Modeling Within-Host Effects of Drugs on Plasmodium falciparum Transmission and Prospects for Malaria Elimination (original) (raw)
Figure 3
Modeled post-treatment gametocyte prevalence and treatment effect sizes.
Treated and untreated malaria infections were simulated using our within-host malaria infection model. Modeled treatments differed according to the assumed level of gametocyte killing. Model treatment was assumed to start 5 days after the first onset of fever; all model outputs represent the mean of 1,000 runs. (A) The number of individuals predicted to be gametocyte positive by microscopy (threshold 5 gametocytes per µL) was tracked over time. Untreated model outputs are shown in black. Treatment was assumed to be a combination therapy with a short-lived component (active for 3 days) and a longer-lived component with the pharmacokinetic profile of mefloquine. The green line illustrates the effects of treatment assuming no gametocytocidal activity (‘Schizonticide’). The assumed gametocytocidal activity of each component was progressively increased and compared to field data to generate the rest of the curves, each labeled with their corresponding antimalarial (chloroquine, CQ; artemisinin-based combination therapy, ACT; primaquine, PQ). The curves labeled ‘ACT+PQ’ assumed the presence of a second short-lived partner that strongly killed both early and late stage gametocytes; the number indicates the day on which the simulated PQ component was administered. (B) Total effect sizes (fold-reductions in transmission) for each of the modeled drug parameterizations as a function of treatment coverage, including the oocidal effects of drugs, assuming net untreated infectivity of 30.5 days, and using the ‘Jeffery-Eyles’ density-to-infectivity parameterization for treated individuals (Table 2; [23]). Each drug class is depicted in a different color. The variation in each class is due to the different simulated levels of gametocytocidal activity for that drug type. Each line within a given drug class represents the result of 1,000 simulation runs; the black lines indicate the mean effect sizes for each class of drug. The horizontal line illustrates a six-fold reduction in transmission. The dotted vertical lines indicate the levels of treatment coverage needed to reach a six-fold reduction in total human-to-mosquito transmission for each drug class. The y-axis is in log-scale.