Surveillance to track and characterize antimalarial resistance trends in Ugandan Plasmodium falciparum parasites (STARTUP)

PROJECT SUMMARY/ABSTRACT: New studies in Uganda and Rwanda have reported increasing prevalence of mutations in pfkelch13 (K13) associated with delayed parasite clearance following clinical or in vitro treatment with artemisinins, suggesting that fears that resistance of Plasmodium falciparum to artemisinins will emerge in Africa, where >90% of malaria cases and deaths occur, have been realized. However, the extent of resistance to components of artemisinin-based combination therapies (ACTs) is not well understood. Our ongoing research activities and well-established infrastructure in Uganda put us in a unique position to rapidly address urgent needs for improved surveillance and characterization of resistance to artemisinins and partner drugs in Uganda. Benefitting from a network of 80 surveillance sites across the country and modern laboratories in Kampala and Tororo, we will use molecular, parasitological and epidemiological approaches a) to evaluate the origins, prevalence and distribution of known markers of artemisinin and ACT partner drug resistance and to characterize the genetic background(s) that facilitate the establishment and spread of resistance phenotypes, b) assess associations between genotypes and drug susceptibility/fitness phenotypes, and c) assess ecological and epidemiological factors that facilitate the evolution of resistance. With resistance to important drugs still geographically focal, our goal is to identify key drivers of its emergence and spread, and then to promptly inform public health leaders on the best means of blunting the spread of resistance across Africa.