Monitoring antimalarial drug resistance with molecular tools

Millions of people get treated for malaria every year so its important to use an antimalarial which works. Treatment failures result in a prolonged illness for the patient with an increased risk of severe malaria and death. In addition, they contribute to increased malaria transmission. Makes sense right? However, the parasite has an amazing ability to develop drug resistance and it’s hard to know what works ahead of time. Point-of-care diagnostics to identify drug resistance are not available and nor would they likely be practical given the low-cost and short course of malaria treatments. Rather, population level monitoring of drug resistance is used to inform the national drug policy which specifies a fixed treatment strategy.

Presently, in vivo efficacy trials are the gold standard for anti-malarial drug resistance monitoring. In vivo trials involve treating a cohort of malaria patients and subsequently checking their blood at regular intervals to detect parasites. Thus, in vivo studies are not direct measures of parasite resistance per se – as other factors such as host immunity and pharmacokinetics play a role, but the outcome (treatment failure) is directly relevant to programs. However, implementing in vivo studies presents several challenges in endemic settings including cost, well-trained staff, lengthy periods of patient follow-up (28 to 63 days), and the need to distinguish treatment failures as recrudescences or reinfections. Since most malaria control programs have limited resources, only a few in vivo trials can be conducted each year. An alternate method to extend the surveillance of antimalarial efficacy is to measure molecular markers of drug resistance.

We employed a molecular surveillance system in Cambodia (Emerging Infectious Diseases Journal – open access) to help detect ACT resistance. This new tool does not replace the standard in vivo trial but rather enables a more efficient use of existing resources. Using this system, a high level of artesunate-mefloquine failures (which were previously believed to be confined to the Thai border) was discovered in the center of the country. Here’s a quick summary of the benefits:

Monitoring changes in antimalarial efficacies is essential for control programs in an era of multi-drug resistance. However, such studies are resource intensive. In Cambodia, for example, the National Malaria Control Program can manage to conduct in vivo studies at only 2-3 sites per year because of limited funds and trained staff. Molecular markers can help target in vivo studies to where they are needed the most. Molecular surveillance is high-throughput and can be performed in a central laboratory on dried blood spots, which are easily collected in the field. Expanded molecular surveillance could also accurately help map anti-malarial resistance and enable sub-national treatment policies in countries with marked geographic variation in drug susceptibility.

What excites me about this work is the translation of molecular knowledge into a monitoring tool for informing policy and improving malaria control operations. I think the last two sentences of the paper say it all:

pfmdr1 assays are now routinely performed in Cambodia by National Malaria Control Program staff. National and regional molecular surveillance by malaria-endemic countries is a real possibility.


1 Response to “Monitoring antimalarial drug resistance with molecular tools”

  1. 1 Containing artemisinin resistant malaria | topnaman | Malaria blog Trackback on January 28, 2009 at 8:19 am
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