Protecting high risk groups from Plasmodium knowlesi malaria

Malaria, an infection caused by Plasmodium parasites transmitted through infective mosquito bites can cause severe illness and remains a significant global health concern. In Southeast Asia, while progress has been made against major human malaria parasites, simian malaria parasites, including Plasmodium knowlesi, have emerged as a major source of zoonotic infections. In Malaysia, P. knowlesi now accounts for all malaria cases and together with recent outbreaks also reported in Thailand this parasite presents a major challenge to malaria elimination in the region. P.knowlesi is not affected by standard malaria control approaches and Malaysia, which has made exceptional progress in reducing P.vivax and P.falciparum is unable to be certified malaria free by WHO because it has P.knowlesi cases. Currently WHO guidlines are that P.knowlesi should be at ‘negligible’ risk, which will require a significant reduction in the number of zoonotic malaria cases in Malaysia. This proposal aims to facilitate that reduction. Our previous work has identified areas of rapid land use and land cover change as areas associated with both the primate host and mosquito vectors host of P.knowlesi. Thus individuals who work in these areas such as loggers and plantation workers are at highest risk of infection and developing disease. Our work will comprise of 3 aims. Firstly, we will work with partners to refine the P.knowlesi risk maps to identify using contemporary environmental and case report data. We will focus on the identification of specific sites for this study but the approach will provide a national and regional resource for future surveillance and control activities. Secondly, using the sites in aim 1 we will identify high risk populations withon these areas and evaluate control methods to reduce the incidence of infection in these people. The primary intervention for which the study will be be powered is a cross-over chemoprophlatic study monthly using Dihydroartemisinin piperaquine in individuals. Infection will be assessed by a novel Loop-mediated isothermal amplification (LAMP) which has emerged as a promising tool for molecular malaria diagnosis due to its simplicity and rapidity. Our preliminary studies suggest LAMP's effectiveness in diagnosing simian malaria species. We will also evaluate the accpetability and utility of personalised vector control namely insect repellent (DEET)-impregnated anklets and wristbands. These have shown promise in reducing mosquito bites, however, their effectiveness against zoonotic malaria vectors remains unexplored and we therefore aim to evaluate this personal-level protection in high risk workers. Thirdly, we will work with local and national stakeholders (local small scale farming communities, plantation owners, MoH) to understand if and how the approaches can be adopted and used more widely. We will examine different potential delivery and funding scenarios to advise regional and national control programmes on optimal methods to reduce P.knowlesi in these high risk groups. Together these aims will reduce the burden of P.knowlesi at individual and community levels in Malaysia and allow wider adoption in affected areas.