Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study.

The Lancet Infectious Diseases
Mallika ImwongNicholas J. White

Abstract

The Greater Mekong subregion is a recurrent source of antimalarial drug resistance in Plasmodium falciparum malaria. This study aimed to characterise the extent and spread of resistance across this entire region between 2007 and 2018. P falciparum isolates from Myanmar, Thailand, Laos, and Cambodia were obtained from clinical trials and epidemiological studies done between Jan 1, 2007, and Dec 31, 2018, and were genotyped for molecular markers (pfkelch, pfcrt, pfplasmepsin2, and pfmdr1) of antimalarial drug resistance. Genetic relatedness was assessed using microsatellite and single nucleotide polymorphism typing of flanking sequences around target genes. 10 632 isolates were genotyped. A single long pfkelch Cys580Tyr haplotype (from -50 kb to +31·5 kb) conferring artemisinin resistance (PfPailin) now dominates across the eastern Greater Mekong subregion. Piperaquine resistance associated with pfplasmepsin2 gene amplification and mutations in pfcrt downstream of the Lys76Thr chloroquine resistance locus has also developed. On the Thailand-Myanmar border a different pfkelch Cys580Tyr lineage rose to high frequencies before it was eliminated. Elsewhere in Myanmar the Cys580Tyr allele remains widespread at low allele frequencies. ...Continue Reading

Citations

Jul 14, 2020·British Journal of Clinical Pharmacology·Borimas Hanboonkunupakarn, Nicholas J White
Nov 4, 2020·Antimicrobial Agents and Chemotherapy·Kathrin WitmerJake Baum
Nov 5, 2020·The American Journal of Tropical Medicine and Hygiene·Fatema Tuj JohoraMohammad Shafiul Alam
Feb 11, 2021·Journal of Natural Products·Jin Woo LeeRobert H Cichewicz
Oct 17, 2020·Trends in Parasitology·Rob W van der PluijmArjen M Dondorp
May 11, 2021·ACS Infectious Diseases·Melissa R Rosenthal, Caroline L Ng
Jun 6, 2021·International Journal for Parasitology. Drugs and Drug Resistance·Faiza Amber SiddiquiLiwang Cui
Jul 2, 2021·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·Katharina LastUNKNOWN Trainee Association of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
Jul 28, 2021·Expert Opinion on Pharmacotherapy·Erik KoehneAndrea Kreidenweiss
Aug 13, 2021·ELife·Colin Sutherland, Didier Menard
Jul 17, 2021·Current Opinion in Infectious Diseases·Mehul DhordaArjen M Dondorp

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Methods Mentioned

BETA
PCR
genotyping

Software Mentioned

Bioedit
Genotyper
Genescan

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