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7 páginas., In 2020, WHO recognised the importance of strongyloidiasis alongside soil-transmitted helminths (STH) in their 2021–30 roadmap, which aspires to target Strongyloides stercoralis with preventive chemotherapy by use of ivermectin. Combination treatment with both albendazole, the primary drug used to treat STH, and ivermectin, would improve the efficiency of mass drug administration targeting both STH and S stercoralis. In this Personal View, we discuss the challenges and opportunities towards the development of an efficient control programme for strongyloidiasis, particularly if it is to run concurrently with STH control. We argue the need to define the prevalence threshold to implement preventive chemotherapy for S stercoralis, the target populations and optimal dosing schedules, and discuss the added benefits of a fixed-dose coformulation of ivermectin and albendazole. Implementation of an efficient control programme will require improvements to current diagnostics, and validation of new diagnostics, to target and monitor S stercoralis infections, and consideration of the challenges of multispecies diagnostics for S stercoralis and STH control. Finally, the evolution of ivermectin resistance represents a credible risk to control S stercoralis; we argue that genome-wide approaches, together with improved genome resources, are needed to characterise and prevent the emergence of resistance. Overcoming these challenges will help to reduce strongyloidiasis burden and enhance the feasibility of controlling it worldwide., Our group, the Stopping Transmission of intestinal Parasites (STOP) consortium, is funded by the EDCTP2 programme supported by the European Union (RIA2017NCT-1845-STOP). The Barcelona Institute for Global Health (ISGlobal) acknowledges support from the Spanish Ministry of Science and Innovation and State Research Agency through the Centro de Excelencia Severo Ochoa 2019–2023 Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. SRD is supported by a UK Research and Innovation Future Leaders Fellowship [MR/T020733/1] and the Wellcome Trust through core funding to the Wellcome Sanger Institute [108413/A/15/D]. MC-P is supported by the Junta de Castilla y León and Fondo Social Europeo. The funders of the study had no role in the manuscript preparation or the decision to publish. The views, opinions, assumptions, or any other information set out in this Personal View are solely those of the authors and should not be attributed to the funders or any person connected with the funders.

Background Schistosomiasis control programmes primarily use school-based surveys to identify areas for mass drug administration of preventive chemotherapy. However, as the spatial distribution of schistosomiasis can be highly focal, transmission may not be detected by surveys implemented at districts or larger spatial units. Improved mapping strategies are required to accurately and cost-effectively target preventive chemotherapy to remaining foci across all possible spatial distributions of schistosomiasis. Methods Here, we use geostatistical models to quantify the spatial heterogeneity of Schistosoma haematobium and S. mansoni across sub-Saharan Africa using the most comprehensive dataset available on school-based surveys. Applying this information to parameterise simulations, we assess the accuracy and cost of targeting alternative implementation unit sizes across the range of plausible schistosomiasis distributions. We evaluate the consequences of decisions based on survey designs implemented at district and subdistrict levels sampling different numbers of schools. Cost data were obtained from field surveys conducted across multiple countries and years, with cost effectiveness evaluated as the cost per correctly identified school. Results Models identified marked differences in prevalence and spatial distributions between countries and species; however, results suggest implementing surveys at subdistrict level increase the accuracy of treatment classifications across most scenarios. While sampling intensively at the subdistrict level resulted in the highest classification accuracy, this sampling strategy resulted in the highest costs. Alternatively, sampling the same numbers of schools currently recommended at the district level but stratifying by subdistrict increased cost effectiveness. Conclusions This study provides a new tool to evaluate schistosomiasis survey designs across a range of transmission settings. Results highlight the importance of considering spatial structure when designing sampling strategies, illustrating that a substantial proportion of children may be undertreated even when an implementation unit is correctly classified. Control programmes need to weigh the increased accuracy of more detailed mapping strategies against the survey costs and treatment priorities. Graphical Abstract

Summary Background Few studies have been done of patterns of treatment during mass drug administration (MDA) to control neglected tropical diseases. We used routinely collected individual-level treatment records that had been collated for the Tuangamize Minyoo Kenya Imarisha Afya (Swahili for Eradicate Worms in Kenya for Better Health [TUMIKIA]) trial, done in coastal Kenya from 2015 to 2017. In this analysis we estimate the extent of and factors associated with the same individuals not being treated over multiple rounds of MDA, which we term systematic non-treatment. Methods We linked the baseline population of the TUMIKIA trial randomly assigned to receive biannual community-wide MDA for soil-transmitted helminthiasis to longitudinal records on receipt of treatment in any of the four treatment rounds of the study. We fitted logistic regression models to estimate the association of non-treatment in a given round with non-treatment in the previous round, controlling for identified predictors of non-treatment. We also used multinomial logistic regression to identify factors associated with part or no treatment versus complete treatment. Findings 36 327 participants were included in our analysis: 16 236 children aged 2–14 years and 20 091 adults aged 15 years or older. The odds of having no treatment recorded was higher if a participant was not treated during the previous round of MDA (adjusted odds ratio [OR] 3·60, 95% CI 3·08–4·20 for children and 5·58, 5·01–6·21 for adults). For children, school attendance and rural residence reduced the odds of receiving part or no treatment, whereas odds were increased by least poor socioeconomic status and living in an urban or periurban household. Women had higher odds than men of receiving part or no treatment. However, when those with pregnancy or childbirth in the previous 2 weeks were excluded, women became more likely to receive complete treatment. Adults aged 20–25 years were the age group with the highest odds of receiving part (OR 1·41, 95% CI 1·22–1·63) or no treatment (OR 1·81, 95% CI 1·53–2·14). Interpretation Non-treatment was associated with specific sociodemographic groups and characteristics and did not occcur at random. This finding has important implications for MDA programme effectiveness, the relevance of which will intensify as disease prevalence decreases and infections become increasingly clustered. Funding Bill & Melinda Gates Foundation, Joint Global Health Trials Scheme of the Medical Research Council, UK Department for International Development, Wellcome Trust, Children's Investment Fund Foundation, and London Centre for Neglected Tropical Diseases.

Over 95% of the global burden of Buruli ulcer disease (BU) caused by Mycobacterium ulcerans occurs in equatorial Africa. National and sub-national programs have implemented various approaches to improve detection and reporting of incident cases over recent decades. Regional incidence rates are currently in decline; however, surveillance targets outlined in 2012 by WHO have been missed and detection bias may contribute to these trends. In light of the new 2030 NTD roadmap and disease-specific targets, BU programs are required to strengthen case detection and begin a transition towards integration with other skin-NTDs. This transition comes with new opportunities to enhance existing BU surveillance systems and develop novel approaches for implementation and evaluation.In this review, we present a breakdown and assessment of the methods and approaches that have been the pillars of BU surveillance systems in Africa: (1) Passive case detection, (2) Data systems, (3) Clinical training, (4) Active case finding, (5) Burden estimation, and (6) Laboratory confirmation pathways. We discuss successes, challenges, and relevant case studies before highlighting opportunities for future development and evaluation including novel data collection tools, risk-based surveillance, and integrated skin-NTD surveillance. We draw on both experience and available literature to critically evaluate methods of BU surveillance in Africa and highlight new approaches to help achieve 2030 roadmap targets.

Over 95% of the global burden of Buruli ulcer disease (BU) caused by Mycobacterium ulcerans occurs in equatorial Africa. National and sub-national programs have implemented various approaches to improve detection and reporting of incident cases over recent decades. Regional incidence rates are currently in decline; however, surveillance targets outlined in 2012 by WHO have been missed and detection bias may contribute to these trends. In light of the new 2030 NTD roadmap and disease-specific targets, BU programs are required to strengthen case detection and begin a transition towards integration with other skin-NTDs. This transition comes with new opportunities to enhance existing BU surveillance systems and develop novel approaches for implementation and evaluation.In this review, we present a breakdown and assessment of the methods and approaches that have been the pillars of BU surveillance systems in Africa: (1) Passive case detection, (2) Data systems, (3) Clinical training, (4) Active case finding, (5) Burden estimation, and (6) Laboratory confirmation pathways. We discuss successes, challenges, and relevant case studies before highlighting opportunities for future development and evaluation including novel data collection tools, risk-based surveillance, and integrated skin-NTD surveillance. We draw on both experience and available literature to critically evaluate methods of BU surveillance in Africa and highlight new approaches to help achieve 2030 roadmap targets.

BackgroundOnchocerciasis (river blindness) is a filarial disease targeted for elimination of transmission. However, challenges exist to the implementation of effective diagnostic and surveillance strategies at various stages of elimination programs. To address these challenges, we used a network data analytics approach to identify optimal diagnostic scenarios for onchocerciasis elimination mapping (OEM).MethodsThe diagnostic network optimization (DNO) method was used to model the implementation of the old Ov16 rapid diagnostic test (RDT) and of new RDTs in development for OEM under different testing strategy scenarios with varying testing locations, test performance and disease prevalence. Environmental suitability scores (ESS) based on machine learning algorithms were developed to identify areas at risk of transmission and used to select sites for OEM in Bandundu region in the Democratic Republic of Congo (DRC) and Uige province in Angola. Test sensitivity and specificity ranges were obtained from the literature for the existing RDT, and from characteristics defined in the target product profile for the new RDTs. Sourcing and transportation policies were defined, and costing information was obtained from onchocerciasis programs. Various scenarios were created to test various state configurations. The actual demand scenarios represented the disease prevalence at IUs according to the ESS, while the counterfactual scenarios (conducted only in the DRC) are based on adapted prevalence estimates to generate prevalence close to the statistical decision thresholds (5% and 2%), to account for variability in field observations. The number of correctly classified implementation units (IUs) per scenario were estimated and key cost drivers were identified.ResultsIn both Bandundu and Uige, the sites selected based on ESS had high predicted onchocerciasis prevalence >10%. Thus, in the actual demand scenarios in both Bandundu and Uige, the old Ov16 RDT correctly classified all 13 and 11 IUs, respectively, as requiring CDTi. In the counterfactual scenarios in Bandundu, the new RDTs with higher specificity correctly classified IUs more cost effectively. The new RDT with highest specificity (99.8%) correctly classified all 13 IUs. However, very high specificity (e.g., 99.8%) when coupled with imperfect sensitivity, can result in many false negative results (missing decisions to start MDA) at the 5% statistical decision threshold (the decision rule to start MDA). This effect can be negated by reducing the statistical decision threshold to 2%. Across all scenarios, the need for second stage sampling significantly drove program costs upwards. The best performing testing strategies with new RDTs were more expensive than testing with existing tests due to need for second stage sampling, but this was offset by the cost of incorrect classification of IUs.ConclusionThe new RDTs modelled added most value in areas with variable disease prevalence, with most benefit in IUs that are near the statistical decision thresholds. Based on the evaluations in this study, DNO could be used to guide the development of new RDTs based on defined sensitivities and specificities. While test sensitivity is a minor driver of whether an IU is identified as positive, higher specificities are essential. Further, these models could be used to explore the development and optimization of new tools for other neglected tropical diseases.

Recently, the World Health Organization established the Diagnostic Technical Advisory Group to identify and prioritize diagnostic needs for neglected tropical diseases, and to ultimately describe the minimal and ideal characteristics for new diagnostic tests (the so-called target product profiles (TPPs)). We developed two generic frameworks: one to explore and determine the required sensitivity (probability to correctly detect diseased persons) and specificity (probability to correctly detect persons free of disease), and another one to determine the corresponding samples sizes and the decision rules based on a multi-category lot quality assurance sampling (MC-LQAS) approach that accounts for imperfect tests. We applied both frameworks for monitoring and evaluation of soil-transmitted helminthiasis control programs. Our study indicates that specificity rather than sensitivity will become more important when the program approaches the endgame of elimination and that the requirements for both parameters are inversely correlated, resulting in multiple combinations of sensitivity and specificity that allow for reliable decision making. The MC-LQAS framework highlighted that improving diagnostic performance results in a smaller sample size for the same level of program decision making. In other words, the additional costs per diagnostic tests with improved diagnostic performance may be compensated by lower operational costs in the field. Based on our results we proposed the required minimal and ideal diagnostic sensitivity and specificity for diagnostic tests applied in monitoring and evaluating of soil-transmitted helminthiasis control programs., Author summary The World Health Organization established an advisory group to identify and prioritize diagnostic needs for neglected tropical diseases, and to ultimately describe the minimal and ideal characteristics for new diagnostic tests. To support this advisory group, we developed two generic frameworks, which we applied to soil-transmitted helminthiases: one to explore and determine the required sensitivity (probability to correctly detect a diseased person) and specificity (probability to correctly detect a person free of disease), and another one to determine the corresponding samples size and decision rules during surveys. We showed that specificity rather than sensitivity will become more important when the program approaches the endgame of elimination and that the requirements for both parameters are inversely correlated, resulting in multiple combinations of sensitivity and specificity that allow for reliable decision making. We also highlighted that improving diagnostic performance results in smaller sample sizes for the same level of program decision making. In other words, the additional costs per diagnostic tests with improved diagnostic performance can be compensated by the lower operational costs in the field. Based on our results we proposed to the advisory group the required performance characteristics of diagnostic tests for soil-transmitted helminthiasis control programs.

The original version of this Article contained an error in the Introduction where, “We utilise weekly MSOA level population mobility data against observed confirmed COVID-19 case data to assess the impact mobility reduction at small-area scale has had on case transmission, and counterfactually what the magnitude may have been under the scenario of no mobility loss.” now reads: “We utilise weekly Clinical Commission Group (CCG) level population mobility data against observed confirmed COVID-19 case data to assess the impact mobility reduction at small-area scale has had on case transmission, and counterfactually what the magnitude may have been under the scenario of no mobility loss.” In addition, in Table 2, the Spatial resolution was incorrectly given in the column “Model component”, rows “Covariate (daily varying)” and “Covariates (annual estimates, weekly fixed), Elderly population proportion living in deprivation”. The correct and incorrect values appear below. Incorrect: (Table presented.) Correct: (Table presented.) Finally, in the Methods section, under the subheadings ‘Data’, and ‘Data analysis”, “Daily population movement data by MSOA was extracted from the COVID-19 Impact monitor (https:// www. oxford- covid- 19. com/).” now reads: “Daily population movement data by Clinical Commission Group (CCG) was extracted from the COVID-19 Impact monitor (https:// www. oxford- covid- 19. com/). Weekly mobility in a given MSOA where assumed to be the same as the weekly mobility in the higher level CCG containing most of that MSOA.” “Here b = (b0, b1, b2) is the vector of regression coefficients for the intercept (representing the log-transformed baseline transmission rate across all locations), mobility represents the observed weekly mobility by MSOA;” now reads: “Here b = (b0, b1, b2) is the vector of regression coefficients for the intercept (representing the log-transformed baseline transmission rate across all locations), mobility represents the observed weekly mobility in a given MSOA based on the mobility in the CCG containing most of that MSOA;” The original Article has been corrected. © The Author(s) 2021

Recent global commitments to shift responsibility for Neglected Tropical Disease (NTD) control to affected countries reflect a renewed emphasis on sustainability, away from aid-dependency. This calls for a better understanding of how domestic stakeholders perceive investments in different strategies for NTD control. Soil transmitted helminths (STH) are among the NTDs targeted for elimination as a public health problem by international agencies through mass drug administration, provided periodically to at-risk population groups, often using drugs donated by pharmaceutical companies. This study was conducted in Kenya at a time when responsibilities for long running STH programmes were transitioning from external to national and sub-national agencies. Following an initial assessment in which we identified key domestic stakeholders and reviewed relevant scientific and government documents, the perspectives of stakeholders working in health, education, community engagement and sanitation were investigated through semi-structured interviews with national level policymakers, county level policymakers, and frontline implementers in one high-STH burden county, Kwale. Our conceptual framework on sustainability traced a progression in thinking, from ensuring financial stability through the technical ability to adapt to changing circumstances, and ultimately to a situation where a programme is prioritised by domestic policymakers because empowered communities demand it. It was clear from our interviews that most Kenyan stakeholders sought to be at the final stage in this progression. Interviewees criticised long-term investment in mass drug administration, the approach favoured predominantly by external agencies, for failing to address underlying causes of STH. Instead they identified three synergistic priority areas for investment: changes in institutional structures and culture to reduce working in silos; building community demand for and ownership; and increased policymaker engagement on underlying socioeconomic and environmental causes of STH. Although challenging to implement, the shift in responsibility from external agencies to domestic stakeholders may lead to emergence of new strategic directions.

Background Podoconiosis is a type of elephantiasis characterised by swelling of the lower legs. It is often confused with other causes of tropical lymphedema and its global distribution is uncertain. Here we synthesise the available information on the presence of podoconiosis to produce evidence consensus maps of its global geographical distribution. Methods and findings We systematically searched available data on podoconiosis in SCOPUS and MEDLINE from inception, updated to 10 May, 2019, and identified observational and population-based studies reporting podoconiosis. To establish existence of podoconiosis, we used the number of cases reported in studies and prevalence data with geographical locations. We then developed an index to assess evidence quality and reliability, assigning each country an evidence consensus score. Using these summary scores, we then developed a contemporary global map of national-level podoconiosis status. There is evidence of podoconiosis in 17 countries (12 in Africa, three in Latin America, and two in Asia) and consensus on presence in six countries (all in Africa). We have identified countries where surveillance is required to further define the presence or absence of podoconiosis. We have highlighted areas where evidence is currently insufficient or conflicting, and from which more evidence is needed. Conclusion The global distribution of podoconiosis is not clearly known; the disease extent and limits provided here inform the best contemporary map of the distribution of podoconiosis globally from available data. These results help identify surveillance needs, direct future mapping activities, and inform prevention plans and burden estimation of podoconiosis., Author summary The global distribution of podoconiosis is uncertain. With our current understanding of its distribution still incomplete, many of the countries suspected to be endemic for podoconiosis are based on expert opinion and lack published evidence of confirmed cases. In this study, we used multiple data sources and health metrics to identify countries with presence and absence of podoconiosis with appropriate uncertainties. After assembling a database of different evidence types we constructed a weighted score for each country called ‘evidence consensus scores’. We used these scores to measure the certainty of the presence and absence of podoconiosis. The maps produced help to identify evidence gaps and uncertainties in the current global distribution of podoconiosis. Countries with evidence of podoconiosis are mostly clustered in Africa, and a few in Asia and Latin America. We have also identified countries with indeterminate status on the presence and absences of podoconiosis. These countries are characterised by weak health systems and multiple co-endemic diseases causing lower leg swelling, potentially leading to misdiagnosis of podoconiosis. Given these challenges, we recommend intensified disease surveillance and active case searching be implemented in areas where evidence is lacking.

The World Health Organization’s (WHO’s) 2030 road map for neglected tropical diseases (NTDs) emphasizes the importance of strengthened, institutionalized “post-elimination” surveillance. The required shift from disease-siloed, campaign-based programming to routine, integrated surveillance and response activities presents epidemiological, logistical, and financial challenges, yet practical guidance on implementation is lacking. Nationally representative survey programs, such as demographic and health surveys (DHS), may offer a platform for the integration of NTD surveillance within national health systems and health information systems. Here, we describe characteristics of DHS and other surveys conducted within the WHO Africa region in terms of frequency, target populations, and sample types and discuss applicability for post-validation and post-elimination surveillance. Maximizing utility depends not only on the availability of improved diagnostics but also on better understanding of the spatial and temporal dynamics of transmission at low prevalence. To this end, we outline priorities for obtaining additional data to better characterize optimal post-elimination surveillance platforms.

Many sanitation interventions suffer from poor sustainability. Failure to maintain or replace toilet facilities risks exposing communities to environmental pathogens, yet little is known about the factors that drive sustained access beyond project life spans. Using data from a cohort of 1666 households in Kwale County, Kenya, we investigated the factors associated with changes in sanitation access between 2015 and 2017. Sanitation access is defined as access to an improved or unimproved facility within the household compound that is functional and in use. A range of contextual, psychosocial, and technological covariates were included in logistic regression models to estimate their associations with (1) the odds of sustaining sanitation access and (2) the odds of gaining sanitation access. Over two years, 28.3% households sustained sanitation access, 4.7% lost access, 17.7% gained access, and 49.2% remained without access. Factors associated with increased odds of households sustaining sanitation access included not sharing the facility and presence of a solid washable slab. Factors associated with increased odds of households gaining sanitation access included a head with at least secondary school education, level of coarse soil fragments, and higher local sanitation coverage. Results from this study can be used by sanitation programs to improve the rates of initial and sustained adoption of sanitation.

We confirmed endemicity and autochthonous transmission of yaws in Liberia after a population-based, community-led burden estimation (56,825 participants). Serologically confirmed yaws was rare and focal at population level (24 cases; 2.6 [95% CI 1.4-3.9] cases/10,000 population) with similar clinical epidemiology to other endemic countries in West Africa. Unsupervised classification of spatially referenced case finding data indicated that yaws was more likely to occur in hard-to-reach communities; healthcare-seeking was low among communities, and clinical awareness of yaws was low among healthcare workers. We recovered whole bacterial genomes from 12 cases and describe a monophyletic clade of Treponema pallidum subspecies pertenue, phylogenetically distinct from known TPE lineages, including those affecting neighboring nonhuman primate populations (Tai Forest, Cote d'Ivoire). Yaws is endemic in Liberia but exhibits low focal population prevalence with evidence of a historical genetic bottleneck and subsequent local expansion. Reporting gaps appear attributable to challenging epidemiology and low disease awareness.

Malawi has successfully leveraged multiple delivery platforms to scale-up and sustain the implementation of preventive chemotherapy (PCT) for the control of morbidity caused by soil-transmitted helminths (STH). Sentinel monitoring demonstrates this strategy has been successful in reducing STH infection in school-age children, although our understanding of the contemporary epidemiological profile of STH across the broader community remains limited. As part of a multi-site trial evaluating the feasibility of interrupting STH transmission across three countries, this study aimed to describe the baseline demographics and the prevalence, intensity and associated risk factors of STH infection in Mangochi district, southern Malawi. Between October-December 2017, a community census was conducted across the catchment area of seven primary healthcare facilities, enumerating 131,074 individuals across 124 villages. A cross-sectional parasitological survey was then conducted between March-May 2018 in the censused area as a baseline for a cluster randomised trial. An age-stratified random sample of 6,102 individuals were assessed for helminthiasis by Kato-Katz and completed a detailed risk-factor questionnaire. The age-cluster weighted prevalence of any STH infection was 7.8% (95% C.I. 7.0%-8.6%) comprised predominantly of hookworm species and of entirely low-intensity infections. The presence and intensity of infection was significantly higher in men and in adults. Infection was negatively associated with risk factors that included increasing levels of relative household wealth, higher education levels of any adult household member, current school attendance, or recent deworming. In this setting of relatively high coverage of sanitation facilities, there was no association between hookworm and reported access to sanitation, handwashing facilities, or water facilities. These results describe a setting that has reduced the prevalence of STH to a very low level, and confirms many previously recognised risk-factors for infection. Expanding the delivery of anthelmintics to groups where STH infection persist could enable Malawi to move past the objective of elimination of morbidity, and towards the elimination of STH. Trial registration: NCT03014167., Author summary The major public health strategy to control soil-transmitted helminths (STH) is preventive chemotherapy, whereby those at greatest risk of morbidity–including children and women of childbearing age–are presumptively treated with a safe, effective and inexpensive anthelminthic drug. In Malawi, this has been successfully sustained for nearly a decade through annual school-based deworming, in addition to integration within child health campaigns and antenatal care. Routine surveillance of schoolchildren demonstrates that STH has been reduced to very low levels in this age group, but few community-based epidemiological surveys have been conducted to investigate STH in the broader population. In this study, we observed that while infection with STH has been reduced to low levels overall, it is much higher in adults and particularly in males, with the odds of being infected greater in those from less wealthy households or from households with lower levels of adult education. These results underline that while preventive chemotherapy has likely been key to reductions in STH; sub-populations not routinely targeted by preventive chemotherapy, and the most disadvantaged members of society, continue to be disproportionately affected. We propose that evaluation of more comprehensive control strategies–such as entire-community deworming–could overcome these limitations, and present a route to STH elimination.

Buruli ulcer (BU) is a disabling and stigmatising neglected tropical disease (NTD). Its distribution and burden are unknown because of underdiagnosis and underreporting. It is caused by Mycobacterium ulcerans, an environmental pathogen whose environmental niche and transmission routes are not fully understood. The main control strategy is active surveillance to promote early treatment and thus limit morbidity, but these activities are mostly restricted to well-known endemic areas. A better understanding of environmental suitability for the bacterium and disease could inform targeted surveillance, and advance understanding of the ecology and burden of BU. We used previously compiled point-level datasets of BU and M. ulcerans occurrence, evidence for BU occurrence within national and sub-national areas, and a suite of relevant environmental covariates in a distribution modelling framework. We fitted relationships between BU and M. ulcerans occurrence and environmental predictors by applying regression and machine learning based algorithms, combined in an ensemble model to characterise the optimal ecological niche for the disease and bacterium across Africa at a resolution of 5km x 5km. Proximity to waterbodies was the strongest predictor of suitability for BU, followed potential evapotranspiration. The strongest predictors of suitability for M. ulcerans were deforestation and potential evapotranspiration. We identified patchy foci of suitability throughout West and Central Africa, including areas with no previous evidence of the disease. Predicted suitability for M. ulcerans was wider but overlapping with that of BU. The estimated population living in areas predicted suitable for the bacterium and disease was 46.1 million. These maps could be used to inform burden estimations and case searches which would generate a more complete understanding of the spatial distribution of BU in Africa, and may guide control programmes to identify cases beyond the well-known endemic areas., Author summary Like many neglected tropical diseases primarily affecting the rural poor, Buruli ulcer (BU) is under-detected and under-reported within routine health information systems. As such, the burden and distribution are not fully known, impeding appropriate targeting of health resources, control, and care for people affected. Having previously evaluated and mapped the existing evidence for BU and its causative agent M. ulcerans, we concluded that the disease was likely to occur beyond the range of known endemic areas. However, we were left with the question of where exactly these undetected cases might be occurring. Answering this question required a more fine-scale approach: BU is highly focal, presumably due to local variation in the environmental factors which determine suitability for M. ulcerans survival and transmission to humans. We used the compiled evidence and geographical datasets to build statistical models representing the relationship between environmental factors and previously reported cases. This allowed us to define the ecological niche of BU, and subsequently to identify areas across Africa where this niche was met, providing suitable conditions for the disease. We constructed separate models of suitability for M. ulcerans, using locations where its DNA had been detected in environmental sources. Unsurprisingly, suitability for M. ulcerans was predicted to be wider than, but geographically overlapping with that for BU. This implies that beyond the conditions necessary for survival of the bacterium, additional factors are required for transmission to humans. The high-resolution suitability maps we present are intended to guide case search activities which may identify endemic areas beyond the known endemic range. Data on the true prevalence of BU from targeted case searches within predicted-suitable areas will also allow us to validate and refine the models, and potentially to predict the probability of cases occurring within predicted suitable areas.

COVID-19 caseloads in England have passed through a first peak, and at the time of this analysis appeared to be gradually increasing, potentially signalling the emergence of a second wave. To ensure continued response to the epidemic is most effective, it is imperative to better understand both retrospectively and prospectively the geographical evolution of COVID-19 caseloads and deaths at small-area resolution, identify localised areas in space–time at significantly higher risk, quantify the impact of changes in localised population mobility (or movement) on caseloads, identify localised risk factors for increased mortality and project the likely course of the epidemic at high spatial resolution in coming weeks. We applied a Bayesian hierarchical space–time SEIR model to assess the spatiotemporal variability of COVID-19 caseloads (transmission) and deaths at small-area scale in England [Middle Layer Super Output Area (MSOA), 6791 units] and by week (using observed data from week 5 to 34 of 2020), including key determinants, the modelled transmission dynamics and spatial–temporal random effects. We also estimate the number of cases and deaths at small-area resolution with uncertainty projected forward in time by MSOA (up to week 51 of 2020), the impact mobility reductions (and subsequent easing) have had on COVID-19 caseloads and quantify the impact of key socio-demographic risk factors on COVID-19 related mortality risk by MSOA. Reductions in population mobility during the course of the first lockdown had a significant impact on the reduction of COVID-19 caseloads across England, however local authorities have had a varied rate of reduction in population movement which our model suggest has substantially impacted the geographic heterogeneity in caseloads at small-area scale. The steady gain in population mobility, observed from late April, appears to have contributed to a slowdown in caseload reductions towards late June and subsequent start of the second wave. MSOA with higher proportions of elderly (70+ years of age) and elderly living in deprivation, both with very distinct geographic distributions, have a significantly elevated COVID-19 mortality rates. While non-pharmaceutical interventions (that is, reductions in population mobility and social distancing) had a profound impact on the trajectory of the first wave of the COVID-19 outbreak in England, increased population mobility appears to have significantly contributed to the second wave. A number of contiguous small-areas appear to be at a significant elevated risk of high COVID-19 transmission, many of which are also at increased risk for higher mortality rates. A geographically staggered re-introduction of intensified social distancing measures is advised and limited cross MSOA movement if the magnitude and geographic extent of the second wave is to be reduced.

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.

We present a general framework which describes the systematic (binary) scenario of individuals either taking treatment or not for any reason, over the course of mass drug administration (MDA)—which we refer to as ‘adherence’ and ‘non-adherence’. The probability models developed can be informed by observed adherence behaviour as well as employed to explore how different patterns influence the impact of MDA programmes, by the use of mathematical models of transmission and control. We demonstrate the interpretative value of the developed probability model employing a dataset collected in the TUMIKIA project, a randomised trial of deworming strategies to control soil-transmitted helminths (STH) by MDA conducted in coastal Kenya. We stratify our analysis by age and sex, although the framework which we introduce here may be readily adapted to accommodate other stratifications. Our findings include the detection of specific patterns of non-adherence in all age groups to varying extents. This is particularly apparent in men of ages 30+. We then demonstrate the use of the probability model in stochastic individual-based simulations by running two example forecasts for the elimination of STH transmission employing MDA within the TUMIKIA trial setting with different adherence patterns. This suggested a substantial reduction in the probability of elimination (between 23-43%) when comparing observed adherence patterns with an assumption of independence, with important implications for programmes. The results here demonstrate the considerable impact and utility of considering non-adherence on the success of MDA programmes to control neglected tropical diseases (NTDs)., Author summary Mass drug administration (MDA) is an important tool in the prevention of morbidity caused by various NTDs and in the reduction of their transmission. Due to a variety of social and behavioural reasons, many people will either not be offered or refuse such treatment, and if this behaviour is recurring at an individual level, then control measures may face a challenge in achieving their stated goals. Accurately describing the patterns of individual adherence or non-adherence to MDA control measures for NTDs from data, followed by their use in simulated scenarios is a relatively recent development in the study of NTDs. Past analyses assessing individual adherence have informed the approach we take in this work. However, we have sought to provide a framework which encapsulates as many types of adherence behaviour as possible to facilitate the assessment of impact in mathematical models of parasite transmission and control. Our example application to the TUMIKIA data highlights the importance of such a general framework as we find a dependence on past behaviour that may have been missed in standard statistical analyses.

Background Driven by global targets to eliminate soil-transmitted helminths as a public health problem, governments have rapidly rolled out control programmes using school and community-based platforms. To justify and target ongoing investment, quantification of impact and identification of remaining high-risk areas are needed. We aimed to assess regional progress towards these targets. Methods We did a continental-scale ecological analysis using a Bayesian space–time hierarchical model to estimate the effects of known environmental, socioeconomic, and control-related factors on the prevalence of soil-transmitted helminths, and we mapped the probability that implementation units had achieved moderate-to-heavy intensity infection prevalence of less than 2% among children aged 5–14 years between Jan 1, 2000, and Dec 31, 2018. Findings We incorporated data from 26 304 georeferenced surveys, spanning 3096 (60%) of the 5183 programmatic implementation units. Our findings suggest a reduction in the prevalence of soil-transmitted helminths in children aged 5–14 years in sub-Saharan Africa, from 44% in 2000 to 13% in 2018, driven by sustained delivery of preventive chemotherapy, improved sanitation, and economic development. Nevertheless, 1301 (25%) of 5183 implementation units still had an estimated prevalence of moderate-to-heavy intensity infection exceeding the 2% target threshold in 2018, largely concentrated in nine countries (in 1026 [79%] of 1301 implementation units): Nigeria, Democratic Republic of the Congo, Ethiopia, Cameroon, Angola, Mozambique, Madagascar, Equatorial Guinea, and Gabon. Interpretation Our estimates highlight the areas to target and strengthen interventions, and the areas where data gaps remain. If elimination of soil-transmitted helminths as a public health problem is to be achieved in sub-Saharan Africa by 2030, continued investment in treatment and prevention activities are essential to ensure that no areas are left behind. Funding Bill & Melinda Gates Foundation.

Scabies is known to be a public health problem in many settings but the majority of recent data is from rural settings in the Pacific. There is a need for high quality data from sub-Saharan Africa and peri-urban settings to inform scale up of scabies control efforts. There have been anecdotal reports of scabies being a public health problem in Liberia but robust data are lacking. We conducted a cross-sectional cluster-randomised prevalence survey for scabies in a peri-urban community in Monrovia, Liberia in February-March 2020. Participants underwent a standardised examination conducted by trained local health care workers. Health related quality of life (HRQoL) was assessed using age-appropriate versions of the dermatology life quality index (DLQI). Prevalence estimates were calculated accounting for clustering at community and household levels and associations with key demographic variables assessed through multivariable random-effects logistic regression. 1,318 participants from 477 households were surveyed. The prevalence of scabies was 9.3% (95% CI: 6.5–13.2%), across 75 (19.7%) households; impetigo or infected scabies prevalence was 0.8% (95% CI: 0.4–1.9%). The majority (52%) of scabies cases were classified as severe. Scabies prevalence was lower in females and higher in the youngest age group; no associations were found with other collected demographic or socio-economic variables. DLQI scores indicated a very or extremely large effect on HRQoL in 29% of adults and 18% of children diagnosed with scabies. Our study indicates a substantial burden of scabies in this peri-urban population in Liberia. This was associated with significant impact on quality of life, highlighting the need for action to control scabies in this population. Further work is needed to assess the impact of interventions in this context on both the prevalence of scabies and quality of life., Author summary Scabies is an infestation with a microscopic mite which affects many people living in low-resource tropical countries. It causes intense itching, which can lead to complications through bacterial infection and poor quality of life. To help develop global scabies control programmes, we need a better understanding of how common it is across different tropical settings. We conducted a survey to assess the burden of scabies and bacterial skin infection in a random sample of people living in a community in Monrovia, Liberia. Information about participants and their household were collected and their skin was examined; those with skin conditions were asked about its impact on quality of life. We examined 1,318 participants and found that almost 10% of people had scabies. Scabies was more common in young children and more common in male children than female children. We found that there was a large impact on quality of life due mostly to the itching that scabies causes and to people feeling embarrassed or sad because of their skin condition. This scabies survey is one of the first conducted across all age groups in recent years in sub-Saharan Africa and indicates a substantial burden and impact on quality of life. More work is needed to understand how common scabies is in different settings and the impact that different treatment strategies may have.

Background: COVID-19 caseloads in England appear have passed through a first peak, with evidence of an emerging second wave. To ensure continued response to the epidemic is most effective, it is imperative to better understand both retrospectively and prospectively the geographical evolution of COVID-19 caseloads and deaths, identify localised areas in space-time at significantly higher risk, quantify the impact of changes in localised population mobility (or movement) on caseloads, identify localised risk factors for increased mortality and project the likely course of the epidemic at small-area resolution in coming weeks.Methods: We applied a Bayesian space–time SEIR model to assess the spatiotemporal variability of COVID-19 caseloads (transmission) and deaths at small-area scale in England (Middle Layer Super Output Area [MSOA], 6791 units) and by week (using observed data from week 5 to 34), including key determinants, the modelled transmission dynamics and spatial-temporal random effects. We also estimate the number of cases and deaths at small-area resolution with uncertainty projected forward in time by MSOA (up to week 51 of 2020), the impact mobility reductions (and subsequent easing) have had on COVID-19 caseloads and quantify the impact of key socio-demographic risk factors on COVID-19 related mortality risk by MSOA.Results: Reductions in population mobility due the course of the first lockdown had a significant impact on the reduction of COVID-19 caseloads across England, however local authorities have had a varied rate of reduction in population movement which our model suggest has substantially impacted the geographic heterogeneity in caseloads at small-area scale. The steady gain in population mobility, observed from late April, appears to have contributed to a slowdown in caseload reductions towards late June and subsequent steady increase signalling the start of the second wave. MSOA with higher proportions of elderly (70+ years of age) and elderly living in deprivation, both with very distinct geographic distributions, have a significantly elevated COVID-19 mortality rates.Conclusions: While non-pharmaceutical interventions (that is, reductions in population mobility and social distancing) had a profound impact on the trajectory of the first wave of the COVID-19 outbreak in England, increased population mobility appears to have contributed to the current increase signalling the start of the second wave. A number of contiguous small-areas appear to be at a significant elevated risk of high COVID-19 transmission, many of which are also at increased risk for higher mortality rates. A geographically staggered re-introduction of intensified social distancing measures is advised and limited cross MSOA movement if the magnitude and geographic extent of the second wave is to be reduced.

Background Schistosomiasis control programmes primarily use school-based surveys to identify areas for mass drug administration of preventive chemotherapy. However, as the spatial distribution of schistosomiasis can be highly focal, transmission may not be detected by surveys implemented at districts or larger spatial units. Improved mapping strategies are required to accurately and cost effectively target preventive chemotherapy to remaining foci across all possible spatial distributions of schistosomiasis. Methods Here, we use geostatistical models to quantify the spatial heterogeneity of Schistosoma haematobium and S. mansoni across Sub-Saharan Africa using the most comprehensive dataset available on school-based surveys. Applying this information to parameterise simulations, we assess the accuracy and cost of targeting alternative implementation unit sizes across the range of plausible schistosomiasis distributions. We evaluate the consequences of decisions based on survey designs implemented at district and subdistrict levels sampling different numbers of schools. Cost data was obtained from field surveys conducted across multiple countries and years, with cost effectiveness evaluated as the cost per correctly identified school. Results Models identified marked differences in prevalence and spatial distributions between countries and species; however, results suggest implementing surveys at subdistrict level increase the accuracy of treatment classifications across most scenarios. While intensively at subdistrict level resulted in the highest classification accuracy, this sampling strategy resulted in the highest costs. Alternatively, sampling the same numbers of schools currently recommended at district levels but stratifying by subdistrict increased cost effectiveness. Conclusions This provides a new tool to evaluate schistosomiasis survey designs across a range of transmission settings. Results highlight the importance of considering spatial structure when designing sampling strategies, illustrating that a substantial proportion of children may be undertreated even when an implementation unit is correctly classified. Control programmes need to weigh the increased accuracy of more detailed mapping strategies against the survey costs and treatment priorities.

Background The International Alliance for the Control of Scabies (IACS) recently published expert consensus criteria for scabies diagnosis. Formal validation of these criteria is needed to guide implementation. We conducted a study to provide detailed description of the morphology and distribution of scabies lesions as assessed by dermatologists and validate the IACS criteria for diagnosis by both expert and non-expert examiners. Methods Participants from a community in Monrovia, Liberia, were independently assessed by two dermatologists and six non-expert examiners. Lesion morphology and distribution were documented based on the dermatologist examination. Diagnoses were classified by IACS criteria and the sensitivity and specificity of non-expert examiner assessments calculated. Results Papules were the most common lesions (97.8%). Burrows were found in just under half (46.7%) and dermatoscopy was positive in a minority (13.3%). Scabies lesions were found in all body regions but more than 90% of patients could have been diagnosed by an examination of only the limbs. Severity of itch was associated with lesion number (p = 0.003). The sensitivity of non-expert examiners to detect typical scabies ranged between 69–83% and specificity 70–96%. The sensitivity of non-expert examiners was higher in more extensive disease (78–94%). Conclusions The IACS criteria proved a valid tool for scabies diagnosis. For the purposes of implementation papules and burrows represent truly ‘typical’ scabies lesions. Non-expert examiners are able to diagnose scabies with a high degree of accuracy, demonstrating they could form a key component in population-level control strategies., Author summary Scabies is a very common skin condition in both high- and low-income settings with hundreds of millions of people affected each year. Recently standardised criteria have been proposed to help improve the quality of scabies diagnosis, in particular in low income settings where the access to a skin specialist is very limited. In this study, conducted in Liberia, expert examiners conducted a thorough examination and recorded what different types of skin problems they found in participants with and without scabies. We then compared the accuracy of a diagnosis of scabies made by dermatologists to that made by non-specialist healthcare workers who had received a short training course over three days. We found that papules were the most common type of scabies lesion and were found in almost every single patient with scabies. A second type of skin lesion called a burrow was the next most common and was found in just under half of the participants. Other types of scabies lesions which have been described were rare in this study. We found that after the short training course the non-specialists were able to detect the majority of the cases of scabies correctly. Our study has helped provide detailed data on exactly what types of skin changes are typical of scabies and demonstrated how short training programmes can help improve the skill of non-specialist examiners in diagnosing scabies.

BackgroundScabies is known to be a public health problem in many settings but the majority of recent data is from rural settings in the Pacific. There is a need for high quality data from sub-Saharan Africa and peri-Urban settings to inform scale up of scabies control efforts. There have been anecdotal reports of scabies being a public health problem in Liberia but robust data are lacking.MethodsWe conducted a cross-sectional cluster-randomised prevalence survey for scabies in a peri-urban community in Monrovia, Liberia in February-March 2020. Participants underwent a standardised examination conducted by trained local health care workers. Health related quality of life (HRQoL) was assessed using age-appropriate dermatology life quality indices (DLQIs). Prevalence estimates were calculated accounting for clustering at community and household levels and associations with key demographic variables assessed through multivariable random-effects logistic regression.Results1,318 participants from 477 households were surveyed. The prevalence of scabies prevalence was 9.3% (95% CI: 6.5-13.2%), across 75 (19.7%) households; impetigo or infected scabies prevalence was 0.8% (95% CI: 0.4-1.9%). The majority (52%) of scabies cases were classified as severe. Scabies prevalence was lower in females and higher in the youngest age group; no associations were found with other collected demographic or socio-economic variables. DLQI scores indicated a very or extremely large effect on HRQoL in 29% of adults and 18% of children diagnosed with scabies.ConclusionsOur study indicates a substantial burden of scabies in this peri-Urban population in Liberia. This was associated with significant impact on quality of life, highlighting the need for action to control scabies in this population. Further work is needed to assess the impact of interventions in this context on both the prevalence of scabies and quality of life.Plain English summaryScabies is an infestation with a microscopic mite which affects many people living in low-resource tropical countries. It causes intense itching, which can lead to complications through bacterial infection and poor quality of life. To help develop global scabies control programmes, we need a better understanding of how common it is across different tropical settings. We conducted a survey to assess the burden of scabies and bacterial skin infection in a random sample of people living in a community in Monrovia, Liberia. Information about participants and their household were collected and their skin was examined; those with skin conditions were asked about its impact on quality of life.We examined 1,318 participants and found that almost 10% of people had scanies. Scabies was more common in young children, and was more common in male children than female children. We found that there was a large impact on quality of life due mostly to the itching that scabies causes and to people feeling embarrassed or sad because of their skin condition. This scabies survey is one of the first conducted across all age groups in recent years in sub-Saharan Africa and indicates a substantial burden and impact on quality of life. More work is needed to understand how common scabies is in different settings and the impact that different treatment strategies may have.

Background Soil-transmitted helminths (STH) are intestinal parasites estimated to infect over 1.5 billion people. Current treatment programmes are aimed at morbidity control through school-based deworming programmes (targeting school-aged children, SAC) and treating women of reproductive age (WRA), as these two groups are believed to record the highest morbidity. More recently, however, the potential for interrupting transmission by treating entire communities has been receiving greater emphasis and the feasibility of such programmes are now under investigation in randomised clinical trials through the Bill & Melinda Gates Foundation funded DeWorm3 studies. Helminth parasites are known to be highly aggregated within human populations, with a small minority of individuals harbouring most worms. Empirical evidence from the TUMIKIA project in Kenya suggests that aggregation may increase significantly after anthelminthic treatment. Methods A stochastic, age-structured, individual-based simulation model of parasite transmission is employed to better understand the factors that might induce this pattern. A simple probabilistic model based on compounded negative binomial distributions caused by age-dependencies in both treatment coverage and exposure to infection is also employed to further this understanding. Results Both approaches confirm helminth aggregation is likely to increase post-mass drug administration as measured by a decrease in the value of the negative binomial aggregation parameter, k. Simple analytical models of distribution compounding describe the observed patterns well. Conclusions The helminth aggregation that was observed in the field was replicated with our stochastic individual-based model. Further work is required to generalise the probabilistic model to take account of the respective sensitivities of different diagnostics on the presence or absence of infection.

BackgroundBuruli ulcer (BU) is a disabling and stigmatising neglected tropical disease (NTD). Its distribution and burden are unknown because of underdiagnosis and underreporting. It is caused by Mycobacterium ulcerans, an environmental pathogen whose environmental niche and transmission routes are not fully understood. Active BU case searches can limit morbidity by identifying cases and linking them to treatment, but these are mostly restricted to well-known endemic areas. A better understanding of environmental suitability for environmental reservoirs of M. ulcerans and BU disease would advance understanding of the disease’s ecology and burden, and could inform targeted surveillance.Methodology/Principal FindingsWe used previously compiled point-level datasets of BU and M. ulcerans occurrence, evidence for BU occurrence within national and sub-national areas, and diverse environmental datasets. We fitted relationships between BU and M. ulcerans occurrence and environmental predictors by applying regression and machine learning based algorithms, combined in an ensemble model to characterise the optimal ecological niche for the disease and bacterium across Africa at a resolution of 5km × 5km. Climate and atmospheric variables were the strongest predictors of both distributions, while indicators of human disturbance including damming and deforestation, drove local variation in suitability. We identified patchy foci of suitability throughout West and Central Africa, including areas with no previous evidence of the disease. Predicted suitability for M. ulcerans was wider but overlapping with that of BU. The estimated population living in areas predicted suitable for the bacterium and disease was 29.1 million.Conclusions/SignificanceThese maps could be used to inform burden estimations and case searches which would generate a more complete understanding of the spatial distribution of BU in Africa, and may guide control programmes to identify cases beyond the well-known endemic areas.Author summaryLike many neglected tropical diseases primarily affecting the rural poor, Buruli ulcer (BU) is under-detected and under-reported within routine health information systems. As such, the burden and distribution are not fully known, impeding appropriate targeting of health resources, control, and care for people affected. Having previously evaluated and mapped the existing evidence for BU and its causative agent M. ulcerans, we concluded that the disease was likely to occur beyond the range of known endemic areas. However, we were left with the question of where exactly these undetected cases might be occurring. Answering this question required a more fine-scale approach: BU is highly focal, presumably due to local variation in the environmental factors which determine suitability for M. ulcerans survival and transmission to humans. We used the compiled evidence and geographical datasets to build statistical models representing the relationship between environmental factors and previously reported cases. This allowed us to define the ecological niche of BU, and subsequently to identify areas across Africa where this niche was met, providing suitable conditions for the disease. We constructed separate models of suitability for M. ulcerans, using locations where its DNA had been detected in environmental sources. Unsurprisingly, suitability for M. ulcerans was predicted to be wider than, but geographically overlapping with that for BU. This implies that beyond the conditions necessary for survival of the bacterium, additional factors are required for transmission to humans. The high-resolution suitability maps we present are intended to guide case search activities which may identify endemic areas beyond the known endemic range. Data on the true prevalence of BU from targeted case searches within predicted-suitable areas will also allow us to validate and refine the models, and potentially predict the actual probability of cases occurring within predicted suitable areas.

Global malaria burden is reducing with effective control interventions, and surveillance is vital to maintain progress. Health management information system (HMIS) data provide a powerful surveillance tool; however, its estimates of burden need to be better understood for effectiveness. We aimed to investigate the relationship between HMIS and cohort incidence rates and identify sources of bias in HMIS-based incidence. Malaria incidence was estimated using HMIS data from 15 health facilities in three subcounties in Uganda. This was compared with a gold standard of representative cohort studies conducted in children aged 0.5 to < 11 years, followed concurrently in these sites. Between October 2011 and September 2014, 153,079 children were captured through HMISs and 995 followed up through enhanced community cohorts in Walukuba, Kihihi, and Nagongera subcounties. Although HMISs substantially underestimated malaria incidence in all sites compared with data from the cohort studies, there was a strong linear relationship between these rates in the lower transmission settings (Walukuba and Kihihi), but not the lowest HMIS performance highest transmission site (Nagongera), with calendar year as a significant modifier. Although health facility accessibility, availability, and recording completeness were associated with HMIS incidence, they were not significantly associated with bias in estimates from any site. Health management information systems still require improvements; however, their strong predictive power of unbiased malaria burden when improved highlights the important role they could play as a cost-effective tool for monitoring trends and estimating impact of control interventions. This has important implications for malaria control in low-resource, high-burden countries.

Soil-transmitted helminthiases (STH) are one of 17 neglected tropical diseases (NTDs) earmarked for control or elimination by 2020 in the WHO’s Roadmap on NTDs. Deworming programs for STH have thus far been focused on treating pre-school and school-aged children; however, there is a growing consensus that to achieve elimination of STH transmission, programs must also target adults, potentially through community-wide mass drug administration (MDA). There is currently a gap in the literature on what components are required to deliver community-wide MDA for STH in order to achieve high intervention reach and uptake. Nested within the TUMIKIA Project, a cluster randomized trial in Kenya evaluating the effectiveness of school-based deworming versus community-wide MDA, we collected qualitative data from program implementers and recipients in eight clusters where community-wide MDA was delivered. Data collection included semi-structured in-depth interviews (n = 72) and focus group discussions (n = 32). A conceptual framework for drug distribution was constructed to help build an analysis codebook. Case memos were developed for each top-level theme. Community-wide MDA for STH was perceived as a complex intervention with key administrative and social mobilization domains. Key actionable themes included: (1) developing an efficient strategy to allocate reasonable workload for implementers to cover all targeted households; (2) maximizing community drug distributors’ motivation through promoting belief in the effectiveness of the intervention and providing sufficient financial incentives; (3) developing effective capacity building strategies for implementers; and (4) implementing a context-adapted community engagement strategy that leverages existing community structures and takes into consideration past community experiences of MDAs. Transitioning from STH control to elimination goals requires significant planning and action to ensure community-wide MDA is delivered with sufficient reach and uptake. We present findings that can inform national deworming programs to increase intervention delivery capacity., Author summary Infections by soil-transmitted worms are common in tropical and subtropical areas. Control strategies usually involve distributing deworming drugs to children, who are most affected. However, recent evidence suggests that distributing these drugs to whole communities, including adults, might help to achieve the elimination of these worms as a public health problem. As part of a large trial in Kenya evaluating the distribution of deworming drugs to communities, we conducted a qualitative study to explore the perspectives of drug delivery among drug distributors and recipient communities. We conducted and analyzed in-depth interviews and focus group discussions. For community deworming to be implemented well, it requires distributors to be highly motivated and follow a plan that fits well with the characteristics of the target community. In order to accept the deworming drugs, communities need to know about the health problem and the intervention, and trust the delivery system. These findings should prove useful to national deworming programs planning to distribute drugs to whole communities when developing their delivery strategies.

Podoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa are uncertain. We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the environmental suitability and human population at risk of podoconiosis in Africa. Environmental suitability for podoconiosis was predicted in 29 African countries. In the year 2020, the total population in areas suitable for podoconiosis is estimated at 114.5 million people, (95% uncertainty interval: 109.4–123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units (typically second administrative-level units, such as districts) defined by the World Health Organization in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of implementation units with high environmental suitability are located in Angola (80, 4.8%), Cameroon (170, 10.3%), the DRC (244, 14.7%), Ethiopia (495, 29.9%), Kenya (217, 13.1%), Uganda (116, 7.0%) and Tanzania (112, 6.8%). Of the 1,655 environmentally suitable implementation units, 960 (58.0%) require more detailed community-level mapping. Our estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes., Author summary Podoconiosis is one of the major causes of tropical lymphedema and results in massive swelling of the lower limbs. It is caused by exposure to mineral particle-induced inflammation among genetically susceptible individuals. People affected by the disease often suffer both physical and psychological comorbidities, which can include painful swelling, distress, depression, stigma and discrimination. In spite of its presence among some African countries, its geographical distribution and burden in Africa are uncertain. We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data (elevation, annual precipitation, land surface temperature, vegetation index, and soil characteristics such as clay and silt fraction) and overlaying population figures, we predicted both the environmental suitability as well as the human population at risk for podoconiosis in Africa. Environmental suitability for podoconiosis was predicted in 29 African countries. Our estimates provide key evidence that will help decision-makers to better plan more integrated intervention programmes.

Background Skin neglected tropical diseases (NTDs) such as Buruli ulcer (BU) and leprosy produce significant stigma and disability. Shared clinical presentations and needs for care present opportunities for integrated case management in co-endemic areas. As global policies are translated into local integrated services, there remains a need to monitor what new configurations of care emerge and how individuals experience them. Methods To explore patient experiences of integrated case management for skin NTDs, in 2018, we conducted a field-based qualitative case series in a leprosy rehabilitation centre in Ganta, Liberia where BU services were recently introduced. Twenty patients with BU (n = 10) and leprosy (n = 10) participated in in-depth interviews that incorporated photography methods. We contextualised our findings with field observations and unstructured interviews with health workers. Findings The integration of care for BU and leprosy prompted new conceptualisations of these diseases and experiences of NTD stigma. Some patients felt anxiety about using services because they feared being infected with the other disease. Other patients viewed the two diseases as ‘intertwined’: related manifestations of the same condition. Configurations of inter-disease stigma due to fear of transmission were buffered by joint health education sessions which also appeared to facilitate social support between patients in the facility. For both diseases, medication and wound care were viewed as the cornerstones of care and appreciated as interventions that led to rehabilitation of the whole patient group through shared experiences of healing, avoidance of physical deformities and stigma reduction. Patient accounts of intense pain during wound care for BU and inability of staff to manage severe complications, however, exposed some shortcomings of medical care for the newly integrated service, as did patient fears of long-lasting disability due to lack of physiotherapy services. Significance Under integrated care policies, the possibility of new discourses about skin NTD identities emerging along with new configurations of stigma may have unanticipated consequences for patients' experiences of case management. The social experience of integrated medication and wound dressing has the potential to link patients within a single, supportive patient community. Control programmes with resource constraints should anticipate potential challenges of integrating care, including the need to ameliorate lasting disability and provide adequate clinical management of severe BU cases., Author summary Buruli ulcer and leprosy are disfiguring diseases of the skin that lead to disability and stigma. Although they are both present in overlapping population groups in West Africa, efforts to care for people affected have usually had a single disease focus. Since both conditions require wound care and long courses of medications, and the risk for transmission is minimal, it has been recommended that they could be managed together. However, there are few reports on how people affected by these diseases experience being brought together.At the border between Liberia and Guinea, a rehabilitation centre has recently integrated care for Buruli ulcer with leprosy care. We conducted a qualitative study in this facility to explore experiences of integrated care for these two diseases. We found that people experience these diseases in a similar way, to the extent that some considered both diseases to be related, and perceive receiving their medications and wound care together favourably.We identified some negative experiences including unjustified fear of acquiring the other disease, intense pain during the process of wound cleaning, and permanent disability due to lack of physiotherapy. In the future, programmes that implement integrated care should anticipate and address these negative experiences to mitigate the burden of these diseases.

Background: Soil-transmitted helminths (STH) are among the most widespread neglected tropical diseases (NTDs) and infect over 1 billion people worldwide, with sub-Saharan Africa (SSA) accounting for >80% of disease burden. Driven by elimination targets, governments across SSA have rapidly rolled out control programmes using school and community based platforms. To justify and target ongoing investment in control, there is an urgent need to quantify their likely impact across SSA, and identify areas that remain at highest risk and unlikely to attain elimination thresholds. We examined the changes in STH prevalence amongst school-aged children in SSA from 2000 to 2018 at the programmatic implementation unit (IU) level to assess regional progress towards elimination. Methods: We used quantitative survey data for Africa that consisted of 23,356 georeferenced survey data points from 2000-2018, and spanning 3,011 of the 5,183 programmatic IUs within the spatial extents of STH in SSA. The data were used within a joint multivariable Bayesian space-time hierarchical framework with covariates to estimate STH prevalence and intensity at IU level from 2000 to 2018. Findings: Our findings suggest a steady decline in the prevalence of STH in SSA school-aged children, from 35% (or 74.6 million cases) in 2000 to 11% (or 33.9 million cases) in 2018, with the largest regional period decline for hookworm (23% to 5%), followed by Ascaris lumbricoides (14% to 7%) and Trichuris trichiura (5% to 2%), with convergence of hookworm and A. lumbricoides levels in 2013. By 2018, approximately 37% (1,938 of 5,183) of IU’s in SSA still had an estimated prevalence of moderate-to-heavy intensity infection exceeding the 1% target threshold, largely concentrated in five countries: Democratic Republic of Congo, Ethiopia, Nigeria, Mozambique and Cameroon. The strongest factors driving reductions in prevalence were sustained effective preventative chemotherapy treatments, followed by improved sanitation, and lastly economic development. Interpretation: Our estimates provide an important tool for identifying where to target and further strengthen interventions, and where data gaps remain. If elimination of STH as a public health problem is to be achieved in SSA by 2030, renewed and increased investment in STH treatment and prevention activities are urgently required to accelerate reductions and ensure that no areas are left behind. Funding Statement: This work was primarily supported by the grant OPP1182963 from the Bill & Melinda Gates Foundation. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Not required.

Background: Success of mass drug administration (MDA) for control of neglected tropical diseases depends on treatment coverage and patterns across rounds. There has been limited opportunity to explore these features within programmes at scale. Here we use routinely-collected individual-level treatment records collated for the TUMIKIA trial, conducted in coastal Kenya from 2015-2017, to estimate the extent of -- and factors associated with -- systematic non-treatment in the targeted population. Methods: The trial baseline population (N=36327) was linked with treatment records from four rounds of biannual community-wide MDA for soil-transmitted helminthiasis. We fit logistic regression models to estimate the association of non-treatment with treatment status during the previous round, controlling for identified predictors of non-treatment, and used multinomial logistic regression to identify factors associated with partial or no treatment versus complete treatment. Findings: Children aged 2-14 years and individuals aged 15+ years were more likely to remain untreated if they were not treated during the previous MDA. For children, school attendance and rural residence were protective against receiving partial and no treatment. Women were more likely than men to receive partial and no treatment, unless periods of pregnancy and recent childbirth were excluded; then, women more likely received complete treatment. Adults aged 20-25 years were most likely to receive partial or no treatment. Interpretation: We identified eligible populations who received incomplete treatment across multiple MDA rounds and found that this non-treatment did not occur at random. This finding has important implications for MDA programme effectiveness and will be increasingly important as prevalence reaches low levels. Funding Statement: Funding for TUMIKIA was received from the Bill & Melinda Gates Foundation, the Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, the Wellcome Trust, and the Children’s Investment Fund Foundation. This analysis was supported by the London Centre for Neglected Tropical Diseases. SK is supported by THRiVE-2, a DELTAS Africa grant # DEL-15-011 from Wellcome Trust grant # 107742/Z/15/Z and the UK government. Declaration of Interests: RMA was a non-executive director of GlaxoSmithKline during the TUMIKIA trial. GlaxoSmithKline had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. SJB is currently employed by the Bill & Melinda Gates Foundation (BMGF) but was employed by the London School of Hygiene & Tropical Medicine when TUMIKIA was designed and commenced. GlaxoSmithKline and BMGF played no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All other authors declare no competing interests. Ethics Approval Statement: The TUMIKIA trial protocol, including measurement of treatment coverage and adherence using routine and household survey data, was approved by the Kenya Medical Research Institute and National Ethics Review Committee (SSC Number 2826) and the London School of Hygiene & Tropical Medicine (LSHTM) Ethics Committee (7177). Written informed consent was sought from the household head or adult answering the household-level questionnaire. All information and consent procedures were conducted in Kiswahili.

Introduction Few studies have simultaneously examined the role of sanitation conditions at the home, school, and community on soil-transmitted helminth (STH) infection. We examined the contribution of each domain that children inhabit (home, village, and school) to STH infection and estimated the association of STH infection with sanitation in each domain. Methods Using data from 4,104 children from Kwale County, Kenya, who reported attending school, we used logistic regression models with cross-classified random effects to calculate measures of general contextual effects and estimate associations of village sanitation coverage (percentage of households with reported access to sanitation), school sanitation coverage (number of usable toilets per enrolled pupil), and sanitation access at home with STH infection. Findings We found reported use of a sanitation facility by households was associated with reduced prevalence of hookworm infection but not with reduced prevalence of T. trichiura infection. School sanitation coverage > 3 toilets per 100 pupils was associated with lower prevalence of hookworm infection. School sanitation was not associated with T. trichiura infection. Village sanitation coverage > 81% was associated with reduced prevalence of T. trichiura infection, but no protective association was detected for hookworm infection. General contextual effects represented by residual heterogeneity between village and school domains had comparable impact upon likelihood of hookworm and T. trichiura infection as sanitation coverage in either of these domains. Conclusion Findings support the importance of providing good sanitation facilities to support mass drug administration in reducing the burden of STH infection in children., Author summary Infection by the soil-transmitted helminths (STH) whipworm and hookworm results from either ingestion of eggs or larvae or through skin exposure to larvae. These eggs and larvae develop in suitable soils contaminated with openly-deposited human faeces. Safe disposal of faeces should reduce transmission of STH, yet evidence of the impact of sanitation on STH transmission remains limited. A large, community-wide survey was conducted in 2015 to measure prevalence of STH infections in Kwale County, Kenya. Here, we used this data and observations made in schools to examine the relationship between sanitation conditions at home, school, and village and the presence of STH infection among 4,104 children who attend school. We found that sanitation access at home and school sanitation coverage (number of usable toilets per enrolled pupil), but not the overall level of village sanitation coverage (percentage of households with reported access to sanitation), was protective against hookworm infection. In contrast, only high village sanitation coverage, but not home or school sanitation, was protective against whipworm infection. Current STH control strategies emphasise periodic deworming of at-risk populations, including school-age children. Our findings highlight the need for continued efforts, alongside deworming, to extend access to good sanitation facilities at homes, schools, and across communities.