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Antimicrobial Agents and Chemotherapy, May 2008, p. 1799-1805, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.00755-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Effects of Plasmodium falciparum Parasite Population Size and Patient Age on Early and Late Parasitological Outcomes of Antimalarial Treatment in Children

Steffen Borrmann,^1,2*, Pierre-Blaise Matsiegui,^3,4, Michel Anoumou Missinou,^3,4 and Peter G. Kremsner^3,4

Institute of Hygiene, University of Heidelberg School of Medicine, Heidelberg, Germany,¹ Kenya Medical Research Institute, Centre for Geographical Medicine Research—Coast, Kilifi, Kenya,² Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon,³ Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany⁴

Received 11 June 2007/ Returned for modification 22 August 2007/ Accepted 16 February 2008

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 1 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/µl have a lower recrudescence rate (13%; 95% confidence interval [CI], 8% to 21%) than patients aged <5 years with parasite densities of >10,000/µl (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/µl, 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.

Published ahead of print on 25 February 2008.

These authors contributed equally to the work.