Containing artemisinin resistant malaria

The NY Times featured artemisinin resistance along the Thai-Cambodia border yesterday (though it wasn’t written by Donald McNeil who is the author for most of their global health work). I’ve previously discussed the topic (here, and here), and I am part of a team which researches malaria drug resistance in Cambodia. First, my use of the term “resistance” rather than “tolerance” is deliberate – I don’t think we need to mince words. Sure, you can debate the semantics but the conclusion is the same: parasites with decreased susceptibility to artemisinin are a severe threat. Second, its important to recognize that resistance (to any drug) will eventually spread. The purpose of containment is to delay that spread and thus prolong the utility of artemisinin combination therapies. Two questions arise: 1) does containment for artemisinin resistance make biological sense? 2) How do we execute a containment program?

Broadly, the molecular mechanisms for resistance are changes in drug targets (which prevent the drug from binding) and changes in transport proteins (which prevent the drug from entering, or pump the drug out of cells). Resistance to artemisinin is not well understood, though some studies have associated increases in the number of copies of a gene called pfmdr1 (a transport protein). The trouble with pfmdr1 is that an increase in the copies of the gene can occur at many sites in the chromosome, and occurs fairly frequently. Thus, if increased pfmdr1 is the primary mechanism of artemisinin resistance, a concept of “containment” may not be valid as resistance would be expected to arise in many locations. Any area which maintains sufficient drug pressure will then select for resistant strains, so the key is to reduce drug pressure. Unfortunately, promoting rational drug use is a difficult task (previously discussed here, and here) but must be, and hopefully will be, included as a component of long-term strategy.

I’ve heard mass drug administration with atovaquone-proguanil is in the works as part of the containment plan. Reaching the migrant gem-mining laborers, particularly those who travel to the Thai-Burma border area, will require some creativity in delivery. The article mentions scaling standard interventions such as insecticide treated nets, but it is not clear what other new strategies will be employed. Regardless of the intervention, improving coordination across the border where there is little infrastructure health or otherwise, might be the most important obstacle to overcome. Agreement between the health agencies of Thailand and Cambodia is great, but I hope the cooperation extends across other government departments which will need to be engaged in this effort. After all, both countries had just recently amassed thousands of troops along their border…


2 Responses to “Containing artemisinin resistant malaria”

  1. 1 Erik February 1, 2009 at 7:05 pm

    Very good post! I believe containment is going to be very difficult and also wanted note the fact that resistance is with artemisinin treatment as mono-therapy. I agree that combination therapy is likely the most important weapon, thus far.



  2. 2 barmak February 2, 2009 at 7:08 pm

    hey, erik, great site and blog. it’s in my rss as is topnaman, now.

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