Abstract
BACKGROUND: Asymptomatic carriage of malaria parasites persists even as malaria transmission declines. Low-density infections are often submicroscopic, not detected with rapid diagnostic tests (RDTs) or microscopy but detectable by polymerase chain reaction (PCR). METHODS: To characterize submicroscopic Plasmodium falciparum carriage in an area of declining malaria transmission, asymptomatic persons >5 years of age in rural Bagamoyo District, Tanzania, were screened using RDT, microscopy, and PCR. We investigated the size of the submicroscopic reservoir of infection across villages, determined factors associated with submicroscopic carriage, and assessed the natural history of submicroscopic malaria over 4 weeks. RESULTS: Among 6076 participants, P. falciparum prevalences by RDT, microscopy, and PCR were 9%, 9%, and 28%, respectively, with roughly two-thirds of PCR-positive individuals harboring submicroscopic infection. Adult status, female sex, dry season months, screened windows, and bed net use were associated with submicroscopic carriage. Among 15 villages encompassing 80% of participants, the proportion of submicroscopic carriers increased with decreasing village-level malaria prevalence. Over 4 weeks, 23% of submicroscopic carriers (61 of 266) became RDT positive, with half exhibiting symptoms, while half (133 of 266) were no longer parasitemic at the end of 4 weeks. Progression to RDT-positive patent malaria occurred more frequently in villages with higher malaria prevalence. CONCLUSIONS: Microheterogeneity in transmission observed at the village level appears to affect both the size of the submicroscopic reservoir and the likelihood of submicroscopic carriers developing patent malaria in coastal Tanzania.