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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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Manuel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The 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., Methods: We 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., Results: Across 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., Conclusion: Implementation 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 Registration: NCT03014167., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Kazura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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: 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sheahan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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 (χ2 = 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 (χ2 = 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 (χ2 = 3.83, P = 0.05 and χ2 = 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Aruldas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2022. The Author(s).)

Background: DeWorm3 is an ongoing multi-country community-based cluster-randomized trial assessing the feasibility of interrupting transmission of soil-transmitted helminths (STH) with community-wide mass drug administration (cMDA). In Tamil Nadu, India, community drug distributors (CDDs) worked with DeWorm3 field staff to counsel community members and deliver door-to-door deworming treatment. As CDDs were likely to influence successful delivery of cMDA, we describe drivers of CDDs' knowledge, attitudes, and motivation toward delivery of cMDA. Methods: In this convergent mixed-methods study, a questionnaire on STH and cMDA was administered to 104 CDDs and 17 focus group discussions (FGDs) were conducted. Key outcomes in the quantitative and qualitative analyses included CDDs' knowledge about STH and cMDA and attitudes toward cMDA for STH. Univariate and multivariable logistic regression analyses were performed to determine the strength of associations between independent and outcome variables. The FGDs were analyzed using a priori thematic coding. Results: CDDs who completed at least secondary school education [adjusted odds ratio (aOR): 2.71, 95% CI: 1.16-6.33] and had prior experience in health programs (aOR: 2.72, 95% CI: 1.15-6.44) were more knowledgeable about STH and cMDA. CDDs belonging to the scheduled castes and scheduled tribes (aOR: 2.37, 95% CI: 1.04-5.39), and to households engaged in a skilled occupation (aOR: 2.77, 95% CI: 1.21-6.34) had a more positive attitude toward cMDA for STH. The FGDs showed that while there were myths and misconceptions about STH, many CDDs believed that the adult population in their communities were infected with STH, and that a door-to-door drug delivery strategy would be optimal to reach adults. Conclusions: Educational and socioeconomic backgrounds and experience in health programs should be considered while designing CDD trainings. Along with cMDA delivery for STH, as CDD do share community myths and misconceptions around STH, they should be proactively addressed during the CDD training to strengthen competency in counseling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aruldas, Kaliappan, Israel, Palanisamy, Johnson, Titus, Walson, Means and Ajjampur.)

Background: Current soil-transmitted helminth (STH) control programs target pre-school and school-age children with mass drug administration (MDA) of deworming medications, reducing morbidity without interrupting ongoing transmission. However, evidence suggests that STH elimination may be possible if MDA is delivered to all community members. Such a change to the STH standard-of-care would require substantial systems redesign. We measured baseline structural readiness to launch community-wide MDA for STH in Benin, India, and Malawi., Methods: After field piloting and adaptation, the structural readiness survey included two constructs: Organizational Readiness for Implementing Change and Organizational Capacity for Change. Sub-constructs of organizational readiness include change commitment and change efficacy. Sub-constructs of organizational capacity include flexibility, organizational structure, and demonstrated capacity. Survey items were also separately organized into seven implementation domains. Surveys were administered to policymakers, mid-level managers, and implementers in each country using a five-point Likert scale. Item, sub-construct, construct, and domain-level medians and interquartile ranges were calculated for each stakeholder level within each country., Results: Median organizational readiness for change scores were highest in Malawi (5.0 for all stakeholder groups). In India, scores were 5.0, 4.0, and 5.0 while in Benin, scores were 4.0, 3.0, and 4.0 for policymakers, mid-level managers, and implementers, respectively. Median change commitment was equal to or higher than median change efficacy across all countries and stakeholder groups. Median organizational capacity for change was highest in India, with a median of 4.5 for policymakers and mid-level managers and 5.0 for implementers. In Malawi, the median capacity was 4.0 for policymakers and implementers, and 3.5 for mid-level managers. In Benin, the median capacity was 4.0 for policymakers and 3.0 for mid-level managers and implementers. Median sub-construct scores varied by stakeholder and country. Across countries, items reflective of the implementation domain 'policy environment' were highest while items reflective of the 'human resource' domain were consistently lower., Conclusion: Across all countries, stakeholders valued community-wide MDA for STH but had less confidence in their collective ability to effectively implement it. Perceived capacity varied by stakeholder group, highlighting the importance of accounting for multi-level stakeholder perspectives when determining organizational preparedness to launch new public health initiatives., Trial Registration: NCT03014167., (© 2021. The Author(s).)

Magnetic resonance imaging (MRI) of knee has become the integral part of knee evaluation, hence any MRI based study adds more value if it helps in the decision-making process, especially for surgery in treating patellofemoral pain. We tried to determine normal patellar indices using knee MR images and the correlation between them and also compared the results with different ethnic population. We analyzed the prospectively collected MR images of 117 knees/patients, and Insall-Salvati (IS) index, modified IS index, patellotrochlear (PT) index, and patellophyseal (PP) index were calculated. Two standard deviations from the mean were used to define the normal and abnormal patellar position. Cohen's kappa values were used to assess the agreement between the indices and the correlation between them was analyzed using Pearson's correlation. The mean values for IS index, modified IS index, PT index, and PP index were 1.00, 1.53, 0.40, and 0.58, respectively. There was very good agreement between PT index and PP index. There was weak correlation between all the indices except the one between PT and PP indices which had a strong negative correlation. Based on commonly used methodology, there were 4% of asymptomatic patients who were outside the standardized cut-off values and different indices classified different knees as abnormal. This indicates patellar position should be one among the many other factors, not as a sole factor when making a surgical decision in patellofemoral pain. We also noted that the indices compared fairly with other populations. Further research is needed to determine the clinical applicability of these indices., Competing Interests: None declared., (Thieme. All rights reserved.)

The high burden of soil-transmitted helminth infections has been studied in India; however, little data exist on zoonotic helminths, and on animal-associated exposure to soil-transmitted helminths. Our study took place in the Jawadhu Hills, which is a tribal region in Tamil Nadu, India. Using a One Health approach, we included animal and environmental samples and human risk factors to answer questions about the associations among infected household soil, domestic animals, and human risk factors. Helminth eggs were identified by microscopy in animal and soil samples, and a survey about risk factors was administered to the head of the household. Contact with animals was reported in 71% of households. High levels of helminth infections were found across domestic animal species, especially in goats, chickens, and dogs. Helminth eggs were recorded in 44% of household soil (n = 43/97) and separately in 88% of soil near a water source (n = 28/32). Animal contact was associated with 4.05 higher odds of having helminth eggs in the household soil (P = 0.01), and also having a water source at the household was associated with a 0.33 lower odds of having helminth eggs in the household soil (P = 0.04). Soil moisture was a mediator of this association with a significant indirect effect (P < 0.001). The proportion mediated was 0.50. While our work does not examine transmission, these results support consideration of animal-associated exposure to STH and potentially zoonotic helminths in future interventions to reduce helminth burden. Our study provides support for further investigation of the effects of animals and animal fecal matter on human health.

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., Competing Interests: The authors have declared that no competing interests exist.

We developed an electronic treatment register for the DeWorm3 Project, a cluster-randomised, controlled trial in Benin, India, and Malawi testing the feasibility of interrupting transmission of soil-transmitted helminths through community-wide mass drug administration. The electronic treatment register was designed in xlsform, deployed via the SurveyCTO mobile data collection platform, and implemented on smartphones running the Android operating system. The versatile system enables collection of census and treatment status information, facilitates data aggregation and visualisation, and permits real-time feedback loops during implementation of mass drug administration. Here we describe the system's design and use within the DeWorm3 Project and key features, and by sharing the register here, we hope our readers will further explore its use within their research and disease-control activities.

Identification of the causes of poor oral vaccine immunogenicity in low-income countries might lead to more effective vaccines. We measured mucosal and systemic immune parameters at the time of vaccination with oral poliovirus vaccine (OPV) in 292 Indian infants aged 6-11 months, including plasma cytokines, leukocyte counts, fecal biomarkers of environmental enteropathy and peripheral blood T-cell phenotype, focused on gut-homing regulatory CD4+ populations. We did not find a distinct immune phenotype associated with OPV immunogenicity, although viral pathogens were more prevalent in stool at the time of immunization among infants who failed to seroconvert (63.9% vs. 45.6%, p  = 0.002). Using a machine-learning approach, we could predict seroconversion a priori using immune parameters and infection status with a median 58% accuracy (cross-validation IQR: 50-69%) compared with 50% expected by chance. Better identification of immune predictors of OPV immunogenicity is likely to require sampling of mucosal tissue and improved oral poliovirus infection models., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

Soil-transmitted helminth infections propagate poverty and slow economic growth in low-income countries. As with many other neglected tropical diseases, environmental conditions are important determinants of soil-transmitted helminth transmission. Hence, remotely sensed data are commonly utilised in spatial risk models intended to inform control strategies. In the present study, we build upon the existing modelling approaches by utilising fine spatial resolution Landsat 8 remotely sensed data in combination with topographic variables to predict hookworm prevalence in a hilly tribal area in southern India. Hookworm prevalence data collected from two field surveys were used in a random forest model to investigate the predictive capacity of 15 environmental variables derived from two remotely sensed images acquired during dry and rainy seasons. A variable buffer radius (100-1000 m) was applied to the point-prevalence locations in order to integrate environmental conditions around the village centroids into the modelling approach and understand where transmission is more likely. Elevation and slope were the most important variables in the models, with lower elevation and higher slope correlating with higher transmission risk. A modified normalised difference water index was among other recurring important variables, likely responsible for some seasonal differences in model performance. The 300 m buffer distance produced the best model performance in this setting, with another spike at 700 m, and a marked drop-off in R 2 values at 1000 m. In addition to assessing a large number of environmental correlates with hookworm transmission, the study contributes to the development of standardised methods of spatial linkage of continuous environmental data with point-based disease prevalence measures for the purpose of spatially explicit risk profiling., (Copyright © 2019 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

Background: Oral poliovirus vaccine (OPV) is less immunogenic in low- or middle-income than in high-income countries. We tested whether bacterial and viral components of the intestinal microbiota are associated with this phenomenon., Methods: We assessed the prevalence of enteropathogens using TaqMan array cards 14 days before and at vaccination in 704 Indian infants (aged 6-11 months) receiving monovalent type 3 OPV (CTRI/2014/05/004588). Nonpolio enterovirus (NPEV) serotypes were identified by means of VP1 sequencing. In 120 infants, the prevaccination bacterial microbiota was characterized using 16S ribosomal RNA sequencing., Results: We detected 56 NPEV serotypes on the day of vaccination. Concurrent NPEVs were associated with a reduction in OPV seroconversion, consistent across species (odds ratio [95% confidence interval], 0.57 [.36-.90], 0.61 [.43-.86], and 0.69 [.41-1.16] for species A, B, and C, respectively). Recently acquired enterovirus infections, detected at vaccination but not 14 days earlier, had a greater interfering effect on monovalent type 3 OPV seroresponse than did persistent infections, with enterovirus detected at both time points (seroconversion in 44 of 127 infants [35%] vs 63 of 129 [49%]; P = .02). The abundance of specific bacterial taxa did not differ significantly according to OPV response, although the microbiota was more diverse in nonresponders at the time of vaccination., Conclusion: Enteric viruses have a greater impact on OPV response than the bacterial microbiota, with recent enterovirus infections having a greater inhibitory effect than persistent infections., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Soil-transmitted helminth (STH) infections continue to be a major global cause of morbidity, with a large proportion of the burden of STH infections occurring in India. In addition to direct health impacts of these infections, including anaemia and nutritional deficiencies in children, these infections also significantly impact economic development, as a result of delays in early childhood cognitive development and future income earning potential. The current World Health Organization strategy for STH is focused on morbidity control through the application of mass drug administration to all pre-school-aged and school-aged children. In India, the control of STH-related morbidity requires mobilization of significant human and financial resources, placing additional burdens on limited public resources. Infected adults and untreated children in the community act as a reservoir of infection by which treated children get rapidly reinfected. As a result, deworming programmes will need to be sustained indefinitely in the absence of other strategies to reduce reinfection, including water, hygiene and sanitation interventions (WASH). However, WASH interventions require sustained effort by the government or other agencies to build infrastructure and to promote healthy behavioural modifications, and their effectiveness is often limited by deeply entrenched cultural norms and behaviours. Novel strategies must be explored to provide a lasting solution to the problem of STH infections in India other than the indefinite provision of deworming for morbidity control., Competing Interests: None

Background: Tuberculosis (TB) patients face substantial delays prior to treatment initiation, and out of pocket (OOP) expenditures often surpass the economic productivity of the household. We evaluated the pre-diagnostic cost and health seeking behaviour of new adult pulmonary TB patients registered at Primary Health Centres (PHCs) in Vellore district, Tamil Nadu, India., Methods: This descriptive study, part of a randomised controlled trial conducted in three rural Tuberculosis Units from Dec 2012 to Dec 2015, collected data on number of health facilities, dates of visits prior to the initiation of anti-tuberculosis treatment, and direct OOP medical costs associated with TB diagnosis. Logistic regression analysis examined the factors associated with delays in treatment initiation and OOP expenditures., Results: Of 880 TB patients interviewed, 34.7% presented to public health facilities and 65% patients sought private health facilities as their first point of care. The average monthly individual income was $77.79 (SD 57.14). About 69% incurred some pre-treatment costs at an average of $39.74. Overall, patients experienced a median of 6 days (3-11 IQR) of time to treatment initiation and 21 days (10-30 IQR) of health systems delay. Age ≤ 40 years (aOR: 1.73; CI: 1.22-2.44), diabetes (aOR: 1.63; CI: 1.08-2.44) and first visit to a private health facility (aOR: 17.2; CI: 11.1-26.4) were associated with higher direct OOP medical costs, while age ≤ 40 years (aOR: 0.64; CI: 0.48-0.85) and first visit to private health facility (aOR: 1.79, CI: 1.34-2.39) were associated with health systems delay., Conclusion: The majority of rural TB patients registering at PHCs visited private health facilities first and incurred substantial direct OOP medical costs and delays prior to diagnosis and anti-tuberculosis treatment initiation. This study highlights the need for PHCs to be made as the preferred choice for first point of contact, to combat TB more efficiently.

Background: Soil-transmitted helminth (STH) infections are among the most prevalent neglected tropical diseases (NTD) worldwide. Since the publication of the WHO road map to combat NTD in 2012, there has been a renewed commitment to control STH. In this study, we analysed the geographical distribution and effect of community type on prevalence of hookworm, Trichuris and Ascaris in south Asia and south east Asia., Methodology: We conducted a systematic review of open-access literature published in PubMed Central and the Global Atlas of Helminth Infection. A total of 4182 articles were available and after applying selection criteria, 174 studies from the region were retained for analysis., Principal Findings: Ascaris was the commonest STH identified with an overall prevalence of 18% (95% CI, 14-23%) followed by Trichuris (14%, 9-19%) and hookworm (12%, 9-15%). Hookworm prevalence was highest in Laos, Vietnam and Cambodia. We found a geographical overlap in countries with high prevalence rates for Trichuris and Ascaris (Malaysia, Philippines, Myanmar, Vietnam and Bangladesh). When the effect of community type was examined, prevalence rates of hookworm was comparable in rural (19%, 14-24%) and tribal communities (14%, 10-19%). Tribal communities, however, showed higher prevalence of Trichuris (38%, 18-63%) and Ascaris (32%, 23-43%) than rural communities (13%, 9-20% and 14%, 9-20% respectively). Considerable between and within country heterogeneity in the distribution of STH (I2 >90%) was also noted. When available data from school aged children (SAC) were analysed, prevalence of Ascaris (25% 16-31%) and Trichuris (22%, 14-34%) were higher than among the general population while that of hookworm (10%, 7-16%) was comparable., Conclusions/significance: Our analysis showed significant variation in prevalence rates between and within countries in the region. Highlighting the importance of community type in prevalence and species mix, we showed that tribal and rural communities had higher hookworm infections than urban communities and for ascariasis and trichuriasis, tribal populations had higher levels of infection than rural populations. We also found a higher prevalence of ascariasis and trichuriasis in SAC compared to the general population but comparable levels of hookworm infections. These key findings need to be taken into account in planning future MDA and other interventions.

Macrolides are among the most widely prescribed antibiotics worldwide. However, their impact on the gut's bacterial microbiota remains uncertain. We characterised the intestinal microbiota in 6-11 month-old infants in India who received a 3-day course of azithromycin or placebo during a randomised trial of oral poliovirus vaccine immunogenicity (CTRI/2014/05/004588). In 60 infants per study arm, we sequenced the V4 region of the bacterial 16S rRNA gene in stool samples collected before and 12 days after finishing treatment. We also tested for the presence of common bacterial, viral, and eukaryotic enteropathogens in the same samples using real-time PCR in a Taqman array card (TAC) format. Azithromycin induced a modest decline in microbiota richness and a shift in taxonomic composition driven by a reduction in the relative abundance of Proteobacteria and Verrucomicrobia (specifically Akkermansia muciniphila). The former phylum includes pathogenic strains of Escherichia coli and Campylobacter spp. that declined in prevalence based on the TAC assay. These findings differ from previous observations among older children and adults in Europe and North America, suggesting that the effects of azithromycin on the bacterial microbiota may be specific to the age and geographic setting of its recipients.

Background: Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries, similarly to other oral vaccines. The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem. Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens, we aimed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity., Methods: We did a double-blind, randomised, placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district, India. Infants were eligible to participate if they were 6-11 months old, available for the study duration, and lacked serum neutralising antibodies to serotype-3 poliovirus. Infants were randomly assigned (1:1) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days, followed by serotype-3 monovalent oral poliovirus vaccine on day 14. The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per-protocol population (ie, all those who received azithromycin or placebo, oral poliovirus vaccine, and provided a blood sample according to the study protocol). Safety outcomes were assessed in all infants enrolled in the study. The trial is registered with the Clinical Trials Registry India, number CTRI/2014/05/004588., Findings: Between Aug 5, 2014, and March 21, 2015, 754 infants were randomly assigned: 376 to receive azithromycin and 378 to placebo. Of these, 348 (93%) of 376 in the azithromycin group and 357 (94%) of 378 infants in the placebo group completed the study per protocol. In the azithromycin group, 175 (50%) seroconverted to serotype-3 poliovirus compared with 192 (54%) in the placebo group (risk ratio 0·94, 95% CI 0·81-1·08; p=0·366). Azithromycin reduced faecal biomarkers of environmental enteropathy (calprotectin, myeloperoxidase, α1-antitrypsin) and the prevalence of bacterial but not viral or eukaryotic pathogens. Viral pathogens were associated with lower seroconversion. Three serious adverse events were reported (two in the azithromycin group and one in the placebo group), but none was considered related to the study interventions., Interpretation: Azithromycin did not improve the immunogenicity of oral poliovirus vaccine despite reducing biomarkers of environmental enteropathy and the prevalence of pathogenic intestinal bacteria. Viral interference and innate antiviral immune mechanisms might be more important determinants of the immunogenicity of live-virus oral vaccines., Funding: Bill & Melinda Gates Foundation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: It is generally assumed that hookworm infections in humans are caused by Necator americanus and Ancylostoma duodenale. However, previous studies have also reported the presence of the animal hookworm A. ceylanicum in human stools., Methods: We determined hookworm infections in children in a tribal community in Tamil Nadu, India, using a semi-nested PCR-RFLP approach., Results: The results indicate that human species account for a majority of the hookworm infections (N. americanus 39/41 [95%]; A. duodenale 6/41 [15%]), whereas the animal hookworm A. ceylanicum only accounts for a minority of the infections (5%; 2/41)., Conclusions: The results emphasize the need to consider zoonotic ancylostomiasis while developing strategies to control hookworm infections., (© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To estimate the prevalence, spatial patterns and clustering in the distribution of soil-transmitted helminth (STH) infections, and factors associated with hookworm infections in a tribal population in Tamil Nadu, India., Methods: Cross-sectional study with one-stage cluster sampling of 22 clusters. Demographic and risk factor data and stool samples for microscopic ova/cysts examination were collected from 1237 participants. Geographical information systems mapping assessed spatial patterns of infection., Results: The overall prevalence of STH was 39% (95% CI 36%–42%), with hookworm 38% (95% CI 35–41%) and Ascaris lumbricoides 1.5% (95% CI 0.8–2.2%). No Trichuris trichiura infection was detected. People involved in farming had higher odds of hookworm infection (1.68, 95% CI 1.31–2.17, P < 0.001). In the multiple logistic regression, adults (2.31, 95% CI 1.80–2.96, P < 0.001), people with pet cats (1.55, 95% CI 1.10–2.18, P = 0.011) and people who did not wash their hands with soap after defecation (1.84, 95% CI 1.27–2.67, P = 0.001) had higher odds of hookworm infection, but gender and poor usage of foot wear did not significantly increase risk. Cluster analysis, based on design effect calculation, did not show any clustering of cases among the study population; however, spatial scan statistic detected a significant cluster for hookworm infections in one village., Conclusion: Multiple approaches including health education, improving the existing sanitary practices and regular preventive chemotherapy are needed to control the burden of STH in similar endemic areas.