Complicated malaria: A rare presentation of Plasmodium ovale

Introduction

In the year 2013, the World Health Organization (WHO) estimated that over 198 million clinical cases of malaria are detected annually, with estimated deaths around 584,000. There are 3.2 billion people at risk of malaria. ¹ P. falciparum, P. vivax and Plasmodium knowlesi (P. knowlesi) are known to cause severe disease.^1,2 Severe disease due to P. ovale in the form of multiorgan failure has rarely been reported.^3,4

Case presentation

A 75-year-old man, a resident of Uttar Pradesh, India, presented with a history of fever associated with chills and rigors for 6 days, yellowish discoloration of eyes with dark urine for 3 days and abdominal discomfort for 1 day. There was also a history of decreased urine output over the last 2 days. There was no history of bleeding from any site, headache, vomiting or burning micturition. Recent travel history was negative. On examination the patient was febrile with an oral temperature of 39℃ with mild pallor and icterus. His blood pressure at presentation was 70/40 mmHg and his pulse rate was 120/min. There was also mild tender hepatosplenomegaly. Examination of the cardiovascular, respiratory and nervous systems was unremarkable.

Investigations revealed thrombocytopenia with a platelet count 28 × 10⁹/L (normal range: 150–400 × 10⁹/L). Also there was derangement of kidney function (serum cretanine 140 µmol/L) and liver function (total bilirubin 3.4 µmol/L; serum alanine aminotransferase 150 U/L; serum aspartate aminotransferase 119 U/L). The peripheral smear was positive for P. ovale and the same was confirmed by multiplex polymerase chain reaction (PCR) for P. ovale. A concomitant P. falciparum and P. vivax infection was unlikely because of a negative rapid diagnostic test (antigen detection test) done on the sixth day of fever. Dengue NS1 antigen and immunoglobulin (Ig) M dengue serology was negative. HIV, anti HAV, anti HEV, HbsAg and anti HCV test by ELISA (Enzyme Linked Immune Assay) method was found to be negative. Blood and urine cultures were negative.

In view of persistent hypotension, the patient was re-hydrated and given inotropic support, along with intravenous (IV) artesunate, IV Ceftriaxone and antipyretics. After 3 days of treatment, the fever and jaundice started to subside. His blood pressure and haematological parameters also improved and became normal over 2 days. A test for G6PD deficiency was negative. The patient was discharged on oral Primaquine for 14 days.

Discussion

The WHO, in their 2013 report, estimated that annually there are over 198 million clinical cases of malaria, with estimated deaths around 584,000 of which 90% occur in Africa. ¹ It was also observed that 3.2 billion people worldwide are still at risk of developing malaria. ¹ In the year 2011, a total of 1.31 million cases and 463 deaths from malarial fever were reported in India. ⁵ Malaria is caused by five different distinct species, namely P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.

In India, P. falciparum accounts for 50% of the malaria infection; while 4–8% are due to mixed infection, less than 1% are due to P. malariae and the rest are ascribed to P. vivax. ⁵ The prevalence of infection due to P. ovale is in the range of 3–5% and more than 10% if found in the areas of West and Central Africa. ⁶ Two forms of P. ovale occur globally namely Plasmodium ovale curtisi and Plasmodium ovale wallikeri. The incubation period of P. ovale is 10–17 days.

Severe disease due to P. falciprum and P. vivax is quite common and its pathophysiology has been explained by multiple factors, the most probable being the cytoadherance and sequestration of ingested red blood cells in the microvasculature. However, severe disease in P. ovale infection is rare and its pathophysiology is yet to be elucidated owing to the fact that low parasitaemia and the small distinction between P. ovale from P. vivax, based on traditional light microscopy, makes diagnosis difficult. Thus the true burden of P. ovale disease is probably underestimated. Even immunochromatography-based rapid test fails to detect P. ovale infection owing to its poor sensitivity; the PCR based test is costly and is not readily available in all health facilities. ⁶

P. ovale usually causes mild disease with a low parasitaemia.^6,8 There are only few case reports in the literature describing severe and complicated cases due to P. ovale infection. These include presentations with ARDS, jaundice, renal failure, incipient bleeding, metabolic acidosis, hypotension, splenic rupture and splenic infarction; with death occurring in three out of 10 cases reported.^4,9–17 Our patient was diagnosed with P. ovale infection complicated with jaundice, thrombocytopenia, hypotension and acute renal failure and responded excellently with IV artesunate, which is the treatment of choice for severe malaria according to WHO guidelines. As P. ovale is known to cause relapse after 2 to 3 years, prophylaxis with Primaquine was also prescribed for the patient. He is, nonetheless, likely to be semi-immune to malaria as he was resident of Uttar Pradesh (India), where malaria is of low to moderate intensity and P. vivax is predominant occurring in the lean period and P. falciparum during periodic exacerbations. ⁵

Possible alternative explanations for his illness are: (1) septicaemia with incidental P. ovale infection; (2) fulminant viral infection; or (3) dual infection of P. ovale with P. falciparum or P. vivax with a low density of the falciparum or vivax parasites because most were sequestered (rapid test should have detected this but none is 100% sensitive).

This case highlights the importance of being vigilant to identify the rare life-threatening complications of P. ovale infection early, so that timely necessary interventions can prevent mortality.