Relative contribution of low-density and asymptomatic infections to transmission in the Amazon: pooled analysis of individual participant data from population-based cross-sectional surveys.

BACKGROUND

Low-density and asymptomatic infections remain largely undetected and untreated and may contribute significantly to malaria transmission in the Amazon.

METHODS

We analysed individual participant data from population-based surveys that measured prevalence by microscopy and polymerase chain reaction (PCR) between 2002 and 2015 and modelled the relationship between parasite density and infectiousness to vectors using membrane feeding assay data. We estimated the proportion of sub-patent (i.e., missed by microscopy) and asymptomatic infections and examined how parasite density relates to clinical manifestations and mosquito infection in Amazonian settings.

FINDINGS

We pooled 24,986 observations from six sites in Brazil and Peru. was detected in 6·8% and 2·1% of them by PCR and microscopy, respectively. 58·5% to 92·6% of infections were asymptomatic and 61·2% to 96·3% were sub-patent across study sites. density thresholds associated with clinical symptoms were one order of magnitude higher in children than in adults. We estimate that sub-patent parasite carriers are minimally infectious and contribute 12·7% to 24·9% of the community-wide transmission, while asymptomatic carriers are the source of 28·2% to 79·2% of mosquito infections.

INTERPRETATION

Asymptomatic carriers constitute a vast infectious reservoir that, if targeted by malaria elimination strategies, could substantially reduce malaria transmission in the Amazon. Infected children may remain asymptomatic despite high parasite densities that elicit clinical manifestations in adults.

FUNDING

US National Institutes of Health, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Belgium Development Cooperation.