Deaths From Plasmodium knowlesi Malaria: Case Series and Systematic Review

Abstract

Background: Plasmodium knowlesi causes severe and fatal malaria, and incidence in Southeast Asia is increasing. Factors associated with death are not clearly defined.

Methods: All malaria deaths in Sabah, Malaysia, from 2015 to 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 (CFRs) during 2010-2017 were calculated using incidence data from the Sabah Department of Health.

Results: Six malaria deaths occurred in Sabah during 2015-2017, all from P. knowlesi. Median age was 40 (range, 23-58) years; 4 cases (67%) were male. Three (50%) had significant cardiovascular comorbidities and 1 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 of 32 (34%), 26 of 29 (90%), and 11 of 31 (36%) cases, respectively. The overall CFR during 2010-2017 was 2.5/1000: 6.0/1000 for women and 1.7/1000 for men (P = .01). Independent risk factors for death included female sex (odds ratio, 2.6; P = .04), and age ≥45 years (odds ratio, 4.7; P < .01).

Conclusions: Earlier presentation, more rapid diagnosis, and administration of intravenous artesunate may avoid fatal outcomes, particularly in females, older adults, and patients with cardiovascular comorbidities.

Keywords: deaths; knowlesi; malaria; pregnancy; sex differences.

Figure 1.

Flow diagram of systematic review. ^aFour retrospective case series or studies [4, 9, 12, 14], 2 prospective observational studies [10, 11], 1 case-control study [15], 2 case reports [13, 16], and 1 review of autopsies [35]. ^bFour reported deaths were excluded from further review as sufficient individual patient data were not available [15]. ^cNineteen deaths occurred in Sabah and 7 in Sarawak, Malaysia, all during 2001–2014.