Multi-drug resistant malaria strain spreads in Southeast Asia

Genomic surveillance has revealed that malaria resistance to two first-line antimalarial drugs has spread rapidly from Cambodia to neighbouring countries in Southeast Asia. Researchers discovered that descendants of one multi-drug resistant malaria strain are replacing the local parasite populations in Vietnam, Laos and northeastern Thailand[1]. They also found the resistant strain has picked up additional new genetic changes, which may be enhancing resistance even further.

Over the last decade, the first-line treatment for malaria in many areas of Asia has been a combination of two antimalarial drugs, known as DHA-PPQ (Dihydroartemisinin and Piperaquine). However, a previous study identified a strain of malaria that had become resistant to this treatment. Researchers found that this resistant strain, named KEL1/PLA1, because of its combination of genetic mutations that cause resistance, had spread across Cambodia under the radar between 2007 and 2013.

In their study of malaria parasites in Southeast Asia, the team sequenced and analysed the DNA of 1,673 Plasmodium falciparum parasites, taken from the blood of malaria patients between 2008 and 2018. Their analysis, focusing on the KEL1 and PLA1 gene variants, revealed that the situation had got much worse since 2013. The multidrug resistant KEL1/PLA1 parasites had spread internationally, replacing local malaria parasites, in some regions making up more than 80 per cent of the parasites analysed.

The spread is likely to have occurred because resistant parasites had an evolutionary advantage, as DHA-PPQ was the first-line treatment in most of these areas. This killed other malaria strains but was less effective against KEL1/PLA1 malaria.

The researchers discovered that not only had this resistant strain spread geographically, but it had evolved and picked up new mutations in the chloroquine resistance transporter gene (crt). A related paper on clinical outcomes revealed that these crt mutations were associated with complete treatment failure of DHA-PPQ[2]. This supported the finding that the resistance had not only spread, but worsened as the parasite evolved under further drug pressure.

[1] Hamilton et al: Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study in The Lancet – 2019
[2] Ménard, Fidock: Accelerated evolution and spread of multidrug-resistant Plasmodium falciparum takes down the latest first-line antimalarial drug in southeast Asia in The Lancet – 2019