Plasmodium falciparum malaria challenge by the bite of aseptic Anopheles stephensi mosquitoes: results of a randomized infectivity trial.
BACKGROUND
Experimental infection of malaria-naïve volunteers by the bite of Plasmodium falciparum-infected mosquitoes is a preferred means to test the protective effect of malaria vaccines and drugs. The standard model relies on the bite of five infected mosquitoes to induce malaria. We examined the efficacy of malaria transmission using mosquitoes raised aseptically in compliance with current Good Manufacturing Practices (cGMPs).


RESULTS
Eighteen adults aged 18-40 years were randomized to receive 1, 3 or 5 bites of Anopheles stephensi mosquitoes infected with the chloroquine-sensitive NF54 strain of P. falciparum. Seventeen participants developed malaria; fourteen occurring on Day 11. The mean prepatent period was 10.9 days (9-12 days). The geometric mean parasitemia was 15.7 parasites/µL (range: 4-70) by microscopy. Polymerase chain reaction (PCR) detected parasites 3.1 (range: 0-4) days prior to microscopy. The geometric mean sporozoite load was 16,753 sporozoites per infected mosquito (range: 1,000-57,500). A 1-bite participant withdrew from the study on Day 13 post-challenge and was PCR and smear negative.


CONCLUSIONS
The use of aseptic, cGMP-compliant P. falciparum-infected mosquitoes is safe, is associated with a precise prepatent period compared to the standard model and appears more efficient than the standard approach, as it led to infection in 100% (6/6) of volunteers exposed to three mosquito bites and 83% (5/6) of volunteers exposed to one mosquito bite.


BACKGROUND
ClinicalTrials.gov NCT00744133.
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America. KLyke@medicine.umaryland.edu
Kirsten E
KE
Lyke
Matthew
M
Laurens
Matthew
M
Adams
Peter F
PF
Billingsley
Adam
A
Richman
Mark
M
Loyevsky
Sumana
S
Chakravarty
Christopher V
CV
Plowe
B Kim Lee
BK
Sim
Robert
R
Edelman
Stephen L
SL
Hoffman
D000293:Adolescent; D000328:Adult; D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D005260:Female; D006801:Humans; D007299:Insect Bites and Stings; D016778:Malaria, Falciparum / Q000635:transmission*; D008297:Male; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction