Abstract
BackgroundPlasmodium knowlesi is recognized as the fifth Plasmodium species causing malaria in humans. It is morphologically similar to the human malaria parasite Plasmodium malariae, so molecular detection should be used to clearly discriminate between these Plasmodium species. This study aimed to quantify the rate at which P. knowlesi is misidentified as P. malariae by microscopy in endemic and non-endemic areas.MethodsThe protocol of this systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID = CRD42020204770). Studies reporting the misidentification of P. knowlesi as P. malariae by microscopy and confirmation of this by molecular methods in MEDLINE, Web of Science and Scopus were reviewed. The risk of bias in the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). The pooled prevalence and 95% confidence interval (CI) of the misidentification of P. knowlesi as P. malariae by microscopy were estimated using a random effects model. Subgroup analysis of the study sites was performed to demonstrate any differences in the misidentification rates in different areas. Heterogeneity across the included studies was assessed and quantified using Cochran’s Q and I2 statistics, respectively. Publication bias in the included studies was assessed using the funnel plot, Egger’s test and contour-enhanced funnel plot.ResultsAmong 375 reviewed studies, 11 studies with a total of 1569 confirmed P. knowlesi cases in humans were included. Overall, the pooled prevalence of the misidentification of P. knowlesi as P. malariae by microscopy was estimated at 57% (95% CI 37–77%, I2: 99.3%). Subgroup analysis demonstrated the highest rate of misidentification in Sawarak, Malaysia (87%, 95% CI 83–90%, I2: 95%), followed by Sabah, Malaysia (85%, 95% CI 79–92%, I2: 85.1%), Indonesia (16%, 95% CI 6–38%), and then Thailand (4%, 95% CI 2–9%, I2: 95%).ConclusionAlthough the World Health Organization (WHO) recommends that all P. malariae-positive diagnoses made by microscopy in P. knowlesi endemic areas be reported as P. malariae/P. knowlesi malaria, the possibility of microscopists misidentifying P. knowlesi as P. malariae is a diagnostic challenge. The use of molecular techniques in cases with malariae-like Plasmodium with high parasite density as determined by microscopy could help identify human P. knowlesi cases in non-endemic countries.
Highlights
Plasmodium knowlesi is recognized as the fifth Plasmodium species causing malaria in humans
P. knowlesi is well documented in Malaysia, the pooled quantification of the misidentification of this species as P. malariae has not been previously described
This indicated that the highest number of P. malariae cases identified by microscopy in the last decade was caused by the emergence of P. knowlesi malaria, as these two species are morphologically similar and difficult to distinguish from each other using microscopy
Summary
Plasmodium knowlesi is recognized as the fifth Plasmodium species causing malaria in humans. Plasmodium knowlesi was first recognized as a cause of simian malaria in long-tailed or pig-tailed macaques [1]. It was recognized as a cause of human malaria in 1965 [2]. The large focus on P. knowlesi as a cause of human malaria was reported in Sarawak, Malaysia, in 2004 [3]. P. knowlesi malaria has been reported in travellers returning from endemic countries [41,42,43,44,45,46,47,48,49,50,51,52,53,54]. A recent study suggested that the transmission of P. knowlesi malaria between humans might occur with mosquitoes as vectors, given the presence of family clustering [14]
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