Background Children with disabilities experience lower school enrolment rates and may be systematically excluded from school-based deworming programmes. The DeWorm3 trial provided an opportunity to evaluate whether community-wide mass drug administration (cMDA) could reduce these disparities by reaching children outside the education system.Methods We conducted a secondary analysis of the data from the DeWorm3 trial in Tamil Nadu, India. Children aged 5–17 years (n=82 417) who participated in at least one of the six rounds of cMDA were included. Disability was assessed using the UNICEF/Washington Group’s Child Functioning Module. Mixed-effects logistic regression models examined associations between disability status and treatment coverage, adjusting for sociodemographic factors.Results Children with disabilities (1.1% of the population) had higher unadjusted odds of not receiving deworming treatment compared with children without disabilities (OR=1.49, 95% CI 1.19 to 1.84), though this association was attenuated after adjustment (adjusted OR=1.10, 95% CI 0.86 to 1.37). Among school-attending children who received treatment, those with disabilities had significantly lower odds of receiving school-based treatment (adjusted OR=0.57, 95% CI 0.44 to 0.73). Subgroup analyses revealed that age, school attendance, parental marital status, geographical location and the COVID-19 pandemic significantly modified these associations.Conclusion While cMDA reduced some disparities in deworming coverage, children with disabilities remained less likely to receive school-based treatment. Public health programmes should combine school-based approaches with targeted community outreach strategies to ensure equitable inclusion of children with disabilities, particularly those experiencing multiple vulnerabilities.

ABSTRACT Purpose Childhood immunisation witnessed reduced coverage and delays globally during the Covid19 pandemic. This study aimed to identify gaps in routine childhood immunisation in southern India and the effect of the pandemic in censused rural and tribal populations. Methods This study was conducted between August and September 2021 in a hard-to-reach tribal block (Jawadhu Hills) and rural (Timiri) block in Tamil Nadu. The proportion of full immunisation coverage (FIC), age-appropriate coverage and vaccination delays were calculated in the pre-pandemic (prior to March 2020) and pandemic (lockdown) period. Results Among 2746 children (aged <30 months, with immunisation cards available) surveyed in these populations, overall FIC among children between 12-23 months of age was 50.8% (95%CI: 46.6-55.0) in Jawadhu and 83.7%; (81.1-86.2) in Timiri. In Jawadhu, coverage of oral polio vaccine3 (OPV3) decreased from 78.3% (73.4-82.6) pre-pandemic to 70.0% (66.6-73.2) during the pandemic; inactivated polio vaccine2 (IPV2) from 76.9% (72.1-81.2) to 69.1% (65.5-72.4); Pentavalent3 from 78.0% (73.1-82.4) to 70.2% (66.8-73.5); and Measles containing vaccine1 (MCV1) from 74.6% (67.6-80.8) to 56.7% (53.3-60.1). In Timiri, only MCV1 coverage decreased from 92.9% (88.7-95.9) to 85.4% (83.3-87.3). Factors associated with not receiving MCV1 included due date of vaccination falling during the pandemic lock downs, higher birth order, younger and less educated parents, and residing in the tribal block. Conclusion This study highlighted differences in routine childhood immunisation vaccine coverage and impact of the pandemic in a geographically remote tribal block in contrast to a more accessible, rural block. Resilient health systems are essential to ensure sustainability in gains in vaccination coverage, especially in remote areas, and should be part of pandemic preparedness.

BACKGROUND:Soil-transmitted helminths are targeted for elimination as a public health problem. This study assessed whether, with high coverage, community-wide mass drug administration (MDA) could lead to transmission interruption. METHODS:DeWorm3 is an open-label, community cluster-randomised controlled trial in Benin, India, and Malawi. In each country, a single governmental administrative unit (population ≥80 000 individuals) with soil-transmitted helminth endemicity and participation in at least five rounds of community-wide MDA for lymphatic filariasis, was divided into 40 clusters (population ≥1650 individuals), which were randomly assigned (1:1) to community-wide MDA versus school-based deworming. Laboratory personnel were masked to exposure status and all investigators were masked to post-baseline outcome data until unmasking. In all clusters, preschool-aged and school-aged children received school-based deworming as per national guidelines for 3 years. In intervention clusters, door-to-door community-wide MDA (a single oral dose of 400 mg albendazole) was delivered to all eligible individuals biannually by community drug distributors for 3 years. All individuals aged 12 months and older in India and Benin and aged 24 months and older in Malawi were eligible for treatment, except women in the first trimester of pregnancy, those with adverse reactions to benzimidazoles, those who were acutely ill or intoxicated, or those reporting treatment within the previous 2 weeks. The co-primary outcomes were individual-level prevalence and cluster-level transmission interruption (ie, weighted prevalence of predominant species of ≤2%) of the predominant soil-transmitted helminth species, assessed by quantitative PCR (qPCR) 24 months after the last round of MDA. The analysis set contained a subset of randomly selected participants per cluster who enrolled in the endline assessment, provided a stool sample, and had a qPCR result. All individuals who received treatment were eligible for inclusion in the safety population. This trial is registered with ClinicalTrials.gov (NCT03014167), and is active but not recruiting. FINDINGS:Between Oct 10, 2017, and Feb 17, 2023, 120 clusters (40 clusters per country, comprising 357 716 individuals) were randomly assigned, 60 to community-wide MDA and 60 to school-based deworming. 184 030 (51·4%) individuals in the clusters at baseline were female, 173 663 (48·5%) were male, and 23 (<0·1%) were other. The analysis set consisted of 58 827 individuals in the control group and 58 554 in the intervention group 24 months after the cessation of all deworming, Necator americanus prevalence (the predominant species at all sites) in the community-wide MDA group was lower than the school-based deworming group in Benin (adjusted prevalence ratio [aPR] 0·44 [95% CI 0·34-0·58]), India (0·41 [0·32-0·52]), and Malawi (0·40 [0·34-0·46]). Transmission interruption was achieved for N americanus in 11 (55%) of 20 intervention clusters versus six (30%) of 20 control clusters in Benin (p=0·20), in one (5%) intervention cluster versus no control clusters in India (p=1·00), and in no clusters in either group in Malawi (p=1·00). 984 adverse events were reported among 487 participants over the study, of which 32 among 13 participants resulted in hospitalisation and were classified as serious adverse events (three of which were related to study procedures). INTERPRETATION:Soil-transmitted helminth transmission interruption might be possible in focal geographies but does not appear to be programmatically feasible within the evaluated timeframe. Community-wide MDA should be considered as an alternative strategy to school-based deworming programmes to improve equity and outcomes in helminth-endemic areas. FUNDING:The Gates Foundation.

BackgroundThe control of soil-transmitted helminths (STH) is achieved through mass drug administration (MDA) with deworming medications targeting children and other high-risk groups. Recent evidence suggests that it may be possible to interrupt STH transmission by deworming individuals of all ages via community-wide MDA (cMDA). However, a change in delivery platforms will require altering implementation processes.MethodsWe used process mapping, an operational research methodology, to describe the activities required for effective implementation of school-based and cMDA in 18 heterogenous areas and over three years in Benin, India, and Malawi. Planned activities were identified during workshops prior to initiation of a large cMDA trial (the DeWorm3 trial). The process maps were updated annually post-implementation, including adding or removing activities (e.g., adaptations) and determining whether activities occurred according to plan. Descriptive analyses were performed to quantify differences and similarities at baseline and over three implementation years. Comparative analyses were also conducted between study sites and areas implementing school-based vs. cMDA. Digitized process maps were developed to provide a visualization of MDA processes and inspected to identify implementation bottlenecks and inefficient activity flows.ResultsAcross three years and all clusters, implementation of cMDA required an average of 13 additional distinct activities and was adapted more often (5.2 adaptations per year) than school-based MDA. An average of 41% of activities across both MDA platforms did not occur according to planned timelines; however, deviations were often purposeful to improve implementation efficiency or effectiveness. Visualized process maps demonstrated that receipt of drugs at the local level may be an implementation bottleneck. Many activities rely on the effective setting of MDA dates and estimating quantity of drugs, suggesting that the timing of these activities is important to meet planned programmatic outcomes.ConclusionImplementation processes were heterogenous across settings, suggesting that MDA is highly context and resource dependent and that there are many viable ways to implement MDA. Process mapping could be deployed to support a transition from a school-based control program to community-wide STH transmission interruption program and potentially to enable integration with other community-based campaigns.Trial registrationNCT03014167.

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.

Background One-fifth of the global population is infected with soil-transmitted helminths (STH). Mass drug administration (MDA) with deworming medication is widely implemented to control morbidity associated with STH infections. However, surveillance of human infection prevalence by collecting individual stool samples is time-consuming, costly, often stigmatized, and logistically challenging. Current methods of STH detection are poorly sensitive, particularly in low-intensity and low-prevalence populations. Methodology/Principal findings We aimed to develop a sensitive and specific molecular method for detecting STH DNA in large volumes of soil (20 g) by conducting laboratory and proof of concept studies across field sites in Kenya, Benin, and India. We collected human stool (n = 669) and soil (n = 478) from 322 households across the three study sites. We developed protocols for DNA extraction from 20 g of soil and qPCR to detect Ascaris lumbricoides, Trichuris trichiura, Necator americanus, and Ancylostoma duodenale. Agreement between detection of STH via qPCR, digital droplet PCR (ddPCR), and microscopy-based methods was assessed using the Cohen’s Kappa statistic. Finally, we estimated associations between soil characteristics and detection of STH in soil by qPCR, as well as between STH detected in soil and STH detected in stool from matched households, adjusting for soil characteristics. The overall prevalence of STH in soil by qPCR was 31% for A. lumbricoides, 3% for T. trichiura, and 13% for any hookworm species. ddPCR and qPCR performed similarly. However, there was poor agreement between STH detected in soil by qPCR versus light microscopy. Microscopy underestimated the prevalence of A. lumbricoides and N. americanus and overestimated T. trichiura. Detection of an STH species in household soil was strongly associated with increased odds of a household member being infected with that same species. Conclusions/Significance Soil surveillance for STH has several benefits over stool-based surveillance, including lower cost and higher success rates for sample collection. Considering that delivery of MDA occurs at the community level, environmental surveillance using molecular methods could be a cost-effective alternate strategy for monitoring STH in these populations.

Despite the large number of children in India, there is little information on the impact of children's disability on school enrolment, and how this differs by population. We estimated the prevalence of childhood disability in two sites in Tamil Nadu, southern India, and the effect of functional difficulty on school enrolment. We used a parent-reported survey containing the UNICEF-Washington Group questions to identify children aged 5 to 17 years with functional difficulty during a census conducted for an ongoing trial. We estimated pooled- and gender-specific prevalence of functional difficulty among 29,044 children. We fitted regression models to identify subgroups with higher rates of functional difficulty and the effect of functional difficulty on reported school enrolment. We estimated the modification of the effect of functional difficulty by age, gender, socioeconomic status, household education, and sub-site, on additive and multiplicative scales. We found of 29,044 children, 299 (1.0%) had any functional difficulty, equal among boys and girls. Being understood (0.5%) and walking (0.4%) were the most common difficulties. Functional difficulty was strongly associated with non-enrolment in school (Prevalence ratio [PR] 4.59, 95% CI: 3.87, 5.43) after adjusting for age, gender, and site. We show scale-dependent differences between age and socioeconomic groups in the effect of functional difficulty on enrolment. This study shows that at least one in a hundred children in this region have severe functional difficulties and nearly half of these children are not enrolled in school, highlighting the need for further efforts and evidence-based interventions to increase school enrolment among these groups.

Mass drug administration (MDA) is a key strategy for the control of soil-transmitted helminths (STHs). Within MDA programs, poor and non-random compliance threaten successful control of STHs. A case-control study was conducted comparing perceptions among non-compliant participants with compliant participants during a community-wide MDA (cMDA) with albendazole in southern India. Common reasons cited for non-compliance were that the individual was not infected with STH (97.4%), the perception that he/she was healthy (91%), fear of side-effects (12.8%), and dislike of consuming tablets (10.3%). Noncompliance was associated with poor awareness of intestinal worms (odds ratio [OR]: 9.63, 95% CI: 2.11-43.84), the perception that cMDA was only required for those with worms (OR: 2.14, 95% CI: 1.06-4.36), and the perception that the drug is not safe during pregnancy (OR: 2.19, 95% CI: 1.18-4.07) or when on concomitant medications (OR: 3.14, 95% CI: 1.38-7.15). Understanding of perceptions driving noncompliance can provide valuable insights to optimize participation during MDA for STHs.

Background Experiencing adverse events (AEs) during mass drug administration (MDA) could affect participation in future MDAs. This study aims to understand the potential influence of AEs during a community-wide MDA (cMDA) trial for soil-transmitted helminths (STH) in India on intention to participate in future cMDAs. Methods This study was conducted using a multi-method quantitative and qualitative approach among 74 participants who experienced an AE during STH cMDA and the 12 participants who subsequently refused cMDA treatment of the ongoing DeWorm3 trial. Path analysis and thematic analysis guided by the Theory of Planned Behaviour, was used. Principal findings Among 74 individuals who reported an AE, 12% refused treatment in the cMDA immediately subsequent to their AE and 4% refused in all subsequent cMDAs. Of these 74 individuals, 59 (80%) completed a survey and eight participated in in-depth interviews. A positive attitude towards deworming and perceived ability to participate in cMDA (perceived behavioural control) were significant predictors of intention to participate in cMDA (p<0.05). A positive attitude towards cMDA was associated with caste (χ 2 = 3.83, P = 0.05), particularly among the scheduled caste/scheduled tribe (SC/ST) (62%). Perceived behavioural control in cMDA participation was associated with occupation (χ 2 = 5.02, P <0.05), with higher perceived control among those engaged in skilled occupations (78%). Intention to participate in subsequent cMDAs was associated with caste and family type (χ 2 = 3.83, P = 0.05 and χ 2 = 7.50, P <0.05 respectively) and was higher among SC/ST (62%) and those with extended families (67%). In-depth interviews demonstrated that perceived severe AEs may lead to treatment refusal in future, particularly if children were affected. Conclusions Intention to participate in future STH cMDAs was associated with caste (SC/ST) and family type (extended families). Therefore, community mobilization messages about potential AEs and their management may need to intentionally target non-SC/ST households, nuclear families, and those engaged in unskilled occupations to increase cMDA participation given the possibility of AEs occurring. Trial registration NCT03014167 , ClinicalTrials.gov.

ObjectivesWith increasing mobile phone subscriptions, phone-based surveys are gaining popularity with public health programmes. Despite advantages, systematic exclusion of participants may limit representativeness. Similar to control programmes for neglected tropical diseases (NTDs), the DeWorm3 trial of biannual community-wide mass drug administration (MDA) for elimination of soil-transmitted helminth infection used in-person coverage evaluation surveys to measure the proportion of the at-risk population treated during MDA. Due to lockdown during the COVID-19 pandemic, a phone-based coverage evaluation survey was necessary, providing an opportunity for the current study to compare representativeness and implementation (including non-response) of these two survey modes.DesignComparison of two cross-sectional surveys.SettingThe DeWorm3 trial site in Tamil Nadu, India, includes Timiri, a rural subsite, and Jawadhu Hills, a hilly, hard-to-reach subsite inhabited predominantly by a tribal population.ParticipantsIn the phone-based and in-person coverage evaluation surveys, all individuals residing in 2000 randomly selected households (50 in each of the 40 trial clusters) were eligible to participate. Here, we characterise household participation.ResultsOf 2000 households, 1780 (89.0%) participated during the in-person survey. Of 2000 households selected for the phone survey, 346 (17.3%) could not be contacted as they had not provided a telephone number during the census and 1144 (57.2%) participated. Smaller households, households with lower socioeconomic status and those with older, women or less educated household-heads were under-represented in the phone-based survey compared with censused households. Regression analysis revealed non-response in the phone-based survey was higher among households from the poorest socioeconomic quintile (prevalence ratio (PR) 2.3, 95% CI 2.0 to 2.7) and lower when heads of households had completed secondary school or higher education (PR 0.7, 95% CI 0.6 to 0.8).ConclusionsOur findings suggest phone-based surveys under-represent households likely to be at higher risk of NTDs and in-person surveys are more appropriate for measuring MDA coverage within programmatic settings.Trial registration numberNCT03014167.

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

Objectives Current soil-transmitted helminth (STH) morbidity control guidelines primarily target deworming of preschool and school-age children. Emerging evidence suggests that community-wide mass drug administration (cMDA) may interrupt STH transmission. However, the success of such programmes depends on achieving high treatment coverage and uptake. This formative analysis was conducted to evaluate the implementation climate for cMDA and to determine barriers and facilitators to launch. Settings Prior to the launch of a cMDA trial in Benin, India and Malawi. Participants Community members (adult women and men, children, and local leaders), community drug distributors (CDDs) and health facility workers. Design We conducted 48 focus group discussions (FGDs) with community members, 13 FGDs with CDDs and 5 FGDs with health facility workers in twelve randomly selected clusters across the three study countries. We used the Consolidated Framework for Implementation Research to guide the design of the interview guide and thematic analysis. Results Across all three sites, aspects of the implementation climate that were facilitators to cMDA launch included: high community member demand for cMDA, integration of cMDA into existing vaccination campaigns and/or health services, and engagement with familiar health workers. Barriers to launching cMDA included mistrust towards medical interventions, fear of side effects and limited perceived need for interrupting STH transmission. We include specific recommendations from community members regarding cMDA distribution sites, personnel requirements, delivery timing and incentives, leaders to engage and methods for mobilising participants. Conclusions Prior to launching the cMDA programme as an alternative to school-based MDA, cMDA was found to be generally acceptable across diverse geographical and demographic settings. Community members, CDDs and health workers felt that engaging communities and tailoring programmes to the local context are critical for success. Potential barriers may be mitigated by identifying local concerns and addressing them via targeted community sensitisation prior to implementation. Trial registration number NCT03014167 ; Pre-results.

ABSTRACT. We assessed the impact of the national lockdown on a rural and tribal population in Tamil Nadu, southern India. A mixed-methods approach with a pilot-tested, semi-structured questionnaire and focus group discussions were used. The impact of the lockdown on health, finances, and livelihood was studied using descriptive statistics. Multivariable logistic regression was carried out to identify factors associated with households that borrowed loans or sold assets during the lockdown, and unemployment during the lockdown. Of the 607 rural and tribal households surveyed, households from comparatively higher socioeconomic quintiles (adjusted odds ratio [aOR], 1.84; 95% CI, 1.01–3.34), with no financial savings (aOR, 2.91; 95% CI, 1.17–7.22), and with larger families (aOR, 1.76; 95% CI, 1.22–2.53), took loans or sold assets during the lockdown. Previously employed individuals from rural households (aOR, 5.07; 95% CI, 3.30–7.78), lower socioeconomic households (aOR, 3.08; 95% CI, 1.74, 5.45), and households with no savings (aOR, 1.78; 95% CI, 1.30–2.44) became predominantly unemployed during the lockdown. Existing government schemes for the elderly, differently abled, and widows were shown to be accessible to 89% of the individuals requiring these schemes in our survey. During the focus group discussions, the limited reach of online classes for schoolchildren was noted and attributed to the lack of smartphones and poor Internet connectivity. Although the sudden, unannounced national lockdown was imposed to flatten the COVID-19 curve, aspects related to livelihood and financial security were affected for both the rural and tribal populations.

Background Recent evidence suggests that community-wide mass drug administration (MDA) may interrupt the transmission of soil-transmitted helminths (STH), a group of intestinal worms that infect 1.5 billion individuals globally. Although current operational guidelines provide best practices for effective MDA delivery, they do not describe which activities are most essential for achieving high coverage or how they work together to produce effective intervention delivery. We aimed to identify the various packages of influential intervention delivery activities that result in high coverage of community-wide MDA for STH in Benin, India, and Malawi. Methods We applied coincidence analysis (CNA), a novel cross-case analytical method, to process mapping data as part of the implementation science research of the DeWorm3 Project, a Hybrid Type 1 cluster randomized controlled trial assessing the feasibility of interrupting the transmission of STH using bi-annual community-wide MDA in Benin, India, and Malawi. Our analysis aimed to identify any necessary and/or sufficient combinations of intervention delivery activities (i.e., implementation pathways) that resulted in high MDA coverage. Activities were related to drug supply chain, implementer training, community sensitization strategy, intervention duration, and implementation context. We used pooled implementation data from three sites and six intervention rounds, with study clusters serving as analytical cases ( N = 360). Secondary analyses assessed differences in pathways across sites and over intervention rounds. Results Across all three sites and six intervention rounds, efficient duration of MDA delivery (within ten days) singularly emerged as a common and fundamental component for achieving high MDA coverage when combined with other particular activities, including a conducive implementation context, early arrival of albendazole before the planned start of MDA, or a flexible community sensitization strategy. No individual activity proved sufficient by itself for producing high MDA coverage. We observed four possible overall models that could explain effective MDA delivery strategies, all which included efficient duration of MDA delivery as an integral component. Conclusion Efficient duration of MDA delivery uniquely stood out as a highly influential implementation activity for producing high coverage of community-wide MDA for STH. Effective MDA delivery can be achieved with flexible implementation strategies that include various combinations of influential intervention components.

OBJECTIVES:Current guidelines for the control of soil-transmitted helminths (STH) recommend deworming children and other high-risk groups, primarily using school-based deworming (SBD) programmes. However, targeting individuals of all ages through community-wide mass drug administration (cMDA) may interrupt STH transmission in some settings. We compared the costs of cMDA to SBD to inform decision-making about future updates to STH policy. DESIGN:We conducted activity-based microcosting of cMDA and SBD for 2 years in Benin, India and Malawi within an ongoing cMDA trial. SETTING:Field sites and collaborating research institutions. PRIMARY AND SECONDARY OUTCOMES:We calculated total financial and opportunity costs and costs per treatment administered (unit costs in 2019 USD ($)) from the service provider perspective, including costs related to community drug distributors and other volunteers. RESULTS:On average, cMDA unit costs were more expensive than SBD in India ($1.17 vs $0.72) and Malawi ($2.26 vs $1.69), and comparable in Benin ($2.45 vs $2.47). cMDA was more expensive than SBD in part because most costs (~60%) were 'supportive costs' needed to deliver treatment with high coverage, such as additional supervision and electronic data capture. A smaller fraction of cMDA costs (~30%) was routine expenditures (eg, drug distributor allowances). The remaining cMDA costs (~10%) were opportunity costs of staff and volunteer time. A larger percentage of SBD costs was opportunity costs for teachers and other government staff (between ~25% and 75%). Unit costs varied over time and were sensitive to the number of treatments administered. CONCLUSIONS:cMDA was generally more expensive than SBD. Accounting for local staff time (volunteers, teachers, health workers) in community programmes is important and drives higher cost estimates than commonly recognised in the literature. Costs may be lower outside of a trial setting, given a reduction in supportive costs used to drive higher treatment coverage and economies of scale. TRIAL REGISTRATION NUMBER:NCT03014167.

Objectives Targeted deworming is the current strategy for control of morbidity associated with soil-transmitted helminths (STH) among at-risk populations: preschool-aged children, school-aged children and women of childbearing age. We report the prevalence and intensity of STH in a district after lymphatic filariasis (LF) mass drug administration (MDA) in southern India where albendazole was co-administered from 2001. Methods Children aged 2 to 15 years and adults (defined as >= 15 years) in a rural administrative block of Tamil Nadu were recruited using a probability proportional to size method. Stool samples were screened and eggs per gram (EPG) determined by Kato-Katz method. Multilevel logistic regression (MLR) and multilevel negative binomial regression (MNBR) analyses were used to identify factors associated with infection and intensity, respectively. Results Of 862 participants who provided samples, 60 (7.0%; 95% confidence interval (CI): 5.3-8.7) were positive for STH with a predominance of hookworm infections (n = 57, 6.6%; 95% CI: 5.0-8.3). Increasing age (odds ratio (OR): 1.09; 95% CI: 1.04-1.15) and regular usage of the toilet (OR: 0.32; 95% CI: 0.12-0.88) were independently associated with hookworm infection and age was significantly associated with increasing intensity of hookworm infection (infection intensity ratio (IIR): 1.28; 95% CI: 1.19-1.37). A brief review of STH prevalence in endemic settings before and after the stoppage of LF MDA indicated that, in most settings, a substantial reduction in STH prevalence is seen. Conclusion Community-wide MDA in all age groups in these post-LF MDA districts with low prevalence and light intensity infections could result in transmission interruption of STH.

Objective To present a costing study integrated within the DeWorm3 multi-country field trial of community-wide mass drug administration (cMDA) for elimination of soil-transmitted helminths. Design Tailored data collection instruments covering resource use, expenditure and operational details were developed for each site. These were populated alongside field activities by on-site staff. Data quality control and validation processes were established. Programmed routines were used to clean, standardise and analyse data to derive costs of cMDA and supportive activities. Setting Field site and collaborating research institutions. Primary and secondary outcome measures A strategy for costing interventions in parallel with field activities was discussed. Interim estimates of cMDA costs obtained with the strategy were presented for one of the trial sites. Results The study demonstrated that it was both feasible and advantageous to collect data alongside field activities. Practical decisions on implementing the strategy and the trade-offs involved varied by site; trialists and local partners were key to tailoring data collection to the technical and operational realities in the field. The strategy capitalised on the established processes for routine financial reporting at sites, benefitted from high recall and gathered operational insight that facilitated interpretation of the estimates derived. The methodology produced granular costs that aligned with the literature and allowed exploration of relevant scenarios. In the first year of the trial, net of drugs, the incremental financial cost of extending deworming of school-aged children to the whole community in India site averaged US$1.14 (USD, 2018) per person per round. A hypothesised at-scale routine implementation scenario yielded a much lower estimate of US$0.11 per person treated per round. Conclusions We showed that costing interventions alongside field activities offers unique opportunities for collecting rich data to inform policy toward optimising health interventions and for facilitating transfer of economic evidence from the field to the programme. Trial registration number NCT03014167; Pre-results.

Since 2015, India has coordinated the largest school-based deworming program globally, targeting soil-transmitted helminths (STH) in ~250 million children aged 1 to 19 years twice yearly. Despite substantial progress in reduction of morbidity associated with STH, reinfection rates in endemic communities remain high. We conducted a community based parasitological survey in Tamil Nadu as part of the DeWorm3 Project-a cluster-randomised trial evaluating the feasibility of interrupting STH transmission at three geographically distinct sites in Africa and Asia-allowing the estimation of STH prevalence and analysis of associated factors. In India, following a comprehensive census, enumerating 140,932 individuals in 36,536 households along with geospatial mapping of households, an age-stratified sample of individuals was recruited into a longitudinal monitoring cohort (December 2017-February 2018) to be followed for five years. At enrolment, a total of 6089 consenting individuals across 40 study clusters provided a single adequate stool sample for analysis using the Kato-Katz method, as well as answering a questionnaire covering individual and household level factors. The unweighted STH prevalence was 17.0% (95% confidence interval [95%CI]: 16.0-17.9%), increasing to 21.4% when weighted by age and cluster size. Hookworm was the predominant species, with a weighted infection prevalence of 21.0%, the majority of which (92.9%) were light intensity infections. Factors associated with hookworm infection were modelled using mixed-effects multilevel logistic regression for presence of infection and mixed-effects negative binomial regression for intensity. The prevalence of both Ascaris lumbricoides and Trichuris trichiura infections were rare (<1%) and risk factors were therefore not assessed. Increasing age (multivariable odds ratio [mOR] 21.4, 95%CI: 12.3-37.2, p<0.001 for adult age-groups versus pre-school children) and higher vegetation were associated with an increased odds of hookworm infection, whereas recent deworming (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and belonging to households with higher socioeconomic status (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and higher education level of the household head (mOR 0.4, 95%CI: 0.3-0.6, p<0.001) were associated with lower odds of hookworm infection in the multilevel model. The same factors were associated with intensity of infection, with the use of improved sanitation facilities also correlated to lower infection intensities (multivariable infection intensity ratio [mIIR] 0.6, 95%CI: 0.4-0.9, p<0.016). Our findings suggest that a community-based approach is required to address the high hookworm burden in adults in this setting. Socioeconomic, education and sanitation improvements alongside mass drug administration would likely accelerate the drive to elimination in these communities. Trial Registration: NCT03014167.

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 paper, 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 firstly 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 endpoint. In India and Malawi, measured prevalence in the intervention arm is below the threshold with a high probability (90% and 95%, respectively), but that in Benin the heterogeneity between clusters prevents the arm prevalence 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 assessing 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.