title: Safety and clinical outcome of experimental challenge of human volunteers with Plasmodium falciparum-infected mosquitoes: an update.
abstract: BACKGROUND
  Challenge of volunteers by the bites of membrane-fed anopheline mosquitoes infected with Plasmodium falciparum was reported in 1986. In 1997, an analysis of experience with 118 volunteers indicated that mosquito inoculation of P. falciparum could be a safe, well-tolerated, reproducible, and efficient method of challenge.
  
  
  METHODS
  We reviewed the records of 47 volunteers challenged at our institution with the NF54 isolate of P. falciparum between 1998 and 2002. We also reviewed data from 17 published studies of experimental challenge conducted since 1996.
  
  
  RESULTS
  At our institution, the time to onset of first symptoms (incubation period) was 8.9 days, and the time to first detectable parasitemia on blood smear (prepatent period) was 10.5 days. All volunteers became symptomatic. Most symptoms were mild to moderate, although 21% of volunteers had at least 1 severe symptom. None developed complicated or severe malaria, and all were cured. Laboratory assessments demonstrated modest, short-term abnormalities typical of malaria. Review of 17 published studies demonstrated that an additional 367 volunteers received experimental challenge safely with similar outcomes.
  
  
  CONCLUSIONS
  In total, data from 532 volunteers demonstrate that experimental challenge is safe and results in predictable incubation and prepatent periods. Our findings support the continued use of this method for testing efficacy of vaccines and drugs against P. falciparum.
authors.affiliation: Malaria Program, Naval Medical Research Center, Silver Spring, MD, 20910, USA. epsteinj@nmrc.navy.mil.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Epstein
authors.forename: Suchitra
authors.initials: S
authors.lastname: Rao
authors.forename: Frank
authors.initials: F
authors.lastname: Williams
authors.forename: Daniel
authors.initials: D
authors.lastname: Freilich
authors.forename: Thomas
authors.initials: T
authors.lastname: Luke
authors.forename: Martha
authors.initials: M
authors.lastname: Sedegah
authors.forename: Patricia
authors.initials: P
authors.lastname: de la  Vega
authors.forename: John
authors.initials: J
authors.lastname: Sacci
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D009033:Culicidae / Q000469:parasitology*; D005260:Female; D006805:Human Experimentation; D006801:Humans; D007299:Insect Bites and Stings; D016778:Malaria, Falciparum / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development*; D012449:Safety; D013997:Time Factors