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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in parasite biology

Plasmodium knowlesi: reservoir hosts and tracking the emergence in humans and macaques.

LSHTM investigators:
David Conway
External collaborators:
Balbir Singh, Kim-Sung Lee, Paul Divis, Siti Khatijah Zakaria & Roynston Julin (Universite Malaysia Sarawak, Malaysia); Janet Cox-Singh (St George’s Hospital, UK); Asmad Matusop (Sarawak State Health Department, Malaysia).
Funding body:
Wellcome Trust & Malaysian Ministry of Science, Technology and Innovation.

We previously described Plasmodium knowlesi, a malaria parasite originally thought to be restricted to macaques in Southeast Asia, as a significant cause of human malaria.

More recently, to extend understanding of the epidemiology and evolutionary history of P. knowlesi, we examined 108 wild macaques for malaria parasites in the Kapit District of Sarawak, Malaysia, and sequenced the circumsporozoite protein (csp) gene and mitochondrial (mt) DNA of parasites from macaques and humans. We detected five species of Plasmodium (P. knowlesi, P. inui, P. cynomolgi, P. fieldi and P. coatneyi) in long-tailed and pig-tailed macaques. Macaques had a higher number of P. knowlesi genotypes per infection than humans, and diverse alleles of the P. knowlesi csp gene and certain mtDNA haplotypes were shared between both hosts. There were no mtDNA lineages associated exclusively with either host. Furthermore, our analyses of the mtDNA data reveal that P. knowlesi is derived from an ancestral parasite population that existed prior to human settlement in Southeast Asia, and underwent significant population expansion approximately 30,000-40,000 years ago. These results indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis with wild macaques as the reservoir hosts.