bites, venom and venom type, envenomation, symptoms and signs, vaccines, venom expenditure, strike behaviour and venom-metering + Ghana, West Africa, Africa, World. We also reviewed data from the District Health Information Management System (DHIMS) of the Ghana Health Service (GHS). Outcome variables were organized as follows: common name (s), species, habitat/habit, species-specific toxin, clinical manifestation, antivenom availability, WHO category. Findings: Snake bites and SBE were grouped by the activity of the expressed venom into neurotoxic, cardiotoxic, haemorrhagic, cytotoxic, myotoxic, nephrotoxic and procoagulants. Neurotoxic snake bites were largely due to elapids. Expressed venoms with cardiotoxic, haemorrhagic, nephrotoxic and procoagulant activities principally belonged to the family Viperidae. Snakes with venoms showing myotoxic activity were largely alien to Ghana and the West African sub-region. Venoms showing cytotoxic activity are expressed by a wide range of snakes though more prevalent among the Viperidae family. Snakes with neurotoxic and haemorrhagic venom activities are prevalent across all the agro-ecological zones in Ghana. Conclusion/Significance: Understanding the characteristics of snakes and their venoms is useful in the management of SBE. The distribution of snakes by their expressed venoms across the agro-ecological zones is also instructive to species identification and diagnosis of SBE. Author summary: We observed rudimentary data on snake bites and a paucity of venom characterization in the health records of patients in health facilities in Ghana. Knowledge of the distribution of snake species across the agro-ecological zones of the country was also limited. We set out to complement this data by doing a structured thematic desk review of peer reviewed papers, books and reports from repositories including PubMed, WHO and the District Health Information Management System (DHIMS) of the Ghana Health Service (GHS). Our findings revealed that, snake bites were largely grouped according to the activity of the expressed venom into neurotoxic, cardiotoxic, haemorrhagic, cytotoxic, myotoxic and in some documentations nephrotoxic and procoagulants. Neurotoxic snake bites were largely due to cobras and mambas. Snake expressing venoms with cardiotoxic, haemorrhagic, nephrotoxic and procoagulant activities were principally vipers. Snakes with venoms showing myotoxic activity were largely alien to Ghana and the West African sub-region. Venoms showing cytotoxic activity are expressed by a wide range of snakes though more prevalent among vipers. In Ghana, snakes expressing venoms with neurotoxic and haemorrhagic activities are prevalent across all the agro-ecological zones of the country. We identified 3 antivenoms registered by the Ghana Food and Drug Authority. [ABSTRACT FROM AUTHOR]

Introduction: Act to End NTDs | West, a USAID-funded program that supports national governments to eliminate or control five neglected tropical diseases (NTDs) in West Africa including trachoma, lymphatic filariasis (LF), onchocerciasis, schistosomiasis and soil-transmitted helminthiasis, conducted a gender and social inclusion analysis to determine how NTDs differentially impact various populations and how gender and social norms impact NTD programs to inform future programming. Methods: The study used a mixed methods approach including a literature review; primary qualitative data collection; and monitoring data in Côte d'Ivoire, Sierra Leone, and Ghana. Results: Women and girls face additional health risks from many NTDs compared to men and boys. In addition to differential health burden, the social and economic impacts of NTD-related disability or infertility can be particularly dire for women and girls. Men were somewhat less likely to participate in mass drug administration (MDAs) due to: lack of information about campaigns, lack of access due to work, and higher levels of mistrust of the government and concerns about side effects of the medicines. Pregnant and breastfeeding women were sometimes excluded by community drug distributors (CDDs) from certain types of MDAs for which they are eligible. Training participation rates for CDDs and supervisors were universally higher for men than women, even though feedback on the effectiveness of female CDDs was overwhelmingly positive, and female CDDs often have more access to other women in conservative households. The role of a CDD can lead to career and social opportunities for women. However, challenges faced by CDDs were seen as a greater barrier for women, including transportation, safety, household responsibilities, lower education levels, and low or lack of wages. Discussion: Programs to address NTDs can promote equity and improve programming by increasing women's participation as CDDs and providing financial compensation. Additionally, programs should prioritize inclusive training for CDDs, and inclusive messaging about MDA for communities. Author summary: The Act to End NTDs | West program supports USAID's efforts to control or eliminate trachoma, lymphatic filariasis (LF), onchocerciasis, schistosomiasis and soil-transmitted helminthiasis in 11 West African countries using mass drug administration.Act | West conducted a gender and social inclusion analysis to inform a strategy for the program to improve outcomes and more meaningfully engage and empower women and marginalized individuals in program implementation. Our objective was to identify how gender and social norms and stigma differentially impact men's and women's adoption of healthy practices around NTD prevention, use of NTD services, participation in programing, and opportunities to engage in identifying solutions, using an intersectional lens inclusive of disability, ethnic identity, and geographic location. Several studies have looked at gender dimensions of staffing for NTD programming, analyzed differential risk factors and prevalence of NTDs between males and females, or presented data on gender and national mass drug administration (MDA) coverage to combat NTDs. This paper aims to consolidate these findings through a literature review as well as a qualitative study conducted in Côte d'Ivoire, Ghana, and Sierra Leone, to provide a comprehensive look at gender and social inclusion within NTD programming across various contexts and diseases. This study found that women and girls face additional health risks from five NTDs compared to men and boys. In addition to the health burden, the social and economic impacts of NTD-related disability or infertility can be particularly severe for women and girls. Additionally, men were somewhat less likely to participate in mass drug administration (MDAs) and pregnant and breastfeeding women were sometimes excluded by community drug distributors (CDDs) from certain types of MDAs for which they are eligible due to misunderstanding on the part of CDDs and community members on eligibility criteria. Training participation rates for CDDs and supervisors were universally higher for men than women, even though feedback on the effectiveness of female CDDs was overwhelmingly positive, and female CDDs often have more access to other women in conservative households. Additionally, challenges faced by CDDs were seen as a greater barrier for women to serve in that capacity. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer disease (BUD) results in disabilities and deformities in the absence of early medical intervention. The extensive role of caregiving in BUD is widely acknowledged, however, associated caregiver burden is poorly understood. In this paper we assessed the burden which caregivers experience when supporting patients with BUD in Ghana. Method/ principal findings: This qualitative study was conducted in 3 districts in Ghana between August and October 2019. 13 semi-structured interviews were conducted on caregivers of BUD patients in the local language of Twi. Data was translated into English, coded into broad themes, and direct content analysis approach was used to analyse results. The results show the caregivers face financial, psychological and health issues as a consequence of their caregiving role. Conclusion/ significance: This study found significant caregiver burden on family members. It also highlighted the psychological burden caregivers experience and the limited knowledge of the disease within endemic communities. Further research is needed to quantify the caregiver burden of BUD at different economic levels in order to better understand the impact of possible caregiver interventions on patient outcomes. Author summary: Buruli ulcer disease (BUD) is a stigmatizing skin condition caused by the bacteria, Mycobacterium ulcerans. The disease results in permanent functional limitations in the absence of early medical intervention. The disabling BUD conditions, financial constraints and frequent hospital visits support the role of caregiving for affected individuals. Caregiver burden is poorly understood although the role and need for caregiving is widely recognised in BUD. This study identified a previously unrecognized burden on the caregivers of BUD patients in 3 endemic districts in Ghana. Specifically, we identified significant financial and psychological pressure on affected families in meeting healthcare related costs and physical care while also providing for their own and other family members' needs. We also highlight the emotional burden experienced by caregivers, their reduced work productivity, the barriers caregivers face in accessing healthcare with BUD patients and the limited support available for caregivers. Our study highlights the serious social consequences of BUD in Ghana. Further quantitative research within different economic regions affected by BUD is warranted to better understand the caregiver burden of BUD. [ABSTRACT FROM AUTHOR]

Background: This paper reports on the baseline prevalence and associated risk factor findings of a pilot, longitudinal study exploring community-wide treatment of schistosomiasis and soil-transmitted helminthiasis, using albendazole plus praziquantel in the Greater Accra region of Ghana. Method: From three communities, at least, 658 individuals were enrolled into the study via random household selection. Prevalence and intensity of schistosomiasis and STH infection were determined from stool and urine samples with a questionnaire being administered in order to explore other morbidities and risk factors. Factor analysis of household demographic variables was undertaken to generate a socioeconomic score; this was then further categorised into tertiles. Proportional-odds cumulative logit generalised estimating equation (GEE) models were used to investigate categorical ordinal intensity of infection associations with morbidity. Separately, logistic GEE models were used to investigate risk factor associations with infection prevalence. Results: Both Schistosoma haematobium and S. mansoni were prevalent in the three communities, with the prevalence of S. haematobium ranging from 3.3% (24/679; 95% CI = 1.9–4.7) to 19% (114/632; 95% CI = 15.8–22.2) and S. mansoni ranging from 30% (202/679; 95% CI = 26.5–33.5) to 78.3% (409/536; 95% CI = 74.7–81.9). The total prevalence of STH across all three sites was negligible at 1.3% (24/1847; 95% CI = 0.8–1.9) comprising mainly hookworm (10/1847). Multivariable statistical models indicated males to be 2.3 (95% CI = 1.7–3.3) times more likely to have a high intensity S. mansoni infection and 1.5 (95% CI = 1.1–2) times more likely to have a high intensity of S. haematobium infection compared to females. There was no significant difference in the likelihood of infection with S. mansoni between adults and school age children (SAC), however S. haematobium infections were found to be 2.5 (95% CI = 1.8–3.5) times more likely to occur in school age children than in adults. Multivariable statistical models (adjusted for age and sex) indicated an association between schistosomiasis and a number of self-reported morbidity indicators (notably diarrhoea and blood in stool and urine). Low socio-economic status was also associated with SCH infection (OR: 2; 95% CI = 1.3–3.2). Conclusion: The communities targeted by this study showed a range of Schistosoma prevalence's of infection, from hypo-endemic through to meso-endemic and hyper-endemic. The prevalence of SCH across the different age groups in the study locations highlights the large number of individuals currently being left out of the standard morbidity control method of annual treatment of the SAC. Author summary: In this manuscript we detail the baseline results of a broader study investigating the feasibility of expanding access of albendazole and praziquantel to additional at-risk groups in three communities (Tomefa, Maheam and Torgahkope-Adakope) located around the Weija reservoir in the Greater Accra district of Ghana. Our results show that intestinal schistosomiasis was the most common form of disease across all three sites (44.2%) with Tomefa possessing the highest prevalence at 78.3%. The prevalence of urinary schistosomiasis was found to be 11.9% with the highest prevalence found in Torgahkope-Adakope (19%). STH was found to have a very low prevalence across the three communities with only 1.3% of participants found to be positive. No significant difference in STH prevalence was observed between males (0.92%; 95% CI = 0.4–1.81) and females (1.07%; 95% CI = 0.51–1.95). Statistical analysis revealed that males were more likely to be infected and to have high intensity infections of both forms of schistosomiasis. Pre-school age children (PSAC) were found to be less likely to be infected for either form of schistosomiasis in communities with low to medium prevalence of disease, however in Tomefa, where prevalence of intestinal schistosomiasis is high, there was little difference in the prevalence of disease between PSAC, school-age children (SAC) and adults. Our study shows that there is a need to treat the wider community outside of the current morbidity control strategy of mass-drug administration to SAC. [ABSTRACT FROM AUTHOR]

Introduction: The Global Strategy to Eliminate Lymphatic Filiariasis (GFELF) through Mass Drug Administration (MDA) has been implemented in Ghana since the year 2000 and transmission has been interrupted in 76 of 98 endemic districts. To improve the MDA in the remaining districts with microfilaria (MF) prevalence above the 1% threshold for the interruption of transmission, there is a need to identify and implement appropriate quality improvement (QI) strategies. This paper describes the use of intervention mapping to select QI strategies to improve an existing evidence-based MDA program in Northern Ghana. Methods: Due to the complexities associated with implementing evidence-based programs (EBP) such as the lymphatic filariasis MDA and variability in the context, an initial assessment to identify implementation bottlenecks associated with the quality of implementation of lymphatic filariasis MDA in the Bole District of Ghana was conducted using a mixed methods approach. Based on the findings of the initial assessment, a context specific QI strategy was designed and operationalized using intervention mapping strategy in terms of seven domains: actor, the action, action targets, temporality, dose, implementation outcomes addressed, and theoretical justification. Results: The initial needs assessment shows that the persistent transmission of lymphatic filariasis in the Bole District is characterized by high levels of refusal to ingest the drug, high levels of reported adverse drug reactions, low MDA coverage at community level, poor adherence to the MDA protocol and non-participants’ responsiveness. Conclusion: This study has shown that it is feasible to develop a context specific QI strategy for an existing evidence-based intervention based on an initial needs assessment through stakeholder participation using the IM approach. However, working (towards) QI requires more time than is usually available in public health service. Sufficient theoretical knowledge of implementation research and experience with technical IM experts must be available. [ABSTRACT FROM AUTHOR]

Background: Despite several years of LF-MDA implementation, Ghana still has some districts with mf prevalence >1%, partly due to poor treatment coverage levels resulting from non-participation in MDA. To address the challenges, we implemented an Engage & Treat (E&T) and Test & Treat (T&T) strategies for individuals who miss or refuse MDA respectively, in a hotspot district, enabling us to reach many of those who seldom, or never, take part in MDA. This financial cost study was undertaken to analyse data on the LF-MDA, E&T and T&T implementation in 2021 and the financial cost to inform the rollout of the E&T and T&T as mop-up strategies in future LF-MDAs. Methods: This costing study analysed cost data from the 2021 LF-MDA implementation activities carried out by the Neglected Tropical Diseases (NTD) programme of the Ghana Health Service and the SENTINEL study, carried out in Ahanta West district for the two interventions (i.e., E&T and T&T). The 2021 Ghana Population and Housing Census data was used to estimate the LF-MDA-eligible population. The financial cost per person treated was estimated and these costs were applied to the projected population to obtain the financial cost for subsequent years. Results: Implementing MDA mop-up strategies either through the E&T or T&T to improve coverage comes at an additional cost to the elimination goals. For example, in 2024 the projected cost per person treated by the routine LF-MDA is estimated at US$0.83. The cost using the integrated LF-MDA and the E&T, T&T led by the NTD programme or T&T integrated into the health system was estimated at US$1.62, US$2.88, and US$2.33, respectively, for the same year. Despite the increased cost, the proposed combined LF-MDA and mop-up strategies will have a higher estimated population treated for 2024 (i.e., 1,392,211) compared to the routine LF-MDA approach (i.e., 988,470) for the same year. Conclusion: Combining LF-MDA with E&T/T&T mop-up strategies, despite their high costs, may provide NTD Programmes with the options of improving treatment coverage and reaching the LF elimination target sooner, given that the routine LF-MDA alone approach has been implemented for many years with some districts yet to reach the elimination targets. Author summary: In Ghana, despite many years of efforts to eliminate lymphatic filariasis (LF) through mass drug administration (MDA), some districts still have a prevalence of infection above the threshold required to eliminate the disease as a public health problem. This is partly because not everyone in these districts is participating in the MDA program. To tackle this challenge, new strategies called Engage & Treat (E&T) and Test & Treat (T&T) were implemented in a hotspot district. These strategies focus on reaching individuals who either miss or refuse MDA, ensuring that even those who rarely or never participate are covered. A financial cost study was undertaken to analyze the data from LF-MDA, E&T, and T&T implementations in 2021 to understand the financial implications for future LF-MDA efforts. The study looked at the cost data from LF-MDA activities conducted by the Neglected Tropical Diseases (NTD) program of the Ghana Health Service and the SENTINEL study in the Ahanta West district for the E&T and T&T interventions. Population data from the 2021 Ghana Population and Housing Census were used to estimate the LF-MDA-eligible population in the country. The study found that implementing these strategies, either through E&T or T&T, to improve coverage comes with an additional cost to the LF elimination goals. For example, in 2024, the projected cost per person treated by the routine LF-MDA alone is estimated at US$0.83. However, when combining LF-MDA with E&T or T&T, the costs increase to US$1.62, US$2.88, and US$2.33, respectively, for the same year. Despite the higher costs, the combined LF-MDA and mop-up strategies are estimated to treat a larger population in 2024 (1,392,211) compared to the routine LF-MDA approach (988,470) for the same year. In summary, although the combined LF-MDA and mop-up strategies have higher costs, they may offer NTD Programs the option to improve treatment coverage and achieve the LF elimination target sooner. This is particularly important as the routine LF-MDA alone approach has been in place for many years, with some districts still facing challenges in reaching elimination targets. [ABSTRACT FROM AUTHOR]

Background: Stigma related to skin neglected tropical diseases like Buruli ulcer (BU) and yaws has remained underexplored and existing studies are limited to individual diseases despite the WHO call for integration in disease management. Within two districts in central Ghana, we explored stigma associated with BU and yaws to understand overlaps and disease-specific nuances to help guide integrated interventions. Methodology/Principal findings: In-depth interviews were conducted with 31 current or formerly affected individuals to assess the experiences, effects and coping strategies adopted to manage disease related stigma. Data were analysed along broad themes based on the sociological construct of macro and micro interaction and Goffman's treatise on stigma. Disapproving community labels fueled by misconceptions were noted among BU participants which contributed to macro stigma experiences, including exclusion, discrimination and avoidance. In contrast, a high level of social acceptance was reported among yaws participants although some micro-level stigma (anticipated, felt and self-stigma) were noted by individuals with both diseases. While younger participants experienced name-calling and use of derogatory words to address affected body parts, older participants and caregivers discussed the pain of public staring. Stigma experiences had negative consequences on psychosocial well-being, schooling, and social relations, particularly for BU affected people. Problem-focused strategies including confrontation, selective disclosure and concealment as well as emotion-focused strategies (religious coping and self-isolation) were noted. Conclusions and significance: The types and levels of stigma varied for BU and yaws. Stigma experiences also differed for adults and children in this setting and these differences should be accounted for in integrated interventions for these skin NTDs. School health programs need to prioritize educating school teachers about skin NTDs and the negative impact of stigma on the wellbeing of children. Author summary: Stigma related to Neglected Tropical Diseases (NTDs) constitutes a burden on the social and economic life of affected people, their caregivers and communities. Current evidence on stigma has been limited to a small number of NTDs. The WHO recommends integration approaches to NTDs are therefore understanding stigma and its differential impact is important. We explored stigma experiences, effects and coping strategies simultaneously in BU and yaws in two districts in central Ghana. Findings showed nuances for macro-level stigma associated with BU; individuals were stigmatized by community members; interestingly, this was not noted for yaws. Negative effects of stigma found included psychosocial burden, effects on academic work and straining of social relationships. Some affected individuals dealt with the source of stigma actively avoiding disclosure, selective disclosure, concealment with clothing and confrontation. Emotion-focused strategies such as religious coping and self-isolation were reported; these were noted to aggravate psychosocial problems being experienced by affected people. We propose that, the differences in stigma among people affected by BU and yaws, and the role of age in determining types of stigma identified in this study should be considered in integrated interventions for skin NTDs. School health programs are encouraged to educate teachers about skin NTDs and the negative effects of stigma on students. [ABSTRACT FROM AUTHOR]

The Global Program to Eliminate Lymphatic Filariasis (GPELF) advocates for the treatment of entire endemic communities, in order to achieve its elimination targets. LF is predominantly a rural disease, and achieving the required treatment coverage in these areas is much easier compared to urban areas that are more complex. In Ghana, parts of the Greater Accra Region with Accra as the capital city are also endemic for LF. Mass Drug Administration (MDA) in Accra started in 2006. However, after four years of treatment, the coverage has always been far below the 65% epidemiologic coverage for interrupting transmission. As such, there was a need to identify the reasons for poor treatment coverage and design specific strategies to improve the delivery of MDA. This study therefore set out to identify the opportunities and barriers for implementing MDA in urban settings, and to develop appropriate strategies for MDA in these settings. An experimental, exploratory study was undertaken in three districts in the Greater Accra region. The study identified various types of non-rural settings, the social structures, stakeholders and resources that could be employed for MDA. Qualitative assessment such as in-depth interviews (IDIs) and focus group discussions (FGDs) with community leaders, community members, health providers, NGOs and other stakeholders in the community was undertaken. The study was carried out in three phases: pre-intervention, intervention and post-intervention phases, to assess the profile of the urban areas and identify reasons for poor treatment coverage using both qualitative and quantitative research methods. The outcomes from the study revealed that, knowledge, attitudes and practices of community members to MDA improved slightly from the pre-intervention phase to the post-intervention phase, in the districts where the interventions were readily implemented by health workers. Many factors such as adequate leadership, funding, planning and community involvement, were identified as being important in improving implementation and coverage of MDA in the study districts. Implementing MDA in urban areas therefore needs to be given significant consideration and planning, if the required coverage rates are to be achieved. This paper, presents the recommendations and strategies for undertaking MDA in urban areas. [ABSTRACT FROM AUTHOR]

In this article, we provide an in-depth analysis on the drug-resistance phenotypic characteristics of a cohort of 325 tuberculosis and characterize by Whole Genome Sequencing 24 isolates from Nigeria belonging to L4, L5 and L6. Our results suggest an alarming rate of drug-resistance of the L4.6.2.2 Mycobacterium tuberculosis complex (MTBC) lineage and a high diversity of L5. We compiled these new Sequence Read Archives (SRAs) to previously published ones from available Bioprojects run in Nigeria. We performed RAxML phylogenetic reconstructions of larger samples that include public NCBI SRAs from some neighboring countries (Cameroon, Ghana). To confront phylogenetic reconstruction to metadata, we used a new proprietary database named TB-Annotator. We show that L5 genomes in Northern Nigeria belong to new clades as the ones described until now and allow an update of the taxonomy of L5. In addition, we describe the L4.6.2.2 lineage in Nigeria, Cameroon and Ghana. We provide computations on the likely divergence time of L4.6.2.2 and suggest a new hypothesis concerning its origin. Finally we provide a short overview on M. bovis diversity in Nigeria. This study constitutes a baseline knowledge on the global genomic diversity, phylogeography and phylodynamics of MTBC in Nigeria, as well as on the natural history of this largely ignored but densely populated country of Africa. These results highlight the need of sequencing additional MTBC genomes in Nigeria and more generally in West-Africa, both for public health and for academic reasons. The likelihood of replacement of L5-L6 by L4.6.2.2 isolates, leave potentially little time to gather historical knowledge informative on the ancient history of tuberculosis in West-Africa. Author summary: Nigeria is a rapidly evolving and young country that still suffers from a high-burden of tuberculosis (TB), whether linked to poverty, to HIV co-infection, or to drug-resistant TB. Genomic remains poorly implemented in Nigeria, and previous studies on the genetic diversity of the pathogen agent, Mycobacterium tuberculosis complex (MTBC), studied by targeted genotyping methods has first shown the high prevalence of the L4.6.2, a sublineage of the Euro-American L4 lineage. It also stressed the remaining importance of L5-L6, formerly designated as Mycobacterium africanum, two frequent yet poorly investigated ecotypes. Previous studies also suggested that MDR-TB transmission is alarming in Nigeria. Within a scientific project whose aim is to better analyze the genetic diversity of MTBC in Northern Nigeria and to reconstruct the evolutionary history of L5, we investigate in this article, some phenotypic and genomic characteristics of MTBC isolates obtained in a cohort of 325 TB patient from Northern Nigeria. We show an alarming rate of resistance to rifampin and isoniazid, but few indications of MDR-TB transmission. We gathered and studied a global collection of 495 Whole-genome SRA from Nigeria (n = 116), Cameroon (n = 202) and Ghana (n = 175), that includes 24 new SRAs from Northern Nigeria. The distribution of the various lineages found in these three countries support Nigeria or the border between Nigeria and Cameroon, as being the potential cradle of L4.6.2. We show that the L5 lineage is more diverse than expected and deserves more studies to better understand its evolutionary history, given the current scarcity of published L5-L6 data relatively to the wealth of L2-L4 sequences in the NCBI databases. [ABSTRACT FROM AUTHOR]

Background: Mapping the distribution of schistosomiasis is essential to determine where control programs should operate, but because it is impractical to assess infection prevalence in every potentially endemic community, model-based geostatistics (MBG) is increasingly being used to predict prevalence and determine intervention strategies. Methodology/Principal Findings: To assess the accuracy of MBG predictions for Schistosoma haematobium infection in Ghana, school surveys were evaluated at 79 sites to yield empiric prevalence values that could be compared with values derived from recently published MBG predictions. Based on these findings schools were categorized according to WHO guidelines so that practical implications of any differences could be determined. Using the mean predicted values alone, 21 of the 25 empirically determined 'high-risk' schools requiring yearly praziquantel would have been undertreated and almost 20% of the remaining schools would have been treated despite empirically-determined absence of infection – translating into 28% of the children in the 79 schools being undertreated and 12% receiving treatment in the absence of any demonstrated need. Conclusions/Significance: Using the current predictive map for Ghana as a spatial decision support tool by aggregating prevalence estimates to the district level was clearly not adequate for guiding the national program, but the alternative of assessing each school in potentially endemic areas of Ghana or elsewhere is not at all feasible; modelling must be a tool complementary to empiric assessments. Thus for practical usefulness, predictive risk mapping should not be thought of as a one-time exercise but must, as in the current study, be an iterative process that incorporates empiric testing and model refining to create updated versions that meet the needs of disease control operational managers. Author Summary: The challenge of accurately mapping schistosomiasis is a daunting one – particularly because of the highly focal distribution of the disease. Ideally, of course, each specific treatment area would be assessed for infection prevalence and then treated appropriately based on guidelines of the World Health Organization. In practice, however, this is not possible, and a variety of short-cutting techniques have been developed to meet these mapping needs, including geospatial predictive mapping. This paper assesses the accuracy of model-based geostatistics (MBG) predictions for determining treatments projections in Ghana by comparing previously published data using MBG predictions with empirically derived prevalence values for schistosomiasis from school surveys completed at 79 sites. We found that using predictive mapping alone would not have provided reliable information for mass drug administration (MDA) planning – resulting in overtreatment in some areas and most importantly under-treatment in areas that needed it most. Based on our findings, predictive risk mapping cannot be a one-time exercise but must instead be a process that incorporates empiric testing and model refining to create optimised spatial decision support tools that meet the needs of disease control operational managers. [ABSTRACT FROM AUTHOR]

Background: The reservoir and mode of transmission of Mycobacterium ulcerans, the causative agent of Buruli ulcer, remain unknown. Ecological, genetic and epidemiological information nonetheless suggests that M. ulcerans may reside in aquatic protozoa. Methodology/Principal Findings: We experimentally infected Acanthamoeba polyphaga with M. ulcerans and found that the bacilli were phagocytised, not digested and remained viable for the duration of the experiment. Furthermore, we collected 13 water, 90 biofilm and 45 detritus samples in both Buruli ulcer endemic and non-endemic communities in Ghana, from which we cultivated amoeboid protozoa and mycobacteria. M. ulcerans was not isolated, but other mycobacteria were as frequently isolated from intracellular as from extracellular sources, suggesting that they commonly infect amoebae in nature. We screened the samples as well as the amoeba cultures for the M. ulcerans markers IS2404, IS2606 and KR-B. IS2404 was detected in 2% of the environmental samples and in 4% of the amoeba cultures. The IS2404 positive amoeba cultures included up to 5 different protozoan species, and originated both from Buruli ulcer endemic and non-endemic communities. Conclusions/Significance: This is the first report of experimental infection of amoebae with M. ulcerans and of the detection of the marker IS2404 in amoeba cultures isolated from the environment. We conclude that amoeba are potential natural hosts for M. ulcerans, yet remain sceptical about their implication in the transmission of M. ulcerans to humans and their importance in the epidemiology of Buruli ulcer. Author Summary: Buruli ulcer (BU) is a devastating skin disease caused by Mycobacterium ulcerans, an environmental bacterium that is probably linked to slow-running water. It is unlikely to occur free-living, but even though M. ulcerans DNA has been detected in quite a few different organisms (with most studies focusing on insects), it is still not clear what its real reservoir is. Amoeboid protozoa, inhabitants of biofilms in slow flowing water, are good candidates since all previously tested mycobacteria are resistant to the digestion by these macrophage-like organisms. In this paper we demonstrate that M. ulcerans can indeed infect Acanthamoeba polyphaga in the lab, and remain viable intracellularly. We also collected water, biofilm and detritus samples in BU endemic and non-endemic regions in Ghana. We found that several mycobacteria species commonly occur intracellularly in protozoa in these environments. Amoebae were isolated from almost all samples, and an M. ulcerans marker (IS2404) was detected in 4% of the amoeba cultures. We conclude that amoebae are potential hosts for M. ulcerans. However, because these IS2404 positive amoebae originated from both BU endemic and non-endemic areas, we remain sceptical about their implication in the transmission of M. ulcerans to humans. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU), caused by Mycobacterium ulcerans infection, is a debilitating disease of the skin and underlying tissue. The first phase of a BU prevention and treatment programme (BUPaT) was initiated from 2005–2008, in the Ga-West and Ga-South municipalities in Ghana to increase access to BU treatment and to improve early case detection and case management. This paper assesses achievements of the BUPaT programme and lessons learnt. It also considers the impact of the programme on broader interests of the health system. Methods: A mixed-methods approach included patients' records review, review of programme reports, a stakeholder forum, key informant interviews, focus group discussions, clinic visits and observations. Principal Findings: Extensive collaboration existed across all levels, (national, municipality, and community), thus strengthening the health system. The programme enhanced capacities of all stakeholders in various aspects of health services delivery and demonstrated the importance of health education and community-based surveillance to create awareness and encourage early treatment. A patient database was also created using recommended World Health Organisation (WHO) forms which showed that 297 patients were treated from 2005–2008. The proportion of patients requiring only antibiotic treatment, introduced in the course of the programme, was highest in the last year (35.4% in the first, 23.5% in the second and 42.5% in the third year). Early antibiotic treatment prevented recurrences which was consistent with programme aims. Conclusions: To improve early case management of BU, strengthening existing clinics to increase access to antibiotic therapy is critical. Intensifying health education and surveillance would ultimately increase early reporting and treatment for all cases. Further research is needed to explain the role of environmental factors for BU contagion. Programme strategies reported in our study: collaboration among stakeholders, health education, community surveillance and regular antibiotic treatment can be adopted for any BU-endemic area in Ghana. Author Summary: Buruli ulcer (BU), caused by Mycobacterium ulcerans infection, is a debilitating disease of the skin and underlying tissue which starts as a painless nodule, oedema or plaque and could develop into painful and massive ulcers if left untreated. Using a combination of quantitative and qualitative methods, the study assessed the effectiveness of the BUPaT programme to improve early detection and management of BU in an endemic area in Ghana. The results of the study showed extensive collaboration across all levels, (national, municipality and community), which contributed to strengthening the programme. Health staff were trained to manage all BU cases. School teachers, municipal environmental staff and community surveillance volunteers were trained to give the right health messages, screen for detection of early cases and refer for medical treatment. WHO-recommended antibiotics improved treatment and cure, particularly for early lesions, and prevented recurrences. Improving access to antibiotic treatment is critical for early case management. Health education is required to emphasise the effectiveness of treatment with antibiotics to reduce deformities and the importance of seeking medical treatment for all skin lesions. Further research is needed to explain the role of environmental factors in BU contagion. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis. Methods and findings: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with two oral doses of ivermectin (150 μg/kg) separated by at least 6 months prior to treatment with either a single oral dose of ivermectin 150 μg/kg plus albendazole 400 mg (IA), a single oral dose of IDA (IDA1, IA plus diethylcarbamazine (DEC. 6 mg/kg) or three consecutive daily doses of IDA (IDA3). These treatments were tolerated equally well. While adverse events were common (approximately 30% overall), no severe or serious treatment-emergent adverse events were observed. Skin microfilariae were absent or present with very low densities after all three treatments through 18 months, at which time nodules were excised for histological assessment. Nodule histology was evaluated by two independent assessors who were masked regarding participant infection status or treatment assignment. Significantly lower percentages of female worms were alive and fertile in nodules recovered from study participants after IDA1 (40/261, 15.3%) and IDA3 (34/281, 12.1%) than after IA (41/180, 22.8%). This corresponds to a 40% reduction in the percentage of female worms that were alive and fertile after IDA treatments relative to results observed after the IA comparator treatment (P = 0.004). Percentages of female worms that were alive (a secondary outcome of the study) were also lower after IDA treatments (301/574, 52.4%) than after IA (127/198, 64.1%) (P = 0.004). Importantly, some comparisons (including the reduced % of fertile female worms after IDA1 vs IA treatment, which was the primary endpoint for the study) were not statistically significant when results were adjusted for intraclass correlation of worm fertility and viability for worms recovered from individual study participants. Conclusions: Results from this pilot study suggest that IDA was well tolerated after ivermectin pretreatment. They also suggest that IDA was more effective than the comparator treatment IA for killing or sterilizing female O. volvulus worms. No other short-course oral treatment for onchocerciasis has been demonstrated to have macrofilaricidal activity. However, this first study was too small to provide conclusive results. Therefore, additional studies will be needed to confirm these promising findings. Trial registration: The study is registered at Cinicaltrials.gov under the number NCT04188301. Author summary: Why was this study done?: Onchocerciasis is a neglected tropical disease caused by parasitic round worms. The infective worm larvae are transmitted by black flies that breed near rivers in sub-Saharan Africa. The parasites cause severe skin disease with itching and ocular disease; the common name for the infection is "river blindness". WHO has targeted onchocerciasis for elimination and mass drug administration is the key intervention strategy. There is an urgent need for improved treatments to kill or permanently sterilize the adult parasites. This study tested a combination drug treatment that is quite effective for treating other related worm infections. What did the researchers do and find?: We performed a randomized clinical trial that compared a triple drug combination with a standard of care two-drug treatment that is widely used in Africa. We found that the new treatment was as safe as the standard treatment. More importantly, analysis of adult female worms surgically removed from study participants suggested that the new treatment might be more effective than the standard treatment for killing or permanently sterilizing the parasites. However, this first study was too small to provide conclusive results. What do these findings mean?: An improved treatment could improve chances for eliminating onchocerciasis in Africa. Results from this study can be used to better plan follow-up studies to explore the value of this and other new combination treatments for onchocerciasis. [ABSTRACT FROM AUTHOR]

Introduction: Onchocerciasis is one of the eleven neglected tropical diseases (NTDs) recently targeted by the World Health Organization (WHO) for elimination. Mass drug administration (MDA) of ivermectin has become the main intervention for reducing the burden of onchocerciasis and controlling its transmission. However, despite the considerable gains in the fight against onchocerciasis in Ghana, the infection remains endemic in some communities. This study aimed to ascertain community members' acceptability levels and factors associated with ivermectin MDA for the elimination of onchocerciasis in the Asante Akim South Municipal in the Ashanti Region of Ghana. Methods: A cross-sectional, questionnaire-based study was conducted in six communities in the Asante Akim South Municipal from 7th May to 9th July, 2021. The study population comprised all persons aged 18 years and above who had lived in the study communities for more than three months prior to the study. The main outcome variable was the acceptability of ivermectin MDA by the community members. This was measured using a composite acceptability score adapted from the Intervention Rating Profile tool. The explanatory variables were the respondents' socio-demographic characteristics, self-rated knowledge of onchocerciasis, perceived side effects of ivermectin, and self-reported level of education received on MDA activities. Results: Out of 450 community members included in the study, 50.4% were male while 49.6% were female. The respondents' mean age was 39.57±10.64 years. The mean acceptability score for ivermectin MDA was 20.52±2.91 (range, 9–36). Acceptability of ivermectin MDA was positively associated with gender, educational status, employment status, self-rated knowledge of onchocerciasis, and level of education received on MDA; and negatively associated with perceived side effect of ivermectin. Conclusion: This study provides valuable information to inform policy decisions on planning and implementing MDA programs for the elimination of onchocerciasis in the study area and the country as a whole. Author summary: Mass drug administration (MDA) using ivermectin is considered the main intervention for controlling the transmission of onchocerciasis. The program involves administering the drug to an entire target population irrespective of infection status or symptom. In most instances, administration of ivermectin is done annually in areas with low transmission and biannually in high transmission settings. However, when a proportion of the population fails to participate in an MDA program, a potential reservoir for the parasite is left untreated, opening the door to recrudescence of microfilaremia and reducing the probability of successful elimination of the disease. Thus, community participation is considered vital in addressing the gaps in MDA coverage and uptake. There is a link between participation and acceptability of a health intervention. For instance, once communities deem MDA to be acceptable, they are more likely to be motivated to participate in the intervention. Measures of acceptability provide a clearer understanding of factors that might be associated with compliance with a heath intervention. This study, therefore, assesses factors influencing community acceptability of MDA for the elimination of onchocerciasis. The findings provide useful information that could inform policy decisions on strategies to address MDA implementation gaps. [ABSTRACT FROM AUTHOR]

Purpose: The Neglected Tropical Diseases programme since its implementation has improved the lives of many in the tropical and sub-tropical areas. Though witnessed many successes, the programme is continually facing challenges thus, preventing the attainment of various objectives. This study seeks to assess the challenges of implementation of the neglected tropical diseases programme in Ghana. Design/Methodology/Approach: The thematic analysis approach was used to analyze qualitative data collected from 18 key public health managers selected through purposive and snowballing procedures from the national, regional and district levels of Ghana Health Service. Data collection was done through in-depth interviews using semi-structured interview guides in line with the objective of the study. Findings: The Neglected Tropical Diseases Programme though received funding from external sources, faces multiple challenges which cut across financial, human and capital resources to external control. Specifically, inadequate resources, dwindling volunteerism, poor social mobilization, weak governmental commitment and weak monitoring were major challenges to implementation. These factors work individually and in combination to impede effective implementation. Ensuring state ownership, re-structuring implementation approaches to include top-down and bottom-up approaches and building capacity in monitoring and evaluation are recommended in order to meet the programme objectives and ensure sustainability. Originality: This study forms part of an original study on Implementation of the NTDs programme in Ghana. Aside the key issues discussed, it presents first-hand information on major implementation challenges that are relevant to researchers, students, practitioners and the general public and will apply widely to vertically implemented programmes in Ghana. Author summary: Diseases classified as neglected continue to affect the poorest of people across the world especially in the Sub-Saharan Africa region. Although efforts have been made, several barriers continually exist to delay attainment of programme objectives. This study assessed the challenges of implementation of the neglected tropical diseases programme in Ghana from the major state implementation agency (GHS) at the national, regional and district levels. We found the challenges of implementation that acted independently and synergistically to be inadequate resources, dwindling volunteerism, poor social mobilization, weak governmental commitment and weak monitoring and evaluation. [ABSTRACT FROM AUTHOR]

Background: The estimated five million snakebites per year are an important health problem that mainly affect rural poor populations. The global goal is to halve both mortality and morbidity from this neglected tropical disease by 2030. Data on snakebite morbidity are sparse and mainly obtained from hospital records. Methods: This community-based study was conducted among 379 rural residents with or without a history of snakebite in the Ashanti and Upper West regions of Ghana. All participants in the snakebite group were bitten at least six months before the day of survey. The World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0) and the Buruli Ulcer Functional Limitation Score were used to obtain patient-reported measure of functioning and disability. Long-term consequences were evaluated based on the severity of the symptoms at the time of the snakebite. Findings: The median (IQR) time since the snakebite was 8.0 (3.5–16.5) years. The relative risk of disability was 1.54 (95% CI, 1.17–2.03) in the snakebite group compared to the community controls. Among patients with clinical symptoms suggesting envenoming at the time of bite, 35% had mild/moderate disabilities compared to 20% in the control group. The disability domains mainly affected by snakebite envenoming were cognition level, mobility, life activities and participation in society. A combination of the severity of symptoms at the time of the bite, age, gender and region of residence most accurately predicted the odds of having functional limitations and disabilities. Conclusion: The burden of snakebite in the community includes long-term disabilities of mild to moderate severity, which need to be considered when designing appropriate public health interventions. Estimating the total burden of snakebite is complicated by geographic differences in types of snakes and their clinical manifestations. Author summary: Snakebite is a neglected tropical disease of public health concern. The majority of cases occur in tropical rural regions where access to adequate medical interventions is limited. The outcome of these bites may cause a range of manifestations, varying from local lesions to life threatening effects and death. Available estimates of snakebite burden are often based on severe complications such as death and amputations and are limited to health facility-based evaluations. We conducted a community-based study to identify the long-term consequences of snakebite by comparing participants with or without a history of snakebite in two regions in Ghana. A history of snakebite was associated with the chance of having disabilities. Combining community estimates of mild to moderate complications with data on severe complications from the health system level provides a more comprehensive overview of the overall snakebite burden. The incorporation of mental health and rehabilitation interventions into integrated neglected tropical diseases (NTD) programmes can reduce the risk of disabilities and improve the wellbeing of snakebite and other NTD patients. [ABSTRACT FROM AUTHOR]

Background: As prevalence decreases in pre-elimination settings, identifying the spatial distribution of remaining infections to target control measures becomes increasingly challenging. By measuring multiple antibody responses indicative of past exposure to different pathogens, integrated serological surveys enable simultaneous characterisation of residual transmission of multiple pathogens. Methodology/Principal findings: Here, we combine integrated serological surveys with geostatistical modelling and remote sensing-derived environmental data to estimate the spatial distribution of exposure to multiple diseases in children in Northern Ghana. The study utilised the trachoma surveillance survey platform (cross-sectional two-stage cluster-sampled surveys) to collect information on additional identified diseases at different stages of elimination with minimal additional cost. Geostatistical modelling of serological data allowed identification of areas with high probabilities of recent exposure to diseases of interest, including areas previously unknown to control programmes. We additionally demonstrate how serological surveys can be used to identify areas with exposure to multiple diseases and to prioritise areas with high uncertainty for future surveys. Modelled estimates of cluster-level prevalence were strongly correlated with more operationally feasible metrics of antibody responses. Conclusions/Significance: This study demonstrates the potential of integrated serological surveillance to characterise spatial distributions of exposure to multiple pathogens in low transmission and elimination settings when the probability of detecting infections is low. Author summary: Following implementation of successful interventions, one of the primary challenges for neglected tropical disease programmes is identifying areas with remaining disease transmission. As disease prevalence decreases, these infections become increasingly rare and hard to detect. Serological assays measure long-lived disease-specific antibody responses indicating past exposure to pathogens and increase the probability of detecting disease transmission. Here, we integrate serological assays with environmental and spatial data to map priority areas for surveillance for multiple neglected tropical diseases in Northern Ghana using the two-stage cluster-based survey platform established for trachoma surveillance. The use of multiplex bead assays measuring exposure to multiple pathogens allows integrated surveillance of diseases of interest to the national control programme. We identify areas with high risks of transmission to selected diseases as well as areas with high uncertainty which are priorities for future control and surveillance efforts. Together, this highlights the utility of multiplex serological platforms as a tool for integrated surveillance and mapping of neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Background: In onchocerciasis endemic areas in Africa, heterogenous biting rates by blackfly vectors on humans are assumed to partially explain age- and sex-dependent infection patterns with Onchocerca volvulus. To underpin these assumptions and further improve predictions made by onchocerciasis transmission models, demographic patterns in antibody responses to salivary antigens of Simulium damnosum s.l. are evaluated as a measure of blackfly exposure. Methodology/Principal findings: Recently developed IgG and IgM anti-saliva immunoassays for S. damnosum s.l. were applied to blood samples collected from residents in four onchocerciasis endemic villages in Ghana. Demographic patterns in antibody levels according to village, sex and age were explored by fitting generalized linear models. Antibody levels varied between villages but showed consistent patterns with age and sex. Both IgG and IgM responses declined with increasing age. IgG responses were generally lower in males than in females and exhibited a steeper decline in adult males than in adult females. No sex-specific difference was observed in IgM responses. Conclusions/Significance: The decline in age-specific antibody patterns suggested development of immunotolerance or desensitization to blackfly saliva antigen in response to persistent exposure. The variation between sexes, and between adults and youngsters may reflect differences in behaviour influencing cumulative exposure. These measures of antibody acquisition and decay could be incorporated into onchocerciasis transmission models towards informing onchocerciasis control, elimination, and surveillance. Author summary: Onchocerciasis, a disease caused by the helminth parasite Onchocerca volvulus, is transmitted by the bites of female Simulium blackflies. The disease is still endemic in many African countries, and the World Health Organization has proposed elimination of its transmission in 12 countries by 2030. Understanding the heterogeneity in human exposure to vector bites can help discern which portion of the population is at higher risk of acquiring/ transmitting infection and is fundamental to identifying target groups for serological monitoring and transmission control. Traditionally, blackfly biting rates are estimated by performing human landing catches, a method that is often considered unethical and which can be unreliable as a representative measure. Therefore, we used our recently developed immunoassays to measure human antibody responses to antigens contained in the saliva of blackflies and deposited into human skin when they bloodfeed. In onchocerciasis endemic communities in Ghana, we measured antibody responses to understand age- and/or sex-related demographic patterns in vector exposure. We observed lower antibody responses in males compared to in females, and a substantial decline with increasing age, suggesting that high blackfly biting pressure induces desensitization in the human host. [ABSTRACT FROM AUTHOR]

Background: Simulium damnosum sensu lato (s.l.) blackflies transmit Onchocerca volvulus, a filarial nematode that causes human onchocerciasis. Human landing catches (HLCs) is currently the sole method used to estimate blackfly biting rates but is labour-intensive and questionable on ethical grounds. A potential alternative is to measure host antibodies to vector saliva deposited during bloodfeeding. In this study, immunoassays to quantify human antibody responses to S. damnosum s.l. saliva were developed, and the salivary proteome of S. damnosum s.l. was investigated. Methodology/Principal findings: Blood samples from people living in onchocerciasis-endemic areas in Ghana were collected during the wet season; samples from people living in Accra, a blackfly-free area, were considered negative controls and compared to samples from blackfly-free locations in Sudan. Blackflies were collected by HLCs and dissected to extract their salivary glands. An ELISA measuring anti-S. damnosum s.l. salivary IgG and IgM was optimized and used to quantify the humoral immune response of 958 individuals. Both immunoassays differentiated negative controls from endemic participants. Salivary proteins were separated by gel-electrophoresis, and antigenic proteins visualized by immunoblot. Liquid chromatography mass spectrometry (LC–MS/MS) was performed to characterize the proteome of S. damnosum s.l. salivary glands. Several antigenic proteins were recognized, with the major ones located around 15 and 40 kDa. LC–MS/MS identified the presence of antigen 5-related protein, apyrase/nucleotidase, and hyaluronidase. Conclusions/Significance: This study validated for the first time human immunoassays that quantify humoral immune responses as potential markers of exposure to blackfly bites. These assays have the potential to facilitate understanding patterns of exposure as well as evaluating the impact of vector control on biting rates. Future studies need to investigate seasonal fluctuations of these antibody responses, potential cross-reactions with other bloodsucking arthropods, and thoroughly identify the most immunogenic proteins. Author summary: Measuring biting rates of bloodsucking arthropods has been proved to be a crucial tool in understanding transmission dynamics and evaluating control measures against vector-borne diseases. Blackflies of the S. damnosum sensu lato (s.l.) complex are the prime vectors of Onchocerca volvulus, a filarial nematode and causative agent of human onchocerciasis (or river blindness) in Africa. Blackfly biting rates are typically measured by human attractant vector collectors who capture host-seeking female flies as they alight on their skin but before they take a blood meal. Apart from the ethical concerns raised by this method, estimates thus obtained do not reflect true exposure to vector bites. An understanding of whether there are people who receive more bites than others and who may be at higher risk of acquiring the infection is crucial to modelling control interventions. Therefore, in the present study we developed IgG- and IgM-based immunoassays to quantify antibody responses in human populations to salivary antigens of S. damnosum s.l. in onchocerciasis-endemic communities of Ghana. The proteome of S. damnosum s.l. salivary glands was also investigated to potentially identify salivary antigens that could be employed as exposure markers against this important vector group. [ABSTRACT FROM AUTHOR]

Background: Ghana is endemic for some neglected tropical diseases (NTDs) including schistosomiasis, onchocerciasis and lymphatic filariasis. The major intervention for these diseases is mass drug administration of a few repeatedly recycled drugs which is a cause for major concern due to reduced efficacy of the drugs and the emergence of drug resistance. Evidently, new treatments are needed urgently. Medicinal plants, on the other hand, have a reputable history as important sources of potent therapeutic agents in the treatment of various diseases among African populations, Ghana inclusively, and provide very useful starting points for the discovery of much-needed new or alternative drugs. Methodology/Principal findings: In this study, extracts of fifteen traditional medicines used for treating various NTDs in local communities were screened in vitro for efficacy against schistosomiasis, onchocerciasis and African trypanosomiasis. Two extracts, NTD-B4-DCM and NTD-B7-DCM, prepared from traditional medicines used to treat schistosomiasis, displayed the highest activity (IC50 = 30.5 μg/mL and 30.8 μg/mL, respectively) against Schistosoma mansoni adult worms. NTD-B2-DCM, also obtained from an antischistosomal remedy, was the most active against female and male adult Onchocera ochengi worms (IC50 = 76.2 μg/mL and 76.7 μg/mL, respectively). Antitrypanosomal assay of the extracts against Trypanosoma brucei brucei gave the most promising results (IC50 = 5.63 μg/mL to 18.71 μg/mL). Incidentally, NTD-B4-DCM and NTD-B2-DCM, also exhibited the greatest antitrypanosomal activities (IC50 = 5.63 μg/mL and 7.12 μg/mL, respectively). Following the favourable outcome of the antitrypanosomal screening, this assay was selected for bioactivity-guided fractionation. NTD-B4-DCM, the most active extract, was fractionated and subsequent isolation of bioactive constituents led to an eupatoriochromene-rich oil (42.6%) which was 1.3-fold (IC50 <0.0977 μg/mL) more active than the standard antitrypanosomal drug, diminazene aceturate (IC50 = 0.13 μg/mL). Conclusion/Significance: These findings justify the use of traditional medicines and demonstrate their prospects towards NTDs drug discovery. Author summary: The discovery of new drugs is vital to achieving the World Health Organization eradication targets for neglected tropical diseases (NTDs). Traditional medicines serve as sources of primary healthcare needs for most affected populations and therefore represent a valuable resource in this regard, albeit largely underdeveloped. We investigated extracts of a selection of traditional medicines for efficacy and safety to justify their use for treating NTDs in Ghana. We screened the extracts for activity against schistosomiasis (Schistosoma mansoni), onchocerciasis (Onchocera ochengi) and trypanosomiasis (Trypanosoma brucei brucei). Generally, more extracts effectively inhibited O. ochengi than S. mansoni lifecycle stages. Further, S. mansoni juvenile and O. ochengi adult-stage male worms were more susceptible to the extracts than adult-stage S. mansoni and O. ochengi female worms. Overall, the extracts were most active against the trypanosomes. Hence, we selected the antitrypanosomal assay to identify active principles and this resulted in a non-toxic oil which was more active than the extract, and also more effective than the standard antitrypanosomal drug, diminazene aceturate. The major oil constituent, eupatriochromene, has demonstrated antitrypanosomal activity in other studies. We recommend that the quality of traditional medicines is improved. [ABSTRACT FROM AUTHOR]

Ghana has been implementing Mass Drug Administration (MDA) since the year 2001, and Lymphatic Filariasis transmission has been interrupted in 76 out of the 98 targeted districts. The remaining districts have a microfilaria prevalence above the 1% threshold needed for the interruption of transmission. This study assesses the level of lymphatic filariasis MDA coverage and explored factors affecting the quality of implementation of the MDA in the Bole and Central Gonja Districts of Northern Ghana. A concurrent mixed methods study design approach was used to provide both a quantitative and qualitative insight. A descriptive analysis was carried out, and the results are presented in tables and charts. The transcripts of the qualitative interviews were imported into Nvivo and framework methods of analysis were used. The results were summarized based on the themes and buttressed with narratives with key quotes presented within the texts. The overall MDA coverage in Central Gonja is 89.3% while that of Bole district is 82.9%. Refusal to ingest the drug and adverse drug reactions were higher in Bole district than the Central Gonja District. The persistent transmission of lymphatic filariasis in Bole District was characterized by poor community mobilization and sensitization, nonadherence to the directly observed treatment strategy, refusal to ingest the drug due to the fear of adverse drug reactions, inadequate knowledge and misconceptions about the disease. Reported mass drug administration coverage will not necessarily result into interruption of transmission of the disease without strict compliance to the directly observed treatment strategy, strong stakeholder engagement coupled with evidence-based context-specific multi-channel community education strategies with key educational messages on the cause of the disease and adverse drug reactions. While the clock for the elimination of lymphatic filariasis by the year 2020 and meeting of the Sustainable Development Goal 3 target 3.3 by 2030 is ticking, there is an urgent need for a concerted effort to improve the fidelity of the ongoing lymphatic filariasis MDA campaigns in the Bole District of Northern Ghana. Author summary: After 18 years of implementing the global strategy to eliminate lymphatic filariasis in Ghana, the prevalence of the transmission of the disease is still above the threshold needed to interrupt transmission of the disease as a public health problem in some districts. This study showed that, the persistent transmission of the lymphatic filariasis in the Bole District is characterized with a refusal to ingest the drug; reported adverse drug reactions; poor knowledge and misconceptions of the disease, and poor adherence to the mass drug administration protocol. High reported mass drug administration coverage will not lead to interruption of transmission of lymphatic filariasis without strict adherence to the direct observe treatment strategy, strong stakeholder engagement coupled with evidence-based context-specific multi-channel community education strategies with key educational messages on adverse drug reactions and the cause of the disease. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is endemic in Ghana, and the country has implemented the GPELF strategy since 2000 with significant progress made in the control of the disease. However, after several years of mass drug administration (MDA) implementation, there is persistent transmission in 17 of the 98 endemic districts in the country. Current approaches to surveillance are clearly unable to target untreated individuals and new strategies are required to address the endgame challenges to enhance LF elimination as a public health problem in endemic countries. Community registers are used during MDAs to enumerate community members, their age, gender, house numbers, and records of their participation in MDAs. These MDA registers represent an untapped opportunity to identify and characterize non-compliance and inform appropriate programmatic actions. In this study, we analyzed the data presented in the registers to assess the coverage and individuals' compliance in MDA. Methods: The information in the MDA registers were assessed to verify the reported coverages obtained from the district. The community registers were obtained from the district health offices and the data from each individual record was entered into a database. A simple questionnaire was used to cross-check the participation of study participants in the 2017 MDA. The questionnaire solicited data on: participation in the 2017 MDA, reasons for not taking part in the MDA, adverse events experienced, what was done for the adverse events, and willingness to participate in subsequent MDAs. Results: We found that 40.1% of the population in the registers missed at least one MDA in 3 years (2016–2018) and the majority of them were between 10–30 years of age. The results of the questionnaire assessment indicated that 13.8% of the respondents did not receive treatment in 2017 for various reasons, the most prominent among them being "absence/travel" (37.1%). Data in the registers were used to verify the treatment coverage for the years 2017 and 2018, and reviewed against the reported coverage obtained from the district. Significant differences between the reported and verified coverages were only observed in four communities. However, the assessment also revealed that the reported coverage was only accurate in 33.3% of cases. Conclusions: The MDA registers allow for the identification of eligible individuals who were not reached during any MDA round. Thus, the MDA registers could be utilized at the community and programme levels to identify missing and untreated individuals, appropriately address their non-compliance to MDA, and thereby improve MDA coverage in each implementation unit and monitor the progress towards elimination of LF. The challenges observed through the review of the registers also offer opportunities to improve the training given to the community drug distributors. Author summary: Elephantiasis is a disease that is common in Ghana. Since the year 2000 the country has implemented a control programme aimed at eliminating the disease as a public health problem, through the yearly treatment of entire communities in districts where the disease is found. Achievements have been made, and treatment has stopped in many districts; however, some districts have received many years of treatment without successfully reducing the infections below the targeted levels. Many individuals go untreated every year, as can be observed from the low reported treatment coverage after MDA. This untreated population may explain why some districts have failed to achieve the criteria for stopping treatment. Fortunately, the treatments are recorded in community registers, which contain the details of all community members, as well as their treatment participation. These registers can therefore be used to identify people who have not received treatment and design appropriate interventions to reach them. Through these registers, we were able to identify and characterize individuals who were not treated between 2016 and 2018 in 10 communities. We found that 4 out of 10 people missed at least one treatment between 2016 and 2018, and the majority of them were 10–30 years of age. Using the information from the registers we were also able to verify the proportion of people who took part in the treatments in 2017 and 2018, and compared this to what was reported. This comparison revealed that the reporting was only accurate in 33% of cases. A questionnaire was also used to cross-check the participation of study participants in the 2017 MDA, with results indicating that 13.8% of the respondents did not receive treatment for various reasons, the most prominent among them being "absence/travel" (37.1%). Although these registers are seldom used by the Lymphatic Filariasis Control Programme for anything other than recording and reporting treatment information, this study shows that the registers provide an opportunity to identify individuals who have not received treatment, develop a plan to appropriately address their reasons for not taking part in the treatments, target these untreated individuals to improve the overall proportion of people taking part in MDA, and assess the accuracy of reported coverage information. These activities will allow the programme to better monitor the progress towards, and ultimately achieve, elimination of lymphatic filariasis as a public health problem. [ABSTRACT FROM AUTHOR]

We recently developed a superhydrophobic cone-based method for the collection of mosquito excreta/feces (E/F) for the molecular xenomonitoring of vector-borne parasites showing higher throughput compared to the traditional approach. To test its field applicability, we used this platform to detect the presence of filarial and malaria parasites in two villages of Ghana and compared results to those for detection in mosquito carcasses and human blood. We compared the molecular detection of three parasites (Wuchereria bancrofti, Plasmodium falciparum and Mansonella perstans) in mosquito E/F, mosquito carcasses and human blood collected from the same households in two villages in the Savannah Region of the country. We successfully detected the parasite DNA in mosquito E/F from indoor resting mosquitoes, including W. bancrofti which had a very low community prevalence (2.5–3.8%). Detection in the E/F samples was concordant with detection in insect whole carcasses and human blood, and a parasite not vectored by mosquitoes was detected as well.Our approach to collect and test mosquito E/F successfully detected a variety of parasites at varying prevalence in the human population under field conditions, including a pathogen (M. perstans) which is not transmitted by mosquitoes. The method shows promise for further development and applicability for the early detection and surveillance of a variety of pathogens carried in human blood. Author summary: Molecular xenomonitoring of parasites or viruses using mosquitoes as "flying syringes" is a promising and non-invasive tool for early detection and surveillance of various pathogens, particularly in low prevalence settings, but there is a need for cost-effective and higher throughput alternatives. We recently developed a novel approach based on the collection of mosquito excreta/feces (E/F) using a superhydrophobic cone that directs the sample into a tube at the bottom of the collection cup. We tested this method's ability to detect the presence of filarial and malaria parasite DNA from households in two endemic rural communities of Ghana and compared it to the molecular detection from blood and mosquito carcass samples from corresponding households. The detection of parasite DNA in mosquito E/F was successful for all three pathogens, and it showed good concordance with the detection in the insects' whole carcasses. Given the successful detection of Mansonella perstans, which is not transmitted by mosquitoes, our tool shows promise for use as an alternative method for the early and non-invasive detection and surveillance of various pathogens in human blood, including those not strictly mosquito-borne, in endemic settings. [ABSTRACT FROM AUTHOR]

Background: Ghana started its national programme to eliminate lymphatic filariasis (LF) in 2000, with mass drug administration (MDA) with ivermectin and albendazole as main strategy. We review the progress towards elimination that was made by 2016 for all endemic districts of Ghana and analyze microfilaria (mf) prevalence from sentinel and spot-check sites in endemic districts. Methods: We reviewed district level data on the history of MDA and outcomes of transmission assessment surveys (TAS). We further collated and analyzed mf prevalence data from sentinel and spot-check sites. Results: MDA was initiated in 2001–2006 in all 98 endemic districts; by the end of 2016, 81 had stopped MDA after passing TAS and after an average of 11 rounds of treatment (range 8–14 rounds). The median reported coverage for the communities was 77–80%. Mf prevalence survey data were available for 430 communities from 78/98 endemic districts. Baseline mf prevalence data were available for 53 communities, with an average mf prevalence of 8.7% (0–45.7%). Repeated measurements were available for 78 communities, showing a steep decrease in mean mf prevalence in the first few years of MDA, followed by a gradual further decline. In the 2013 and 2014 surveys, 7 and 10 communities respectively were identified with mf prevalence still above 1% (maximum 5.6%). Fifteen of the communities above threshold are all within districts where MDA was still ongoing by 2016. Conclusions: The MDA programme of the Ghana Health Services has reduced mf prevalence in sentinel sites below the 1% threshold in 81/98 endemic districts in Ghana, yet 15 communities within 13 districts (MDA ongoing by 2016) had higher prevalence than this threshold during the surveys in 2013 and 2014. These districts may need to intensify interventions to achieve the WHO 2020 target. [ABSTRACT FROM AUTHOR]

Background: Worldwide, snakebite envenomations total ~2.7 million reported cases annually with ~100,000 fatalities. Since 2009, snakebite envenomation has intermittently been classified as a very important ‘neglected tropical disease’ by the World Health Organisation. Despite this emerging awareness, limited efforts have been geared towards addressing the serious public health implications of snakebites, particularly in sub-Saharan Africa, where baseline epidemiological and ecological data remain incomplete. Due to poverty as well as limited infrastructure and public health facilities, people in rural Africa, including Ghana, often have no other choice than to seek treatment from traditional medical practitioners (TMPs). The African ‘snakebite crisis’ is highlighted here using regionally representative complementary data from a community-based epidemiological and ecological study in the savanna zone of northern Ghana. Methodology and findings: Our baseline study involved two data collection methods in the Savelugu-Nanton District (in 2019 the district was separated into Savelugu and Nanton districts) in northern Ghana, comprising a cross-sectional study of 1,000 residents and 24 TMPs between December 2008 and May 2009. Semi-structured interviews, as well as collection of retrospective snakebite and concurrent rainfall records from the Savelugu-Nanton District Hospital and Ghana Meteorological Authority respectively over 10-years (1999–2008) were used in the study. Variables tested included demography, human activity patterns, seasonality, snake ecology and clinical reports. Complementary data showed higher snakebite prevalence during the rainy season, and a hump-shaped correlation between rainfall intensity and snakebite incidences. Almost 6% of respondents had experienced a personal snakebite, whereas ~60% of respondents had witnessed a total of 799 snakebite cases. Out of a total of 857 reported snakebite cases, 24 (~2.8%) died. The highest snakebite prevalence was recorded for males in the age group 15–44 years during farming activities, with most bites occurring in the leg/foot region. The highest snakebite rate was within farmlands, most severe bites frequently caused by the Carpet viper (Echis ocellatus). Conclusion: The relatively high community-based prevalence of ~6%, and case fatality ratio of ~3%, indicate that snakebites represent an important public health risk in northern Ghana. Based on the high number of respondents and long recording period, we believe these data truly reflect the general situation in the rural northern savanna zone of Ghana and West Africa at large. We recommend increased efforts from both local and international health authorities to address the current snakebite health crisis generally compromising livelihoods and productivity of rural farming communities in West Africa. [ABSTRACT FROM AUTHOR]

Background: Urogenital schistosomiasis is endemic throughout Ghana with elevated infection levels in certain areas e.g. Lake Volta Region. While the primary focus of the national control program is on mass drug administration of praziquantel to school-aged children, Female Genital Schistosomiasis (FGS), a disease-specific affliction of girls and women, has been largely overlooked. To better focus future actions, our study investigated the perceptions, knowledge and understanding of FGS amongst community members and health providers. Method/Principal findings: We used qualitative methods including 12 focus group discussions and 34 in-depth interviews. We purposively selected 16 communities along the Lake Volta in the Shai-Osudoku District. Participant selection was based on gender, age and occupation; providing an opportunity to explore community understanding of FGS through participants own words and perceptions. Awareness of schistosomiasis was reported and is commonly experienced among children (12–17 years) and younger adults (18–25 years) in the study communities but is typically considered a boy's disease. Knowledge of FGS was lacking in women, girls and front-line health workers. There was a general misconception that FGS may be the result of sexual promiscuity. Adolescent girls reporting vaginal discharge and itching were often stigmatized by health workers and treated for sexually transmitted infections. Limited alternatives to the river as key source of water meant that all members of the community faced the regular risk of schistosomiasis. Conclusion/Significance: There is a clear imperative for the national control program to better engage on FGS and implement interventions to meet girls and women's needs. The key consideration is to integrate more adequately preventive services with sexual and reproductive primary health care with future training of health workers for improved management of FGS cases. More broadly, harmonizing the portfolio of all actions on FGS is needed, especially with a call for improved access to safe water and sanitation for all those at current or future risk. [ABSTRACT FROM AUTHOR]

Background: Validation of elimination of trachoma as a public health problem is based on clinical indicators, using the WHO simplified grading system. Chlamydia trachomatis (Ct) infection and anti-Ct antibody responses (anti-Pgp3) have both been evaluated as alternative indicators in settings with varying levels of trachoma. There is a need to evaluate the feasibility of using tests for Ct infection and anti-Pgp3 antibodies at scale in a trachoma-endemic country and to establish the added value of the data generated for understanding transmission dynamics in the peri-elimination setting. Methodology/Principal findings: Dried blood spots for serological testing and ocular swabs for Ct infection testing (taken from children aged 1–9 years) were integrated into the pre-validation trachoma surveys conducted in the Northern and Upper West regions of Ghana in 2015 and 2016. Ct infection was detected using the GeneXpert PCR platform and the presence of anti-Pgp3 antibodies was detected using both the ELISA assay and multiplex bead array (MBA). The overall mean cluster-summarised TF prevalence (the clinical indicator) was 0.8% (95% CI: 0.6–1.0) and Ct infection prevalence was 0.04% (95%CI: 0.00–0.12). Anti-Pgp3 seroprevalence using the ELISA was 5.5% (95% CI: 4.8–6.3) compared to 4.3% (95%CI: 3.7–4.9) using the MBA. There was strong evidence from both assays that seropositivity increased with age (p<0.001), although the seroconversion rate was estimated to be very low (between 1.2 to 1.3 yearly events per 100 children). Conclusions/Significance: Infection and serological data provide useful information to aid in understanding Ct transmission dynamics. Elimination of trachoma as a public health problem does not equate to the absence of ocular Ct infection nor cessation in acquisition of anti-Ct antibodies. [ABSTRACT FROM AUTHOR]

Background: Buruli Ulcer (BU) is one of the most neglected debilitating tropical diseases caused by Mycobacterium ulcerans, which causes considerable morbidity and disability. Building on earlier findings that community-based interventions could enhance case detection and reduce treatment dropout and defaulter rates, we established an active surveillance-response system in an endemic sub-district in the Ga West municipality of Ghana to enhance early case detection, diagnosis and treatment to reduce or eliminate severe ulcers and its related disabilities. Methods: We established surveillance response system, implemented in collaboration with the sub-district disease control officers, selected clinical staff and trained community-based volunteers. The active community-based surveillance- response system was implemented for 12 months. Also, pre and post intervention surveys were conducted to document any change in perceptions on BU in the study population over the period. The baseline and endline surveys were conducted in August 2016 and August 2017 respectively. Results: On average, each person was seen 11 times in 12 months. In all 75 skin lesions were detected during surveillance rounds, out of which 17 were suspected to be BU and 12 out of the 17 were confirmed as BU using Polymerase chain reaction (PCR). Out of the 12, five, three and four were categories I, II and III lesions respectively. Physical examination was done on 94% of the people seen during the surveillance rounds. Knowledge on BU has also increased in the communities at the end of the study. Conclusion: The findings from this study have demonstrated that it is possible to establish surveillance-response system for BU and by extension, other neglected tropical diseases to enhance control and elimination efforts through the use of community-based volunteers. [ABSTRACT FROM AUTHOR]

Introduction: The WHO yaws eradication strategy consists of one round of total community treatment (TCT) of single-dose azithromycin with coverage of > 90%.The efficacy of the strategy to reduce the levels on infection has been demonstrated previously in isolated island communities in the Pacific region. We aimed to determine the efficacy of a single round of TCT with azithromycin to achieve a decrease in yaws prevalence in communities that are endemic for yaws and surrounded by other yaws-endemic areas. Methods: Surveys for yaws seroprevalence and prevalence of skin lesions were conducted among schoolchildren aged 5–15 years before and one year after the TCT intervention in the Abamkrom sub-district of Ghana. We used a cluster design with the schools as the primary sampling unit. Among 20 eligible primary schools in the sub district, 10 were assigned to the baseline survey and 10 to the post-TCT survey. The field teams conducted a physical examination for skin lesions and a dual point-of-care immunoassay for non-treponemal and treponemal antibodies of all children present at the time of the visit. We also undertook surveys with non-probabilistic sampling to collect lesion swabs for etiology and macrolide resistance assessment. Results: At baseline 14,548 (89%) of 16,287 population in the sub-district received treatment during TCT. Following one round of TCT, the prevalence of dual seropositivity among all children decreased from 10.9% (103/943) pre-TCT to 2.2% (27/1211) post-TCT (OR 0.19; 95%CI 0.09–0.37). The prevalence of serologically confirmed skin lesions consistent with active yaws was reduced from 5.7% (54/943) pre-TCT to 0.6% (7/1211) post-TCT (OR 0.10; 95% CI 0.25–0.35). No evidence of resistance to macrolides against Treponema pallidum subsp. pertenue was seen. Discussion: A single round of high coverage TCT with azithromycin in a yaws affected sub-district adjoining other endemic areas is effective in reducing the prevalence of seropositive children and the prevalence of early skin lesions consistent with yaws one year following the intervention. These results suggest that national yaws eradication programmes may plan the gradual expansion of mass treatment interventions without high short-term risk of reintroduction of infection from contiguous untreated endemic areas. [ABSTRACT FROM AUTHOR]

The author discusses the implementation of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) by the World Health Organization (WHO) that aim to eradicate the lymphatic filariasis (LF) in Ghana. Topics discussed include the effect of mass drug administration (MDA) in the immunoparasitological indicators, the use of albendazole (ALB) and ivermectin (IVM) as a treatment for lymphatic filariasis, and the challenges encountered while implementing the national program.

Background: Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting. Methodology: We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1–15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%. Findings: The mean age of participants was 9.5 years (S.D.3.1, range: 1–15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2–100) in the azithromycin group and 96.9% (95% CI: 94.1–99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9–64.9) in the azithromycin group and 49.1% (95% CI: 41.2–56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority. Conclusions: A single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular benzathine penicillin for the treatment of early yaws among Ghanaian patients, and provides additional support for the WHO policy for use of oral azithromycin for the eradication of yaws in resource-poor settings. Trial Registration: Pan African Clinical Trials Registry [ABSTRACT FROM AUTHOR]

Background: This study was conducted with the aim to understand some of the cultural belief systems in the management of wounds and patients practices that could contaminate wounds at the Obom sub-district of the Ga South Municipality of Ghana. Methods: This was an ethnographic study using in-depth interviews, Focus Group Discussions and participant observation techniques for data collection. Observations were done on Buruli ulcer patients to document how they integrate local and modern wound management practices in the day-to-day handling of their wounds. Content analysis was done after the data were subjected to thematic coding and representative narratives selected for presentation. Results: It was usually believed that wounds were caused by charms or spirits and, therefore, required the attention of a native healer. In instances where some patients’ wounds were dressed in the hospital by clinicians whose condition/age/sex contradict the belief of the patient, the affected often redress the wounds later at home. Some of the materials often used for such wound dressing include urine and concoctions made of charcoal and gunpowder with the belief of driving out evil spirits from the wounds. Conclusion: Clinicians must therefore be aware of these cultural beliefs and take them into consideration when managing Buruli ulcer wounds to prevent redressing at home after clinical treatment. This may go a long way to reduce secondary infections that have been observed in Buruli ulcer wounds. [ABSTRACT FROM AUTHOR]

Background: Ghana is affected by regular cholera epidemics and an annual average of 3,066 cases since 2000. In 2014, Ghana experienced one of its largest cholera outbreaks within a decade with more than 20,000 notified infections. In order to attribute this rise in cases to a newly emerging strain or to multiple simultaneous outbreaks involving multi-clonal strains, outbreak isolates were characterized, subtyped and compared to previous epidemics in 2011 and 2012. Methodology/Principal Findings: Serotypes, biotypes, antibiotic susceptibilities were determined for 92 Vibrio cholerae isolates collected in 2011, 2012 and 2014 from Southern Ghana. For a subgroup of 45 isolates pulsed-field gel electrophoresis, multilocus sequence typing and multilocus-variable tandem repeat analysis (MLVA) were performed. Eighty-nine isolates (97%) were identified as ctxB (classical type) positive V. cholerae O1 biotype El Tor and three (3%) isolates were cholera toxin negative non-O1/non-O139 V. cholerae. Among the selected isolates only sulfamethoxazole/trimethoprim resistance was detectable in 2011, while 95% of all 2014 isolates showed resistance towards sulfamethoxazole/trimethoprim, ampicillin and reduced susceptibility to ciprofloxacin. MLVA achieved the highest subtype discrimination, revealing 22 genotypes with one major outbreak cluster in each of the three outbreak years. Apart from those clusters genetically distant genotypes circulate during each annual epidemic. Conclusions/Significance: This analysis suggests different endemic reservoirs of V. cholerae in Ghana with distinct annual outbreak clusters accompanied by the occurrence of genetically distant genotypes. Preventive measures for cholera transmission should focus on aquatic reservoirs. Rapidly emerging multidrug resistance must be monitored closely. [ABSTRACT FROM AUTHOR]

Background: The activities of the Global Programme for the Elimination of Lymphatic Filariasis have been in operation since the year 2000, with Mass Drug Administration (MDA) undertaken yearly in disease endemic communities. Information collected during MDA–such as population demographics, age, sex, drugs used and remaining, and therapeutic and geographic coverage–can be used to assess the quality of the data reported. To assist country programmes in evaluating the information reported, the WHO, in collaboration with NTD partners, including ENVISION/RTI, developed an NTD Data Quality Assessment (DQA) tool, for use by programmes. This study was undertaken to evaluate the tool and assess the quality of data reported in some endemic communities in Ghana. Methods: A cross sectional study, involving review of data registers and interview of drug distributors, disease control officers, and health information officers using the NTD DQA tool, was carried out in selected communities in three LF endemic Districts in Ghana. Data registers for service delivery points were obtained from District health office for assessment. The assessment verified reported results in comparison with recounted values for five indicators: number of tablets received, number of tablets used, number of tablets remaining, MDA coverage, and population treated. Furthermore, drug distributors, disease control officers, and health information officers (at the first data aggregation level), were interviewed, using the DQA tool, to determine the performance of the functional areas of the data management system. Findings: The results showed that over 60% of the data reported were inaccurate, and exposed the challenges and limitations of the data management system. The DQA tool is a very useful monitoring and evaluation (M&E) tool that can be used to elucidate and address data quality issues in various NTD control programmes. [ABSTRACT FROM AUTHOR]

Background: African animal trypanosomosis (AAT) is a major constraint to sustainable development of cattle farming in sub-Saharan Africa. The habitat of the tsetse fly vector is increasingly fragmented owing to demographic pressure and shifts in climate, which leads to heterogeneous risk of cyclical transmission both in space and time. In Burkina Faso and Ghana, the most important vectors are riverine species, namely Glossina palpalis gambiensis and G. tachinoides, which are more resilient to human-induced changes than the savannah and forest species. Although many authors studied the distribution of AAT risk both in space and time, spatio-temporal models allowing predictions of it are lacking. Methodology/Principal Findings: We used datasets generated by various projects, including two baseline surveys conducted in Burkina Faso and Ghana within PATTEC (Pan African Tsetse and Trypanosomosis Eradication Campaign) national initiatives. We computed the entomological inoculation rate (EIR) or tsetse challenge using a range of environmental data. The tsetse apparent density and their infection rate were separately estimated and subsequently combined to derive the EIR using a “one layer-one model” approach. The estimated EIR was then projected into suitable habitat. This risk index was finally validated against data on bovine trypanosomosis. It allowed a good prediction of the parasitological status (r2 = 67%), showed a positive correlation but less predictive power with serological status (r2 = 22%) aggregated at the village level but was not related to the illness status (r2 = 2%). Conclusions/Significance: The presented spatio-temporal model provides a fine-scale picture of the dynamics of AAT risk in sub-humid areas of West Africa. The estimated EIR was high in the proximity of rivers during the dry season and more widespread during the rainy season. The present analysis is a first step in a broader framework for an efficient risk management of climate-sensitive vector-borne diseases. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU), one of 17 neglected tropical diseases, is a debilitating skin and soft tissue infection caused by Mycobacterium ulcerans. In tropical Africa, changes in land use and proximity to water have been associated with the disease. This study presents the first analysis of BU at the village level in southwestern Ghana, where prevalence rates are among the highest globally, and explores fine and medium-scale associations with land cover by comparing patterns both within BU clusters and surrounding landscapes. Methodology/Principal Findings: We obtained 339 hospital-confirmed BU cases in southwestern Ghana between 2007 and 2010. The clusters of BU were identified using spatial scan statistics and the percentages of six land cover classes were calculated based on Landsat and Rapid Eye imagery for each of 154 villages/towns. The association between BU prevalence and each land cover class was calculated using negative binomial regression models. We found that older people had a significantly higher risk for BU after considering population age structure. BU cases were positively associated with the higher percentage of water and grassland surrounding each village, but negatively associated with the percent of urban. The results also showed that BU was clustered in areas with high percentage of mining activity, suggesting that water and mining play an important and potentially interactive role in BU occurrence. Conclusions/Significance: Our study highlights the importance of multiple land use changes along the Offin River, particularly mining and agriculture, which might be associated with BU disease in southwestern Ghana. Our study is the first to use both medium- and high-resolution imagery to assess these changes. We also show that older populations (≥ 60 y) appear to be at higher risk of BU disease than children, once BU data were weighted by population age structures. Author Summary: We studied the relationship between a neglected tropical disease, Buruli Ulcer (BU), and landscape disturbance. We hypothesized that the increased presence of BU was related to landscape disturbance, especially alluvial mining, in endemic areas of the disease. We characterized recent cases of BU in southwestern Ghana and characterized six types of land cover classes at different spatial extents at the village level. We illustrated that mining and water areas were prevalent in BU clustered areas and may potentially play an interactive role in BU occurrence, a finding that should be explored further. No previous study has quantified the relationship between mining and BU at the village level. In addition, we found that people ≥ 60 years old had a higher prevalence than other age groups, when data was weighted by the population age structure. To our knowledge, these findings have not been reported in Ghana before and might provide new insight in BU disease intervention and control. While it is unclear how people come in contact with the bacterial source, our study shows that the importance of where people live (specifically, what land activities are occurring in the area) seems to play a large role in determining disease risk. [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]

Background: The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected African countries. Current control focuses on community-directed treatment with ivermectin (CDTI). In Ghana, persistent transmission has been reported despite long-term control. We present spatial and temporal patterns of onchocerciasis transmission in relation to ivermectin treatment history. Methodology/Principal Findings: Host-seeking and ovipositing blackflies were collected from seven villages in four regions of Ghana with 3–24 years of CDTI at the time of sampling. A total of 16,443 flies was analysed for infection; 5,812 (35.3%) were dissected for parity (26.9% parous). Heads and thoraces of 12,196 flies were dissected for Onchocerca spp. and DNA from 11,122 abdomens was amplified using Onchocerca primers. A total of 463 larvae (0.03 larvae/fly) from 97 (0.6%) infected and 62 (0.4%) infective flies was recorded; 258 abdomens (2.3%) were positive for Onchocerca DNA. Infections (all were O. volvulus) were more likely to be detected in ovipositing flies. Transmission occurred, mostly in the wet season, at Gyankobaa and Bosomase, with transmission potentials of, respectively, 86 and 422 L3/person/month after 3 and 6 years of CDTI. The numbers of L3/1,000 parous flies at these villages were over 100 times the WHO threshold of one L3/1,000 for transmission control. Vector species influenced transmission parameters. At Asubende, the number of L3/1,000 ovipositing flies (1.4, 95% CI = 0–4) also just exceeded the threshold despite extensive vector control and 24 years of ivermectin distribution, but there were no infective larvae in host-seeking flies. Conclusions/Significance: Despite repeated ivermectin treatment, evidence of O. volvulus transmission was documented in all seven villages and above the WHO threshold in two. Vector species influences transmission through biting and parous rates and vector competence, and should be included in transmission models. Oviposition traps could augment vector collector methods for monitoring and surveillance. Author Summary: The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected African countries. The success of elimination using ivermectin treatment alone will depend on several interacting factors including baseline endemicity, treatment coverage and vector species mix. In Ghana, transmission persists despite prolonged control. We investigated entomological determinants of this persistence. Blackflies were collected from seven villages with 3–24 years of ivermectin treatment. A total of 12,196 flies was dissected, with 463 larvae (all Onchocerca volvulus) in 97 infected and 62 infective flies. Transmission indices in the wet season, at Gyankobaa and Bosomase, amounted to, respectively, 86 and 422 infective larvae/person/month after 3 and 6 years of ivermectin treatment. Infection levels at these villages were over 100 times the WHO threshold of one L3/1,000 parous flies. At Asubende, an infective fly was caught among ovipositing flies in nearby breeding sites, indicating that infection was just over the WHO threshold despite extensive ivermectin and vector control. Spatial and seasonal vector species composition influences the magnitude of transmission indices through variations in biting and parous rates, and vectorial competence and capacity, and should be reflected in transmission models. Oviposition traps could enhance vector collection for transmission monitoring and surveillance. [ABSTRACT FROM AUTHOR]

Efforts to control the spread of Buruli ulcer – an emerging ulcerative skin infection caused by Mycobacterium ulcerans - have been hampered by our poor understanding of reservoirs and transmission. To help address this issue, we compared whole genomes from 18 clinical M. ulcerans isolates from a 30km2 region within the Asante Akim North District, Ashanti region, Ghana, with 15 other M. ulcerans isolates from elsewhere in Ghana and the surrounding countries of Ivory Coast, Togo, Benin and Nigeria. Contrary to our expectations of finding minor DNA sequence variations among isolates representing a single M. ulcerans circulating genotype, we found instead two distinct genotypes. One genotype was closely related to isolates from neighbouring regions of Amansie West and Densu, consistent with the predicted local endemic clone, but the second genotype (separated by 138 single nucleotide polymorphisms [SNPs] from other Ghanaian strains) most closely matched M. ulcerans from Nigeria, suggesting another introduction of M. ulcerans to Ghana, perhaps from that country. Both the exotic genotype and the local Ghanaian genotype displayed highly restricted intra-strain genetic variation, with less than 50 SNP differences across a 5.2Mbp core genome within each genotype. Interestingly, there was no discernible spatial clustering of genotypes at the local village scale. Interviews revealed no obvious epidemiological links among BU patients who had been infected with identical M. ulcerans genotypes but lived in geographically separate villages. We conclude that M. ulcerans is spread widely across the region, with multiple genotypes present in any one area. These data give us new perspectives on the behaviour of possible reservoirs and subsequent transmission mechanisms of M. ulcerans. These observations also show for the first time that M. ulcerans can be mobilized, introduced to a new area and then spread within a population. Potential reservoirs of M. ulcerans thus might include humans, or perhaps M. ulcerans-infected animals such as livestock that move regularly between countries. Author Summary: In this study we use the power of whole genome sequence comparisons to track the spread of Mycobacterium ulcerans, the causative agent of Buruli ulcer, through several villages in the Ashanti region of Ghana, providing new insights on the behaviour of this enigmatic and emerging pathogen. [ABSTRACT FROM AUTHOR]

Background: The relevance of Cryptosporidium infections for the burden of childhood diarrhoea in endemic settings has been shown in recent years. This study describes Cryptosporidium subtypes among symptomatic and asymptomatic children in rural Ghana to analyse subtype-specific demographic, geographical, seasonal and clinical differences in order to inform appropriate control measures in endemic areas. Methodology/Principal Findings: Stool samples were collected from 2232 children below 14 years of age presenting with and without gastrointestinal symptoms at the Agogo Presbyterian Hospital in the rural Ashanti region of Ghana between May 2007 and September 2008. Samples were screened for Cryptosporidium spp. by PCR and isolates were classified into subtypes based on sequence differences in the gp60 gene. Subtype specific frequencies for age, sex, location and season have been determined and associations with disease symptoms have been analysed within a case-control study. Cryptosporidium infections were diagnosed in 116 of 2232 (5.2%) stool samples. Subtyping of 88 isolates revealed IIcA5G3 (n = 26, 29.6%), IbA13G3 (n = 17, 19.3%) and IaA21R3 (n = 12, 13.6%) as the three most frequent subtypes of the two species C. hominis and C. parvum, known to be transmitted anthroponotically. Infections peak at early rainy season with 67.9% and 50.0% of infections during the months April, May and June for 2007 and 2008 respectively. C. hominis infection was mainly associated with diarrhoea (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 1.2–4.9) whereas C. parvum infection was associated with both diarrhoea (OR = 2.6; CI: 1.2–5.8) and vomiting (OR = 3.1; 95% CI: 1.5–6.1). Conclusions/Significance: Cryptosporidiosis is characterized by seasonal anthroponotic transmission of strains typically found in Sub-Saharan Africa. The infection mainly affects young infants, with vomiting and diarrhoea being one of the leading symptoms in C. parvum infection. Combining molecular typing and clinical data provides valuable information for physicians and is able to track sources of infections. Author Summary: Cryptosporidium spp. are a frequent cause of diarrhoea worldwide. While both animal-to-human and human-to-human transmission has been reported from industrialized countries, human-to-human transmission clearly prevails in Sub-Saharan Africa. However, data on the distribution of zoonotic and human subtypes is limited for rural African regions, where children are in very close contact to animals. We conducted a case-control study with 2232 stool samples from symptomatic and asymptomatic children living in the rural Ashanti region of Ghana. The combination of molecular typing results and clinical data helped to untangle transmission routes and to analyze the association of clinical symptoms with specific Cryptosporidium subtypes. Our study results demonstrate seasonal transmission with no clusters of specific subtypes. All subtypes detected have so far been only encountered from human specimens, strongly suggesting a predominantly human-human transmission among children living in the rural Ghana, despite close contact to livestock. Therefore, public health control programmes need to primarily focus on hygienic conditions among young infants below the age of two years. Of interest for practicing physicians, vomiting is a frequent symptom, especially in C. parvum infections. [ABSTRACT FROM AUTHOR]

Introduction: Diarrheal diseases are among the most frequent causes of morbidity and mortality in children worldwide, especially in resource-poor areas. This case-control study assessed the associations between gastrointestinal infections and diarrhea in children from rural Ghana. Methods: Stool samples were collected from 548 children with diarrhea and from 686 without gastrointestinal symptoms visiting a hospital from 2007–2008. Samples were analyzed by microscopy and molecular methods. Results: The organisms most frequently detected in symptomatic cases were Giardia lamblia, Shigella spp./ enteroinvasive Escherichia coli (EIEC), and Campylobacter jejuni. Infections with rotavirus (adjusted odds ratio [aOR] = 8.4; 95% confidence interval [CI]: 4.3–16.6), C. parvum/hominis (aOR = 2.7; 95% CI: 1.4–5.2) and norovirus (aOR = 2.0; 95%CI: 1.3–3.0) showed the strongest association with diarrhea. The highest attributable fractions (AF) for diarrhea were estimated for rotavirus (AF = 14.3%; 95% CI: 10.9–17.5%), Shigella spp./EIEC (AF = 10.5%; 95% CI: 3.5–17.1%), and norovirus (AF = 8.2%; 95% CI 3.2–12.9%). Co-infections occurred frequently and most infections presented themselves independently of other infections. However, infections with E. dispar, C. jejuni, and norovirus were observed more often in the presence of G. lamblia. Conclusions: Diarrheal diseases in children from a rural area in sub-Saharan Africa are mainly due to infections with rotavirus, Shigella spp./EIEC, and norovirus. These associations are strongly age-dependent, which should be considered when diagnosing causes of diarrhea. The presented results are informative for both clinicians treating gastrointestinal infections as well as public health experts designing control programs against diarrheal diseases. Author Summary: Gastrointestinal infections are frequent in many low-income countries. However, their role in diarrheal diseases is still under discussion. Many epidemiological studies focus on individuals with diarrheal symptoms only, ignoring the fact that infections may progress asymptomatically as well. In order to identify infectious agents associated with diarrhea it is imperative to consider cases without symptoms as a control group. We conducted a case-control study, including 548 children with diarrhea and 651 children without gastrointestinal symptoms in order to untangle the role of gastrointestinal infections in diarrheal disease. As shown in other studies infections with rotavirus, Shigella spp./EIEC and norovirus are responsible for the main diarrhea burden. Co-infections are frequently observed in our study group and some organisms occur more frequently in the presence of a second one. Especially Giardia lamblia, which is not associated with diarrhea, is more often observed along with Campylobacter jejuni and norovirus, which are responsible for a high number of diarrheal episodes. This may be of particular interest since G. lamblia is, with a frequency of 40% within the study group, the most prevalent organism observed. Furthermore, the high number of co-infections challenged the identification of causative pathogens since diagnosing a particular isolate may not rule out the effect of another potentially infectious agent in diarrheal disease. We observed a strong effect of age on the course of an infection, which may guide clinicians when diagnosing causes of diarrhea. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. Previous studies have shown that wounds of BU patients are colonized with M. ulcerans and several other microorganisms, including Staphylococcus aureus, which may interfere with wound healing. The present study was therefore aimed at investigating the diversity and topography of S. aureus colonizing BU patients during treatment. Methodology: We investigated the presence, diversity, and spatio-temporal distribution of S. aureus in 30 confirmed BU patients from Ghana during treatment. S. aureus was isolated from nose and wound swabs, and by replica plating of wound dressings collected bi-weekly from patients. S. aureus isolates were characterized by multiple-locus variable number tandem repeat fingerprinting (MLVF) and spa-typing, and antibiotic susceptibility was tested. Principal Findings: Nineteen (63%) of the 30 BU patients tested positive for S. aureus at least once during the sampling period, yielding 407 S. aureus isolates. Detailed analysis of 91 isolates grouped these isolates into 13 MLVF clusters and 13 spa-types. Five (26%) S. aureus-positive BU patients carried the same S. aureus genotype in their anterior nares and wounds. S. aureus isolates from the wounds of seven (37%) patients were distributed over two different MLVF clusters. Wounds of three (16%) patients were colonized with isolates belonging to two different genotypes at the same time, and five (26%) patients were colonized with different S. aureus types over time. Five (17%) of the 30 included BU patients tested positive for methicillin-resistant S. aureus (MRSA). Conclusion/Significance: The present study showed that the wounds of many BU patients were contaminated with S. aureus, and that many BU patients from the different communities carried the same S. aureus genotype during treatment. This calls for improved wound care and hygiene. Author Summary: Buruli ulcer (BU) is a disease of the skin and soft tissue caused by Mycobacterium ulcerans. The resulting skin lesions provide a niche for survival of other microorganisms such as Staphylococcus aureus, which may cause delayed wound healing. This study investigated the presence, diversity, and spatio-temporal distribution of S. aureus in BU patients from Ghana during treatment by isolating the bacteria from nose and wound swabs or wound dressings. S. aureus isolates were subsequently characterized by two complementary DNA typing approaches. This showed that 19 (63%) of the 30 investigated BU patients carried S. aureus. Five (26%) of these 19 BU patients carried the same S. aureus type in their anterior nares and wounds. Seven (37%) patients carried the same S. aureus type in their wounds, which is indicative of transmission. Three of them (16%) carried at least two different S. aureus types at the same time in their wounds, while five (26%) carried different S. aureus types over time. Notably, five (17%) BU patients tested positive for methicillin-resistant S. aureus (MRSA). These findings imply that the spatio-temporal diversity of S. aureus in BU is most likely related to factors such as antibiotic pressure, and insufficient wound care and hygiene. [ABSTRACT FROM AUTHOR]

Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5–17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes. Author Summary: Yaws is a chronic bacterial infection of the skin and bones that is endemic in Ghana. Since 2012, mass distribution of the antibiotic azithromycin has become the cornerstone of the WHO yaws eradication campaign. Accurate surveillance data are necessary to guide decisions about where MDA is required. Many national surveillance systems report only clinical cases without laboratory confirmation, which may lead to misdiagnosis. Mass distribution of azithromycin, at a lower dose than is used for yaws, is also used in the control of the eye disease trachoma. Between 2001 and 2008, two regions of Ghana undertook distribution of azithromycin to eliminate trachoma. These regions still report cases of yaws, and it is unclear if these are due to drug resistant yaws or other causes. We conducted a survey of patients with skin ulcers that looked like yaws in one of these regions of Ghana. Blood tests for yaws were negative in all the individuals examined and molecular testing of the ulcers did not show evidence of yaws caused by drug resistant Treponema pallidum ssp. pertenue. Our data suggest that previous treatment for trachoma may have also treated yaws in these districts. These findings highlight the need for yaws control programmes to integrate diagnostic testing into surveillance. [ABSTRACT FROM AUTHOR]

Although several studies have associated Mycobacterium ulcerans (MU) infection, Buruli ulcer (BU), with slow moving water bodies, there is still no definite mode of transmission. Ecological and transmission studies suggest Variable Number Tandem Repeat (VNTR) typing as a useful tool to differentiate MU strains from other Mycolactone Producing Mycobacteria (MPM). Deciphering the genetic relatedness of clinical and environmental isolates is seminal to determining reservoirs, vectors and transmission routes. In this study, we attempted to source-track MU infections to specific water bodies by matching VNTR profiles of MU in human samples to those in the environment. Environmental samples were collected from 10 water bodies in four BU endemic communities in the Ashanti region, Ghana. Four VNTR loci in MU Agy99 genome, were used to genotype environmental MU ecovars, and those from 14 confirmed BU patients within the same study area. Length polymorphism was confirmed with sequencing. MU was present in the 3 different types of water bodies, but significantly higher in biofilm samples. Four MU genotypes, designated W, X, Y and Z, were typed in both human and environmental samples. Other reported genotypes were only found in water bodies. Animal trapping identified 1 mouse with lesion characteristic of BU, which was confirmed as MU infection. Our findings suggest that patients may have been infected from community associated water bodies. Further, we present evidence that small mammals within endemic communities could be susceptible to MU infections. M. ulcerans transmission could involve several routes where humans have contact with risk environments, which may be further compounded by water bodies acting as vehicles for disseminating strains. Author Summary: Buruli ulcer is a skin disease, which is endemic in over thirty countries, mostly in West Africa, with affected populations being largely rural. The causative organism, Mycobacterium ulcerans (MU), is an environmental mycobacterium and although transmission is unclear, frequent exposure to these MU-contaminated environments have been suggested as risk factors. We conducted this study on the premise that if patients are infected from MU-contaminated water bodies, then the genotype of MU strains in these patients should be identical to those in their community associated water bodies and wetlands. Using Variable Number Tandem Repeat (VNTR) as a genetic tool, we determined the genotypes of MU from both water bodies and patient samples. Comparison and overlap of these genotypes, within each community, suggest that patients were possibly infected from at least one water body. Additionally, we present evidence that small mammals within endemic communities could be susceptible to MU infections and may be acting as reservoirs. Our findings suggest that future ecological and molecular studies in the hope of elucidating a definite transmission route, should focus on source-tracking MU infections to community associated risk environments while employing a OneHealth approach in the process. [ABSTRACT FROM AUTHOR]

Background: The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis) also called Bacillus Calmette-Guérin (BCG). Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD). The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD. Methodology: The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors. Principal Findings: After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31), sex (p = 0.24), age (p = 0.96), and presence of a BCG scar (p = 0.07) did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions. Conclusions: In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD. Author Summary: After tuberculosis and leprosy, Buruli Ulcer Disease (BUD) is the third most common human mycobacterial disease. The only available vaccine that could be potentially beneficial against these diseases is BCG. Even though BCG vaccine is widely used, the results on its effectiveness are partially contradictory, probably since different BCG strains are used. The aim of this study was to evaluate the possible protective effect of BCG vaccines on BUD. The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors. Considering the three countries, sex, and age, the analysis confirmed that the BCG vaccination did not significantly decrease the risk for developing BUD or for developing severe forms of BUD. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or to time to healing of lesions. In our study, we could not find any evidence of a protective effect of routine BCG vaccination on BUD. [ABSTRACT FROM AUTHOR]

Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex (MTBC) and an important cause of human tuberculosis in West Africa that is rarely observed elsewhere. Here we genotyped 613 MTBC clinical isolates from Ghana, and searched for associations between the different phylogenetic lineages of MTBC and patient variables. We found that 17.1% (105/613) of the MTBC isolates belonged to M. africanum, with the remaining belonging to M. tuberculosis sensu stricto. No M. bovis was identified in this sample. M. africanum was significantly more common in tuberculosis patients belonging to the Ewe ethnic group (adjusted odds ratio: 3.02; 95% confidence interval: 1.67–5.47, p<0.001). Stratifying our analysis by the two phylogenetic lineages of M. africanum (i.e. MTBC Lineages 5 and 6) revealed that this association was mainly driven by Lineage 5 (also known as M. africanum West Africa 1). Our findings suggest interactions between the genetic diversity of MTBC and human diversity, and offer a possible explanation for the geographical restriction of M. africanum to parts of West Africa. Author Summary: Tuberculosis remains one of the main global public health problems. Human tuberculosis is caused by bacteria known as the Mycobacterium tuberculosis complex (MTBC). The MTBC includes a variant called Mycobacterium africanum, which causes up to half of all tuberculosis cases in West Africa. For reasons unknown, M. africanum does not occur in other parts of the world. To explore the possible reasons for this geographic restriction of M. africanum, we analysed a large collection of bacterial strains isolated from tuberculosis patients in Ghana. We genetically characterized these bacterial isolates and collected relevant socio-demographic and epidemiological data. We found tuberculosis patients infected with M. africanum were more likely to belong to the Ewe ethnic group, compared to patients carrying other MTBC bacteria. The Ewes are indigenous inhabitants of coastal regions in West Africa that have previously been shown to harbour a high prevalence of M. africanum. Our findings support the hypothesis that different variants of MTBC have adapted to different human populations, and offer a possible explanation for the geographical restriction of M. africanum to West Africa. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans. Its exact mode of transmission is not known. Previous studies have identified demographic, socio-economic, health and hygiene as well as environment related risk factors. We investigated whether the same factors pertain in Suhum-Kraboa-Coaltar (SKC) and Akuapem South (AS) Districts in Ghana which previously were not endemic for BU. Methods: We conducted a case control study. A case of BU was defined as any person aged 2 years or more who resided in study area (SKC or AS District) diagnosed according to the WHO clinical case definition for BU and matched with age- (+/−5 years), gender-, and community controls. A structured questionnaire on host, demographic, environmental, and behavioural factors was administered to participants. Results: A total of 113 cases and 113 community controls were interviewed. Multivariate conditional logistic regression analysis identified presence of wetland in the neighborhood (OR = 3.9, 95% CI = 1.9–8.2), insect bites in water/mud (OR = 5.7, 95% CI = 2.5–13.1), use of adhesive when injured (OR = 2.7, 95% CI = 1.1–6.8), and washing in the Densu river (OR = 2.3, 95% CI = 1.1–4.96) as risk factors associated with BU. Rubbing an injured area with alcohol (OR = 0.21, 95% CI = 0.008–0.57) and wearing long sleeves for farming (OR = 0.29, 95% CI = 0.14–0.62) showed protection against BU. Conclusion: This study identified the presence of wetland, insect bites in water, use of adhesive when injured, and washing in the river as risk factors for BU; and covering limbs during farming as well as use of alcohol after insect bites as protective factors against BU in Ghana. Until paths of transmission are unraveled, control strategies in BU endemic areas should focus on these known risk factors. Author Summary: Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU) which affects the skin, can lead to extensive ulceration, and often results in disabilities. The exact mode of transmission of the disease is still unknown. Previous studies have identified demographic, socio-economic, health and hygiene, as well as environment, related risk factors for BU. This case-control study was done to ascertain the risk factors in a study area in Ghana which was previously non-endemic for BU. The study involved 226 participants, of which 50% were BU confirmed cases and 50% age-, gender-, and community matched controls (persons who had no signs or symptoms of active or inactive BU). This study found presence of wetland, insect bites in water, use of adhesive when injured, and washing in the Densu river as risk factors associated with BU. These factors were similar to previous studies and hence should be used in the implementation of national BU control strategies. [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]