Team of Doctors Zeroes In on Drug-Resistant Malaria Genes

An international team of re­searchers behind the first complete gene map of the world’s deadliest malaria strain say they have narrowed in on the genes responsible for its growing resistance to drugs used to fight the mosquito-borne parasite.

Doctors in Cambodia hope the findings will eventually help them get an early jump on the strain if it spreads, as some studies suggest it already has.

The team published its findings in the magazine Nature Genetics last week. Of malaria’s many strains, it focused on the most deadly, plasmodium falciparum. The strain also happens to be the most common malaria parasite in Cambodia, where it first started showing signs of resistance to artemisinin combination therapy, currently the most powerful medical weapon against malaria, two years ago.

Mapping the strain’s complete genome was “a tremendous ac­complishment” in itself, said Steven Bjorge, a malaria researcher working for the World Health Organi­zation in Cambodia.

But the team went a key step further by looking for the genes that have been rendering ACTs progressively less effective. Iden­tifying those genes, or markers, would be akin to knowing exactly where to look for the needle in the proverbial haystack. While the research team failed to name those markers, it did find some promising candidates.

“Up until now we haven’t had any gene markers for artemisinin resistance, and this is a step forward in that respect,” said Dr Bjorge.

While the team “found some interesting results,” he said, “they can’t definitively say that this paper is the complete answer.”

“If this [test] can be done on a larger scale, maybe one of these markers can be identified,” said Philippe Guyant, malaria program manager in Cambodia for the NGO Partners for Development.

“Those findings could allow for better detection of the emergence of drug resistance to artemisinin in areas where it didn’t exist yet,” he said. “It could allow to monitor the geographic extent and spread of it and to adjust treatment protocol according to it.”

Researchers in Southeast Asia are struggling with questions surrounding the spread of the strain.

Along the Thai-Cambodian border, health workers have responded to the early stages of ACT resistance with a two-year containment plan. However, they are still debating whether the resistant strain has arrived.

At the annual meeting of the American Society of Tropical Medicine and Hygiene in Wash­ington last November, re­searchers presented new data reaffirming earlier findings of ACT resistance in Burma and Vietnam. Both Dr Bjorge and Dr Guyant, however, say any signs of resistance beyond the Thai-Cambodian border remain dubious.

Markers for the strain could settle such doubts quickly and convincingly.

“If we would have a gene marker that could be clearly linked to [ACT] drug resistance…we can know right away and we can treat right away,” Dr Guyant said.

With its deep forests, unlicensed pharmacists and popular migration routes, the Thai-Cambodian border has for decades held the undesired distinction as the epicenter of emerging malaria drug resistance.

On at least three previous occasions, resistance to the leading malaria drug began here before spreading to the rest of Asia and moving to Africa. And as the global economic crisis has put ever more people on the move in search of work, Dr Guyant said, the dangers of spreading ACT resistance—and the need for a gene marker to catch it—have grown apace.

“It is a problem within Cambodia and a problem within the region,” he said.

To better understand that problem, Cambodia’s National Malaria Center has teamed up with the WHO and the US Centers for Disease Control and Prevention for a three-day visit to the border in Pursat province. They return to Phnom Penh today.

“We go to interview some of the mobile migrants,” said the center’s deputy director, Chea Nguon, who hopes to find out more about where those migrants come from and where they go.

Despite a jump in the number of reported malaria cases and deaths last year, both figures are well below what they were 10 years ago. And according to a recent report from the WHO, more than a third of the 108 malaria-endemic countries around the world saw reported cases between 2000 and 2008 drop by more than half.


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