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

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.Fil: Kepha, Stella. Kenya Medical Research Institute; KeniaFil: Mazigo, Humphrey D.. Catholic University of Health and Allied Sciences; TanzaniaFil: Odiere, Maurice R.. Kenya Medical Research Institute; KeniaFil: Mcharo, Carlos. Kenya Medical Research Institute; KeniaFil: Safari, Th'uva. Kenya Medical Research Institute; KeniaFil: Gichuki, Paul M.. Kenya Medical Research Institute; KeniaFil: Omondi, Wykcliff. No especifíca;Fil: Wakesho, Florence. No especifíca;Fil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pullan, Rachel L.. No especifíca;Fil: Mwandawiro, Charles S.. Kenya Medical Research Institute; KeniaFil: Oswald, William E.. No especifíca;Fil: Halliday, Katherine E.. No especifíca

Lessons from enriching Tanzania’s clinical research ethics clinical trials oversight and pharmacovigilance through the ASCEND project

Funding: This study was funded by the EDCTP through grant number CSA2019ERC-2683.Engaging in clinical trials in Africa not only enhances researchers' comprehension of local health concerns but also plays a crucial role in tackling global health challenges. In Tanzania, there has been a surge of clinical research for the past 10 years indicating a need to improve ethical and clinical trial regulatory capacity. Several initiatives to address the clinical trial regulatory and ethics challenges have been done. Lessons from such initiatives are important to inform evidence-based decision-making for sustainability. The ASCEND project with the theme of “Moving Tanzania’s Clinical Research Ethics and Medicines Regulatory Capacity to the Next Level: Fostering Medicine Quality, Safety and Good Clinical Practice (GCP) on Clinical Trials” was implemented in Tanzania Mainland and Zanzibar from November 2020 to December 2023. A thorough review of the project implementation reports and on deliverables was conducted to identify the lessons learned. Inductive content analysis was used to analyze the information. A total of seven lessons were deduced from the reviewed documents. These include capacity building through training on clinical trials review and approval process, research ethics and GCP inspection which cannot be overlooked; engaging the community in reporting adverse drug events is worth considering; digitalization of electronic systems enhances clinical trial control and creates a dynamic regulatory ecosystem; compliance to requirements for clinical trials conduct is enhanced by training of early and mid-career researchers; networking and broad stakeholders’ engagement and participation in ethics and regulations governing clinical trials is a cornerstone for strengthening collaboration between researchers and regulators; the need for electronic systems for monitoring and evaluation of the project is inevitable and the need for adhering to project timelines is crucial for successful implementation of the project. Sustainability is the take-home message from the ASCEND project and should inform stakeholders for future improvement. Continuous investment and advancement in research ethics and regulatory oversight across Africa should be prioritized.Peer reviewe

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 costeffective 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: NCT0239777

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

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

Analysis of the Yellow Bean Corridor in Tanzania

The yellow bean value chain in Tanzania was necessary to understand value chain. The objective of the survey was to characterize and explore trade of yellow bean grain and potential seed. The survey collected data and grain samples from 298 grain traders (including wholesalers, exporters, aggregators, and retailers) and 64 potential seed traders (large and retail traders) from 12 regions across four administrative zones in Tanzania. The grain samples collected were for DNA analyses. Results show existence of an established yellow bean corridor across Tanzania and the region at large (Burundi, DRC, Kenya, Rwanda, Uganda, Zambia) and demonstrated a huge market pull in the Eastern and Southern Africa regions. There are also strong perceptions on the organoleptic quality of various yellow bean grains and varieties that are traced to their sources

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