Knowlesi malaria: Human risk factors, clinical spectrum, and pathophysiology

Nicholas M. Anstey, Matthew J. Grigg, Giri S. Rajahram, Daniel J. Cooper, Timothy William, Steven Kho, Bridget E. Barber

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

14 Citations (Scopus)


Plasmodium knowlesi is endemic across Southeast Asia, and is the commonest cause of zoonotic malaria. The spectrum of clinical disease from P. knowlesi infection ranges from asymptomatic infection, through to severe malaria and death. Over 90% of clinical disease occurs in adults, mostly living in forest edge areas undergoing intensive land use change. With a 24-h asexual life cycle in humans, high parasite counts are possible, but most clinical cases of knowlesi malaria are uncomplicated with low parasitaemia. In co-endemic areas, median parasitaemia in knowlesi malaria is lower than that seen in vivax and falciparum malaria, suggesting a lower fever threshold. Severe malaria occurs in 6–9% of symptomatic adults. Manifestations of severe malaria from P. knowlesi are similar to those seen with falciparum malaria, with the notable absence of coma. Age, parasitaemia, cardiovascular comorbidities and delayed diagnosis are risk factors for severe disease and death, which are only seen in adults. Thrombocytopenia is near-universal in adults, likely related to platelet-red cell binding and clearance. Mechanisms underlying the microvascular sludging seen in fatal disease in non-natural primate hosts and the microvascular accumulation of parasites in fatal human disease are not clear. Marked reductions in deformability of both infected and uninfected red blood cells are associated with disease severity in both humans and other non-natural primate hosts, likely contributing to impaired microvascular perfusion and organ dysfunction. Endothelial activation, endothelial dysfunction, glycocalyx degradation and haemolysis are also associated with, and likely contribute to, severe disease and organ dysfunction, particularly acute kidney injury.

Original languageEnglish
Title of host publicationAdvances in Parasitology
EditorsChris Drakeley
Place of PublicationLondon
PublisherAcademic Press
ISBN (Print)9780323907279
Publication statusPublished - Jan 2021

Publication series

NameAdvances in Parasitology
ISSN (Print)0065-308X

Bibliographical note

Funding Information:
This work was supported by the Australian National Health and Medical Research Council (grant numbers 1037304 and 1045156; fellowships to NMA [1042072], BEB [1088738]; MJG [1138860] and “Improving Health Outcomes in the Tropical North: A multidisciplinary collaboration (HOT NORTH),” [grant 1131932]), and the ZOOMAL project (“Evaluating zoonotic malaria and agricultural land use in Indonesia”; #LS-2019-116), Australian Centre for International Agricultural Research and Department of Foreign Affairs, Australian Government. The Sabah Malaria Research Program is supported by the US NIH.

Publisher Copyright:
© 2021 Elsevier Ltd

Copyright 2021 Elsevier B.V., All rights reserved.


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