In the midst of all the recent political developments in global health, there's an exciting surprise on the scientific front: a new study in the New England Journal of Medicine has found that chloroquine cured 99% of malaria cases in a study of 105 children in Malawi, over 12 years after it was withdrawn due to treatment failure rates of over 50% (as reported in the Seattle Post-Intelligencer and elsewhere). From an evolutionary standpoint, these findings suggest that the survival advantage enjoyed by chloroquine-resistant parasites in the presence of the drug has an associated fitness cost, so that in the absence of chloroquine the parasite population will favor organisms lacking the resistance mutation. This has significant ramifications for pharmaceutical policies and malaria treatment guidelines:
Despite its efficacy in this small study, chloroquine should not be used as monotherapy for malaria where chloroquine-sensitive P. falciparum has reemerged after its use was reduced. Although we did not find clinical or molecular evidence of chloroquine resistance in this study, chloroquine-resistant malaria remains common in neighboring countries, including Mozambique and Zambia, and would probably reemerge rapidly if chloroquine were to be reintroduced for the routine treatment of malaria.
Where its efficacy is impaired, chloroquine should be completely withdrawn from use and replaced by more effective drugs. If chloroquine-susceptible falciparum malaria returns across the region, it may become possible to reintroduce the drug in combination with other drugs to prevent the reemergence of resistance. Chloroquine has many desirable attributes as an antimalarial drug: it is inexpensive, rapid-acting, long-acting, and safe in all age groups and in pregnant women. It is an excellent drug for preventing malaria in travelers and may be an ideal candidate for intermittent preventive treatment, which has shown promise in studies involving pregnant women, infants, and children. If chloroquine can be withdrawn from use throughout Africa as effectively as it was withdrawn in Malawi, it may be possible to include it as one component of a new generation of combination therapy in the not-too-distant future.
The accompanying NEJM opinion piece then links this back to the current policy discussion of a global subsidy for artemisinin combination therapy (proposed by the Institute of Medicine and under consideration by UNITAID).
While this is the first time that a widely used drug has regained effectiveness after a break in use, it undoubtedly has implications for the broader issue of drug resistance for other diseases as well. As the world worries about the impending spread of XDR-TB and other so-called "super bugs," this case serves as a powerful reminder that in addition to developing new products, the global health community should consider ways to better use the existing ones so they remain as effective as possible for as long as possible.
Update: In my excitement, I forgot to note that this comes on the heels of other interesting news about chloroquine: earlier this week, a different team of researchers found evidence suggesting that the drug could also be used to treat metabolic syndrome, which is characterized by insulin resistance and associated with obesity and diabetes (see Forbes for more detail; the original study in Cell Metabolism is available for purchase here). This is an interesting twist on the usual pharmaceutical market dynamics, whereby most developing country products are originally conceived for diseases facing people (or their animals) in wealthy countries.
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