“Silent” Malaria: Defining the Infectious Reservoirs of Plasmodium falciparum in Communities of Southern Malawi.

Abstract

Malaria is a vector-borne disease causing at least 200 million cases and 580,000 deaths annually. Frequent exposure to the Plasmodium parasites that cause malaria induces immunity that prevents symptoms, but not infection. In endemic areas, asymptomatic, or ‘silent,’ human infections are common, potentially representing persistent sources of transmission. To characterize such infectious reservoirs, cross-sectional surveys were undertaken seasonally across three diverse Districts in southern Malawi. Humans can infect mosquitoes that feed on their blood when it contains the Plasmodium gametocyte stage, but gametocytes occur at low densities, and are difficult to detect using traditional microscopy. Blood samples from a subset of the study population were tested using polymerase chain reaction (PCR) for P. falciparum genomic DNA and a novel quantitative reverse transcription-PCR (qRT-PCR) assay for stage-specific messenger RNA (mRNA) transcripts. The qRT-PCR assay was found to be valid for use in this community-based study population, and vastly improved sensitivity for detecting gametocytes over microscopy. These results were then used to analyze the population-level predictors of gametocytemia. Asymptomatically infected people were as likely to be gametocytemic as those reporting symptoms. School-aged children (6-15 years) were the most likely to be gametocytemic, though under-5-year-olds suffer the greatest malaria disease burden. Since untreated infections can persist for months, treatment-seeking behaviors were assessed for their potential to shorten duration of infectiousness. Treatment-seeking was common (>85%) among participants reporting recent fever, but few afebrile subjects sought treatment. Only 25% of P. falciparum-infected people had sought treatment in the previous two weeks. Appropriate testing and antimalarial treatment was most likely to occur at government/private facilities, but school-aged children and adults were more likely to use shops or other sources. These studies demonstrated that gametocyte carriage is common among asymptomatic infections, and that these infections are unlikely to receive antimalarial treatment. School-aged children were key reservoirs of the infectious stage of the Plasmodium parasite. Malaria elimination interventions will need to address these human reservoirs in order to interrupt transmission, but control efforts will benefit from expanding coverage to school-aged populations.