Plasmodium knowlesi causes severe and fatal malaria, and its incidence in Southeast Asia is increasing. Factors associated with death are not clearly defined.All malaria deaths in Sabah, Malaysia, from 2015-2017 were identified from mandatory reporting to the Sabah Department of Health. Case-notes were reviewed, and a systematic review of these and all previously reported fatal P. knowlesi cases was conducted. Case fatality rates (CFR) during 2010-2017 were calculated using incidence data from the Sabah Department of Health.Six malaria deaths occurred in Sabah during 2015-2017, all from PCR-confirmed P. knowlesi. Median age was 40 (range 32-58) years; four (67%) were male. Three (50%) had significant cardiovascular co-morbidities (mitral stenosis, ischemic heart disease, and morbid obesity with heart failure) and one was pregnant. Delays in administering appropriate therapy contributed to 3 (50%) deaths. An additional 26 fatal cases were included in the systematic review. Among all 32 cases, 18 (56%) were male; median age was 56 (range 23-84) years. Cardiovascular-metabolic disease, microscopic misdiagnosis, and delay in commencing intravenous treatment were identified in 11/32 (34%), 26/29 (90%) and 11/31 (36%) cases, respectively. The overall CFR during 2010-2017 was 2.5/1000: 6.0/1000 for females and 1.7/1000 for males (p=0.01). Independent risk factors for death included female sex (odds ratio 2.6, p=0.04), and age ≥45 years (odd ratio 4.7, p<0.01).Earlier presentation, more rapid diagnosis and administration of intravenous artesunate may avoid fatal outcomes, particularly in females, older adults and patients with cardiovascular comorbidities.
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