Safety and Clinical Outcome of Experimental Challenge of Human Volunteers with Plasmodium falciparum-Infected Mosquitoes: An Update

• Published in: The Journal of infectious diseases 2007-07, Vol.196 (1), p.145-154
• Main Authors: Epstein, Judith E., Rao, Suchitra, Williams, Frank, Freilich, Daniel, Luke, Thomas, Sedegah, Martha, Vega, Patricia de la, Sacci, John, Richie, Thomas L., Hoffman, Stephen L.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Animals; Biological and medical sciences; Blood; Culicidae; Culicidae - parasitology; Female; Fundamental and applied biological sciences. Psychology; Human Experimentation; Humans; Infectious diseases; Insect Bites and Stings; Malaria; Malaria, Falciparum - complications; Malaria, Falciparum - drug therapy; Malaria, Falciparum - physiopathology; Male; Medical sciences; Microbiology; Middle Aged; Parasitemia; Parasites; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - growth & development; Polymerase chain reaction; Safety; Sporozoites; Symptoms; Test ranges; Time Factors; Vaccination; Volunteerism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/518510

Background. Challenge of volunteers by the bites of membrane-fed anopheline mosquitoes infected with Plasmodium falciparumwas reported in 1986. In 1997, an analysis of experience with 118 volunteers indicated that mosquito inoculation of P. falciparumcould 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. falciparumbetween 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.