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Fulltext Plasmodium ovale infection in Malaysia: first imported case

Lim YA, Mahmud R, Chew CH, T T, Chua KH

Malar J, 2010;9:272.
PMID: 20929588 DOI: 10.1186/1475-2875-9-272

BACKGROUND:
Plasmodium ovale infection is rarely reported in Malaysia. This is the first imported case of P. ovale infection in Malaysia which was initially misdiagnosed as Plasmodium vivax.

METHODS:
Peripheral blood sample was first examined by Giemsa-stained microscopy examination and further confirmed using a patented in-house multiplex PCR followed by sequencing.

RESULTS AND DISCUSSION:
Initial results from peripheral blood smear examination diagnosed P. vivax infection. However further analysis using a patented in-house multiplex PCR followed by sequencing confirmed the presence of P. ovale. Given that Anopheles maculatus and Anopheles dirus, vectors of P. ovale are found in Malaysia, this finding has significant implication on Malaysia's public health sector.

CONCLUSIONS:
The current finding should serve as an alert to epidemiologists, clinicians and laboratory technicians in the possibility of finding P. ovale in Malaysia. P. ovale should be considered in the differential diagnosis of imported malaria cases in Malaysia due to the exponential increase in the number of visitors from P. ovale endemic regions and the long latent period of P. ovale. It is also timely that conventional diagnosis of malaria via microscopy should be coupled with more advanced molecular tools for effective diagnosis.

Matched MeSH terms: Plasmodium ovale/classification; Plasmodium ovale/cytology; Plasmodium ovale/genetics; Plasmodium ovale/isolation & purification*
Fulltext Two sympatric types of Plasmodium ovale and discrimination by molecular methods

Zaw MT, Lin Z

J Microbiol Immunol Infect, 2017 Oct;50(5):559-564.
PMID: 28065415 DOI: 10.1016/j.jmii.2016.08.004

Plasmodium ovale is widely distributed in tropical countries, whereas it has not been reported in the Americas. It is not a problem globally because it is rarely detected by microscopy owing to low parasite density, which is a feature of clinical ovale malaria. P.o. curtisi and P.o. wallikeri are widespread in both Africa and Asia, and were known to be sympatric in many African countries and in southeast Asian countries. Small subunit ribosomal RNA (SSUrRNA) gene, cytochrome b (cytb) gene, and merozoite surface protein-1 (msp-1) gene were initially studied for molecular discrimination of P.o. curtisi and P.o. wallikeri using polymerase chain reaction (PCR) and DNA sequencing. DNA sequences of other genes from P. ovale in Southeast Asia and the southwestern Pacific regions were also targeted to differentiate the two sympatric types. In terms of clinical manifestations, P.o. wallikeri tended to produce higher parasitemia levels and more severe symptoms. To date, there have been a few studies that used the quantitative PCR method for discrimination of the two distinct P. ovale types. Conventional PCR with consequent DNA sequencing is the common method used to differentiate these two types. It is necessary to identify these two types because relapse periodicity, drug susceptibility, and mosquito species preference need to be studied to reduce ovale malaria. In this article, an easier method of molecular-level discrimination of P.o. curtisi and P.o. wallikeri is proposed.

Matched MeSH terms: Plasmodium ovale/classification*; Plasmodium ovale/genetics*; Plasmodium ovale/isolation & purification; Plasmodium ovale/pathogenicity
Fulltext Prevalence of Asymptomatic and/or Low-Density Malaria Infection among High-Risk Groups in Peninsular Malaysia

Noordin NR, Lee PY, Mohd Bukhari FD, Fong MY, Abdul Hamid MH, Jelip J, et al.

Am J Trop Med Hyg, 2020 09;103(3):1107-1110.
PMID: 32618263 DOI: 10.4269/ajtmh.20-0268

Asymptomatic and/or low-density malaria infection has been acknowledged as an obstacle to achieving a malaria-free country. This study aimed to determine the prevalence of asymptomatic and/or low-density malaria infection in previously reported malarious localities using nested PCR in four states, namely, Johor, Pahang, Kelantan, and Selangor, between June 2019 and January 2020. Blood samples (n = 585) were collected and were extracted using a QIAamp blood kit. The DNA was concentrated and subjected to nested PCR. Thin and thick blood smears were examined as well. Of the 585 samples collected, 19 were positive: 10 for Plasmodium knowlesi, eight for Plasmodium vivax, and one for Plasmodium ovale. Asymptomatic and/or low-density malaria infection is a threat to malaria elimination initiatives. Eliminating countries should develop guidance policy on the importance of low-density malaria infection which includes detection and treatment policy.

Matched MeSH terms: Plasmodium ovale/genetics; Plasmodium ovale/isolation & purification
Fulltext Diagnosis of an imported Plasmodium ovale wallikeri infection in Malaysia

Liew JW, Mahmud R, Tan LH, Lau YL

Malar J, 2016;15:8.
PMID: 26738724 DOI: 10.1186/s12936-015-1070-z

Plasmodium ovale is rare and not exactly known to be autochthonous in Malaysia. There are two distinct forms of the parasite, namely P. ovale curtisi (classic form) and P. ovale wallikeri (variant form). Here, the first sequence confirmed case of an imported P. ovale wallikeri infection in Malaysia is presented. Microscopy found Plasmodium parasites with morphology similar to P. ovale or Plasmodium vivax in the blood films. Further confirmation using polymerase chain reaction (PCR) targeting the small-subunit rRNA gene of the parasite was unsuccessful. Genus-specific PCR was then performed and the product was sequenced and analysed. Sequence analyses confirmed the aetiological agent as P. ovale wallikeri. New species-specific primers (rOVA1v and rOVA2v) were employed and P. ovale wallikeri was finally confirmed. The findings highlight the need to look out for imported malaria infections in Malaysia and the importance of a constantly updated and validated diagnostic technique.

Matched MeSH terms: Plasmodium ovale
Plasmodium knowlesi-mediated zoonotic malaria: A challenge for elimination

Naik DG

Trop Parasitol, 2020 05 20;10(1):3-6.
PMID: 32775284 DOI: 10.4103/tp.TP_17_18

Malaria, a mosquito-transmitted parasitic disease, has been targeted for elimination in many parts of the world. For many years, Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale and Plasmodium malariae have been known to cause malaria in humans. Now, Plasmodium knowlesi is considered to be an important cause of malaria, especially in Southeast Asia. The emergence of P. knowlesi with zoonotic implication is a challenge in the elimination efforts of malaria in Southeast Asia. P. knowlesi is known to cause severe complicated malaria in humans. P. knowlesi parasite is transmitted between humans and wild macaque through mosquito vectors. It appears that the malaria disease severity and host immune evasion depend on antigenic variation exhibited at the surface of the infected erythrocyte. P. knowlesi is sensitive to antimalarial drug artemisinin. Identification of vector species, their biting behavior, timely correct diagnosis, and treatment are important steps in disease management and control. There is a need to identify and implement effective intervention measures to cut the chain of transmissions from animals to humans. The zoonotic malaria definitely poses a significant challenge in elimination and subsequent eradication of all types of malaria from this globe.

Matched MeSH terms: Plasmodium ovale
Fulltext Updates on malaria incidence and profile in Malaysia from 2013 to 2017

Hussin N, Lim YA, Goh PP, William T, Jelip J, Mudin RN

Malar J, 2020 Jan 31;19(1):55.
PMID: 32005228 DOI: 10.1186/s12936-020-3135-x

BACKGROUND: To date, most of the recent publications on malaria in Malaysia were conducted in Sabah, East Malaysia focusing on the emergence of Plasmodium knowlesi. This analysis aims to describe the incidence, mortality and case fatality rate of malaria caused by all Plasmodium species between Peninsular Malaysia and East Malaysia (Sabah and Sarawak) over a 5-year period (2013-2017).
METHODS: This is a secondary data review of all diagnosed and reported malaria confirmed cases notified to the Ministry of Health, Malaysia between January 2013 and December 2017.
RESULTS: From 2013 to 2017, a total of 16,500 malaria cases were notified in Malaysia. The cases were mainly contributed from Sabah (7150; 43.3%) and Sarawak (5684; 34.4%). Majority of the patients were male (13,552; 82.1%). The most common age group in Peninsular Malaysia was 20 to 29 years (1286; 35.1%), while Sabah and Sarawak reported highest number of malaria cases in age group of 30 to 39 years (2776; 21.6%). The top two races with malaria in Sabah and Sarawak were Bumiputera Sabah (5613; 43.7%) and Bumiputera Sarawak (4512; 35.1%), whereas other ethnic group (1232; 33.6%) and Malays (1025; 28.0%) were the two most common races in Peninsular Malaysia. Plasmodium knowlesi was the commonest species in Sabah and Sarawak (9902; 77.1%), while there were more Plasmodium vivax cases (1548; 42.2%) in Peninsular Malaysia. The overall average incidence rate, mortality rate and case fatality rates for malaria from 2013 to 2017 in Malaysia were 0.106/1000, 0.030/100,000 and 0.27%, respectively. Sarawak reported the highest average incidence rate of 0.420/1000 population followed by Sabah (0.383/1000). Other states in Peninsular Malaysia reported below the national average incidence rate with less than 0.100/1000.
CONCLUSIONS: There were different trends and characteristics of notified malaria cases in Peninsular Malaysia and Sabah and Sarawak. They provide useful information to modify current prevention and control measures so that they are customised to the peculiarities of disease patterns in the two regions in order to successfully achieve the pre-elimination of human-only species in the near future.

Matched MeSH terms: Plasmodium ovale/isolation & purification
First evidence of local circulation of Plasmodium ovale curtisi and reliability of a malaria rapid diagnostic test among symptomatic outpatients in Douala, Cameroon

Kojom Foko LP, Kouemo Motse FD, Kamgain Mawabo L, Pande V, Singh V

Infect Genet Evol, 2021 07;91:104797.
PMID: 33676011 DOI: 10.1016/j.meegid.2021.104797

The performances of a commonly used Plasmodium falciparum-detecting rapid diagnostic test (RDT) were determined in symptomatic individuals living in Cameroon. Discrepancies between RDT and light microscopy (LM) results were further investigated, with a focus on non-falciparum malaria (NFM) which are still largely understudied in sub-Saharan Africa (sSA) countries. In the present study, a total of 355 individuals aged 1-65 years were enrolled in the study. Their signs/symptoms and sociodemographic characteristics were documented. The RDT reliability was evaluated using LM as gold standard method. Polymerase chain reaction (PCR) of Plasmodium 18S gene was performed for samples with discordant results between LM and RDT (i.e., RDT-/LM+, and RDT+/LM-). The PCR amplicons of NFM species were sequenced and BLASTed. The prevalence of malaria infection by LM was 95.7% (95% CI: 93.1-97.4%). The sensitivity and specificity of RDT for P. falciparum detection was 94.0% and 66.7%, respectively. By PCR assay, P. ovale curtisi (PoC) was found in 5 of the 30 discordant samples, and on sequence analysis these isolates were found to be phylogenetically closer to sequences reported from China-Myanmar border and Malaysia. This is the first report on molecular characterization of P. ovale subspecies in Cameroon. The study also outlines the good diagnostic performances of the RDT for detection of P. falciparum. Though, the presence of PoC indicated the importance of having RDTs targeting the NFM species in malaria diagnosis and treatment, which is presently limited in the country.

Matched MeSH terms: Plasmodium ovale/isolation & purification*
Fulltext A panel of recombinant proteins from human-infective Plasmodium species for serological surveillance

Müller-Sienerth N, Shilts J, Kadir KA, Yman V, Homann MV, Asghar M, et al.

Malar J, 2020 Jan 17;19(1):31.
PMID: 31952523 DOI: 10.1186/s12936-020-3111-5

BACKGROUND: Malaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures. Serological surveillance will be particularly important in areas of low or periodic transmission because patient antibody responses can provide a measure of historical exposure. While methods for detecting host antibody responses to Plasmodium falciparum and Plasmodium vivax are well established, development of serological assays for Plasmodium knowlesi, Plasmodium ovale and Plasmodium malariae have been inhibited by a lack of immunodiagnostic candidates due to the limited availability of genomic information.
METHODS: Using the recently completed genome sequences from P. malariae, P. ovale and P. knowlesi, a set of 33 candidate cell surface and secreted blood-stage antigens was selected and expressed in a recombinant form using a mammalian expression system. These proteins were added to an existing panel of antigens from P. falciparum and P. vivax and the immunoreactivity of IgG, IgM and IgA immunoglobulins from individuals diagnosed with infections to each of the five different Plasmodium species was evaluated by ELISA. Logistic regression modelling was used to quantify the ability of the responses to determine prior exposure to the different Plasmodium species.
RESULTS: Using sera from European travellers with diagnosed Plasmodium infections, antigens showing species-specific immunoreactivity were identified to select a panel of 22 proteins from five Plasmodium species for serological profiling. The immunoreactivity to the antigens in the panel of sera taken from travellers and individuals living in malaria-endemic regions with diagnosed infections showed moderate power to predict infections by each species, including P. ovale, P. malariae and P. knowlesi. Using a larger set of patient samples and logistic regression modelling it was shown that exposure to P. knowlesi could be accurately detected (AUC = 91%) using an antigen panel consisting of the P. knowlesi orthologues of MSP10, P12 and P38.
CONCLUSIONS: Using the recent availability of genome sequences to all human-infective Plasmodium spp. parasites and a method of expressing Plasmodium proteins in a secreted functional form, an antigen panel has been compiled that will be useful to determine exposure to these parasites.

Matched MeSH terms: Plasmodium ovale/genetics; Plasmodium ovale/immunology
Assessment of Commercial Real-Time PCR Assays for Detection of Malaria Infection in a Non-Endemic Setting

Ramírez AM, Tang THT, Suárez ML, Fernández AÁ, García CM, Hisam S, et al.

Am J Trop Med Hyg, 2021 Oct 12;105(6):1732-1737.
PMID: 34662870 DOI: 10.4269/ajtmh.21-0406

Malaria control and elimination require prompt diagnosis and accurate treatment. Conventional methods such as rapid diagnostic tests (RDTs) and microscopy lack the characteristics to detect low parasitemias, commonly found in asymptomatic parasitemias and/or submicroscopic malaria carriers. On the contrary, molecular methods have higher sensitivity and specificity. This study evaluated the performance of two commercial real-time polymerase chain reaction (PCR) assays, RealStar® Malaria PCR (RealStar-genus) and RealStar Malaria Screen&Type PCR (RealStar-species), compared with the reference Nested Multiplex Malaria PCR, for the detection of the main five Plasmodium species affecting humans. A total of 121 samples were evaluated. Values of sensitivity (98.9% and 97.8%) and specificity (100% and 96.7%) of the RealStar-genus and the RealStar-species assays, respectively, were very good. The limit of detection (LoD) for the RealStar-genus assay showed a mean value of 0.28 parasites/µL with Plasmodium falciparum samples; while, the LoD of the RealStar-species assay ranged from 0.09 parasites/µL for P. vivax to two parasites/µL for P. ovale. The time to complete a diagnosis was established in 4 hours. Our findings showed a very good concordance of both assays compared with the reference method, with a very good analytical sensitivity. RealStar-species assay was able to correctly characterize double and triple infections. Therefore, these RealStar assays have shown to be useful tools in malaria diagnosis in non-endemic countries and even endemic countries, and for malaria control in general, detecting low parasitemias with sensitivity similar to the most sensitive methods as nested PCR, but with lower time to get the results.

Matched MeSH terms: Plasmodium ovale
Fulltext Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome

Lau YL, Lee WC, Tan LH, Kamarulzaman A, Syed Omar SF, Fong MY, et al.

Malar J, 2013 Nov 04;12:389.
PMID: 24180319 DOI: 10.1186/1475-2875-12-389

BACKGROUND: Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research.
METHODS: Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient's condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure.
RESULTS: Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi.
DISCUSSION: In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted.
CONCLUSION: Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission.

Matched MeSH terms: Plasmodium ovale/isolation & purification*

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