Biology subjects

Westaway, J. A.

Publications and source records attributed to Westaway, J. A..

3 recordsLinked to original sources

bioRxiv2026

Pfcrt copy number amplification detected in a Plasmodium falciparum outbreak

Antimalarial resistance is one of the greatest threats to malaria elimination. Following an outbreak of Plasmodium falciparum infection in Sabah Malaysia in 2019, 98 samples were sequenced to search for adaptations driving the outbreak. The genomic data revealed evidence of clonal expansion of a strain carrying multiple copies of the chloroquine resistance transporter gene (pfcrt) in 86 cases. A TaqMan qPCR assay was developed to quantify pfcrt copy number, confirming the in silico evidence of duplication. Whilst point mutations in pfcrt have been associated with resistance to chloroquine and other drugs, copy number amplification has not been widely explored as a resistance mechanism. We investigated the genetic architecture of the duplication, revealing a wildtype haplotype (3D7 reference-type with 76K variant) and a novel mutant (with 76T mutation). Application of the TaqMan assay in 43 P. falciparum cases from neighbouring Palawan Island, the Philippines, identified a further two cases with pfcrt duplication. Assessment of the global genomic data in the MalariaGEN Pf8 repository identified a further 86 cases, including 73 (85%) from West Africa with evidence of pfcrt duplication. Amongst 47 monoclonal MalariaGEN cases, majority (95%) comprised wild type and mutant variants at codon 76. Our study reveals a potential previously unconsidered antimalarial resistance mechanism for P. falciparum and provides an assay for surveillance in other populations.

genomics↗

bioRxiv2026

Integrative genomics of Plasmodium knowlesi reveals parasite-intrinsic regulators of severe human malaria

To dissect parasite determinants of clinical disease severity in Plasmodium knowlesi, we performed the first integrative genome-wide association (GWAS), transcriptomic, and expression quantitative trait locus (eQTL) analysis from clinical malaria isolates. We identify distinct parasite programs associated with WHO-defined severe disease, characterized by transcriptional activation of stress-response and host-interaction pathways. In contrast, invasion-linked programs were more strongly associated with parasite burden, while immune-evasion pathways showed overlapping but distinct associations with both burden and severity. GWAS and eQTL analyses revealed genetic regulation of transcriptional states, including immune-evasion variant antigen families (SICAvar and kir) and chromatin-associated regulators. Mature gametocyte transcripts were detectable across infections, including those with low parasitaemia, indicating that transmission-stage expression occurs independently of both clinical severity and parasite density. Together, these findings show that severe P. knowlesi malaria is associated with genetically regulated parasite transcriptional programs that are not fully explained by parasite burden.

genomics↗

bioRxiv2026

Mapping the global distribution and spread of the Plasmodium vivax-associated virus MaRNAV-1

Matryoshka RNA virus 1 is a bi-segmented and single-stranded RNA virus associated with Plasmodium vivax, a cause of human malaria. Little has been uncovered about the epidemiology and ecology of this virus since its discovery in 2019. To address this, we used a combination of primary and publicly available metatranscriptomic data to map the geographic distribution and host associations of MaRNAV-1. We detected this virus throughout Southeast Asia, in parts of South America, and, for the first time, in Oceania. Despite its broad distribution, MaRNAV-1 was found exclusively in metatranscriptomes containing P. vivax, suggesting that there is a specific virus-host relationship that has shaped the evolutionary history of this virus. We were unable to estimate the emergence date of the MaRNAV-1 lineage; however, phylogeographic mapping analysis suggested that MaRNAV-1 may have radiated from Southeast Asia. Our findings have both evolutionary and public health implications and can serve as the basis for future investigations in these fields.

evolutionary biology↗