Benefits of using multiple first-line therapies against malaria

Edited by Simon A. Levin, Princeton University, Princeton, NJ, and approved June 30, 2008
September 16, 2008
105 (37) 14216-14221

Abstract

Despite the availability of many drugs and therapies to treat malaria, many countries' national policies recommend using a single first-line therapy for most clinical malaria cases. To assess whether this is the best strategy for the population as a whole, we designed an evolutionary-epidemiological modeling framework for malaria and compared the benefits of different treatment strategies in the context of resistance evolution. Our results show that the population-wide use of multiple first-line therapies (MFT) against malaria yields a better clinical outcome than using a single therapy or a cycling strategy where therapies are rotated, either on a fixed cycling schedule or when resistance levels or treatment failure become too high. MFT strategies also delay the emergence and slow the fixation of resistant strains (phenotypes), and they allow a larger fraction of the population to be treated without trading off future treatment of cases that may be untreatable because of high resistance levels. Earlier papers have noted that cycling strategies have the disadvantage of creating a less temporally variable environment than MFT strategies, making resistance evolution easier for the parasite. Here, we illustrate a second feature of parasite ecology that impairs the performance of cycling policies, namely, that cycling policies degrade the mean fitness of the parasite population more quickly than MFT policies, making it easier for new resistant types to invade and spread. The clinical benefits of using multiple first-line therapies against malaria suggest that MFT policies should play a key role in malaria elimination and control programs.

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Acknowledgments.

We thank Hellen Gelband, Carl Bergstrom, and an anonymous referee for comments on an earlier version of this article. This work was funded primarily by Grant no. 44811 from the Bill and Melinda Gates Foundation. M.F.B. is also supported by National Institutes of Health/National Institute of General Medical Sciences Grant P50GM071508.

Supporting Information

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Supporting Information

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 105 | No. 37
September 16, 2008
PubMed: 18780786

Classifications

Submission history

Received: May 13, 2008
Published online: September 16, 2008
Published in issue: September 16, 2008

Keywords

  1. drug resistance
  2. epidemiology
  3. evolution
  4. treatment strategies
  5. cost of resistance

Acknowledgments

We thank Hellen Gelband, Carl Bergstrom, and an anonymous referee for comments on an earlier version of this article. This work was funded primarily by Grant no. 44811 from the Bill and Melinda Gates Foundation. M.F.B. is also supported by National Institutes of Health/National Institute of General Medical Sciences Grant P50GM071508.

Notes

This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0804628105/DCSupplemental.

Authors

Affiliations

Maciej F. Boni [email protected]
Resources for the Future, Washington, DC 20036;
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544;
Princeton Environmental Institute, Princeton, NJ 08544; and
David L. Smith
Department of Zoology and
Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611
Ramanan Laxminarayan
Resources for the Future, Washington, DC 20036;
Princeton Environmental Institute, Princeton, NJ 08544; and

Notes

To whom correspondence should be addressed. E-mail: [email protected]
Author contributions: M.F.B., D.L.S., and R.L. designed research; M.F.B. performed research; and M.F.B. wrote the paper.

Competing Interests

The authors declare no conflict of interest.

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    Benefits of using multiple first-line therapies against malaria
    Proceedings of the National Academy of Sciences
    • Vol. 105
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