title: Calibration of an intrahost malaria model and parameter ensemble evaluation of a pre-erythrocytic vaccine.
abstract: BACKGROUND
  A pre-erythrocytic vaccine could provide a useful tool for burden reduction and eventual eradication of malaria. Mathematical malaria models provide a mechanism for evaluating the effective burden reduction across a range of transmission conditions where such a vaccine might be deployed.
  
  
  METHODS
  The EMOD model is an individual-based model of malaria transmission dynamics, including vector lifecycles and species-specific behaviour, coupled to a mechanistic intrahost model of malaria parasite and host immune system dynamics. The present work describes the extension of the EMOD model to include diagnoses of severe malaria and iterative calibration of the immune system parameters and parasite antigenic variation to age-stratified prevalence, incidence and severe disease incidence data obtained from multiple regions with broadly varying transmission conditions in Africa. An ensemble of calibrated model parameter sets is then employed to evaluate the potential impact of routine immunization with a pre-erythrocytic vaccine.
  
  
  RESULTS
  The reduction in severe malaria burden exhibits a broad peak at moderate transmission conditions. Under sufficiently intense transmission, a vaccine that reduces but does not eliminate the probability of acquisition from a single challenge bite may delay infections but produces minimal or no net reduction. Conversely, under sufficiently weak transmission conditions, a vaccine can provide a high fractional reduction but avert a relatively low absolute number of cases due to low baseline burden.
  
  
  CONCLUSIONS
  Roll-out of routine immunization with pre-erythrocytic malaria vaccines can provide substantial burden reduction across a range of transmission conditions typical to many regions in Africa.
authors.affiliation: Institute for Disease Modeling, 1555 132nd Ave NE, Bellevue, WA 98005, USA. kmccarthy@intven.com.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: McCarthy
authors.forename: Edward A
authors.initials: EA
authors.lastname: Wenger
authors.forename: Grace H
authors.initials: GH
authors.lastname: Huynh
authors.forename: Philip A
authors.initials: PA
authors.lastname: Eckhoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa; D002648:Child; D002675:Child, Preschool; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000635:transmission*; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D014611:Vaccination / Q000379:methods*; D055815:Young Adult
chemical_list: D017780:Malaria Vaccines