Age-related clinical spectrum of Plasmodium knowlesi malaria and predictors of severity

Matthew J. Grigg, Timothy William, Bridget E. Barber, Giri S. Rajahram, Jayaram Menon, Emma Schimann, Kim Piera, Christopher S. Wilkes, Kaajal Patel, Arjun Chandna, Christopher J. Drakeley, Tsin W. Yeo, Nicholas M. Anstey

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)
74 Downloads (Pure)


Background: Plasmodium knowlesi is increasingly reported in Southeast Asia, but prospective studies of its clinical spectrum in children and comparison with autochthonous human-only Plasmodium species are lacking.

Methods: Over 3.5 years, we prospectively assessed patients of any age with molecularly–confirmed Plasmodium monoinfection presenting to 3 district hospitals in Sabah, Malaysia.

Results: Of 481 knowlesi, 172 vivax, and 96 falciparum malaria cases enrolled, 44 (9%), 71 (41%), and 31 (32%) children aged ≤12 years. Median parasitemia was lower in knowlesi malaria (2480/μL [interquartile range,538–8481/μL]) than in falciparum (9600/μL; P < .001) and vivax malaria. InP. knowlesi, World Health Organization–defined anemia was present in 82% (95% confidence interval [CI], 67%–92%) of children vs 36% (95% CI, 31%–41%) of adults. Severe knowlesi malaria occurred in 6.4% (95% CI, 3.9%–8.3%) of adults but not in children; the commonest severity criterion was acute kidney injury. No patient had coma. Age, parasitemia, schizont proportion, abdominal pain, and dyspnea were independently associated with severe knowlesi malaria, with parasitemia >15000/μL the best predictor (adjusted odds ratio, 16.1;negative predictive value, 98.5%; P < .001). Two knowlesi-related adult deaths occurred (fatality rate: 4.2/1000 adults).

Conclusions: Age distribution and parasitemia differed markedly in knowlesi malaria compared to human-only species, with both uncomplicated and severe disease occurring at low parasitemia. Severe knowlesi malaria occurred only in adults; however, anemia was more common in children despite lower parasitemia. Parasitemia independently predicted knowlesi disease severity: Intravenous artesunate is warranted initially for those with parasitemia >15000/μL.


Original languageEnglish
Pages (from-to)350-359
Number of pages10
JournalClinical Infectious Diseases
Issue number3
Early online date5 Mar 2018
Publication statusPublished - 18 Jul 2018


Dive into the research topics of 'Age-related clinical spectrum of Plasmodium knowlesi malaria and predictors of severity'. Together they form a unique fingerprint.

Cite this