Correspondence: The African snakebite Alliance.

The goal to reduce the burden of snakebite envenoming is challenged by the gaps in evidence for clinical care and public health. These evidence gaps and the absence of a strong network are illustrated by bibliometrics. The African Snakebite Alliance is a multidisciplinary group focusing on research themes which will generate evidence needed to shape policy and practice.

Stakeholder perspectives from 15 countries in Africa on barriers in snakebite envenoming research and the potential role of research hubs.

Snakebite envenoming is a debilitating neglected tropical disease disproportionately affecting the rural poor in low and middle-income countries in the tropics and sub-tropics. Critical questions and gaps in public health and policy need to be addressed if major progress is to be made towards reducing the negative impact of snakebite, particularly in the World Health Organisation (WHO) Africa region. We engaged key stakeholders to identify barriers to evidence-based snakebite decision making and to explore how development of research and policy hubs could help to overcome these barriers. We conducted an electronic survey among 73 stakeholders from ministries of health, health facilities, academia and non-governmental organizations from 15 countries in the WHO Africa region. The primary barriers to snakebite research and subsequent policy translation were limited funds, lack of relevant data, and lack of interest from policy makers. Adequate funding commitment, strong political will, building expert networks and a demand for scientific evidence were all considered potential factors that could facilitate snakebite research. Participants rated availability of antivenoms, research skills training and disease surveillance as key research priorities. All participants indicated interest in the development of research and policy hubs and 78% indicated their organization would be willing to actively participate. In conclusion, our survey affirms that relevant stakeholders in the field of snakebite perceive research and policy hubs as a promising development, which could help overcome the barriers to pursuing the WHO goals and targets for reducing the burden of snakebite.

"Our interventions are still here to support communities during the pandemic": Resuming mass drug administration for neglected tropical diseases after COVID-19 implementation delays.

The COVID-19 pandemic disrupted essential health services, including those provided by national neglected tropical disease (NTD) programs. Most mass drug administration (MDA) programs were postponed for 6-12 months following World Health Organization guidance released in April 2020 to temporarily halt NTD programs and launch necessary COVID-19 precautions. While NTD-endemic countries have since resumed MDA activities, it is critical to understand implementers' perspectives on the key challenges and opportunities for program relaunch, as these insights are critical for maximizing gains towards disease control and elimination during public health emergencies. Using data from using online surveys and focus group discussions, this mixed-methods study sought perspectives from Ministry of Health NTD Program Managers and implementing partners from non-governmental organizations working in sub-Saharan Africa. Data analysis revealed that findings converged around several main themes: disruptions for MDA programs included resource shortages due to prioritization of pandemic response, challenges adhering to COVID-19 safety protocols, and community hesitancy due to coronavirus transmission fears. Identified solutions for restarting MDA programs focused on adapting intervention delivery and packaging to minimize disease transmission, embracing technology to optimize intervention planning and delivery, and identifying opportunities to promote program integration between pandemic response strategies and NTD campaign delivery. Findings identifies key challenges due to disruptions to NTD program delivery and provide strategic recommendations for endemic countries to build resilient programs that can continue to perform during and beyond global pandemics.

Malacological Survey and Spatial Distribution of Intermediate Host Snails in Schistosomiasis Endemic Districts of Rwanda.

BACKGROUND: Schistosomiasis, due to S. mansoni, is prevalent in Rwanda. However, there is a paucity of information related to the abundance, species, distribution, and infectivity of Schistosoma intermediate host snails. METHODS: Snails were collected from 71 sites, including lakeshores and wetlands. Snails obtained were morphologically identified, and cercariae were shed using standard procedures. Cercariae were molecularly characterized using PCR. GPS coordinates were used to generate geospatial maps of snail distribution that were overlaid with geospatial distribution of schistosomiasis among pre-school children in the same areas. RESULTS: Overall, 3653 snails were morphologically classified as Bulinus spp. and 1449 as Biomphalaria spp. A total of 306 snails shed cercariae, 130 of which were confirmed as S. mansoni cercaria by PCR. There was no significant difference in the proportion of S. mansoni cercariae in wetlands compared to lakeshores. CONCLUSION: Rwandan water bodies harbor an important number of snails that shed S. mansoni cercariae. Furthermore, a strong spatial correlation was observed between the distribution of schistosomiasis in children and the spatial distribution of snail infectivity with S. mansoni. The presence of Bulinus spp. Suggests a potential risk of S. haematobium, although molecular analysis did not show any current transmission of this parasite.

Research priorities to support the development of integrated national strategies to control skin-neglected tropical diseases.

BACKGROUND: Skin-presenting neglected tropical diseases (skin-NTDs) impose large burdens on affected people, families and communities. The NTD Roadmap 2021-2030 presents a strategic plan to guide collaborative, multisectoral action to overcome these burdens, defining targets to control, eliminate and/or eradicate skin-NTDs by 2030. One of its targets is for 40 countries to adopt integrated skin-NTD strategies. Despite this high-level support for integration, only four countries were implementing integrated skin-NTD strategies in 2020. METHODS: We hosted workshops at the 2021 annual meeting of the Coalition for Operational Research on NTDs, to discuss the operationalisation of Roadmap goals into national strategies and interventions for skin-NTD control. Speakers included NTD Programme Managers from NTD-endemic countries, technical experts and researchers of different aspects of skin-NTDs. RESULTS: Challenges include community perceptions of interventions, demonstrating the cost-effectiveness of integrated care, availability and accessibility of community-based and primary healthcare services, the quality of data on skin-NTD morbidity and changes to operational structures required for integration. Research priorities included the identification of optimal case detection platforms, evaluation of integrated care, understanding the impacts of integration on community members and community health staff and development of point-of-care diagnostics. CONCLUSIONS: The operational research priorities are intended to support the scale-up of integrated skin-NTDs programmes.

Prevalence Mapping of Schistosoma mansoni Among Pre-school Age Children in Rwanda.

Schistosoma mansoni is endemic in Rwanda, and control programs have been implemented with a special focus on school-age children (SAC), ignoring pre-school age children (pre-SAC) for which the actual prevalence of the disease is not well established. This study consisted of a cross-sectional quantitative mapping of the distribution of Schistosoma mansoni and identification of associated risk factors among pre-SAC throughout the country. The study covered all the 17 districts of Rwanda endemic for Schistosoma mansoni, with a total sample of 4,675 children enrolled from 80 purposively selected villages. The parasitological assessment of children's urine and stool samples was conducted using CCA and Kato Katz methods, respectively, for infection detection. A standard questionnaire was used to collect data on the risk factors, and geospatial assessment was performed using tablets and GPS to record geographic coordinates for plotting locations on maps using ArcGIS software. The overall prevalence of S. mansoni infection across the surveyed areas was 24 and 0.8% by CCA and Kato-Katz, respectively. Infection was significantly associated with bathing children in open water bodies. Furthermore, pre-SAC looked after by siblings (sisters) were two times as much likely to be infected compared to those looked after by mothers. Schistosomiasis control interventions are needed for pre-SAC to limit their exposure to open water bodies with expectations of adapted chemotherapy to be availed. Community-based deworming campaigns may be the best way to ensure good treatment coverage of pre-SAC in Rwanda.

Prevalence, Intensity, and Correlates of Soil-Transmitted Helminth Infections among School Children after a Decade of Preventive Chemotherapy in Western Rwanda.

Preventive chemotherapy (PC) is a WHO-recommended core intervention measures to eliminate Soil-Transmitted Helminths (STH) as a public health problem by 2020, defined as a reduction in prevalence to <1% of moderate or high-intensity infection. We conducted a cross-sectional study to investigate the prevalence, intensity, and correlates of STH after a decade of PC in Rwanda. A total of 4998 school children (5-15 years old) from four districts along Lake Kivu in the western province were screened for STH using Kato-Katz. The overall prevalence of Soil-transmitted helminths among school children was 77.7% (range between districts = 54% to 92%). Trichirus trichiura was the most common STH (66.8%, range between districts = 23% to 88.2%), followed by Ascaris lumbricoides (49.9%, range between district = 28.5% to 63.3%) and hookworms (1.9%, range between districts = 0.6% to 2.9%). The prevalence of single, double and of triple parasite coinfection were 48.6%, 50.3%, and 1.1%, respectively. The overall prevalence of moderate or high-intensity infection for Trichirus trichiura and Ascaris lumbricoides was 7.1% and 13.9, respectively. Multivariate logistic regression model revealed that male sex, district, stunting, and schistosomiasis coinfection as significant predictors of STH infection. Despite a decade of PC implementation, STH remain a significant public health problem in Rwanda.

Individual and familial characteristics of patients with podoconiosis attending a clinic in Musanze District, Rwanda: A retrospective study.

BACKGROUND: Podoconiosis is a progressive swelling of the legs affecting genetically susceptible people who live in areas with irritant red clay soils and walk barefoot. The disease is a public health concern in many countries, including Rwanda. METHODS: This retrospective study described individual and familial characteristics of patients with podoconiosis attending the Heart and Sole Africa (HASA) clinics in Rwanda. Data on patient characteristics and family history were retrieved from electronic medical records (January 2013 - August 2019). A multiple regression analysis was used to explore factors influencing age of onset of podoconiosis. RESULTS: Among 467 patients with podoconiosis, the mean (standard deviation) age of onset was 34.4 (19.6) years, 139 (29.8%) patients developed podoconiosis at <20 years of age, 417 (89%) came from Musanze or neighboring Burera Districts, and 238 (51.0%) had a family history of podoconiosis. Increasing patient age was associated with older age at onset of disease (p<0.001), while an increased number of relatives with podoconiosis (p<0.002) was significantly associated with earlier disease onset. CONCLUSION: Most patients with podoconiosis were women, and more than half had a family history of podoconiosis. An increased number of relatives with podoconiosis was associated with a significantly younger age at disease onset.

Nationwide Remapping of Schistosoma mansoni Infection in Rwanda Using Circulating Cathodic Antigen Rapid Test: Taking Steps toward Elimination.

The field standard for the detection of Schistosoma mansoni infection is Kato-Katz (KK), although it misses many active infections, especially light infections. In 2014, a reassessment of S. mansoni prevalence was conducted in Rwanda using the more sensitive point-of-care circulating cathodic antigen (POC-CCA) rapid assay. A total of 19,371 children from 399 schools were selected for testing for single urine CCA. Of these, 8,697 children from 175 schools were also tested with single stool double-slide KK. Samples from eight of these 175 schools were tested again with CCA and additionally with the highly specific and sensitive up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay. Latent class analysis was applied to all four test results to assess sensitivity and specificity of POC-CCA and estimate the proportion of trace results from Rwanda likely to be true infections. The overall prevalence of S. mansoni infection in Rwanda when CCA trace results were considered negative was 7.4% (school interquartile range [IQR] 0-8%) and 36.1% (school IQR 20-47%) when trace was considered positive. Prevalence by KK was 2.0% with a mean intensity of infection of 1.66 eggs per gram. The proportion of active infections among children diagnosed with CCA trace was estimated by statistical analysis at 61% (Bayesian credibility interval: 50-72%). These results indicate that S. mansoni infection is still widespread in Rwanda and prevalence is much underestimated by KK testing. Circulating cathodic antigen is an affordable alternative to KK and more suitable for measuring S. mansoni prevalence in low-intensity regions.

Piloting a surveillance system to monitor the global patterns of drug efficacy and the emergence of anthelmintic resistance in soil-transmitted helminth control programs: a Starworms study protocol.

To eliminate soil-transmitted helminth (STH) infections as a public health problem, the administration of benzimidazole (BZ) drugs to children has recently intensified. But, as drug pressure increases, the development of anthelmintic drug resistance (AR) becomes a major concern. Currently, there is no global surveillance system to monitor drug efficacy and the emergence of AR. Consequently, it is unclear what the current efficacy of the used drugs is and whether AR is already present. The aim of this study is to pilot a global surveillance system to assess anthelmintic drug efficacy and the emergence of AR in STH control programs. For this, we will incorporate drug efficacy trials into national STH control programs of eight countries (Bangladesh, Cambodia, Lao PDR, Vietnam, Ghana, Rwanda, Senegal and a yet to be defined country in the Americas). In each country, one trial will be performed in one program implementation unit to assess the efficacy of BZ drugs against STHs in school-aged children by faecal egg count reduction test. Stool samples will be collected before and after treatment with BZs for Kato-Katz analysis and preserved to purify parasite DNA. The presence and frequency of known single nucleotide polymorphisms (SNPs) in the ß-tubulin genes of the different STHs will subsequently be assessed. This study will provide a global pattern of drug efficacy and emergence of AR in STH control programs. The results will provide complementary insights on the validity of known SNPs in the ß-tubulin gene as a marker for AR in human STHs as well as information on the technical and financial resources required to set up a surveillance system. Finally, the collected stool samples will be an important resource to validate different molecular technologies for the detection of AR markers or to identify novel potential molecular markers associated with AR in STH.

Parasite associations predict infection risk: incorporating co-infections in predictive models for neglected tropical diseases.

BACKGROUND: Schistosomiasis and infection by soil-transmitted helminths are some of the world's most prevalent neglected tropical diseases. Infection by more than one parasite (co-infection) is common and can contribute to clinical morbidity in children. Geostatistical analyses of parasite infection data are key for developing mass drug administration strategies, yet most methods ignore co-infections when estimating risk. Infection status for multiple parasites can act as a useful proxy for data-poor individual-level or environmental risk factors while avoiding regression dilution bias. Conditional random fields (CRF) is a multivariate graphical network method that opens new doors in parasite risk mapping by (i) predicting co-infections with high accuracy; (ii) isolating associations among parasites; and (iii) quantifying how these associations change across landscapes. METHODS: We built a spatial CRF to estimate infection risks for Ascaris lumbricoides, Trichuris trichiura, hookworms (Ancylostoma duodenale and Necator americanus) and Schistosoma mansoni using data from a national survey of Rwandan schoolchildren. We used an ensemble learning approach to generate spatial predictions by simulating from the CRF's posterior distribution with a multivariate boosted regression tree that captured non-linear relationships between predictors and covariance in infection risks. This CRF ensemble was compared against single parasite gradient boosted machines to assess each model's performance and prediction uncertainty. RESULTS: Parasite co-infections were common, with 19.57% of children infected with at least two parasites. The CRF ensemble achieved higher predictive power than single-parasite models by improving estimates of co-infection prevalence at the individual level and classifying schools into World Health Organization treatment categories with greater accuracy. The CRF uncovered important environmental and demographic predictors of parasite infection probabilities. Yet even after capturing demographic and environmental risk factors, the presences or absences of other parasites were strong predictors of individual-level infection risk. Spatial predictions delineated high-risk regions in need of anthelminthic treatment interventions, including areas with higher than expected co-infection prevalence. CONCLUSIONS: Monitoring studies routinely screen for multiple parasites, yet statistical models generally ignore this multivariate data when assessing risk factors and designing treatment guidelines. Multivariate approaches can be instrumental in the global effort to reduce and eventually eliminate neglected helminth infections in developing countries.

Mapping Schistosoma mansoni endemicity in Rwanda: a critical assessment of geographical disparities arising from circulating cathodic antigen versus Kato-Katz diagnostics.

BACKGROUND: Schistosomiasis is a neglected tropical disease caused by Schistosoma parasites. Intervention relies on identifying high-risk regions, yet rapid Schistosoma diagnostics (Kato-Katz stool assays (KK) and circulating cathodic antigen urine assays (CCA)) yield different prevalence estimates. We mapped S. mansoni prevalence and delineated at-risk regions using a survey of schoolchildren in Rwanda, where S. mansoni is an endemic parasite. We asked if different diagnostics resulted in disparities in projected infection risk. METHODS: Infection data was obtained from a 2014 Rwandan school-based survey that used KK and CCA diagnostics. Across 386 schools screened by CCA (N = 19,217). To allow for uncertainty when interpreting ambiguous CCA trace readings, which accounted for 28.8% of total test results, we generated two presence-absence datasets: CCA trace as positive and CCA trace as negative. Samples (N = 9,175) from 185 schools were also screened by KK. We included land surface temperature (LST) and the Normalized Difference Vegetation and Normalized Difference Water Indices (NDVI, NDWI) as predictors in geostatistical regressions. FINDINGS: Across 8,647 children tested by both methods, prevalence was 35.93% for CCA trace as positive, 7.21% for CCA trace as negative and 1.95% for KK. LST was identified as a risk factor using KK, whereas NDVI was a risk factor for CCA models. Models predicted high endemicity in Northern and Western regions of Rwanda, though the CCA trace as positive model identified additional high-risk areas that were overlooked by the other methods. Estimates of current burden for children at highest risk (boys aged 5-9 years) varied by an order of magnitude, with 671,856 boys projected to be infected by CCA trace as positive and only 60,453 projected by CCA trace as negative results. CONCLUSIONS: Our findings show that people in Rwanda's Northern, Western and capital regions are at high risk of S. mansoni infection. However, variation in identification of environmental risk factors and delineation of at-risk regions using different diagnostics likely provides confusing messages to disease intervention managers. Further research and statistical analyses, such as latent class analysis, can be used to improve CCA result classification and assess its use in guiding treatment regimes.