Molecular analysis of Plasmodium ovale variants.
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ABSTRACT:
SUBMITTER: Win TT
PROVIDER: S-EPMC3323326 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Malaria caused by Plasmodium ovale species is considered a neglected tropical disease with limited information about its characteristics. It also remains unclear whether the two distinct species P. ovale curtisi and P. ovale wallikeri exhibit differences in their prevalence, geographic distribution, clinical characteristics, or laboratory parameters. Therefore, this study was conducted to clarify these differences to support global malaria control and eradication programs. Studies reporting the occurrence of P. ovale curtisi and P. ovale wallikeri were explored in databases. Differences in proportion, clinical data, and laboratory parameters between the two species were estimated using a random-effects model and expressed as pooled odds ratios (ORs), mean difference (MD), or standardized MD depending on the types of extracted data. The difference in geographical distribution was visualized by mapping the origin of the two species. A total of 1453 P. ovale cases extracted from 35 studies were included in the meta-analysis. The p-value in the meta-analyses provided evidence favoring a real difference between P. ovale curtisi malaria cases (809/1453, 55.7%) and P. ovale wallikeri malaria cases (644/1453, 44.3%) (p: 0.01, OR 1.61, 95% CI 0.71-3.63, I2: 77%). Subgroup analyses established evidence favoring a real difference between P. ovale curtisi and P. ovale wallikeri malaria cases among the imported cases (p: 0.02, 1135 cases). The p value in the meta-analyses provided evidence favoring a real difference in the mean latency period between P. ovale curtisi (289 cases) and P. ovale wallikeri malaria (266 cases) (p: 0.03, MD: 27.59, 95% CI 1.99-53.2, I2: 94%), total leukocyte count (p < 0.0001, MD: 840, 95% CI 610-1070, I2: 0%, two studies) and platelet count (p < 0.0001, MD: 44,750, 95% CI 2900-60,500, I2: 32%, three studies). Four continents were found to have reports of P. ovale spp., among which Africa had the highest number of reports for both P. ovale spp. in its 37 countries, with a global proportion of 94.46%, and an almost equal distribution of both P. ovale spp., where P. ovale curtisi and P. ovale wallikeri reflected 53.09% and 46.90% of the continent's proportion, respectively. This is the first systematic review and meta-analysis to demonstrate the differences in the characteristics of the two distinct P. ovale species. Malaria caused by P. ovale curtisi was found in higher proportions among imported cases and had longer latency periods, higher platelet counts, and higher total leukocyte counts than malaria caused by P. ovale wallikeri. Further studies with a larger sample size are required to confirm the differences or similarities between these two species to promote malaria control and effective eradication programs.
| S-EPMC7979700 | biostudies-literature
Project description:BackgroundIn Ethiopia Plasmodium falciparum and Plasmodium vivax are the dominant species accounting for roughly 60 and 40% of malaria cases, respectively. Recently a major shift from P. falciparum to P. vivax has been observed in various parts of the country but the epidemiology of the other human malaria species, Plasmodium ovale spp. and Plasmodium malariae remains poorly understood. The aim of this study was to assess P. ovale curtisi and wallikeri infection in north-west Ethiopia by using microscopy and nested PCR.MethodsA health institution-based survey using non-probability sampling techniques was conducted at Maksegnet, Enfranze and Kola Diba health centres and Metema hospital in North Gondar. Three-hundred patients with signs and symptoms consistent with malaria were included in this study and capillary blood was collected for microscopic examination and molecular analysis of Plasmodium species. Samples were collected on Whatman 903 filter papers, stored in small plastic bags with desiccant and transported to Vienna (Austria) for molecular analysis. Data from study participants were entered and analysed by SPSS 20 software.ResultsOut of 300 study participants (167 males and 133 females), 184 samples were classified positive for malaria (133 P. falciparum and 51 P. vivax) by microscopy. By species-specific PCR 233 Plasmodium spp (95% CI: 72.6-82) were detected and the majority 155 (66.5%, 95% CI: 60.2-72.3) were P. falciparum followed by P. vivax 69 (29.6%, 95% CI; 24.1-35.8) and 9 (3.9%, 95% CI: 2-7.2) samples were positive for P. ovale. Seven of P. ovale parasites were confirmed as P. ovale wallikeri and two were confirmed as P. ovale curtisi. None of the samples tested positive for P. malariae. During microscopic examination there were high (16.3%) false negative reports and all mixed infections and P. ovale cases were missed or misclassified.ConclusionThis study indicates that P. ovale malaria is under-reported in Ethiopia and provides the first known evidence of the sympatric distribution of indigenous P. ovale wallikeri and P. ovale curtisi in Ethiopia. Therefore, further studies assessing the prevalence of the rare species P. ovale and P. malariae are urgently needed to better understand the species distribution and to adapt malaria control strategies.
| S-EPMC3849950 | biostudies-literature
Project description:BackgroundMalaria, due to Plasmodium ovale, can be challenging to diagnose due to clinically mild disease and low parasite burden. Two genetically distinct sub-species of P. ovale exist: Plasmodium ovale curtisi (classic) and Plasmodium ovale wallikeri (variant). It is presently unknown if the sub-species causing infection affects performance of malaria diagnostic tests. The aim of this work was to understand how the genetically distinct sub-species, P. o. curtisi and P. o. wallikeri, affect malaria diagnostic tests.MethodsPlasmodium ovale-positive whole blood specimens were sub-speciated by PCR and sequencing of 18S rRNA and dhfr-ts. Parasitaemia, morphology, pan-aldolase positivity, 18S copy number, and dhfr-ts sequences were compared between sub-species.ResultsFrom 2006 to 2015, 49 P. ovale isolates were identified, of which 22 were P. o. curtisi and 27 P. o. wallikeri; 80% were identified in the last five years, and 88% were acquired in West Africa. Sub-species did not differ by parasitaemia, 18S copy number, or pan-aldolase positivity. Lack of Schüffner's stippling was over-represented among P. o. wallikeri isolates (p = 0.02). Several nucleotide polymorphisms between the sub-species were observed, but they do not occur at sites believed to relate to antifolate binding.ConclusionsPlasmodium ovale is increasing among travellers to West Africa, although sub-species do not differ significantly by parasitologic features such as parasitaemia. Absence of Schüffner's stippling may be a feature specific to P. o. wallikeri and is a novel finding.
| S-EPMC5103354 | biostudies-literature
Project description:Plasmodium ovale, considered the rarest of the malaria parasites of humans, consists of two morphologically identical but genetically distinct sympatric species, Plasmodium ovale curtisi and Plasmodium ovale wallikeri. These parasites resemble morphologically to Plasmodium vivax with which they also share a tertian periodicity and the ability to cause relapses, making them easily misidentified as P. vivax. Plasmodium ovale infections are rarely reported, but given the likelihood of misidentification, their prevalence might be underestimated.Morphological and molecular analysis of confirmed malaria cases admitted in Singapore in 2012-2014 detected nine imported P. ovale cases that had been misidentified as P. vivax. Since P. ovale had not been previously officially reported in Singapore, a retrospective analysis of available, frozen, archival blood samples was performed and returned two additional misidentified P. ovale cases in 2003 and 2006. These eleven P. ovale samples were characterized with respect to seven molecular markers (ssrRNA, Potra, Porbp2, Pog3p, dhfr-ts, cytb, cox1) used in recent studies to distinguish between the two sympatric species, and to a further three genes (tufa, clpC and asl).The morphological features of P. ovale and the differential diagnosis with P. vivax were reviewed and illustrated by microphotographs. The genetic dimorphism between P. ovale curtisi and P. ovale wallikeri was assessed by ten molecular markers distributed across the three genomes of the parasite (Genbank KP050361-KP050470). The data obtained for seven of these markers were compared with those published and confirmed that both P. ovale species were present. This dimorphism was also confirmed for the first time on: (1) two genes from the apicoplast genome (tufA and clpC genes); and, (2) the asl gene that was used for phylogenetic analyses of other Plasmodium species, and that was found to harbour the highest number of dimorphic loci between the two P. ovale species.Misidentified P. ovale infections are reported for the first time among imported malaria cases in Singapore. Genetic dimorphism between P. ovale curtisi and P. ovale wallikeri was confirmed using markers from the parasites' three genomes. The apparent increase of imported P. ovale since 2012 (with yearly detection of cases) is puzzling. Given decrease in the overall number of malaria cases recorded in Singapore since 2010 the 'resurgence' of this neglected species raises public health concerns.
| S-EPMC4650842 | biostudies-literature
Project description:It has been proposed that ovale malaria in humans is caused by two closely related but distinct species of malaria parasite, Plasmodium ovale curtisi and Plasmodium ovale wallikeri. It was recently shown that these two parasite types are sympatric at the country level. However, it remains possible that localised geographic, temporal or ecological barriers exist within endemic countries which prevent recombination between the genomes of the two species. Here, using conventional and real-time quantitative PCR (qPCR) methods specifically designed to discriminate P. o. curtisi and P. o. wallikeri, it is shown that both species are present among clinic attendees in Congo-Brazzaville, and occur simultaneously both in lake-side and inland districts in Uganda and on Bioko Island, Equatorial Guinea. Thus P. o. curtisi and P. o. wallikeri in these localities are exactly sympatric in both time and space. These findings are consistent with the existence of a biological barrier, rather than geographical or ecological factors, preventing recombination between P. o. curtisi and P. o. wallikeri. In cross-sectional surveys carried out in Uganda and Bioko, our results show that infections with P. ovale spp. are more common than previously thought, occurring at a frequency of 1-6% in population samples, with both proposed species contributing to ovale malaria in six sites. Malaria elimination programmes in Africa need to include strategies for control of P. o. curtisi and P. o. wallikeri.
| S-EPMC3084460 | biostudies-literature
Project description:Nowadays, Plasmodium ovale is divided into two non-recombinant sympatric species: Plasmodium ovale wallikeri and Plasmodium ovale curtisi. In this mini review, we summarize the available knowledge on the clinical/biological aspects of P. ovale spp. malaria and current techniques for the diagnosis/characterisation of P. ovale curtisi and P. ovale wallikeri. P. ovale wallikeri infections are characterized by a deeper thrombocytopenia and shorter latency compared to P. ovale curtisi infections, indicating that P. ovale wallikeri is more pathogenic than P. ovale curtisi. Rapid diagnosis for effective management is difficult for P. ovale spp., since specific rapid diagnostic tests are not available and microscopic diagnosis, which is recognized as the gold standard, requires expert microscopists to differentiate P. ovale spp. from other Plasmodium species. Neglect in addressing these issues in the prevalence of P. ovale spp. represents the existing gap in the fight against malaria.
| S-EPMC8534334 | biostudies-literature
Project description:Nuclear genome sequences of Plasmodium ovale curtisi.
| PRJEB12678 | ENA
Project description:Nuclear genome sequences of Plasmodium ovale wallikeri.
| PRJEB12679 | ENA
Project description: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.
| S-EPMC7733466 | biostudies-literature