Plasmodium ovale: a case of not-so-benign tertian malaria

  • Kathy-Anne Strydom1Email author,

    Affiliated with

    • Farzana Ismail1 and

      Affiliated with

      • John Frean2, 3

        Affiliated with

        Malaria Journal201413:85

        DOI: 10.1186/1475-2875-13-85

        Received: 12 December 2013

        Accepted: 2 March 2014

        Published: 10 March 2014

        Abstract

        Severe malaria is most commonly associated with Plasmodium falciparum. Plasmodium vivax is increasingly recognized as being capable of causing severe disease. In contrast, Plasmodium ovale is considered as a cause of benign disease and evidence supporting the occurrence of severe or complicated ovale infection is rare. This report describes a case of severe P. ovale infection in a patient presenting with jaundice, respiratory distress, severe thrombocytopenia, petechiae, and hypotension. He had no apparent underlying risk factors for severe disease.

        Keywords

        Plasmodium ovale Severe Malaria Infection

        Background

        Malaria is the most important parasitic disease of man [1]. According to the World Health Organization (WHO) an estimated 3.3 billion people are at risk of malaria [2]. Annually there are over 200 hundred million clinical cases of malaria with an estimated 660,000 deaths, 90% of which occur in sub-Saharan Africa, where children under five years are most severely affected [2].

        Disease in humans is caused by five species of apicomplexan parasites belonging to the genus Plasmodium[1]. Plasmodium falciparum is most commonly associated with severe disease [13]. Severe malaria is also known to occur with Plasmodium vivax and Plasmodium knowlesi[1, 4, 5]. Infection with Plasmodium malariae is generally benign, but has been associated with nephrotic syndrome and severe anaemia [3, 68].

        Although the clinical presentations of Plasmodium ovale and P. vivax infections largely overlap, severe disease due to P. ovale is extremely rare [1, 3, 9]. This case report describes an uncommonly severe case of ovale malaria in a patient with no apparent underlying risk factors for severe disease. The existing literature documenting severe or complicated presentations of P. ovale infection is reviewed.

        Case presentation

        A 42-year-old male, with no significant previous medical history, was referred by a general practitioner to the Steve Biko Academic Hospital, Pretoria, South Africa. The patient presented with fever, nausea and vomiting, general body pains and shortness of breath. He complained of feeling weak and tired for the last three weeks. In the preceding six months he had worked in two malaria-endemic regions: Kalia in the north-west region of Guinea, and most recently Mozambique, from where he had returned a month previously. He had not taken malaria chemoprophylaxis during his stay in these areas.

        Upon physical examination the patient was awake and alert, with no signs of meningism. He was visibly jaundiced. Abdominal examination revealed a tender right upper quadrant, there were bilateral fine crepitations on auscultation of the lungs, and petechiae were visible on his upper and lower limbs. The patient was hypotensive (blood pressure 78/58 mmHg), tachycardic (pulse rate 110 per minute) and tachypnoeic (respiratory rate 28 per minute). The temperature was 39.5°C. The chest x-ray was unremarkable.

        Laboratory evaluation showed a marked thrombocytopenia (platelets 23 × 109/l), mildly deranged renal function (urea 13.2 mmol/l, creatinine 157 μmol/l) and liver function tests (total bilirubin 96 μmol/l, alanine transaminase 43 U/l, aspartate transaminase 74 U/l, γ-glutamyltransferase 66 U/l). The patient had markedly elevated inflammatory markers (C-reactive protein 121.7 mg/l and procalcitonin 105.6 μg/l).

        The diagnosis of malaria was made by microscopic examination of Giemsa-stained blood smears, showing characteristic P. ovale parasites (Figure 1). The parasitaemia was 1.4%. Rapid diagnostic tests for P. falciparum antigen (histidine-rich protein 2) were repeatedly negative. Mixed Plasmodium species infection was excluded and the diagnosis of P. ovale malaria was confirmed by multiplex PCR [10, 11].
        http://static-content.springer.com/image/art%3A10.1186%2F1475-2875-13-85/MediaObjects/12936_2013_3694_Fig1_HTML.jpg
        Figure 1

        Giemsa-stained thick and thin smears. A. Trophozoites of P. ovale in a Giemsa-stained thick smear. B. Trophozoites and C, D. Trophozoites and immature schizonts of P. ovale in a Giemsa-stained thin film. Note slightly enlarged, fimbriated and oval-shaped infected red blood cells, with James’ dots.

        The patient was admitted to high care and treated with a course of intravenous quinine (600 mg eight hourly) and doxycycline (100 mg twelve hourly). Ceftriaxone was added to cover for possible bacterial sepsis. The septic screen investigations, which comprised two sets of blood cultures and a urine culture, were negative. The timing of the blood cultures in relation to antibiotic administration is unclear.

        The patient demonstrated a good clinical response to treatment, and he was stepped down to a general ward. Subsequent laboratory evaluations showed an improvement in full blood count, renal and liver functions as well as inflammatory markers, which returned to normal before discharge. Primaquine, 30 mg orally for 14 days was administered to eradicate hypnozoites and prevent possible relapses.

        Discussion

        Endemic transmission of P. ovale is traditionally described as limited to sub-Saharan Africa and the islands of the western Pacific [9]. Infections with P. ovale have also been documented from India, the Middle East and parts of Southeast Asia [6, 9]. Two non-recombining sympatric forms of P. ovale occur globally [12]. Plasmodium ovale curtisi (classic type) and Plasmodium ovale wallikeri (variant type) have been proposed as two distinct species [12, 13].

        Much of what is currently known regarding the epidemiology of P. ovale is based upon surveys utilising light microscopy as diagnostic tool [6]. From these surveys, the prevalence of P. ovale is generally considered to be low and ranges between 3-5% and greater than 10% in areas of West and Central Africa [6]. The utility of light microscopy is limited by difficulties in distinguishing between P. ovale and P. vivax in smears, as well as the low parasitaemias characteristic of P. ovale infection. In addition, immunochromatography-based rapid diagnostic tests display poor sensitivity for the detection of P. ovale infection [14, 15]. This may lead to underestimating the true burden of disease as is evident when more sensitive diagnostic modalities, such as PCR-based methods targeting small subunit rRNA, are employed [6].

        Plasmodium ovale is known to cause mild disease with a low parasitaemia [6, 9]. Literature describing severe or complicated cases of P. ovale infection is limited. These rare reports include six cases complicated by acute respiratory distress syndrome (ARDS)(one of which further complicated by renal failure and metabolic acidosis), two cases of splenic rupture, and a single case of splenic infarction [1625]. Clinical and therapeutic data for these cases are shown in Table 1.
        Table 1

        Summary of published cases of severe and complicated P. ovale infection

        Reference

        Patient age

        Gender

        Medical history

        Travel history

        Prophylaxis

        Time to presentation

        Parasitaemia

        WHO or other severity criteria

        Treatment

        Outcome

        This case report

        42 yr

        Male

        None

        Kalia, Guinea: 6 months ago Mozambique: 1 month ago

        None

        1-6 months

        1.4%

        Jaundice, respiratory distress, hypotension, incipient bleeding

        IV quinine, 14 days primaquine

        Recovered

        Lee et al. [16]

        31 yr

        Female

        None

        Ghana

        Mefloquine

        10 months

        0.1%

        ARDS

        Chloroquine, 14 days primaquine

        Recovered

        Rojo Marcos et al. [17]

        43 yr

        Male

        Hypertensive, diabetic

        Nigeria

        None

        N/S

        6,000/μL

        ARDS

        Chloroquine, 14 days primaquine

        Recovered

        Haydoura et al. [18]

        46 yr

        Female

        Methylenetetrahydrofolate reductase mutation with secondary portal vein thrombosis

        Acquired by transfusion

        N/A

        1 month following transfusion

        1.11%

        ARDS

        IV quinine and doxycycline, 14 days primaquine

        Recovered

        Roze et al. [19]

        24 yr

        Male

        Tuberous sclerosis

        Chad, Ivory Coast

        Doxycycline

        1 year

        0.1%

        ARDS

        Chloroquine then changed to quinine

        Recovered

        Lau et al. [20]

        59 yr

        Male

        None

        Victoria Island, Nigeria

        Mefloquine

        6 months

        0.18%

        ARDS, acute renal failure, metabolic acidosis

        Chloroquine plus primaquine, changed to quinine, then artesunate

        Demised

        Hashimi et al. [21]

        31 yr

        Male

        Previous pulmonary tuberculosis (20 years ago)

        Democratic Republic of Congo

        N/S

        7 months

        0.2%

        ARDS

        IV quinine

        Demised

        Facer et al. [23]

        51 yr

        Female

        N/S

        Ghana

        None

        12 days

        1.8%

        Splenic rupture

        None

        Demised

        Patel et al. [24]

        42 yr

        Male

        N/S

        South and Central Africa

        Hydroxychloroquine, discontinued during travel

        18 months

        N/S

        Splenic rupture

        Chloroquine and primaquine

        Recovered

        Cinquetti et al. [25]

        34 yr

        Male

        None

        Senegal 2002, Ivory Coast 2004

        Doxycycline

        2-4 years

        0.001%

        Splenic infarction

        IV quinine

        Recovered

        N/S: Not stated; N/A: not applicable; ARDS: Acute respiratory distress syndrome.

        The current WHO treatment guidelines for severe malaria recommend intravenous (IV) artesunate for the treatment of severe malaria due to all Plasmodium species [26]. Intravenous artesunate is currently not registered in South Africa for clinical use and is only available for named patients on application under Section 21 of the Medicines and Related Substances Act, usually at selected sentinel hospitals through the current artesunate access programme. The patient discussed in this case report was treated with IV quinine, which according to the current South African treatment guidelines, is still the treatment of choice for severe malaria in adult patients if IV artesunate is not readily available [27].

        The pathophysiology of P. falciparum as the leading cause of severe malaria has been examined extensively. Various parasite, host, geographic and social factors contribute to severe disease manifestations; however, sequestration of mature parasitized red blood cells is considered to be the key pathogenic event [28, 29].

        Plasmodium vivax, long considered to cause benign infection, is increasingly recognised as a cause of severe malaria [30, 31]. Similar to P. falciparum infection, multiple factors contribute to severe disease [30]. Evidence is emerging that P. vivax infected red blood cells can also cytoadhere and sequestrate in the microvasculature, but to a lesser extent than P. falciparum [32]. It remains to be elucidated to what degree sequestration contributes to severe disease manifestations in vivax infections [30, 32].

        The pathophysiological correlates and risk factors for severe P. ovale infection are not yet fully established. Reports of severe ovale infection remain rare; however, when the diagnostic difficulties both in the detection of a low parasitaemia and distinguishing P. ovale from P. vivax, based on traditional light microscopy is taken into account, severe cases of ovale malaria may actually be underreported.

        Consent

        Verbal consent was obtained from the patient; however, due to his unavailability, written consent could not be obtained. Thus, ethical approval was obtained from the University of Pretoria Ethics Committee. The letter of approval from the Committee is available for review.

        Declarations

        Acknowledgements

        We thank Desiree du Plessis for the PCR testing.

        Authors’ Affiliations

        (1)
        National Health Laboratory Services, Tshwane Academic Division, Department of Medical Microbiology, University of Pretoria
        (2)
        Centre for Opportunistic, Tropical and Hospital Infections, National Institute for Communicable Diseases
        (3)
        Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand

        References

        1. Cook GC, Zumla AI: Malaria. In Manson’s Tropical Diseases. 22nd edition. Edited by: Cook GC, Zumla AI. London: Saunders; 2009:1201–1300.
        2. World Health Organization: 10 Facts on Malaria. Geneva: WHO; 2013. Available: Accessed June 3 2013 http://​www.​who.​int/​features/​factfiles/​malaria/​en/​index.​html
        3. Garcia LS: Malaria. Clin Lab Med 2010, 30:93–129. 10.1016/j.cll.2009.10.001View ArticlePubMed
        4. Price RN, Douglas NM, Anstey NM: New developments in Plasmodium vivax malaria: severe disease and the rise of chloroquine resistance. Curr Opin Infect Dis 2009, 22:430–435. 10.1097/QCO.0b013e32832f14c1View ArticlePubMed
        5. Baird JK: Evidence and implications of mortality associated with acute Plasmodium vivax malaria. Clin Microbiol Rev 2013, 26:36–57. 10.1128/CMR.00074-12View ArticlePubMed CentralPubMed
        6. Mueller I, Zimmerman PA, Reeder JC: Plasmodium malariae and Plasmodium ovale – the 'bashful’ malaria parasites. Trends Parasitol 2007, 23:278–283. 10.1016/j.pt.2007.04.009View ArticlePubMed CentralPubMed
        7. Collins WE, Jeffery GM: Plasmodium malariae : parasite and disease. Clin Microbiol Rev 2007, 20:579–592. 10.1128/CMR.00027-07View ArticlePubMed CentralPubMed
        8. Douglas NM, Lampah DA, Kenangalem , Simpson JA, Poespoprodjo JR, Sugiarto P, Anstey NM, Price RN: Major burden of severe anemia from non-falciparum malaria species in Southern Papua: a hospital-based surveillance study. PLoS Med 2013, 10:e1001575. 10.1371/journal.pmed.1001575View ArticlePubMed CentralPubMed
        9. Collins WE, Jeffery GM: Plasmodium ovale : parasite and disease. Clin Microbiol Rev 2005, 18:570–581. 10.1128/CMR.18.3.570-581.2005View ArticlePubMed CentralPubMed
        10. Padley D, Moody AH, Chiodini PL, Saldanha J: Use of a rapid, single-round, multiplex PCR to detect malarial parasites and identify the species present. Ann Trop Med Parasitol 2003, 97:131–137. 10.1179/000349803125002977View ArticlePubMed
        11. Du Plessis D, Poonsamy B, Frean J: Validation of a malaria multiplex PCR for detection of malaria species in the Parasitology Reference Laboratory, NICD. NICD-NHLS Commun Dis Surveill Bull 2012, 10:33–35.
        12. Sutherland CJ, Tanomsing N, Nolder D, Oguike M, Jennison C, Pukrittayakamee S, Doledcek C, Hien TT, Do Rosario VE, Arez AP, Pinto J, Michon P, Escalante AA, Nosten F, Burke M, Lee R, Blaze M, Otto TD, Barnwell JW, Pain A, Williams J, White NJ, Day NPJ, Snounou G, Lockhart PJ, Chiodini PL, Imwong M, Polley SD: Two non-recombining sympatric forms of the human malaria parasite Plasmodium ovale occur globally. J Infect Dis 2010, 201:1544–1550. 10.1086/652240View ArticlePubMed
        13. Oguike MC, Betson M, Burke M, Nolder D, Stothard JR, Kleinschmidt I, Proietti C, Bousema T, Ndounga M, Tanabe K, Ntege E, Culleton R, Sutherland CJ: Plasmodium ovale curtisi and Plasmodium ovale wallikeri circulate simultaneously in African communities. Int J Parasitol 2011, 41:677–683. 10.1016/j.ijpara.2011.01.004View ArticlePubMed CentralPubMed
        14. Talman AM, Duval L, Legrand E, Hubert V, Yen S, Bell D, Le Bras J, Ariey F, Houze S: Evaluation of the intra- and inter-specific genetic variability of Plasmodium lactate dehydrogenase. Malar J 2007, 6:140. 10.1186/1475-2875-6-140View ArticlePubMed CentralPubMed
        15. Bigaillon C, Fontan E, Cavallo JD, Hernandez E: Ineffectiveness of the Binax NOW malaria test for the diagnosis of Plasmodium ovale malaria. J Clin Microbiol 2005, 3:11.
        16. Lee EY, Maguire JH: Acute pulmonary edema complicating ovale malaria. Clin Infect Dis 1999, 29:697–698. 10.1086/598667View ArticlePubMed
        17. Rojo-Marcos G, Cuadros-Gonzalez J, Mesa-Latorre JM, Culebras-Lopez AM, De Pablo-Sanchez R: Case report: acute respiratory distress syndrome in a case of Plasmodium ovale malaria. Am J Trop Med Hyg 2008, 79:391–393.PubMed
        18. Haydoura S, Mazboudi O, Charafeddine K, Bouakl I, Baban TA, Taher AT, Kanj SS: Transfusion-related Plasmodium ovale malaria complicated by acute respiratory distress syndrome (ARDS) in a non-endemic country. Parasitol Int 2011, 60:114–116. 10.1016/j.parint.2010.10.005View ArticlePubMed
        19. Roze B, Lambert Y, Gelin E, Geffroy F, Hutin P: Plasmodium ovale malaria severity. Med Mal Infect 2011, 41:213–220. 10.1016/j.medmal.2010.07.006View Article
        20. Lau YL, Lee WC, Tan LH, Kamarulzaman A, Syed Omar SF, Fong MY, Cheong FW, Mahmud R: Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome. Malar J 2013, 12:389. 10.1186/1475-2875-12-389View ArticlePubMed CentralPubMed
        21. Hachimi MA, Hatim EA, Moudden MK, Elkartouti A, Errami M, Louzi L, Hanafi SM, Mahmoudi A: The acute respiratory distress syndrome in malaria: is it always the prerogative of Plasmodium falciparum ? Rev Pneumol Clin 2013, 69:283–286. 10.1016/j.pneumo.2013.03.001View ArticlePubMed
        22. Imbert P, Buffet PA RC: Pathological rupture of the spleen in malaria: analysis of 55 cases (1958–2008). Travel Med Infect Dis 2009, 7:147–159. 10.1016/j.tmaid.2009.01.002View ArticlePubMed
        23. Facer CA, Rouse D: Spontaneous splenic rupture due to Plasmodium ovale malaria. Lancet 1991, 338:896.View ArticlePubMed
        24. Patel MI: Spontaneous rupture of a malarial spleen. Med J Aust 1993, 159:836–837.PubMed
        25. Cinquetti G, Banal F, Rondel C, Plancade D, De Saint Roman C, Adriamanantena D, Ragot C, Vedy S, Graffin B: Splenic infarction during Plasmodium ovale acute malaria: first case report. Malar J 2010, 9:288. 10.1186/1475-2875-9-288View ArticlePubMed CentralPubMed
        26. WHO: Management of Severe Malaria. Geneva: World Health Organization; 2012. Available: Accessed February 2014 http://​apps.​who.​int/​iris/​bitstream/​10665/​79317/​1/​9789241548526_​eng.​pdf
        27. National Department of Health: Guidelines for the Treatment of Malaria in South Africa. Pretoria: National Department of Health; 2010. Available: Accessed February 2014 http://​www.​malaria.​org.​za/​Malaria_​Risk/​Treatment/​guidelines2010.​pdf
        28. Miller LH, Baruch DI, Marsh K, Doumbo OK: The pathogenic basis of malaria. Nature 2002, 415:673–679. 10.1038/415673aView ArticlePubMed
        29. Beeson JG, Brown GV: Pathogenesis of Plasmodium falciparum malaria: the roles of parasite adhesion and antigenic variation. Cell Mol Life Sci 2002, 59:258–271. 10.1007/s00018-002-8421-yView ArticlePubMed
        30. Anstey NM, Russel B, Yeo TW, Price RN: The pathophysiology of vivax malaria. Trends Parasitol 2009, 25:220–227. 10.1016/j.pt.2009.02.003View ArticlePubMed
        31. Singh H, Parakh A, Basu S, Rath B: Plasmodium vivax malaria: is it actually benign? J Infect Public Health 2011, 4:91–95. 10.1016/j.jiph.2011.03.002View ArticlePubMed
        32. Carvalho BO, Lopes SCP, Nogueira PA, Orlandi PP, Bargieri DY, Blanco YC, Mamoni R, Leite JA, Rodrigues MM, Soares IS, Oliveira TR, Wunderlich G, Lacerda MVG, Del Portillo HA, Araujo MOG, Russel B, Suwanarusk R, Snounou G, Renia L, Costa FTM: On the cytoadhesion of Plasmodium vivax -infected erythrocytes. J Infect Dis 2010, 202:638–647. 10.1086/654815View ArticlePubMed

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        © Strydom et al.; licensee BioMed Central Ltd. 2014

        This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.

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