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Clin Infect Dis. 2018 Jul 18;67(3):350-359. doi: 10.1093/cid/ciy065.

Age-Related Clinical Spectrum of Plasmodium knowlesi Malaria and Predictors of Severity.

Author information

1
Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
2
Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Malaysia.
3
Jesselton Medical Centre, Kota Kinabalu, Malaysia.
4
Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia.
5
Sabah Department of Health, Kota Kinabalu, Malaysia.
6
London School of Hygiene and Tropical Medicine, United Kingdom.
7
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
8
Communicable Disease Centre, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.

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.

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