Multiple local PfDHFR I164L haplotype expansions drive Plasmodium falciparum antifolate resistance in Uganda
Nature Communications·
- DOI
- 10.1038/s41467-026-76826-4
- PMID
- —
- PMCID
- —
- OpenAlex
- W7208768213
- Study type
- Journal article
- Publisher
- Springer Science and Business Media LLC
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The findings are relevant to malaria control because the studied mutations are associated with antifolate resistance, and the paper describes PfDHFR I164L as conferring higher pyrimethamine resistance. The results indicate that resistance-related patterns may vary across locations using sulfadoxine-pyrimethamine chemoprevention.
Structured evidence summary
Research question
The study examined the distribution and evolutionary patterns of antifolate-resistance mutations in Plasmodium falciparum, with particular attention to PfDHFR I164L, across Uganda.
Study design
This was a genomic surveillance study using genotyping, identity-by-descent analysis, haplotype structure, and extended haplotype homozygosity analysis. Samples were collected annually from 2016 through 2022.
Population and setting
The analysis included 4,725 Plasmodium falciparum isolates obtained from 16 Ugandan health facilities. The setting involved regions where sulfadoxine-pyrimethamine was the primary chemoprevention strategy.
Main findings
PfDHFR I164L frequency rose from 19.4% to 32.4% over the study period. The variant occurred on several haplotype backgrounds and showed localized expansions, while recent positive-selection signals were detected at only one site. The reported pattern was spatially heterogeneous and complex.
Public-health relevance
The findings are relevant to malaria control because the studied mutations are associated with antifolate resistance, and the paper describes PfDHFR I164L as conferring higher pyrimethamine resistance. The results indicate that resistance-related patterns may vary across locations using sulfadoxine-pyrimethamine chemoprevention.
Important limitations
The supplied material does not state explicit study limitations. This summary relies on a single supplied article abstract and bibliographic metadata; the original paper is required for decision-grade assessment of sampling representativeness, analytical assumptions, and uncertainty.
GIDS interpretation
The article is discoverable as Uganda malaria research concerning surveillance and transmission dynamics, with a focus on antifolate-resistance genetics. The supplied evidence describes study-specific observations and does not establish or confirm a live surveillance signal.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 8 auditable classifier relationships to diseases, places, topics, and study design.