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Title: Age-related clinical spectrum of Plasmodium knowlesi malaria and predictors of severity
Authors: Grigg, Matthew J.
William, Timothy
Barber, Bridget E.
Rajahram, Giri S.
Menon, Jayaram
Schimann, Emma
Piera, Kim
Wilkes, Christopher S.
Patel, Kaajal
Chandna, Arjun
Drakeley, Christopher J.
Yeo, Tsin W.
Anstey, Nicholas M.
Keywords: Science::Medicine
Issue Date: 2018
Source: Grigg, M. J., William, T., Barber, B. E., Rajahram, G. S., Menon, J., Schimann, E., ... Anstey, N. M. (2018). Age-related clinical spectrum of Plasmodium knowlesi malaria and predictors of severity. Clinical Infectious Diseases 67(3), 350-359. doi:10.1093/cid/ciy065
Journal: Clinical Infectious Diseases
Abstract: 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. In P. 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 commenst severity criterion was acute kideny 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.
ISSN: 1537-6591
DOI: 10.1093/cid/ciy065
Rights: © 2018 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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