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In the past, malaria control efforts in sub-Saharan Africa have relied on a combination of vector control with effective treatment using chloroquine. With increasing resistance to chloroquine, attention has now turned to alternative treatment strategies to replace this failing drug. Some countries have already changed their official first-line treatment to sulfadoxine-pyrimethamine, while others are contemplating a switch to artemisinin-based combination treatments (ACTs). Although there are strong theoretical arguments in favor of switching to ACTs, the validity of these arguments in the face of financial constraints has not been previously analyzed. In this report, we use a bioeconomic model of malaria transmission and evolution of drug resistance to examine questions of optimal treatment strategy and coverage when drug resistance places an additional constraint on choices available to the policymaker.
Received August 21, 2003. Accepted for publication December 22, 2003.
Acknowledgments: I thank Ellis McKenzie, Rustom Antia, Ian Hastings, and Nick White for useful advice on the epidemiologic model, and Ken Arrow, Dean Jamison, Hellen Gelband, and participants at the Institute of Medicine Workshop on Economic Modeling (Oxford, United Kingdom) for helpful discussions and detailed comments. I am responsible for any errors that remain.
Author’s address: Ramanan Laxminarayan, Resources for the Future, 1616 P Street NW, Washington DC 20036, Telephone: 202-328-5085, Fax: 202-939-3460, E-mail: Ramanan{at}rff.org.
* There is substantial disagreement over the cost of ACTs. Current estimates vary between $1.00 per adult dose (Médecins Sans Frontiéres) and $2.50 for artemether-lumafantrine at the price negotiated by the World Health Organization for developing countries. It is likely that with widespread adoption of new ACTs, the price will decrease significantly and the lower estimate of $1.00 would be a reasonable approximation of the long-term marginal cost of these treatments. The current price for SP is roughly $0.12 per dose.
This situation has already arisen in Southeast Asia.
Although the use of ACTs is less likely to induce resistance than the use of drugs in monotherapy, the probability of increased resistance to ACTs is greater for higher levels of treatment coverage. However, if increasing ACT coverage implies less use of the partner drug in monotherapy, then this could lower the likelihood of resistance to ACTs.
Since this paper was completed, a new report has been published by Koella and Antia12 that incorporates resistance into a model of malaria transmission. Their model differs only in minor respects from the one developed in this paper.
¶ Interventions such as impregnated bed net use will likely reduce this transmission coefficient. Although the use of ACTs is expected to reduce gametocyte carriage and thus parasite transmissions, we shall assume that ACTs reduce transmission primarily by curing patients more rapidly.
# Some of the mathematical epidemiology literature on malaria resistance focuses on the relative importance of transmission rates on evolution of drug resistance.13,14
|| For a discussion of the fitness cost of resistance, see the report by Koella.15
+ It is possible that resistant parasites are less likely to be transmitted from humans to mosquitoes and back and this places them at an evolutionary disadvantage with respect to sensitive parasites. It is also possible that resistant parasites are more likely to be transmitted, which gives them a transmission fitness advantage.16
~ In a recent paper, Snow and others28 report a $1.20 cost for an adult dose of artesunate plus SP (sulfadoxine, 25 mg/kg of body weight over a one-day period; pyrimethamine, 12.5 mg/kg of body weight over a one-day period; artesunate, 4 mg/kg of body weight over a three-day period); $1.30 for an adult dose of artesunate plus amodiaquine (amodiaquine, 25 mg/kg of body weight over a three-day period; artesu-nate, 4 mg/kg of body weight over a three-day period); and $2.40 for an adult dose of Coartem® (lumefantrine, 48 mg/kg of body weight over a three-day period; artemether, 8 mg/kg of body weight over a three-day period).
If non-drug treatment costs were for example $4, then the cost of ACT treatment is only roughly 20% higher than that of SP treatment. With zero non-drug treatment costs, the relative cost of ACT treatment is higher. One reason for including only the drug costs was to examine the problem from the perspective of a Ministry of Health that is concerned about the impact on its drug budget of different treatment strategies.
* See page 395 of Anderson and May8 for a geometric phase plan–based derivation for the basic malaria model.
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