Neurological involvement associated with Plasmodium vivax malaria from Pakistan

Background

Plasmodium vivax is the most common species causing malaria outside Africa with approximately 13.8 million reported cases worldwide. More than 80% of P. vivax malaria cases are estimated to occur in Pakistan, India and Indonesia (WHO, 2015). ¹ P. vivax is associated with increased morbidity but reduced mortality when compared with P. falciparum. Recently, studies from Indonesia, Papua New Guinea, Brazil, India and Pakistan have shown that P. vivax can independently prove fatal or result in severe morbidity. The most common complications of vivax malaria reported globally are anaemia and non-cardiogenic pulmonary oedema/acute respiratory distress syndrome. Other complications are severe thrombocytopenia, pancytopenia, jaundice, splenic rupture, acute renal failure and, rarely, cerebral involvement.

Cerebral malaria is a known complication of P. falciparum with over 575,000 cases leading to neurological, behavioural and cognitive defects reported annually. ² However, cerebral malaria due to P. vivax mono infection is rarely reported. Malaria remains an endemic disease in Pakistan with an estimated healthcare burden of 1.6 million cases annually, with P. vivax accounting for 67% of reported cases. We report a severe P. vivax infection with cerebral involvement in a child.

Case report

A nine-year old boy presented to the emergency department of The Aga Khan University Hospital (AKUH) with a three-day history of high-grade fever accompanied by projectile vomiting and abnormal behaviour. A day prior to his admission, he developed generalised tonic–clonic seizures associated with dizziness and unconsciousness. He had a coma score of 5/15 on presentation with a tachycardia (167/min), tachypnoea (70 breaths/min), oxygen saturation of 92%, blood pressure of 133/87 mmHg and a temperature of 38℃. There was hypertonia in all limbs. The rest of the physical examination was normal. The full blood count showed anaemia (Hb 94 g/L), a leucocytosis (13.1 × 10⁶/mL, neutrophils 75% and monocytes 8%) and normal platelet count (304 × 10⁶/mL). A cerebral CT scan showed oedema with increased intracranial pressure. Thick and thin peripheral smear with Giemsa stain was suggestive of P. vivax with 1–10 per 100 high power fields. Stained blood films were also independently reviewed by an external expert parasitologist who confirmed the original diagnosis. Polymerase chain reaction (PCR) and an immuno-chromatography test (ICT) definitively excluded P. falciparum infection. ³ Prothrombin time and activated partial thrombin time were in the normal range and the direct antiglobulin test was negative. Although no lumbar puncture was performed, empirical therapy for bacterial and viral meningitis was initiated. Initially Vancomycin, Meropenem, Acyclovir, steroids and anticonvulsants were started in emergency.

The patient was mechanically ventilated. He required vasopressor support with norepinephrine. Blood cultures and urine cultures were all negative. Antibiotics were stopped as blood film confirmed malarial parasite P. vivax and started with artemether lumefantrine. On the third day, he developed a high urine output and hyponatremia secondarily, which was managed with fludrocortisone. On presentation, his sodium levels were normal (145 mmol/L) and dropped to 125 mmol/L on the third day. His sodium level was corrected to 135 in 72 h and he gained consciousness. The Glasgow Coma Scale score improved to 15/15 and he was extubated on the sixth day of admission and discharged on the ninth day. Post-treatment microscopy revealed blood films negative for P. vivax.

Discussion

P. vivax malaria has historically been termed ‘Benign Tertian Malaria’ but it is increasingly felt that this is an erroneous label. Rossle in 1921 described a lethal cerebellar haemorrhage in a 21-year-old soldier suffering a vivax infection. ⁴ Patients presenting with cerebral symptoms such as acute febrile encephalopathy, raised intracranial pressure, intracerebral haemorrhage, hemiparesis, aphasia and seizures following vivax malaria have been reported previously.^5,6

Several cases of cerebral malaria attributed to P. vivax infection have been reported in recent years, especially in Asia and South America. This may be due to an overall increase in P. vivax malarial infections. Most of these cases have been reported from India where P. vivax is the predominant species. ⁷ Although the mechanism by which P. vivax causes cerebral malaria is not fully understood, a suggested pathogenesis is the sequestration of infected erythrocytes in cerebral microvascular beds. ⁸

In our case, the peripheral blood smears with Giemsa stain were repeatedly performed and parasitaemia remained low. Immuno-chromatography testing showed no trace of P. falciparum and PCR helped confirm mono-infection by P. vivax. Advances in molecular and serodiagnosis of malaria parasites have increased the sensitivity and specificity, and so the substantial accuracy, of diagnosis of P. vivax.^9,10

Physicians must be aware of the aggressive pathology of severe P. vivax infections and institute prompt and accurate diagnosis in treatment. Furthermore, an increasing incidence of severe malaria cases due to P. vivax are already placing a huge burden on an already strained healthcare system.

Our study was approved by the AKUH ethical review committee (reference no. 3541-Path-ERC-15). Informed consent was obtained from the patient for the publication of this report.