Risk of malaria following untreated sub-patent Plasmodium falciparum infections: Results over 4 years from a cohort in a high transmission area in Western Kenya

Abstract

Background: People with suspected malaria may harbor Plasmodium falciparum undetected by rapid diagnostic test (RDT). The impact is not fully understood of these sub-patent infections on the risk of developing clinical malaria. Methods: We analyzed sub-patent P. falciparum infections using a longitudinal cohort in a high transmission site in Kenya. Weighted Kaplan-Meier models estimated the risk difference (RD) for clinical malaria during the 60 days following a symptomatic sub-patent infection. Stratum- specific estimates by age and transmission season assessed modification.Results: Over 54 months, we observed 1,128 symptomatic RDT-negative suspected malaria episodes, of which 400 (35.5%) harbored sub-patent P. falciparum. Overall 60-day risk of developing clinical malaria was low following all episodes (8.6%,95% Confidence Interval: 6.7%, 10.4%). In the low transmission season, the risk of clinical malaria was slightly higher in those with sub-patent infection, whereas the opposite was true in the high transmission season (RD low season: 2.3%, CI: 0.4%, 4.2%; RD high season: -4.8%, CI: -9.5%, -0.05%). Conclusions: The risk of developing clinical malaria among people with undetected sub-patent infections is low. A slightly elevated risk in the low season may merit alternate management, but RDTs diagnose clinically-relevant infections in the high transmission season.