1265_PK_MY_GRIGG. 1265_PK_MY_GRIGG

Plasmodium knowlesi genomics Aims will include: Development of gold-standard sequencing methodology, variant detection and updated reference genome for P. knowlesi. This will involve initial Illumina sequencing of 100 P. knowlesi isolates from Malaysia, including comparison of raw sequence data of selective whole genome amplification versus no amplification from individual patients. P. knowlesi population genetic epidemiology. A larger dataset of P. knowlesi isolates with known location, date and phenotypic disease severity from state-wide clinical studies in Sabah, Malaysia (Cooper et al. CID 2019. doi.10.1093/cid/ciz237) will be sent separately at a later date and also undergo WGS using the optimised methodology from Aim 1 (approx. 3,400 samples) in order to conduct basic population genetic analyses. P. knowlesi genetic risk factors for severe disease. A GWAS design will evaluate P. knowlesi parasite factors involved in disease severity. This will include around 1000 P. knowlesi isolates, collected primarily from a previously conducted case-control study (Grigg et al. Lancet PH 2017. doi.10.1016/S2542-5196(17)30031-1) with well defined clinical phenotypes conducted in Sabah, Malaysia, in addition to additional severe cases from prospective malaria studies in the same area (Barber et al. CID 2013. doi.10.1093/cid/cis902; Grigg et al. CID 2018. doi.10.1093/cid/ciy065)