Exploring factors associated with Trichuris trichiura infection in school children in a high-transmission setting in Kenya.

Objectives: Kenya has implemented a national school-based deworming program, which has led to substantial decline in the prevalence of soil-transmitted helminths (STHs), although some pockets of infections remain. To effectively design an STH control program that leads to significant reductions of Trichuris trichiura, there is a need to understand the drivers of persistent infection despite ongoing treatment programs. Methods: This study was conducted between July and September 2019 at the south coast of Kenya, using a two-stage sampling design. First, a school-based cross-sectional survey was conducted in 2265 randomly selected school children from selected schools in areas known to be endemic for T. trichiura. After this, we conducted a nested case-control study wherein all children positive for T. trichiura (142) were matched to 148 negative controls based on age and village. A household survey was then conducted with all household members of cases and controls. In addition, a subsample of 116 children found to be infected with T. trichiura were followed up to assess the efficacy of albendazole at day 21 post-treatment. The predictors of presence of T. trichiura were investigated through multilevel logistic regression, considering clustering of infection. Results: Overall, 34.4% of the children were infected with at least one STH species; T. trichiura was the most common (28.3%), 89.1% of those with T. trichiura had light-intensity infections. The prevalence of T. trichiura was significantly higher in male children and was positively associated with younger age and number of people infected with T. trichiura in a household. The parasitological cure rate and egg reduction rate of T. trichiura were 35% and 51%, respectively. Other STHs identified were hookworm (9.6%) and Ascaris lumbricoides (5.7%). Conclusions: T. trichiura remains a significant public health challenge in the study area with albendazole treatment efficacy against the parasite, remaining lower than the World Health Organization-recommended thresholds. Because of the observed focal transmission of T. trichiura in the current area, control efforts tailored to local conditions and targeting lower implementation units should be used to achieve optimal results on transmission.

Patterns and Drivers of Household Sanitation Access and Sustainability in Kwale County, Kenya.

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

Patterns of individual non-treatment during multiple rounds of mass drug administration for control of soil-transmitted helminths in the TUMIKIA trial, Kenya: a secondary longitudinal analysis.

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

Domains of transmission and association of community, school, and household sanitation with soil-transmitted helminth infections among children in coastal Kenya.

INTRODUCTION: Few studies have simultaneously examined the role of sanitation conditions at the home, school, and community on soil-transmitted helminth (STH) infection. We examined the contribution of each domain that children inhabit (home, village, and school) to STH infection and estimated the association of STH infection with sanitation in each domain. METHODS: Using data from 4,104 children from Kwale County, Kenya, who reported attending school, we used logistic regression models with cross-classified random effects to calculate measures of general contextual effects and estimate associations of village sanitation coverage (percentage of households with reported access to sanitation), school sanitation coverage (number of usable toilets per enrolled pupil), and sanitation access at home with STH infection. FINDINGS: We found reported use of a sanitation facility by households was associated with reduced prevalence of hookworm infection but not with reduced prevalence of T. trichiura infection. School sanitation coverage > 3 toilets per 100 pupils was associated with lower prevalence of hookworm infection. School sanitation was not associated with T. trichiura infection. Village sanitation coverage > 81% was associated with reduced prevalence of T. trichiura infection, but no protective association was detected for hookworm infection. General contextual effects represented by residual heterogeneity between village and school domains had comparable impact upon likelihood of hookworm and T. trichiura infection as sanitation coverage in either of these domains. CONCLUSION: Findings support the importance of providing good sanitation facilities to support mass drug administration in reducing the burden of STH infection in children.

Heterogeneity in transmission parameters of hookworm infection within the baseline data from the TUMIKIA study in Kenya.

BACKGROUND: As many countries with endemic soil-transmitted helminth (STH) burdens achieve high coverage levels of mass drug administration (MDA) to treat school-aged and pre-school-aged children, understanding the detailed effects of MDA on the epidemiology of STH infections is desirable in formulating future policies for morbidity and/or transmission control. Prevalence and mean intensity of infection are characterized by heterogeneity across a region, leading to uncertainty in the impact of MDA strategies. In this paper, we analyze this heterogeneity in terms of factors that govern the transmission dynamics of the parasite in the host population. RESULTS: Using data from the TUMIKIA study in Kenya (cluster STH prevalence range at baseline: 0-63%), we estimated these parameters and their variability across 120 population clusters in the study region, using a simple parasite transmission model and Gibbs-sampling Monte Carlo Markov chain techniques. We observed great heterogeneity in R0 values, with estimates ranging from 1.23 to 3.27, while k-values (which vary inversely with the degree of parasite aggregation within the human host population) range from 0.007 to 0.29 in a positive association with increasing prevalence. The main finding of this study is the increasing trend for greater parasite aggregation as prevalence declines to low levels, reflected in the low values of the negative binomial parameter k in clusters with low hookworm prevalence. Localized climatic and socioeconomic factors are investigated as potential drivers of these observed epidemiological patterns. CONCLUSIONS: Our results show that lower prevalence is associated with higher degrees of aggregation and hence prevalence alone is not a good indicator of transmission intensity. As a consequence, approaches to MDA and monitoring and evaluation of community infection status may need to be adapted as transmission elimination is aimed for by targeted treatment approaches.

Community-level epidemiology of soil-transmitted helminths in the context of school-based deworming: Baseline results of a cluster randomised trial on the coast of Kenya.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02397772.

Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial.

BACKGROUND: School-based deworming programmes can reduce morbidity attributable to soil-transmitted helminths in children but do not interrupt transmission in the wider community. We assessed the effects of alternative mass treatment strategies on community soil-transmitted helminth infection. METHODS: In this cluster-randomised controlled trial, 120 community units (clusters) serving 150 000 households in Kenya were randomly assigned (1:1:1) to receive albendazole through annual school-based treatment targeting 2-14 year olds or annual or biannual community-wide treatment targeting all ages. The primary outcome was community hookworm prevalence, assessed at 12 and 24 months through repeat cross-sectional surveys. Secondary outcomes were Ascaris lumbricoides and Trichuris trichiura prevalence, infection intensity of each soil-transmitted helminth species, and treatment coverage and costs. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02397772. FINDINGS: After 24 months, prevalence of hookworm changed from 18·6% (95% CI 13·9-23·2) to 13·8% (10·5-17·0) in the annual school-based treatment group, 17·9% (13·7-22·1) to 8·0% (6·0-10·1) in the annual community-wide treatment group, and 20·6% (15·8-25·5) to 6·2% (4·9-7·5) in the biannual community-wide treatment group. Relative to annual school-based treatment, the risk ratio for annual community-wide treatment was 0·59 (95% CI 0·42-0·83; p<0·001) and for biannual community-wide treatment was 0·46 (0·33-0·63; p<0·001). More modest reductions in risk were observed after 12 months. Risk ratios were similar across demographic and socioeconomic subgroups after 24 months. No adverse events related to albendazole were reported. INTERPRETATION: Community-wide treatment was more effective in reducing hookworm prevalence and intensity than school-based treatment, with little additional benefit of treating every 6 months, and was shown to be remarkably equitable in coverage and effects. FUNDING: Bill & Melinda Gates Foundation, the Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, the Wellcome Trust, and the Children's Investment Fund Foundation.

Interrupting transmission of soil-transmitted helminths: a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya.

INTRODUCTION: In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most cost-effective treatment strategy and delivery system to achieve this goal? METHODS AND ANALYSIS: Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision-termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. ETHICS AND DISSEMINATION: Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and London School of Hygiene and Tropical Medicine. The study has a dedicated web site. TRIAL REGISTRATION NUMBER: NCT02397772.

Impact of intermittent screening and treatment for malaria among school children in Kenya: a cluster randomised trial.

BACKGROUND: Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence of the benefits of alternative school-based malaria interventions or how the impacts of interventions vary according to intensity of malaria transmission. We investigated the effect of intermittent screening and treatment (IST) for malaria on the health and education of school children in an area of low to moderate malaria transmission. METHODS AND FINDINGS: A cluster randomised trial was implemented with 5,233 children in 101 government primary schools on the south coast of Kenya in 2010-2012. The intervention was delivered to children randomly selected from classes 1 and 5 who were followed up for 24 months. Once a school term, children were screened by public health workers using malaria rapid diagnostic tests (RDTs), and children (with or without malaria symptoms) found to be RDT-positive were treated with a six dose regimen of artemether-lumefantrine (AL). Given the nature of the intervention, the trial was not blinded. The primary outcomes were anaemia and sustained attention. Secondary outcomes were malaria parasitaemia and educational achievement. Data were analysed on an intention-to-treat basis. During the intervention period, an average of 88.3% children in intervention schools were screened at each round, of whom 17.5% were RDT-positive. 80.3% of children in the control and 80.2% in the intervention group were followed-up at 24 months. No impact of the malaria IST intervention was observed for prevalence of anaemia at either 12 or 24 months (adjusted risk ratio [Adj.RR]: 1.03, 95% CI 0.93-1.13, p = 0.621 and Adj.RR: 1.00, 95% CI 0.90-1.11, p = 0.953) respectively, or on prevalence of P. falciparum infection or scores of classroom attention. No effect of IST was observed on educational achievement in the older class, but an apparent negative effect was seen on spelling scores in the younger class at 9 and 24 months and on arithmetic scores at 24 months. CONCLUSION: In this setting in Kenya, IST as implemented in this study is not effective in improving the health or education of school children. Possible reasons for the absence of an impact are the marked geographical heterogeneity in transmission, the rapid rate of reinfection following AL treatment, the variable reliability of RDTs, and the relative contribution of malaria to the aetiology of anaemia in this setting. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00878007.

Challenges for consent and community engagement in the conduct of cluster randomized trial among school children in low income settings: experiences from Kenya.

BACKGROUND: There are a number of practical and ethical issues raised in school-based health research, particularly those related to obtaining consent from parents and assent from children. One approach to developing, strengthening, and supporting appropriate consent and assent processes is through community engagement. To date, much of the literature on community engagement in biomedical research has concentrated on community- or hospital-based research, with little documentation, if any, of community engagement in school-based health research. In this paper we discuss our experiences of consent, assent and community engagement in implementing a large school-based cluster randomized trial in rural Kenya. METHODS: Data collected as part of a qualitative study investigating the acceptability of the main trial, focus group discussions with field staff, observations of practice and authors' experiences are used to: 1) highlight the challenges faced in obtaining assent/consent; and 2) strategies taken to try to both protect participant rights (including to refuse and to withdraw) and ensure the success of the trial. RESULTS: Early meetings with national, district and local level stakeholders were important in establishing their co-operation and support for the project. Despite this support, both practical and ethical challenges were encountered during consenting and assenting procedures. Our strategy for addressing these challenges focused on improving communication and understanding of the trial, and maintaining dialogue with all the relevant stakeholders throughout the study period. CONCLUSIONS: A range of stakeholders within and beyond schools play a key role in school based health trials. Community entry and information dissemination strategies need careful planning from the outset, and with on-going consultation and feedback mechanisms established in order to identify and address concerns as they arise. We believe our experiences, and the ethical and practical issues and dilemmas encountered, will be of interest for others planning to conduct school-based research in Africa. TRIAL REGISTRATION: National Institute of Health NCT00878007.