Characterization of the infectious reservoir of malaria with an agent-based model calibrated to age-stratified parasite densities and infectiousness

Abstract: Background Elimination of malaria can only be achieved through removal of all vectors or complete depletion of the infectious reservoir in humans. Mechanistic models can be built to synthesize diverse observations from the field collected under a variety of conditions and subsequently used to query the infectious reservoir in great detail. Methods The EMOD model of malaria transmission was calibrated to prevalence, incidence, asexual parasite density, gametocyte density, infection duration, and infectiousness data from 9 study sites. The infectious reservoir was characterized by diagnostic detection limit and age group over a range of transmission intensities with and without case management and vector control. Mass screen-and-treat drug campaigns were tested for likelihood of achieving elimination. Results The composition of the infectious reservoir by diagnostic threshold is similar over a range of transmission intensities, and higher intensity settings are biased toward infections in children. Recent ramp-ups in case management and use of insecticide-treated bednets reduce the infectious reservoir and shift the composition toward submicroscopic infections. Mass campaigns with antimalarial drugs are highly effective at interrupting transmission if deployed shortly after ITN campaigns. Conclusions Low density infections comprise a substantial portion of the infectious reservoir. Proper timing of vector control, seasonal variation in transmission intensity, and mass drug campaigns allows lingering population immunity to help drive a region toward elimination.