Spread Of A Single Multidrug Resistant Malaria Parasite Lineage (PfPailin) To Vietnam

Where weaponised SARS, H5N1 fails an engineered parasite is now unleashed in ASEAN  

THE LANCET
By Mallika Imwong, Tran T Hien, Nguyen T Thuy-Nhien, Arjen M Dondorp, Nicholas J White
10/2017

The spread of artemisinin resistance in Plasmodium falciparum and the subsequent loss of partner antimalarial drugs in the Greater Mekong subregion1 presents one of the greatest threats to the control and elimination of malaria. 

Artemisinin resistance is associated with mutations in the PfKelchgene. 

Initially multiple independent Kelch mutations were observed,1 but in a recent sinister development, a single dominant artemisinin-resistant P falciparum C580Y mutant lineage has arisen in western Cambodia, outcompeted the other resistant malaria parasites, and subsequently acquired resistance to piperaquine.2 .

Cambodia had adopted dihydroartemisinin-piperaquine as first-line antimalarial treatment, but has now been forced to switch its first line artemisinin combination treatment back to artesunate-mefloquine as a consequence3. 

This dominant multidrug-resistant parasite lineage, identified first in Pailin in western Cambodia and tentatively denoted as PfPailin, then spread to northeastern Thailand and southern Laos2. 

Transnational spread of multidrug resistant PfPailin. The artemisinin resistant Plasmodium falciparum C580Y lineage (PfPailin) was detected first in Pailin, Western Cambodia, in 2008.2 It later acquired piperaquine resistance and spread east. 8 years later it has now reached the south of Vietnam encompassing all four countries of the Eastern Greater Mekong subregion.

We now find that the PfPailin lineage, with associated piperaquine resistance (evidenced by amplification in the PfPlasmepsin2 gene), has spread to the south of Vietnam where it is responsible for alarming rates of failure of dihydroartemisinin-piperaquine—the National first-line treatment (figure).4 Microsatellite typing of 86 of 152 P falciparum isolates from the Binh Phuoc locality in 2016 shows the same flanking sequence surrounding the PfKelch C580Y gene as that observed in parasites from the affected areas of the other three Greater Mekong subregion countries.2 

The evolution and subsequent transnational spread of this single fit multidrug-resistant malaria parasite lineage is of international concern.

We declare no competing interests. This study was supported by Mahidol University, Thailand and the Wellcome Trust. Some of the samples were from the TRAC study supported by the UK Department for International Development (DFID).

References:

Ashley, EA, Dhorda, M, Fairhurst, RM et al. Tracking Resistance to Artemisinin Collaboration (TRAC). Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014; 371: 411–423

Imwong, M, Suwannasin, K, Kunasol, C et al. The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong Subregion: a molecular epidemiology observational study. Lancet Infect Dis. 2017; 17: 491–497

Thanh, NV, Thuy-Nhien, N, Tuyen, NT et al. Rapid decline in the susceptibility of Plasmodium falciparum to dihydroartemisinin-piperaquine in the south of Vietnam. Malar J. 2017; 16: e27.

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