Scoping review maps antimalarial resistance markers across Southeast Asia

A scoping review of 25 studies found that mutations associated with antifolate resistance were widespread across several Southeast Asian countries, while proposed molecular markers of chloroquine resistance had inconsistent links to parasite susceptibility and treatment outcomes. The analysis, published in BMC Infectious Diseases, combined molecular surveillance evidence from Cambodia, Lao PDR, Malaysia, Myanmar, Thailand and the Philippines with the limited available phenotypic and clinical data. It identified no validated molecular marker of artemisinin resistance in Plasmodium vivax and found that evidence concerning resistance to the partner drugs in artemisinin-based combination therapy remained limited and heterogeneous.

The researchers searched PubMed, Google Scholar and EBSCOHost for studies published during the 10 years preceding September 2024. They included studies reporting resistance-associated point mutations in P. vivax in Southeast Asia, then extracted information on study characteristics, geographic and temporal distribution, molecular polymorphisms, and any accompanying phenotypic or clinical evidence. The synthesis followed PRISMA-ScR reporting guidance, and sampling locations were mapped at the highest spatial resolution available in each study. Of 1,560 records identified, 25 met the inclusion criteria, revealing a geographically uneven evidence base: eligible molecular surveillance studies were concentrated in six countries, with limited or no eligible data from several other Southeast Asian countries.

The clearest molecular signal involved sulfadoxine-pyrimethamine resistance. Two multilocus haplotypes were widespread across malaria-endemic areas of Cambodia, Lao PDR, Malaysia, Myanmar and Thailand: the pvdhfr F57I/L+S58R+T61M+S117N/T quadruple genotype and the pvdhps A383G+A553G double-mutant haplotype. Functional studies linked the accumulation of these antifolate-resistance genotypes to reduced drug susceptibility. In some populations, the same multilocus mutations were also associated with slower parasite clearance and a higher rate of sulfadoxine-pyrimethamine treatment failure. The review therefore places antifolate-resistance mutations ahead of the other markers examined in terms of consistency across molecular, functional and clinical evidence.

Evidence for chloroquine was less consistent. The pvcrt-o K10 insertion and several pvmdr1 polymorphisms—particularly T958M, Y976F and F1076L—were reported frequently, but their relationships with phenotypic drug susceptibility and clinical outcomes varied among studies. These polymorphisms should therefore not be treated as uniform predictors of chloroquine resistance. Similarly, mutations in pvK12 were uncommon, and the review found no validated molecular marker capable of identifying artemisinin resistance in P. vivax. Data on resistance to partner drugs used in artemisinin-based combination therapy were too limited and heterogeneous to support a comparable regional marker. The findings also emphasize that molecular detection alone cannot reliably establish the clinical significance of a resistance-associated genotype across the region.

Because this was a descriptive scoping review rather than a meta-analysis, the results summarize the distribution and consistency of available evidence rather than producing pooled effect estimates or a single comparative estimate of treatment failure. Sparse surveillance, uneven geographic coverage, and differences among studies limited the strength of cross-country conclusions. The authors called for integrated molecular, phenotypic and therapeutic surveillance to clarify how resistance-associated polymorphisms correspond to parasite susceptibility and patient outcomes. Within the evidence available through September 2024, antifolate-resistance markers in pvdhfr and pvdhps showed the strongest support, whereas chloroquine and artemisinin-based combination therapy partner-drug markers lacked consistent validation.

Subject of Research: Molecular, phenotypic and clinical evidence of Plasmodium vivax antimalarial resistance in Southeast Asia

Article Title: Unraveling antimalarial resistance in Plasmodium vivax in Southeast Asia: from molecular markers to phenotypic and clinical evidence—A scoping review

Article References: Fauziah, N., Setia Asih, P. B., Alisjahbana, B., Soetanto, I., Faridah, L., Sahiratmadja, E., Nugraha, N. F., Aviani, J. K., & Watanabe, K. (2026). Unraveling antimalarial resistance in Plasmodium vivax in Southeast Asia: from molecular markers to phenotypic and clinical evidence—A scoping review. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14529-3

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14529-3

Keywords: Plasmodium vivax, antimalarial resistance, Southeast Asia, molecular markers, chloroquine resistance, antifolate resistance, artemisinin resistance, malaria surveillance, scoping review, Unraveling, antimalarial, resistance