Effects of Plasmodium falciparum parasite population size and patient age on early and late parasitological outcomes of antimalarial treatment in children

The design and interpretation of trials assessing the chemotherapeutic effects of antimalarial drugs depend on our understanding of how different selection criteria affect treatment outcomes. In this study, we analyzed the effects of baseline parameters on the initial parasite elimination rate and the risk of subsequent recrudescence as a marker for incompletely eliminated asexual blood-stage parasites in pediatric patients with uncomplicated Plasmodium falciparum infection treated with amodiaquine in a high-transmission area. We found that (i) parasite population size and patient age independently determine early and late parasitological treatment outcome measurements; (ii) the rate of recrudescence is higher in patients I to 3 years of age than in patients aged < 1 or > 3 years; (iii) patients aged > 5 years with parasite densities between 2,000 and 10,000/mu l have a lower recrudescence rate (13%; 95% confidence interval [CI], 8% to 21%) than patients aged < 5 years with parasite densities of > 10,000/mu l (40%; 95% CI, 30% to 50%); and (iv) the sensitivity of detecting recrudescences outside this high-risk group, i.e., in patients of > 5 years of age or with parasite densities of < 10,000/mu l, is as low as 27% or 22%, respectively. In conclusion, these findings highlight the need to use adequate selection criteria and to report parasitological outcome results adjusted for the readily available determinants of chemotherapeutic failure, i.e., patient age and baseline parasitemia. The thresholds may vary by transmission intensity and drug regimen. A better understanding of the limitations of antimalarial regimens in high-risk subgroups of patients has important implications for setting policy recommendations.