Can Mass Drug Administration in Malaria-Endemic Areas Lead to Antimalarial Drug Resistance?

Mass drug administration (MDA) in malaria-endemic areas around the world remains a controversial topic among infectious disease and public health specialists—primarily due to the concern that widespread antimalarial drug resistance is an unintended consequence of the approach.

As Nicholas J White, MD, a professor on the faculty of tropical medicine at the Mahidol Oxford Tropical Medicine Research Unit at Mahidol University in Bangkok, who also holds a degree in pharmacology, describes it, MDA as a means of malaria prophylaxis entails the widespread administration of antimalarial drugs in a malaria-endemic area, with the goal of eliminating the disease from the population and/or controlling an ongoing epidemic. In a passionate and thoroughly researched “Personal View” on MDA as a means of malaria prophylaxis, Dr. White argued that while “badly executed, or poorly accepted MDA certainly can lead to resistance, effective MDA can prevent the emergence of resistance, and thereby protect the antimalarial drugs.” His thoughts were published online in the journal The Lancet Infectious Diseases on November 10.

In the past, the approach was used with the antimalarial primaquine to eliminate Plasmodium vivax malaria. More recently, MDA has been employed to target the Plasmodium falciparum strain of the virus. The population is typically given a full drug dose initially, and treatment is repeated 1-2 times at monthly intervals.

Dr. White’s commentary outlined existing research findings with regard to MDA’s potential role in the spread of antimalarial drug resistance, when it is implemented incorrectly, as well as published data demonstrating its ability to actually reduce the spread of resistance, when used correctly. He wrote, “Amplification of resistance occurs when there is heterogeneity in antimalarial drug concentrations in the human population (eg, in variable underdosing or posttreatment elimination profiles). This heterogeneity is reduced by effective MDA. The reduced transmission and thus lower number of symptomatic malaria infections following effective MDA results in fewer opportunities for acquisition of resistant infections, and thus onward spread.”

Indeed, Dr. White advocates for the “deployment” of MDA “during the period with the lowest malaria transmission” in an endemic region—namely, the dry season. Existing research, he wrote, suggests that the risk for acquiring an infection may be up to 10 times lower during the dry season than during the rainy season, thereby reducing the probability of resistance selection post-MDA. Conversely, he added, symptomatic malaria is widespread during the rainy season, and its treatment “provides… windows of selection when there is a greater probability of being bitten by Anopheles spp mosquitos.” He believes that if an MDA deployment is marked by “poor coverage, poor adherence, substantial migration, or surrounding high transmission,” then the risk for selecting resistance is higher.

The author did not respond to requests for comment. However, in his concluding remarks for The Lancet Infectious Diseases commentary, he wrote, “MDA both increases and decreases factors contributing to the emergence and spread of antimalarial drug resistance and so can either increase or reduce the overall risk depending on this balance. Successful MDA that drives malaria to elimination clearly reduces the risk overall. Contrary to general opinion, well-conducted MDA with good adherence deployed during the dry season in areas of low seasonal transmission is likely to reduce the probability of selecting resistance… Paradoxically, delaying MDA deployment because of theoretical fears of resistance could create more resistance than if MDA had been deployed immediately, and could thereby prevent its later use.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.