Interrupting transmission of soil-transmitted helminths: cluster randomised trial evaluating alternative treatment strategies in Kenya

Some 1.45 billion people are estimated to be infected worldwide with intestinal worms, also known as soil-transmitted helminths (STH). Chronic and intense STH infections can contribute to malnutrition and iron-deficiency anaemia, and also can adversely affect physical and mental growth in childhood. Globally, STH result in 4.98 million years lived with disability each year. Fortunately, however, the global community is increasingly committed to tackling these infections, with many countries now successfully implementing geographically-targeted programmes that provide mass treatment to school-aged children delivered through schools. However, whilst school-based deworming has many important benefits for treated children, recent mathematical modelling suggests that treating only school-aged children will rarely stop transmission of these parasites, except in very low transmission settings, and that alternative approaches to treatment, including extending coverage and frequency of treatment, are required. To effectively deliver such expanded treatment, there is an associated need to evaluate the impact and cost-effectiveness of using community health workers to treat adult populations.

We plan to evaluate the impact of school- versus community-based treatment in reducing the transmission of STH species. A range of quantitative and qualitative assessments will evaluate the costs, cost-effectiveness, acceptability and feasibility of the different strategies and delivery systems. The study will be conducted in two contrasting settings in Kenya - south coastal and western regions - where an estimated 20% of the population are infected with STH. In order to maximize public health relevance, the study will be nested within the ongoing national school-based deworming programme, which is currently treating 4.6 million preschool and school children annually. The study drugs will be donated by GlaxoSmithKline and the full costs of delivery through schools and communities will be covered by the Children's Investment Fund Foundation, with additional input from the Government of Kenya. Cofunding for some of the trial activities are already funded by the Bill & Melinda Gates Foundation.

There is tremendous interest in conducting this study. The Government of Kenya, other national governments, funders and international policy makers are seeking clear policy and technical guidance as to the optimal approach to interrupt STH transmission. At the same time, countries are increasingly using community health workers (CHW; community members who provide basic health and medical care to their community, often on a volunteer basis) to deliver a wide range of health interventions, and there is a need to evaluate the benefits of using CHWs to deliver STH treatment. The proposed study, the first of its kind in Africa, will address these policy information gaps. Our proposed study is demand-led at the country level, with partners in Kenya supporting delivery and committed to scaling-up the new strategy, once demonstrated to be beneficial. Not only will the findings inform policy and practice in Kenya and other STH endemic countries, they may also lead to new WHO guidelines on the community control of STH and ultimately have demonstrable benefits for the impoverished communities affected by STH.

In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STH). The mainstay of STH control is school-based deworming, but recent modelling has shown that in all but very low transmission settings, the treatment of school-aged children 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 and delivery strategy to achieve this goal? Two paired cluster randomised trials in are being implemented in distinct settings in western and coastal Kenya. The interventions are annual mass anthelmintic treatment delivered to pre-school and school-aged children, as part of a national school-based deworming programme, or to the entire community delivered by community health workers. In each site, 120 clusters will be randomised to one of three groups: receiving either (i) annual school-based deworming; (ii) annual community-based deworming; (iii) biannual community-based deworming. The primary outcome measure is the prevalence of hookworm infection, assessed by repeat cross-sectional, age-stratified parasitological surveys. Secondary outcomes include intensity of STH species and treatment coverage, and among a randomly selected sub-sample of participants who will be followed longitudinally, worm burden and proportion of eggs unfertilised. A nested process evaluation, using semi-structured interviews, focus group discussion and a stakeholder analysis will investigate the community acceptability, feasibility, and cost-effectiveness of the interventions. Funders and governments are committed to controlling STH, but seek clear policy and technical guidance on the impact and cost-effectiveness of school- versus community-based deworming. This evaluation will be among the first to provide such policy information.

The proposed research has a number of potential direct beneficiaries, ranging from the global through the national to the individual level.

At the global level, a first beneficiary is the World Health Organization (WHO), and the proposed research has the ambition to challenge and change WHO's guidelines on STH control. The main intervention currently recommended by WHO for controlling STH is to regularly administer mass chemotherapy with albendazole or mebendazole to at-risk populations, including preschool and school-aged children. The current global target is to eliminate morbidity due to STH in children by 2020 through regular school-based deworming. The proposed study seeks to move beyond this goal and provide proof-of-principle for interrupting the transmission of STH.

A second group of global beneficiaries are members of the global NTD coalition. In January 2012, the London Declaration brought together a coalition of pharmaceutical companies, donor groups, implementing partners, and national programmes who are working together to tackle the global burden of NTDs. The goal of this coalition, Uniting to Combat NTDs (http://unitingtocombatntds.org), is to support the WHO Roadmap in its aim to reach the control, elimination and eradication targets for 10 NTDs, including STH, by 2020. The results from the proposed trial will help change the approach to STH control.

The third group of global beneficiaries are funders, including the BMGF, CIFF, DFID and USAID, who are supporting national government to implement STH control and are seeking new approach to STH control. The proposed study will provide the first evidence as to the potential of interrupting STH transmission and the optimal strategy as to how this might be achieved. This evidence will help inform subsequent funding and resource allocation.

At the country level, the main beneficiary is the Government of Kenya (GoK). In 2009, the GoK launched its national school-based deworming programme (NSBDP), which successfully treated over 4.6 million preschool and school children in 2013. Notwithstanding these achievements, there are concerns that the school-based programme is not fully integrated within the newly established community health structures in Kenya and does not utilize community health workers (CHWs), who currently deliver a range of public health interventions. The proposed study will evaluate the benefits of community-wide deworming as delivered by CHWs, and thus will inform the scaling-up of a new delivery strategy for STH control in not only Kenya, but also many other STH endemic countries where CHWs support health care delivery.

At the local level, communities will benefit from the study. At present, only preschool and school children receive STH treatment through the NSBDP, yet field surveys in Kenya highlight the burden of STH harboured by adult populations and recent modelling work demonstrates the role of adults in maintaining transmission and limiting the potential wider benefits of deworming. CHWs will benefit from the study as they will have the opportunity to broaden the scope of their activities and contribute to efforts to control STH in their communities. We will work with the GoK to develop relevant training materials for CHWs, which could be readily adapted to other countries.

A final group of beneficiaries are staff working on the project who will be able to develop a range of skills (e.g. project and finance management, communication, trial design and analysis, epidemiology) appropriate to their role in the project, which will be transferable to other work and sectors in the future. Specific individuals will also be able to gain training in clinical trials, monitoring and evaluation and epidemiology, including local students recruited under the LSHTM Collaborative Centre scheme which facilitates reduced fees and multi-site tuition.