Malaria, Asymptomatic Parasitaemia

The goal of this prospective cohort study is to understand the factors responsible for the persistence of malaria transmission in some areas despite intensive control efforts. The study will measure the prevalence and incidence of asymptomatic and sub-patent Plasmodium infections and examine the factors that contribute to persistent transmission among residents of malaria-endemic areas of Odisha, India. The main questions the study aims to answer are: Do asymptomatic and sub-patent Plasmodium infections contribute to persistent malaria transmission in endemic areas of Odisha? What is the frequency of false-negative results and incorrect species identification when microscopy and rapid diagnostic tests (RDTs) are compared with PCR? How is malaria epidemiology changing over time across areas with different transmission patterns, including shifts in Plasmodium species? What is the prevalence of asymptomatic gametocyte carriers, and how might they contribute to ongoing transmission? What are the characteristics and distribution of mosquito vectors in and around households, and how do they relate to transmission patterns? Can novel host- and parasite-derived biomarkers improve the detection of malaria infections, including asymptomatic cases? Participants will provide blood samples for malaria testing by microscopy, RDT and PCR. A subset will provide additional samples for biomarker analysis as part of a nested sub-study. Participants will be followed over time to measure malaria infection prevalence, incidence and changes in transmission patterns. They will also take part in household-level assessments, including surveys and mosquito vector monitoring around their homes.

Previous malaria control studies in Ghana have shown that community-wide approaches can substantially reduce malaria infections. In a mass testing, treatment and tracking (MTTT) study, more than 75% of people in target communities were reached, leading to a 24% reduction in asymptomatic malaria after one year. However, rapid diagnostic tests (RDTs) can miss very low-level infections, meaning some infected individuals are not treated and can continue to spread malaria. A pilot malaria mass drug administration (MDA) study using artemether-lumefantrine (AL) in the Eastern Region of Ghana showed a very large reduction (over 95%) in parasite carriage after repeated rounds of treatment. Despite this success, malaria infections later fluctuated, possibly because some parasites remained in mosquitoes and because mature gametocytes-the parasite stage responsible for transmission-are not fully eliminated by standard malaria medicines. To better interrupt malaria transmission, this study will use MDA with dihydroartemisinin-piperaquine (DHAP) combined with a single low dose of primaquine (PQ), which targets these transmission stages. The intervention will be given to the whole community every two months (six times per year) and compared with the current standard malaria control measures. The study will examine whether this approach reduces malaria parasite carriage, whether malaria returns after treatment stops, and whether repeated MDA affects malaria drug resistance markers in the population. This two-year implementation research will generate practical evidence to guide national malaria policy in Ghana and inform the potential use of MDA in other malaria-endemic African countries.