A longitudinal cohort study of Plasmodium vivax relapses in Central Africa

PROJECT SUMMARY Title: A longitudinal cohort study of Plasmodium vivax relapses in Central Africa Plasmodium vivax (Pv) infections caused by relapse are an important cause of morbidity and source of transmission in malaria endemic areas. Relapses contribute significantly to the challenges in controlling and eliminating vivax malaria. Historically, vivax malaria was considered rare or absent in Central and West Africa because of the dominance of Duffy-negative individuals, who lack expression of the Duffy Antigen Receptor for Chemokines (DARC) Pv required for erythrocyte invasion. However, there is growing evidence documenting Pv cases across different parts of Central and West Africa, beyond its endemic range in the Horn of Africa. Prior studies provide compelling evidence that Duffy negativity is not a definitive barrier to Pv invasion and the potential of widespread Pv transmission within Africa. Relapses are known to account for a high proportion of recurrent Pv infections across diverse geographic locations. In Africa, Pv is understudied and at the public health front-end, Pv infections are vastly overlooked in large parts of Africa. Despite numerous reports of Pv cases in Duffy negatives from West and Central Africa, most malaria cases in health facilities are considered as Pf and treated with artemisinin-based combination therapy (ACT). Information on the frequency and transmission potential of Pv relapses in Duffy negative Africans are largely unknown. This R21 application will address 1) what proportion of Pv infections has relapses, 2) how often (i.e. periodicity) relapses occur, 3) are relapse parasites genetically more diverse than those in primary infections, and 4) does relapse infection lead to transmission. Because relapsing infections are important drivers of transmission of Pv malaria, the proportion of recurrences caused by relapse and gametocyte carriage of relapse infections are critical to existing malaria diagnosis and antimalarial treatment regimens in Central/West Africa. Our prior study in Buea of Cameroon showed ~10% of febrile malaria cases and ~15% of asymptomatic community samples being Pv and all were from Duffy-negative individuals. This study will employ a longitudinal design to follow up a cohort of Pv-infected individuals with ACT and without antimalarial treatment to systematically examine relapse biology of Pv in Duffy-negative individuals in Cameroon, an understudied region.