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

June 3, 2015

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 nine study sites. The infectious reservoir was characterized by age and parasite detectability with diagnostics of varying sensitivity 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 is similar over a range of transmission intensities, and higher intensity settings are biased towards infections in children. Recent ramp-ups in case management and use of insecticide-treated bed nets (ITNs) reduce the infectious reservoir and shift the composition towards sub-microscopic infections. Mass campaigns with anti-malarial drugs are highly effective at interrupting transmission if deployed shortly after ITN campaigns.

Fig. 3. Composition of the infectious reservoir in the absence of interventions. (A) The composition of the infectious reservoir by diagnostic detectability and age in a setting with moderate transmission. A region of EIR = 10 was simulated over three years with seasonal rainfall and temperature based on Burkina Faso climate. The entire population was tested for asexual parasite prevalence daily for three years with diagnostics at three levels of sensitivity: 100 parasites/μL (bottom 3 stripes, pink), 10 parasites/μL (3 stripes second from bottom, yellow), and 0.05 parasites/μL (3 stripes third from bottom, blue). Infections undetectable at 0.05 parasites/μL are shown in grey (top 3 stripes). Infectiousness was calculated by simulating a membrane-feeding test and subsequently scaling by age to approximate surface area effects. The fraction of the infectious reservoir is the normalization of total infectiousness. (B) Annual average composition of the infectious reservoir under a range of transmission intensities.

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 towards elimination.