LAUSR

Background Asymptomatic Plasmodium falciparum infections are common in Malawi; however, the implications of these infections for the burden of malaria illness are unknown. Whether asymptomatic infections eventually progress to malaria illness, persist without causing symptoms, or clear spontaneously remains undetermined. We identified asymptomatic infections and evaluated the associations between persistent asymptomatic infections and malaria illness. Methods Children and adults (N = 120) who presented at a health facility with uncomplicated malaria were followed monthly for 2 years. During follow-up visits, participants with malaria symptoms were tested and, if positive, treated. Samples from all visits were tested for parasites using both microscopy and polymerase chain reaction, and all malaria infections underwent genotyping. Cox frailty models were used to estimate the temporal association between asymptomatic infections and malaria illness episodes. Mixed models were used to estimate the odds of clinical symptoms associated with new versus persistent infections. Results Participants had a median follow-up time of 720 days. Asymptomatic infections were detected during 23% of visits. Persistent asymptomatic infections were associated with decreased risk of malaria illness in all ages (hazard ratio 0.50, P < .001). When asymptomatic infections preceded malaria illness, newly-acquired infections were detected at 92% of subsequent clinical episodes, independent of presence of persistent infections. Malaria illness among children was more likely due to newly-acquired infections (odds ratio, 1.4; 95% confidence interval, 1.3-1.5) than to persistent infections. Conclusions Asymptomatic P. falciparum infections are associated with decreased incidence of malaria illness, but do not protect against disease when new infection occurs.