American Journal of Epidemiology Vol. 145, No. 10: 945-956
Copyright © 1997 by The Johns Hopkins University School of Hygiene and Public Health
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Dose- and Time-dependent Relations between Infective Anopheles Inoculation and Outcomes of Plasmodium falciparum Parasitemia among Children in Western Kenya
1Malaria Program, Naval Medical Research Institute, Bethesda, MD
2Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Ml
3US Army Medical Research Unit, Nairobi and Kisumu, Kenya
4Department of Tropical Medicine, School of Public Health, Tu-lane University, New Orleans, LA
5Department of Infectious Diseases, Walter Reed Army Institute of Research, Washington, DC
6Kenya Medical Research Institute, Vector Biology and Control Research Centre, Kisumu, Kenya
7Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Ml
Reprint requests to Dr. Stephen L Hoffman, Malaria Program, Naval Medical Research Institute, 12300 Washington Ave., Rock-ville, MD 20852.
Blood-stage level Plasmodium falciparum infection (parasitemia density) is generally elevated prior to, or at the time of, clinical presentation of severe pediatric malaria episodes. Intensity of exposure to infective Anopheles mosquito bites is a suspected determinant of higher density parasitemia. Analyses of entomologic and parasitologic data collected in 1986–1987 were conducted to investigate whether the dose of infective bites predicted the incidence or degree of P. faiciparum parasitemia in Kenyan children <6 years old. At 21 consecutive 30-day intervals, a new cohort (n 
50 each) was enrolled, cured of malaria parasites, and monitored over 84 days for recurrent parasitemia. Outcomes included time to parasitemia, time to parasitemia 
5,000/µl, and parasitemia density. Ecologic and individual-level analyses were conducted. The mean infective bite exposure experienced by each cohort was significantly associated with the incidence of parasitemia (age-adjusted r2 = 0.38, p = 0.022) and more strongly associated with the incidence of parasitemia 5,000/µl (age-adjusted r2 = 0.72, p < 0.001). The infective bite dose, analyzed as a time-dependent covariate, was associated with a 2.8 times higher rate of parasitemia 5,000/µl among children exposed to 1 infective bite per day as compared with the referent (rate ratio (RR) = 2.82, 95% confidence interval (Cl) 2.24–3.56). Cumulative infective bite exposure, exposure duration, and age were significant predictors of recurrent parasitemia density in multiple linear regression analyses. The results support the contention that reductions in P. falciparum transmission intensity, in the absence of complete elimination, will reduce higher level parasitemia among African children. Am J Epidemiol 1997; 145: 945–56.
Anopheles; Culicidae; malaria; Plasmodium falciparum
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