title: Controlled human malaria infection.
abstract: BACKGROUND
  Since 1986, investigators at Walter Reed Army Institute of Research (WRAIR) have been using controlled human malaria challenge (CHMI) in malaria-naive adults in order to define the protective efficacy of a malaria vaccine and thus guide programmatic decisions on vaccine candidates. Adapting this model to the dengue field could provide similar evidential support for a vaccine or therapeutic product.
  
  
  METHODS
  After completing a vaccine regimen, volunteers are bitten by 5 malaria-infected female Anopheles mosquitoes in a controlled environment. Volunteers are then monitored daily for peripheral parasitemia in a hotel setting with 24-hour access to a nurse and physician. If a single verified parasite is detected, effective antimalarials are promptly administered.
  
  
  RESULTS
  The vast majority of the over 1000 volunteers having participated in CHMI clinical studies have done so at US military research centers. Numerous pre-erythrocytic and erythrocytic vaccine candidates have been evaluated safely and without any related serious adverse events using this model, including the soon-to-be licensed RTS,S malaria vaccine.
  
  
  CONCLUSIONS
  The lessons learned from over 25 years of experience in consistent, careful preparation and execution of the CHMI model at WRAIR can provide a foundation from which the dengue field can begin to develop a rigorous and safe "CHDI" model.
authors.affiliation: US Military Malaria Vaccine Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland.
authors.forename: Michele
authors.initials: M
authors.lastname: Spring
authors.affiliation: US Military Malaria Vaccine Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Polhemus
authors.affiliation: US Military Malaria Vaccine Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland.
authors.forename: Christian
authors.initials: C
authors.lastname: Ockenhouse
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000962:Antimalarials / Q000627:therapeutic use; D003715:Dengue / Q000517:prevention & control; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D017780:Malaria Vaccines / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000517:prevention & control*; D010963:Plasmodium falciparum; D012107:Research Design; D034101:Sporozoites
chemical_list: D000962:Antimalarials; D017780:Malaria Vaccines
keywords: clinical trial; efficacy; malaria; challenge; mosquito