Deaths from Plasmodium knowlesi malaria: case series and systematic review.

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.