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Most epidemiological studies of soil-transmitted helminth (STH) infections focus on school-going children. The majority of large-scale cross-sectional and longitudinal community-based studies have been conducted prior to the implementation of wide-scale mass drug administration (MDA). This study investigates age-related patterns in prevalence and intensity of STH infection, and associated risk factors, in a region of south coastal Kenya that had previously received three consecutive years of school-based deworming (2012-14) and four rounds of community-based MDA for lymphatic filariasis between 2003 and 2014. Between March and May 2015, a cross-sectional survey was conducted in 120 community clusters as a baseline for a cluster randomised trial. Individuals aged two years and above were randomly selected during household surveys and requested to provide stool samples, which were assessed for presence and intensity of STH using the duplicate Kato-Katz thick smear method. Species-specific predictors of presence and intensity were investigated through multilevel logistic regression and zero-inflated negative binomial regression models. Of the 19,684 individuals who provided a stool sample, 21.5% were infected with at least one STH. Hookworm was the predominant species, with an overall prevalence of 19.1%; Trichuris trichiura prevalence was 3.6% and Ascaris lumbricoides was negligible (0.4% prevalence). The vast majority were light intensity infections. Prevalence and intensity of hookworm infection were significantly higher in adults and males, and were associated with environmental conditions, low socio-economic status, household flooring, individual and household water, sanitation and hygiene (WASH) characteristics and behaviours, previous treatment, lack of shoe-wearing and not attending school. In contrast, T. trichiura was more commonly found in school-aged boys and those living in communities close to the coast, with reduced infection in the least poor individuals with private latrine access. Overall, results show that despite several years of school-based deworming, hookworm infection remains common among untreated adults in this population, suggesting that this strategy alone is insufficient to reduce community-wide hookworm infection and in the longer term to eliminate transmission. Trial registration ClinicalTrials.gov NCT02397772

Schistosomiasis is endemic to Malawi, where preventive chemotherapy by mass drug administration (MDA) has been the foundational public health strategy for over a decade. Despite ongoing control, our understanding of the contemporary epidemiology of schistosomiasis in rural Malawi is limited to infrequent school-based surveys, typically lacking evidence from community-based surveys particularly within non-lakeshore upland communities who may be perceived to be at lower risk. Between July and August 2022, we conducted a cross-sectional parasitological survey amongst a community-representative sub-sample of boys aged 10-15 years who had been randomly selected and recruited to the DeWorm3 endline survey in Namwera, Mangochi District. A total of 306 participants from 38 communities were assessed for S. mansoni by duplicate Kato-Katz thick smears. Of these, 243 (79.4%) subsequently provided a urine sample to be assessed by filtration for S. haematobium and 238 (77.8%) responded to a risk-factor questionnaire. A parallel malacological survey of eight locally important water contact sites was conducted. The overall prevalence of egg-patent schistosomiasis was 50.6% (95% CI 44.2-57.1). The prevalence of S. haematobium was 47.7% (95% CI 41.3-54.2), of which 37.9% (n=44) were heavy intensity infections whereas the prevalence of S. mansoni was 6.5% (95% CI 4.0-9.9), with one moderate intensity infection (0.3%). There was strong evidence of a positive association between detected S. haematobium infection and reporting \"red urine\" (p<0.001) and 'bilharzia' (p=0.005). Biomphalaria spp. were found at two sites while Bulinus spp. were found at five sites. Despite multiple years of MDA at reportedly high coverage, we observed a high egg-patent prevalence with high prevalence of heavy intensity infections amongst boys aged 10-15 years. This evidences engrained and ongoing transmission requiring additional efforts to gain and sustain effective control. Our findings highlight the importance of epidemiological monitoring alongside a schistosomiasis control programme, particularly in areas historically perceived to be at lower risk.

Soil-transmitted helminths (STHs) are intestinal parasites that affect over a billion people worldwide. STH control relies on microscopy-based diagnostics to monitor parasite prevalence and enable post-treatment surveillance; however, molecular diagnostics are rapidly being developed due to increased sensitivity, particularly in low-STH-prevalence settings. The genetic diversity of helminths and its potential impact on molecular diagnostics remain unclear. Using low-coverage genome sequencing, we assess the genetics of STHs within worm, faecal, and purified egg samples from 27 countries, identifying differences in the genetic connectivity and diversity of STH-positive samples across regions and cryptic diversity between closely related human- and pig-infective species. We define substantial copy number and sequence variants in current diagnostic target regions and validate the impact of genetic variation on qPCR diagnostics using in vitro assays. Our study provides insights into the diversity and genomic epidemiology of STHs, highlighting both the challenges and opportunities for developing molecular diagnostics needed to support STH control efforts. This study analysed genetic data of soil-transmitted helminths from 27 countries, revealing diversity impacting molecular test accuracy and highlighting the need to adapt diagnostics for effective STH surveillance.

IntroductionEvidence indicates children who suffer from ill-health are less likely to attend or complete schooling. Malaria is an important cause of morbidity and mortality in school-age children. However, they are less likely to receive malaria treatment at health facilities and evidence for how to improve schoolchildren’s access to care is limited. This study aimed to evaluate the impact of a programme of school-based malaria case management on schoolchildren’s attendance, health and education.MethodsA cluster randomised controlled trial was conducted in 58 primary schools in Zomba District, Malawi, 2011–2015. The intervention, implemented in 29 randomly selected schools, provided malaria rapid diagnostic tests and artemisinin-based combination therapy to diagnose and treat uncomplicated malaria as part of basic first aid kits known as ‘Learner Treatment Kits’ (LTK). The primary outcome was school attendance, assessed through teacher-recorded daily attendance registers and independent periodic attendance spot checks. Secondary outcomes included prevalence of Plasmodium spp infection, anaemia, educational performance, self-reported child well-being and health-seeking behaviour. A total of 9571 children from standards 1–7 were randomly selected for assessment of school attendance, with subsamples assessed for the secondary outcomes.ResultsBetween November 2013 and March 2015, 97 trained teachers in 29 schools provided 32 685 unique consultations. Female schoolchildren were significantly more likely than male to seek a consultation (unadjusted OR=1.78 (95% CI 1.58 to 2.00). No significant intervention effect was observed on the proportion of child-days recorded as absent in teacher registers (n=9017 OR=0.90 (95% CI 0.77 to 1.05), p=0.173) or of children absent during random school visits—spot checks (n=5791 OR=1.09 (95% CI 0.87 to 1.36), p=0.474). There was no significant impact on child-reported well-being, prevalence of Plasmodium spp, anaemia or education scores.ConclusionDespite high community demand, the LTK programme did not reduce schoolchildren’s absenteeism or improve health or education outcomes in this study setting.Trial registration numberClinicalTrials.gov NCT02213211.

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

BackgroundSchool-based approaches are an efficient mechanism for the delivery of basic health services, but may result in the exclusion of children with disabilities if they are less likely to participate in schooling. Community-based ‘door to door’ approaches may provide a more equitable strategy to ensure that children with disabilities are reached, but disability is rarely assessed rigorously in the evaluation of health interventions.ObjectivesTo describe the prevalence and factors associated with disability among children aged 5–17 years and to assess the relative effectiveness of routine school-based deworming (SBD) compared with a novel intervention of community-based deworming (CBD) in treating children with disabilities for soil-transmitted helminths.SettingDeWorm3 Malawi Site (DMS), Mangochi district, Malawi.ParticipantsAll 44 574 children aged 5–17 years residing within the DMS.Primary and secondary outcome measuresDisability was defined as a functional limitation in one or more domains of the Washington Group/UNICEF Child Functioning Module administered as part of a community-based census. Treatment of all children during SBD and CBD was independently observed and recorded. For both intervention types, we performed bivariate analyses (z-score) of the absolute proportion of children with and without disabilities treated (absolute differences (ADs) in receipt of treatment), and logistic regression to examine whether disability status was associated with the likelihood of treatment (relative differences in receipt of treatment).ResultsThe overall prevalence of disability was 3.3% (n=1467), and the most common domains of disability were hearing, remembering and communication. Boys were consistently more likely to have a disability compared with girls at all age groups, and disability was strongly associated with lower school attendance and worse levels of education. There was no significant difference in the proportion of children with disabilities treated during SBD when assessed by direct observation (−1% AD, p=0.41) or likelihood of treatment (adjusted risk ratio (aRR)=1.07, 95% CI 0.89 to 1.28). Treatment of all children during CBD was substantially higher than SBD, but again showed no significant difference in the proportions treated (−0.5% AD, p=0.59) or likelihood of treatment (aRR=1.04, 95% CI 0.99 to 1.10).ConclusionSBD does not appear to exclude children with disabilities, but the effect of consistently lower levels of educational participation of children with disabilities should be actively considered in the design and monitoring of school health interventions.Trial registration numberNCT03014167.

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 .

Background Soil-transmitted helminths (STH) affect approximately 1.5 billion people globally. The current STH control strategy is annual or twice-annual preventive chemotherapy, typically school-based deworming targeting children and women of reproductive age. Mathematical modeling suggests that it may be possible to interrupt STH transmission through high-coverage community-wide mass drug administration (cMDA). DeWorm3 is a cluster randomized trial testing cMDA for prevalence reduction and transmission interruption. The purpose of this study is to describe coverage of cMDA in study clusters over time and correlates of coverage at individual and cluster levels. Methods From 2018–2020, DeWorm3 delivered six rounds of cMDA with 400 mg albendazole at sites in Benin, India, and Malawi. We report coverage, treatment uptake, and directly observed therapy across all rounds. Factors associated with coverage at the cluster level were identified using binomial generalized estimating equations, while factors associated with non-treatment at the individual level were identified using binomial mixed-effects models. Results Coverage was high across all clusters and rounds, exceeding the WHO target of 75% in all sites and across all rounds (78% to 95%); cluster-level coverage tended to increase over time. Younger, unmarried, and migratory adults were more likely to be untreated at all sites; adult males were more likely to be untreated in Benin and Malawi. Among children, girls were more likely to be untreated, as were non-school-attending and migratory children. Higher adult education was associated with greater odds of non-treatment among adults, but lower odds among children in the household. Belonging to a less wealthy or minority language-speaking household was associated with non-treatment among both adults and children. Conclusions It is possible to deliver community-wide MDA with high coverage. Unique individual and community-level factors influence treatment across settings, and these may be addressed through targeted programming. Trial Registration : Field Studies on the Feasibility of Interrupting the Transmission of Soil-transmitted Helminths (STH), NCT03014167.

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. 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. 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. Findings support the importance of providing good sanitation facilities to support mass drug administration in reducing the burden of STH infection in children.

Background The DeWorm3 project is an ongoing cluster-randomised trial assessing the feasibility of interrupting the transmission of soil-transmitted helminths (STH) through mass drug administration (MDA) using study sites in India, Malawi and Benin. In this article, we describe an approach which uses a combination of statistical and mathematical methods to forecast the outcome of the trial with respect to its stated goal of reducing the prevalence of infection to below 2%. Methods Our approach is first to define the local patterns of transmission within each study site, which is achieved by statistical inference of key epidemiological parameters using the baseline epidemiological measures of age-related prevalence and intensity of STH infection which have been collected by the DeWorm3 trials team. We use these inferred parameters to calibrate an individual-based stochastic simulation of the trial at the cluster and study site level, which is subsequently run to forecast the future prevalence of STH infections. The simulator takes into account both the uncertainties in parameter estimation and the variability inherent in epidemiological and demographic processes in the simulator. We interpret the forecast results from our simulation with reference to the stated goal of the DeWorm3 trial, to achieve a target of ≤ 2 % prevalence at a point 24 months post-cessation of MDA. Results Simulated output predicts that the two arms will be distinguishable from each other in all three country sites at the study end point. In India and Malawi, measured prevalence in the intervention arm is below the threshold with a high probability (90% and 95%, respectively), but in Benin the heterogeneity between clusters prevents the arm prevalence from being reduced below the threshold value. At the level of individual study arms within each site, heterogeneity among clusters leads to a very low probability of achieving complete elimination in an intervention arm, yielding a post-study scenario with widespread elimination but a few ‘hot spot’ areas of persisting STH transmission. Conclusions Our results suggest that geographical heterogeneities in transmission intensity and worm aggregation have a large impact on the effect of MDA. It is important to accurately assess cluster-level, or even smaller scale, heterogeneities in factors which influence transmission and aggregation for a clearer perspective on projecting the outcomes of MDA control of STH and other neglected tropical diseases. Graphical Abstract