Drug Resistance in Malaria

P. falciparum gametocytes on a blood smear

The department seminar last week was given by Dr. Timothy Anderson, a scientist working right here in San Antonio at The Texas Biomedical Research Institute.  His lab is looking at genes responsible for drug resistance in the parasite that causes malaria and tracking these mutations as they spread through endemic regions.   Drug resistance is an increasing problem for endemic areas where the drugs that are currently used to treat malaria are becoming less effective.

Before diving into the details, some background: Malaria is caused by parasites of the genus Plasmodium.  These organisms have a complex life cycle and are transmitted by mosquitoes to humans where they infect and kill red blood cells.   Malaria is endemic to tropical regions around the world.  (To learn more about the distribution of malaria, the CDC has a malaria map application here).  The species of plasmodium that causes the most severe infection is P. falciparum and Dr. Anderson's lab is looking at the types and distribution of resistance mutations in this species.

One gene in particular, pfmdr-1, has been well studied and shown to play a role in drug resistance.  Copy number variations, as well as single nucleotide polymorphisms (SNPs) in this gene can lead to drug resistance.  Dr. Anderson's lab genotyped 160 infections from Malawi to determine the rate of CNVs and SNPs associated with resistance*.  All the parasites had a single copy of pfmdr-1.  Although no CNVs were seen in this study, this finding is important for setting a baseline of CNV prevalence for future surveillance studies to reference.  It was also found that 34% of the parasites had variations at 4 of the 5 SNP sites studied.  After determining the prevalence of these mutations in the population, they looked at susceptibility to various anti-malarial drugs and found that several of these genotypes were associated with increased resistance to the drugs tested.

In order to develop effective strategies for drug development and delivery it's important to understand the underlying mechanisms of resistance and how resistance moves through a population.  This study and studies like it are critical for understanding how to minimize the spread of drug resistance and for the implementation of smart drug policies that save lives.

*Nkhoma et al. Parasites bearing a single copy of the multi-drug resistance gene (pfmdr-1) with wild-type SNPs predominate amongst Plasmodium falciparum isolates from Malawi. Acta Trop (2009) vol. 111 (1) pp. 78-81