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10-04-2012 | Genetics | Article

Artemisinin-resistant malaria on the increase


Lancet abstract

MedWire News: Results from research published in The Lancet show that artemisinin-resistant Plasmodium falciparum has arisen along the border of Thailand and has almost reached rates seen in western Cambodia.

Another study, published in Science, found evidence of recent and strong positive natural selection, known as a selective sweep, on an area of chromosome 13 of the artemisinin-resistant P. falciparum genome.

"Spread of drug resistant malaria parasites within Southeast Asia and overspill into sub-Saharan Africa, where most malaria deaths occur, would be a public health disaster resulting in millions of deaths," said one of The Lancet study authors Standwell Nkhoma (Texas Biomedical Research Institute, San Antonio, USA) in a press statement.

"The problem we have is that treatment with artemisinin-based drugs will promote spread of resistance, but there are no viable alternative treatment options in Southeast Asia," he added.

For The Lancet study, François Nosten (Shoklo Malaria Research Institute, Tak, Thailand) and colleagues investigated whether artemisinin-resistant P. falciparum, previously seen only in western Cambodia, had arisen along the border between Thailand and Burma.

The team tested the efficacy of artesunate-containing regimens at clearing the parasite from the blood in 3202 P. falciparum patients attending clinics along the Thai border between 2001 and 2010.

Parasite clearance half-lives on treatment with artemisinin increased from a mean of 2.6 hours in 2001 to 3.7 hours in 2010. The mean clearance half-life for the western Cambodian patients with artemisinin-resistant P. falciparum measured between 2007 and 2010 was 5.5 hours.

Slow clearing (half-life ≥6.2 hours) P. falciparum infections along the Thai border increased from 0.6% in 2001 to 20% in 2010. In comparison, the mean rate of such infections in western Cambodia between 2007 and 2010 was 42%.

Nosten and team say that the proportion of the variance in parasite clearance that could be attributed to genetics also increased over the study period from 30% (2001-2004) to 66% (2007-2010).

Timothy Anderson, also from Texas Biomedical Research Institute, and co-authors of the Science study investigated the genetics of artemisinin resistance further by genotyping 91 resistant P. falciparum parasites collected from Cambodia, Thailand, and Laos (controls).

The team found a selective sweep on chromosome 13 of the Thai and Cambodian parasite genomes that showed a strong association with slow clearance rates for artemisinin.

"Our group wanted to understand what genetic changes have occurred in these parasites," said lead author of the study Ian Cheeseman, a colleague of Andersons at the Texas Biomedical Research Institute.

"This study narrows the search to a region of the parasite genome containing around 10 genes. We haven't yet found the precise changes involved, but we are getting close."

By Helen Albert

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