Cerebral Malaria and Multi-Organ Dysfunction Caused by Plasmodium vivax in an Adult: A case from Oman with a literature review

Summary

Cerebral malaria is a life-threatening complication most commonly associated with Plasmodium falciparum. To the best of the authors' knowledge, this is the first documented case in Oman of a previously healthy 38-year-old Pakistani male who presented to the Emergency Department of a tertiary care hospital in 2025 with cerebral malaria and multi-organ dysfunction syndrome (MODS) caused by Plasmodium vivax, confirmed by peripheral blood smear and polymerase chain reaction (PCR). The patient was treated with intravenous (IV) artesunate and supportive intensive care, resulting in full neurological recovery. This case highlights the importance of considering P. vivax as a potential cause of severe malaria, even in non-endemic regions.

1. Introduction

According to the World Health Organization's (WHO) World Malaria Report 2023, global malaria cases in 2022 surpassed pre-pandemic levels.¹ Although Oman was certified malaria-free in 2010, sporadic imported cases continue to occur, mainly due to travel from endemic areas such as the Indian subcontinent and sub-Saharan Africa.² Since 2013, only isolated locally acquired cases have been reported, and prompt responses have prevented the re-establishment of transmission.²

Cerebral malaria, most commonly caused by Plasmodium falciparum, presents with altered consciousness, seizures, and coma, and carries high morbidity and mortality—particularly in sub-Saharan Africa.³ While Plasmodium vivax has historically been considered less virulent, growing evidence shows that it can cause severe disease, including cerebral malaria, particularly in vulnerable groups such as children and pregnant women, and occasionally in adults.^4,5 Approximately 12.5% of severe P. vivax cases involve cerebral symptoms,⁶ with features including encephalopathy, seizures, hepatic and renal dysfunction, and multi-organ failure. Although mortality remains relatively low (∼0.56%),⁵ fatalities have been reported, with documented cases emerging from India, Pakistan, Sudan, and other endemic regions.^7,8

2. Case report

A 38-year-old Pakistani male presented to the Emergency Department at a tertiary care hospital in 2025 with a one-day history of fever, headache, vomiting, and subsequent altered mental status. He had no known medical comorbidities, was not on regular medication, and had no history of recent hospitalisation. His last travel to Pakistan had been approximately one year prior.

On arrival, his Glasgow Coma Scale score was 10 out of 15 (E3, V3, M4). He was febrile (40 °C), tachypnoeic (respiratory rate: 32 breaths/min), and tachycardic (heart rate: 180 bpm). Pupils were dilated with sluggish reactivity. Arterial blood gas analysis revealed metabolic acidosis (pH 7.25, HCO₃^- 12 mmol/L, pCO₂ 28 mmHg) with elevated lactate (14.4 mmol/L). Laboratory investigations showed thrombocytopenia (82 × 10³/μL; reference range 150–450 × 10³/μL), acute kidney injury (creatinine 221 μmol/L; reference range: 62–106 μmol/L), and elevated liver enzymes: alanine aminotransferase 73 U/L (reference range 4–40 U/L) and alkaline phosphatase 136 U/L (reference range: 36–104 U/L). Total bilirubin was elevated at 30 μmol/L (reference range: 3–19 μmol/L). There were no signs of active haemolysis, and the peripheral smear showed no schistocytes. Troponin T was significantly elevated at 557 ng/L (reference range: 0–14 ng/L). Electrocardiogram revealed sinus tachycardia without ischaemic changes. Transthoracic echocardiography showed preserved left ventricular ejection fraction with grade 2 diastolic dysfunction. A non-contrast computed tomography scan of the brain was unremarkable.

Following the initial evaluation in the ED, his clinical condition deteriorated and he developed supraventricular tachycardia, which responded to synchronised cardioversion and two doses of intravenous (IV) verapamil (5 mg each). He subsequently experienced generalised tonic–clonic seizures, which did not respond to two doses of IV diazepam (5 mg each); however, seizure activity ceased following a loading dose of IV levetiracetam (300 mg). He was sedated with a fentanyl infusion (150–200 μg/hr) and subsequently intubated due to persistent impaired consciousness following the seizures. Mechanical ventilation was initiated in synchronised intermittent mandatory ventilation mode with a tidal volume of 490 mL, respiratory rate 18 breaths/min, positive end-expiratory pressure 5 cm H₂O, and fractional inspired oxygen 40%. The patient was transferred to the neurocritical care unit (NCCU) with a working diagnosis of meningoencephalitis complicated by multi-organ dysfunction syndrome (MODS).

Initial differential diagnoses included viral and bacterial meningoencephalitis, metabolic disturbances, and toxic encephalopathies. A lumbar puncture was performed, revealing an elevated opening pressure of 32 cm H₂O with normal cerebrospinal fluid (CSF) analysis: cell count 3 cells/μL, protein 30 mg/dL, and mildly elevated glucose 5.6 mmol/L (serum glucose 9 mmol/L). CSF Gram stain was unremarkable. Urine toxicology screening was negative. Empirical antimicrobial therapy with IV ceftriaxone (2 g twice daily), IV vancomycin (1 g twice daily), and IV acyclovir (750 mg twice daily) was initiated.

Shortly after admission to the NCCU, laboratory results returned positive for P. vivax. Peripheral blood smear showed P. vivax rings and schizonts, as illustrated in [Fig. 1]; no crescentic gametocytes or multiple ring-infected erythrocytes were observed. Quantitative parasitaemia was not performed. Polymerase chain reaction (PCR) testing for malaria was also positive for P. vivax. Procalcitonin level was unremarkable, supporting the low likelihood of a bacterial aetiology for MODS. Magnetic resonance imaging of the brain was not performed; however, electroencephalography showed intermittent diffuse slowing and intermittent background suppression with no epileptiform discharges.

Fig. 1.

Microscopic images showing the presence of P. vivax in various stages of its intraerythrocytic life cycle. A: A thick blood film revealed the presence of P. vivax ring forms (arrow). B: A corresponding thin blood film demonstrated characteristic ring forms within infected erythrocytes (arrow). C: Further examination identified round gametocytes that nearly filled the red blood cell, exhibiting scattered brown pigment and fine Schüffner's dots (arrow). D: The trophozoite stage displayed an amoeboid cytoplasm with distinct chromatin dots (arrow). E: Mature schizonts containing multiple merozoites were observed in the thin blood film (arrow). F: A ruptured schizont was noted, releasing merozoites into the surrounding plasma (arrow).

In the context of a positive P. vivax smear and PCR, and pending blood and CSF cultures and viral panel results, a diagnosis of cerebral malaria complicated by MODS was made. The patient was started on IV artesunate (140 mg twice daily for two days), along with the empirical antimicrobials. Due to worsening renal function and fluid overload, a furosemide infusion was commenced at 5 mg/hr, and continuous veno-venous haemodialysis (CVVHD) was initiated for eight hours, with a total ultrafiltration of 2.5 L. The patient showed significant clinical improvement, including recovery of consciousness and reduced ventilatory requirements, and was extubated on the second day with full neurological and cognitive recovery. Oral artemether–lumefantrine (20/120 mg twice daily for three days) was subsequently introduced. Blood and CSF cultures later yielded no growth, and the CSF viral panel was unremarkable. Empirical antimicrobials were therefore discontinued, and the patient was continued on primaquine (30 mg daily for 14 days). CVVHD was subsequently transitioned to intermittent haemodialysis

The patient achieved full neurological recovery, with normalisation of renal function, inflammatory markers, and cardiac enzymes. He was discharged in stable condition; however, long-term follow-up was not possible as he returned to his home country shortly after discharge.

3. Discussion

To the best of the authors' knowledge, this is the first documented case of P. vivax-associated cerebral malaria complicated by multi-organ dysfunction syndrome reported in Oman. This case underscores the evolving clinical profile of P. vivax, a parasite traditionally considered benign but now increasingly implicated in severe and life-threatening complications.⁹

The growing recognition of severe complications caused by P. vivax necessitates deeper investigation of its underlying pathophysiology. Unlike P. falciparum, which induces cerebral malaria through cytoadherence of parasitised erythrocytes to cerebral endothelium via receptors such as ICAM-1 and EPCR, P. vivax lacks a comparable sequestration capacity and may instead contribute to neurological manifestations through systemic inflammation, cytokine-mediated endothelial activation, and blood–brain barrier disruption.¹⁰ Elevated inflammatory markers such as tumour necrosis factor alpha and angiopoietin-2 support this hypothesis and align with the broader multi-organ dysfunction literature, which emphasises dysregulated host responses, microvascular injury, and organ cross-talk as central to multi-organ failure.^10,11,12,13 In this case, molecular or genetic characterisation of the P. vivax strain was unavailable, limiting insight into possible strain-specific virulence.

Neurological manifestations of P. vivax cerebral malaria often mimic viral or bacterial encephalitis. Cerebrospinal fluid findings are typically non-specific, and neuroimaging may initially appear normal.⁹ Polymerase chain reaction (PCR) testing for malaria offers high sensitivity (98–100%) and specificity (95–100%), though false negatives may occur in cases of very low parasitaemia.^14,15 Peripheral blood smear microscopy remains the gold standard for malaria diagnosis due to its ability to directly visualize parasites and its high specificity, often approaching 100% in expert hands.¹⁶ However, its sensitivity varies widely, ranging from 72% to over 95% in high-parasitaemia cases, but may drop significantly—sometimes to 40–50%—in patients with low parasitaemia or non-falciparum infections.^17,18 Additionally, the diagnostic accuracy of both microscopy and rapid diagnostic tests can be influenced by the timing of sample collection relative to the parasitaemic cycle.¹⁸ Early clinical suspicion and timely testing therefore remain essential, particularly in resource-limited settings where access to PCR, neuroimaging, or reliable smear analysis may be restricted, leading to potential delays or misdiagnosis.

In this case, the diagnosis of P. vivax cerebral malaria was supported by clinical presentation, peripheral blood smear showing characteristic parasite forms, and confirmatory PCR. Alternative causes, including central nervous system infections, metabolic disturbances, and toxic encephalopathies, were excluded through comprehensive investigations.

Treatment of severe malaria, irrespective of species, requires prompt parenteral therapy, with WHO recommending IV artesunate as the first-line treatment.¹⁹ In P. vivax infections, relapse prevention using primaquine or tafenoquine is essential owing to the risk of hypnozoite-mediated recurrence.⁹ The likely absence of anti-relapse therapy during initial infection in this case may have contributed to delayed severe presentation. Although emerging artesunate resistance is a growing concern, the patient's rapid clinical response suggests this was unlikely.

Multiple reports have documented P. vivax-associated cerebral malaria in adults, with outcomes ranging from full recovery to residual neurological deficits. Confirmed cases from India, Sudan, Peru, and Ethiopia show that P. vivax can cause severe disease even in immunocompetent individuals [Table 1].^{20,21,22,23,24} This case shared key features such as altered consciousness, thrombocytopenia, and multi-organ dysfunction, highlighting the parasite's potential severity in both endemic and non-endemic settings. These reports collectively challenge the long-standing benign perception of P. vivax and stress the need for clinical vigilance, particularly in returning travellers or residents from endemic regions. Beyond cerebral involvement, rare complications such as symmetrical peripheral gangrene have also been described.²⁵

Table 1.

Selected published case reports of cerebral malaria associated with P. vivax in adults.^{20,21,22,23,24}

Authors and publication year	Country (Location)	Age	Gender	Travel history or endemic exposure	Symptom duration prior to admission	ICU/Mechanical ventilation	Treatment and Outcome
Sarkar et al.20 (2008)	India (Varanasi)	3 adult males (>18)	Male (all)	Residents of endemic area	>4 days fever prior to presentation	Yes (ICU for all; no mechanical ventilation)	IV Artesunate × 4 days + supportive care, then Primaquine × 14 days. Recovery with no neurological deficits.
Gupta et al.21 (2016)	India (Manipal)	19	Male	Resident of endemic area	Not stated (presented with acute febrile coma)	Yes (ICU for coma)	IV Artesunate + supportive care. Full recovery (PCR-confirmed P. vivax mono-infection).
Mukhtar et al.22 (2019)	Sudan (Khartoum)	60	Male	Resident of endemic area	2 days fever; coma developed 2 days after admission	Yes (ICU; no mechanical ventilation reported)	IV Quinine (10 mg/kg × 10 days) + Primaquine (15 mg × 14 days). Resolved within 48 h; no sequelae.
Paredes-Obando et al.23 (2022)	Peru (Loreto)	30	Male	Resident of Amazon endemic area	14 days of fever; seizures (5–6/day); 2 days unconscious	Yes (ICU care; no mechanical ventilation reported)	IV Artesunate × 5 days + IV Clindamycin × 5 days + RBC transfusion, then Primaquine × 7 days. Survived with left leg monoparesis.
Habtemariam et al.24 (2024)	Ethiopia (Mizan-Tepi)	31, 28, 42	2 Male, 1 Female	Residents of endemic area	∼2 days of symptoms before presentation	Yes (ICU for all; 2 required mechanical ventilation)	IV Artesunate × 4–5 days + supportive care, including anticonvulsants and mechanical ventilation. All survived with no residual deficits.

ICU = intensive care unit; IV = intravenous; PCR = polymerase chain reaction.

This case reinforces the importance of clinical vigilance in non-endemic settings, where malaria may be overlooked in returning travellers presenting with unexplained encephalopathy. It further highlights the public health implications of imported P. vivax infections in regions such as Oman, emphasising the need for travel-based screening and early diagnostic consideration. As this case involved an adult treated in a tertiary centre with advanced care, the management may not be generalisable to resource-limited environments or to other groups such as children or immunocompromised individuals. Under-recognition and underreporting of P. vivax-related complications in non-endemic regions may underestimate their true incidence, while publication bias could overrepresent severe presentations. In this case, long-term follow-up was not feasible as the patient returned to his home country shortly after discharge. Future studies should explore strain-specific virulence, enhance diagnostic tools in low-incidence settings, and assess long-term neurological and systemic outcomes in survivors.

4. Conclusion

Plasmodium vivax, though historically regarded as a benign malaria species, can cause life-threatening complications such as cerebral malaria and multi-organ failure. In non-endemic regions such as Oman, prompt recognition and management of imported cases are essential to prevent adverse outcomes and possible re-establishment of local transmission. This case emphasises the importance of considering P. vivax infection in patients presenting with febrile encephalopathy and a recent history of travel to endemic areas.

Authors' Contribution

Saba M. Al Kindi: Data Curation, Resources, Writing - Original Draft, Writing - Review & Editing, Visualization, Project Administration. Shabnam Chhetri: Conceptualization. Zahrah Z. Al Aamri: Investigations, Writing - Review & Editing. Suchata D. Dhuri: Investigation. Zakariya Y. Al Balushi: Supervision, Writing - Review & Editing. Faryal Khamis: Supervision, Writing - Review & Editing.

Ethics Statement

Consent for the publication of this case report was obtained from the patient.

Data Availability

Data is available upon reasonable request from the corresponding author.