title: Mass campaigns with antimalarial drugs: a modelling comparison of artemether-lumefantrine and DHA-piperaquine with and without primaquine as tools for malaria control and elimination.
abstract: BACKGROUND
  Antimalarial drugs are a powerful tool for malaria control and elimination. Artemisinin-based combination therapies (ACTs) can reduce transmission when widely distributed in a campaign setting. Modelling mass antimalarial campaigns can elucidate how to most effectively deploy drug-based interventions and quantitatively compare the effects of cure, prophylaxis, and transmission-blocking in suppressing parasite prevalence.
  
  
  METHODS
  A previously established agent-based model that includes innate and adaptive immunity was used to simulate malaria infections and transmission. Pharmacokinetics of artemether, lumefantrine, dihydroartemisinin, piperaquine, and primaquine were modelled with a double-exponential distribution-elimination model including weight-dependent parameters and age-dependent dosing. Drug killing of asexual parasites and gametocytes was calibrated to clinical data. Mass distribution of ACTs and primaquine was simulated with seasonal mosquito dynamics at a range of transmission intensities.
  
  
  RESULTS
  A single mass campaign with antimalarial drugs is insufficient to permanently reduce malaria prevalence when transmission is high. Current diagnostics are insufficiently sensitive to accurately identify asymptomatic infections, and mass-screen-and-treat campaigns are much less efficacious than mass drug administrations. Improving campaign coverage leads to decreased prevalence one month after the end of the campaign, while increasing compliance lengthens the duration of protection against reinfection. Use of a long-lasting prophylactic as part of a mass drug administration regimen confers the most benefit under conditions of high transmission and moderately high coverage. Addition of primaquine can reduce prevalence but exerts its largest effect when coupled with a long-lasting prophylactic.
  
  
  CONCLUSIONS
  Mass administration of antimalarial drugs can be a powerful tool to reduce prevalence for a few months post-campaign. A slow-decaying prophylactic administered with a parasite-clearing drug offers strong protection against reinfection, especially in highly endemic areas. Transmission-blocking drugs have only limited effects unless administered with a prophylactic under very high coverage.
authors.affiliation: Institute for Disease Modeling, Intellectual Ventures, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. jgerardin@intven.com.
authors.forename: Jaline
authors.initials: J
authors.lastname: Gerardin
authors.affiliation: Institute for Disease Modeling, Intellectual Ventures, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. peckhoff@intven.com.
authors.forename: Philip
authors.initials: P
authors.lastname: Eckhoff
authors.affiliation: Institute for Disease Modeling, Intellectual Ventures, 1555 132nd Ave NE, Bellevue, WA, 98005, USA. ewenger@intven.com.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Wenger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000962:Antimalarials / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D015995:Prevalence; D011319:Primaquine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult; D015024:Zambia / Q000453:epidemiology; D010879:Piperazines
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011319:Primaquine; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines