Whole genome sequencing to inform the epidemiology of Plasmodium falciparum malaria in the elimination setting of Malaysia

TL;DR

This study uses whole genome sequencing to determine whether malaria cases in Malaysia are imported or locally transmitted, showing that most cases likely come from other regions.

Contribution

The study demonstrates how genomic data can improve malaria elimination efforts by distinguishing imported from local infections.

Findings

13 out of 15 cases likely originated from endemic regions outside Malaysia.

Two cases showed genomic origins inconsistent with reported travel histories.

Identity-by-descent analysis found clustering in only two cases, suggesting isolated introductions rather than local transmission.

Abstract

Imported malaria cases, driven by human migration and travel, pose a significant challenge to malaria elimination efforts. Genomic approaches have become essential for distinguishing between local transmission and imported infections. The state of Sarawak, Malaysia, provides a pertinent example of a malaria-eliminating setting under pressure from Plasmodium parasite importation.

In this study, we analysed 21 Plasmodium falciparum isolates obtained from archived whole blood samples collected between 2008 and 2010 and compared them to 9,518 publicly available isolates from Central Africa (518), East Africa (849), Horn of Africa (25), Oceania (349), South America (75), South Asia (404) Southeast Asia (5,182) and West Africa (2,116). By applying nanopore sequencing and population genomic analyses, we found that most of the cases (n = 13/15) likely originated from endemic regions outside Malaysia, supported by patient travel histories and high multiplicity of infection levels. These findings and drug resistance profiles are consistent with the historical epidemiology of the suspected source regions. Notably, two cases showed genomic evidence of origins inconsistent with the patients’ reported travel histories, underscoring the limitations of traditional epidemiological methods. Identity-by-descent analysis revealed clustering in only two cases, indicating that the majority of infections were likely isolated introductions rather than evidence of sustained local transmission.

Overall, our results highlight the power of malaria genomics in discerning imported from locally acquired cases and emphasise its critical role in maintaining malaria elimination, particularly in regions situated along major migration and labour exchange corridors.

The online version contains supplementary material available at 10.1186/s12864-026-12653-7.

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