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Drug-resistant malaria spreads in South-East Asia from Cambodia, Sanger Institute finds

Malaria that is resistant to two first line drugs has spread rapidly from Cambodia to neighbouring South-East Asian countries, researchers have discovered.

Scientists at the Wellcome Sanger Institute in Hinxton, University of Oxford and Mahidol University in Bangkok used genomic surveillance to inform global efforts to control the disease, which is spread by mosquitoes and kills 400,000 a year.

A mosquito sucking blood. (14164618)
A mosquito sucking blood. (14164618)

They sequenced and analysed the DNA of 1,673 Plasmodium falciparum parasites, taken from the blood of malaria patients between 2008 and 2018.

The work, published in the The Lancet Infectious Diseases, followed an earlier study that found a strain of malaria, resistant to a leading treatment of two powerful drugs - dihydroartemisinin and piperaquine (DHA-PPQ) - had spread under the radar across Cambodia between 2007-2013.

The researchers discovered the situation had got much worse since, with more than 80 per cent of the parasites analysed found to be resistant in some regions.

Dr Roberto Amato, joint first author from the Wellcome Sanger Institute, said: “We discovered that the multi-drug resistant KEL1/PLA1 malaria strain had spread aggressively, replacing local malaria parasites, and had become the dominant strain in Vietnam, Laos and north-eastern Thailand.

“Our large-scale genomic approach demonstrates how surveillance can provide crucial information to malaria control programmes, supporting them in evaluating available treatment options.”

The World Health Organisation estimates that 220 million people were infected with malaria in 2017. Children under the age of five in sub-Saharan Africa are at most risk.

While the disease can be treated if caught early enough, the spread of resistance, especially in South East Asia, represents a major threat.

The resistant parasites are thought to have had an evolutionary advantage as the use of the same drugs in this region would have killed off other malaria strains.

The resistant strain has also evolved and picked up new mutations in the chloroquine resistance transporter gene.

Anopheles mosquito - dangerous vehicle of infection.. (14164629)
Anopheles mosquito - dangerous vehicle of infection.. (14164629)

Professor Olivo Miotto, a senior author from the Wellcome Sanger Institute, Big Data Institute at University of Oxford and Mahidol University, Bangkok, said: “The speed at which these resistant malaria parasites have spread in Southeast Asia is very worrying. Other drugs may be effective at the moment but the situation is extremely fragile and this study highlights that urgent action is needed to eliminate the parasites from the Greater Mekong Subregion, to prevent them spreading and evolving further.”

Dr Michael Chew, infection and immunobiology portfolio manager at Wellcome said: “This study clearly shows the rapid spread of multi-drug resistant malaria across South-East Asia. Affecting millions globally, malaria is a devastating disease, especially when access to effective treatment is unavailable.

“The spread of drug-resistant strains as demonstrated by this important genetic surveillance, building upon previous research, provides a warning signal. It serves as a reminder that we must not show complacency with the response to malaria. It also shows we have the tools to effectively track drug resistance across borders, which can be used to inform co-ordinated elimination and control efforts.”

Professor Dominic Kwiatkowski, a senior author on the paper from the Wellcome Sanger Institute and the Big Data Institute, said: “Our study provides a clear picture of how malaria that is resistant to the first-line treatment is spreading, and demonstrates the importance of using genetics to detect patterns of resistance in each area. Active genomic surveillance is now vital to inform national malaria control programmes, to help reduce the risk of a major global outbreak.”

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