Interpreting imported malaria genomes: population-genomic sensitivity analyses of West Africa-associated Plasmodium falciparum isolates detected in China

Background Genomes obtained through imported-malaria surveillance can support source attribution and monitoring of parasite movement. However, these genomes are sampled after travel, diagnosis, reporting, and specimen availability, and may not be directly interchangeable with parasites sampled in endemic settings. Comparisons with public reference data may also be affected by geographic composition, sequencing quality, genotype filtering, and within-host infection complexity. Methods We compared West Africa-associated P. falciparum isolates detected through China’s post-elimination malaria surveillance system with West African Pf3K and locally collected comparison isolates. We implemented country-balanced reference subsampling, a geographically restricted and quality-controlled population-structure analysis, and sensitivity analyses restricted to imported isolates with F WS >0.90 or 0.95. Population structure, within-host complexity, identity-by-descent, nucleotide diversity, gene-level F ST , and Tajima’s D were evaluated using analysis-specific variant sets. Results In the quality-controlled D1 analysis, 31 China-imported isolates showed a population-structure distribution that did not fully overlap with the selected West African Pf3K reference panel. This broad placement was qualitatively compatible with the high-F WS D2a subset of four imported isolates. Country-balanced reference subsampling produced similar broad PCA placement. In the D2b analysis of nine imported isolates with F WS >0.90, central gene-level F ST summaries were like those in the original analysis, whereas individual-gene estimates and Tajima’s D contrasts were sensitive to the revised filtering and sample restriction. Conclusions Imported malaria genomes provide a surveillance-defined view of parasite diversity and remain useful for regional population placement and surveillance applications. However, their comparison with endemic reference panels is sensitive to dataset composition, variant filtering, and infection complexity. Imported surveillance genomes should therefore not be interpreted as unbiased or directly interchangeable proxies for parasite populations in presumed source settings. The observed differences cannot be attributed solely to surveillance pathway.