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Background Elimination of malaria can only be achieved through removal of allvectors or complete depletion of the infectious reservoir in humans.Mechanistic models can be built to synthesize diverse observations from thefield collected under a variety of conditions and subsequently used to querythe infectious reservoir in great detail. Methods The EMOD model of malariatransmission was calibrated to prevalence, incidence, asexual parasite density,gametocyte density, infection duration, and infectiousness data from 9 studysites. The infectious reservoir was characterized by diagnostic detection limitand age group over a range of transmission intensities with and without casemanagement and vector control. Mass screen-and-treat drug campaigns were testedfor likelihood of achieving elimination. Results The composition of theinfectious reservoir by diagnostic threshold is similar over a range oftransmission intensities, and higher intensity settings are biased towardinfections in children. Recent ramp-ups in case management and use ofinsecticide-treated bednets reduce the infectious reservoir and shift thecomposition toward submicroscopic infections. Mass campaigns with antimalarialdrugs are highly effective at interrupting transmission if deployed shortlyafter ITN campaigns. Conclusions Low density infections comprise a substantialportion of the infectious reservoir. Proper timing of vector control, seasonalvariation in transmission intensity, and mass drug campaigns allows lingeringpopulation immunity to help drive a region toward elimination.

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