Clinical outcome of experimental human malaria induced by Plasmodium falciparum-infected mosquitoes.
BACKGROUND
Human experimental malaria infections have been safely carried out previously. The objective of this study was to evaluate infection rates and clinical safety of different protocols for human experimental malaria induced by Plasmodium falciparum-infected mosquitoes.


METHODS
Thirty nonimmune volunteers were infected by bites of 1-2 or 4-7 Anopheles stephensi mosquitoes infected with the NF54 strain of P. falciparum.


RESULTS
A 100 or 50% infection rate was obtained after bites of 4-7 and 1-2 infected mosquitoes, respectively. Median prepatent period was 8.8 days. The most common symptoms after a median incubation time of eight days were headache, malaise/fatigue and fever. There was no significant difference in clinical and parasitological presentation between groups infected by 4-7 or 1-2 mosquitoes. Delay of treatment by maximally 48 hours after the first positive thick smear was generally well tolerated but fever was higher and more frequently observed. The most prominent laboratory abnormality was uncomplicated thrombocytopenia. Two volunteers with parasitaemia developed psychiatric side effects after chloroquine treatment.


CONCLUSIONS
With stringent inclusion criteria, close monitoring and immediate administration of treatment upon detection of parasitaemia, experimental human malaria challenges can be considered safe and generally well tolerated.
Verhage
D F
DF
Departments of' Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Telgt
D S C
DS
Bousema
J T
JT
Hermsen
C C
CC
van Gemert
G J A
GJ
van der Meer
J W M
JW
Sauerwein
R W
RW
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D001774:Blood Chemical Analysis; D009033:Culicidae; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006805:Human Experimentation; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D011336:Probability; D012107:Research Design; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D000962:Antimalarials