Ten-year persistence and evolution of Plasmodium falciparum antifolate and antisulfonamide resistance markers pfdhfr and pfdhps in three Asian countries
Issued Date
2022-12-01
Resource Type
eISSN
19326203
Scopus ID
2-s2.0-85144141160
Pubmed ID
36525403
Journal Title
PLoS ONE
Volume
17
Issue
12 December
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS ONE Vol.17 No.12 December (2022)
Suggested Citation
Srisutham S., Madmanee W., Kouhathong J., Sutawong K., Tripura R., Peto T.J., van der Pluijm R.W., Callery J.J., Dysoley L., Mayxay M., Newton P.N., Pongvongsa T., Hongvanthong B., Day N.P.J., White N.J., Dondorp A.M., Imwong M. Ten-year persistence and evolution of Plasmodium falciparum antifolate and antisulfonamide resistance markers pfdhfr and pfdhps in three Asian countries. PLoS ONE Vol.17 No.12 December (2022). doi:10.1371/journal.pone.0278928 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86364
Title
Ten-year persistence and evolution of Plasmodium falciparum antifolate and antisulfonamide resistance markers pfdhfr and pfdhps in three Asian countries
Other Contributor(s)
Abstract
Background The amplification of GTP cyclohydrolase 1 (pfgch1) in Plasmodium falciparum has been linked to the upregulation of the pfdhfr and pfdhps genes associated with resistance to the antimalarial drug sulfadoxine-pyrimethamine. During the 1990s and 2000s, sulfadoxinepyrimethamine was withdrawn from use as first-line treatment in southeast Asia due to clinical drug resistance. This study assessed the temporal and geographic changes in the prevalence of pfdhfr and pfdhps gene mutations and pfgch1 amplification a decade after sulfadoxine-pyrimethamine had no longer been widely used. Methods A total of 536 P. falciparum isolates collected from clinical trials in Thailand, Cambodia, and Lao PDR between 2008 and 2018 were assayed. Single nucleotide polymorphisms of the pfdhfr and pfdhps genes were analyzed using nested PCR and Sanger sequencing. Gene copy number variations of pfgch1 were investigated using real-time polymerase chain reaction assay. Results Sequences of the pfdhfr and pfdhps genes were obtained from 96% (517/536) and 91% (486/536) of the samples, respectively. There were 59 distinct haplotypes, including single to octuple mutations. The two major haplotypes observed included IRNI-AGEAA (25%) and IRNL-SGKGA (19%). The sextuple mutation IRNL-SGKGA increased markedly over time in several study sites, including Pailin, Preah Vihear, Ratanakiri, and Ubon Ratchathani, whereas IRNI-AGEAA decreased over time in Preah Vihear, Champasak, and Ubon Ratchathani. Octuple mutations were first observed in west Cambodia in 2011 and subsequently in northeast Cambodia, as well as in southern Laos by 2018. Amplification of the pfgch1 gene increased over time across the region, particularly in northeast Thailand close to the border with Laos and Cambodia. Conclusion Despite the fact that SP therapy was discontinued in Thailand, Cambodia, and Laos decades ago, parasites retained the pfdhfr and pfdhps mutations. Numerous haplotypes were found to be prevalent among the parasites. Frequent monitoring of pfdhfr and pfdhps in these areas is required due to the relatively rapid evolution of mutation patterns.