SPREAD - Assessment of the factors affecting emergence and spread of artemisinin resistance in Rwanda
Project Abstract
Background: Malaria is a major public health problem globally and resistance to most widely used drugs impedes its control. Artemisinin resistance has emerged and spread in the Greater Mekong Sub region (GMS), followed by artemisinin-based combination therapies (ACTs)’ treatment failure, due to both artemisinin and partner drug resistance. Therefore, there is an urgent need to strengthen surveillance systems beyond the GMS to track the emergence and/or spread of artemisinin resistance in other endemic settings. Worryingly, artemisinin resistance has been recently reported and confirmed in Rwanda; calling for a thorough investigation to understand the factors affecting artemisinin resistance emergence and spread in the African context.
Objectives:
· To assess the dynamics of molecular markers associated with artemisinin and partner drugs resistance
· To assess the factors that have led to the emergence of artemisinin resistance in Rwanda
· To assess the impact of malaria control interventions on the spread of artemisinin resistance
· To monitor ex vivo parasite susceptibility to artemisinin and artemisinin partner drugs
Approach and methods: We will carry out cross-sectional surveys spanning the dry and rainy seasons in four districts in Rwanda, including two districts with confirmed artemisinin resistance and two control districts without artemisinin resistance. We will recruit malaria patients (uncomplicated and severe) and asymptomatic carriers with a positive malaria rapid diagnostic test (RDT), over a two-year period at the district health facilities and from the communities. We will collect clinical and demographic data, and dried blood spots (DBS) from recruited subjects (n≥960); and local malaria epidemiological data will be obtained from the central databases at the Rwanda Biomedical Centre (RBC). DNA will be extracted from DBS and parasitaemia determined by qPCR. Molecular markers of antimalarial drug resistance and parasite population genetic diversity will be characterised by multiplex PCR and next generation sequencing (NGS) -based amplicon sequencing. We will collect whole blood from a subset of patients for ex vivo assays to assess parasite susceptibility to artemisinin and partner drugs from a subset of patients at enrolment and patients with suspected treatment failure. We will perform whole genome sequencing (WGS) on samples showing decreased susceptibility to artemisinin, lumefantrine and piperaquine in vitro to look for additional markers of resistance for the first and second line antimalarial drug treatments in Rwanda.
Expected results: This study will provide important results on the dynamics of molecular markers associated with artemisinin resistance and partner drug in Rwanda. The result will help us to know if resistance has emerged or spread beyond the districts with confirmed artemisinin resistance. In vitro susceptibility of parasites to artemisinin compounds and partner drugs will help us to understand if new mutations are associated with decreased susceptibility to artemisinin and partner drugs in Sub Saharan Africa.
Impact: This project is aiming at strengthening the capacity for antimalarial drug resistance surveillance in Rwanda by establishing an in vitro parasite culture laboratory, and training a PhD student on in vitro assays and advanced molecular techniques to assess molecular markers associated with antimalarial drug resistance. The project will provide robust data to the national health authorities to monitor the spread of artemisinin and partner dug resistance, and will provide an opportunity to build a research network between Rwandan and Swiss scientists, and set up ground for future collaborations between Swiss TPH and the RBC.
