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.

Diagnostic Characteristics of Lactate Dehydrogenase on a Multiplex Assay for Malaria Detection Including the Zoonotic Parasite Plasmodium knowlesi

“…Similarly, there are no P. ovale-and P. malariae-specific RDTs, also leading to the underreporting of these more widely spread forms of human malaria. 31,32 Interestingly, an immunocapture assay has been used to evaluate specificity of monoclonal antibodies against the pLDH isoforms from Plasmodium species. 33,34 A similar reactivity pattern with the pLDH proteins of P. cynomolgi (PcLDH) and P. vivax (PvLDH) indicated the close similarity of pLDH isoforms, whereas the absence of reactivity of the P. falciparum-specific antibodies with other simian parasites except P. knowlesi suggested the possible use of these antibodies to distinguish P. knowlesi from the other simian parasites.…”

Limited Reliability of the Molecular Detection of Plasmodium spp. from Incubated Blood Culture Samples for Forensic Purposes

“…pPOW = probe for the detection of P. ovale wallikeri. 1 FAM and BHQ1 were used as reporter and quencher, respectively. 2 JOE and BHQ1 were used as reporter and quencher, respectively.…”

“…Training options to maintain skills in routine malaria microscopy in non-endemic settings are limited because of scarcely available sample material. Morphologically similar species such as Plasmodium vivax, P. ovale curtisi and P. ovale wallikeri tend to be misinterpreted under the microscope [1][2][3] with more than 10% misidentification of P. vivax and P. ovale complex [1]. P. ovale curtisi and P. ovale wallikeri, in particular, are virtually indistinguishable by routine microscopy.…”

Epidemiological, Physiological and Diagnostic Comparison of Plasmodium ovale curtisi and Plasmodium ovale wallikeri

“…Microscopy remains the gold standard for malaria diagnosis and WHO recommends RDT and microscopic diagnosis for all suspected malaria cases [41]. Morphologically identical, Poc and Pow are indistinguishable even by expert microscopists and mostly misidentified as P. vivax [42].…”