Misidentification of Plasmodium ovale as Plasmodium vivax malaria by a microscopic method: a meta-analysis of confirmed P. ovale cases

Abstract

Plasmodium ovale is a benign tertian malaria parasite that morphologically resembles Plasmodium vivax. P. ovale also shares similar tertian periodicity and can cause relapse in patients without a radical cure, making it easily misidentified as P. vivax in routine diagnosis. Therefore, its prevalence might be underreported worldwide. The present study aimed to quantify the prevalence of P. ovale misidentified as P. vivax malaria using data from studies reporting confirmed P. ovale cases by molecular methods. Studies reporting the misidentification of P. ovale as P. vivax malaria were identified from three databases, MEDLINE, Web of Science, and Scopus, without language restrictions, but the publication date was restricted to 1993 and 2020. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). The random-effects model was used to estimate the pooled prevalence of the misidentification of P. ovale as P. vivax malaria by the microscopic method when compared to those with the reference polymerase chain reaction method. Subgroup analysis of participants was also performed to demonstrate the difference between imported and indigenous P. ovale cases. The heterogeneity of the included studies was assessed using Cochran's Q and I² statistics. Publication bias across the included studies was assessed using the funnel plot and Egger's test, and if required, contour-enhanced funnel plots were used to identify the source(s) of funnel plot asymmetry. Of 641 articles retrieved from databases, 22 articles met the eligibility criteria and were included in the present study. Of the 8,297 malaria-positive cases identified by the PCR method, 453 P. ovale cases were confirmed. The pooled prevalence of misidentification of P. ovale as P. vivax malaria by the microscopic method was 11% (95% CI: 7-14%, I²: 25.46%). Subgroup analysis of the participants demonstrated a higher prevalence of misidentification in indigenous cases (13%, 95% CI: 6-21%, I²: 27.8%) than in imported cases (10%, 95% CI: 6-14%, I²: 24.1%). The pooled prevalence of misidentification of P. vivax as P. ovale malaria by the microscopic method was 1%, without heterogeneity (95% CI: 0-3%, I²: 16.8%). PCR was more sensitive in identifying P. ovale cases than the microscopic method (p < 0.00001, OR: 2.76, 95% CI: 1.83-4.15, I²: 65%). Subgroup analysis of participants demonstrated the better performance of PCR in detecting P. ovale malaria in indigenous cases (p: 0.0009, OR: 6.92, 95% CI: 2.21-21.7%, I²: 68%) than in imported cases (p: 0.0004, OR: 2.15, 95% CI: 1.41-3.29%, I²: 63%). P. ovale infections misidentified as P. vivax malaria by the microscopic method were frequent and led to underreported P. ovale cases. The molecular identification of P. ovale malaria in endemic areas is needed because a higher rate of P. ovale misidentification was found in endemic or indigenous cases than in imported cases. In addition, updated courses, enhanced training, and refreshers for microscopic examinations, particularly for P. ovale identification, are necessary to improve the microscopic identification of Plasmodium species in rural health centres where PCR is unavailable.

Figure 1

Flow chart for study selection.

Figure 2

Methodological quality graph.

Figure 3

Pooled prevalence of misidentification of P. ovale as P. vivax malaria. ES: Estimated prevalence. The pooled prevalence was estimated using STATA Statistical Software version 15.0 (StataCorp. 2017. Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC).

Figure 4

Pooled prevalence of misidentification of P. vivax as P. ovale malaria. ES: Estimated prevalence. The pooled prevalence was estimated using STATA Statistical Software version 15.0 (StataCorp. 2017. Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC).

Figure 5

The performance of PCR to identify P. ovale IV: Inverse Variance, CI: Confidence Interval, Event: number of patients with P. ovale, random: random effects model, Total: number of all P. ovale cases, Lower in PCR: the proportion of P. ovale cases detected by PCR was lower than those detected by the microscopic method. Higher in PCR: the proportion of P. ovale cases detected by PCR was higher than those detected by the microscopic method. The performance of PCR to identify P. ovale malaria was analysed using Review Manager 5.3 (The Cochrane Collaboration, London, UK) available at https://training.cochrane.org/.

Figure 6

Publication bias among the included studies. Publication bias was determined using Review Manager 5.3 (The Cochrane Collaboration, London, UK) available at https://training.cochrane.org/.

Figure 7

The contour enhanced funnel plot. The contour enhanced funnel plot was estimated using STATA Statistical Software version 15.0 (StataCorp. 2017. Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC).