Can malaria cause aseptic meningitis?

Malaria and Aseptic Meningitis

Malaria does not directly cause aseptic meningitis, but it can be associated with neurological complications including a post-malaria neurological syndrome that may present with aseptic meningitis features. 1, 2

Neurological Manifestations of Malaria

• Cerebral malaria, especially caused by Plasmodium falciparum, can present with neurological symptoms including meningism (signs of meningeal irritation without actual meningitis) 3
• Common neurological manifestations include drowsiness, mental confusion, coma, and seizures 3
• Cerebral malaria is confined to the vasculature of the brain as the parasite does not directly invade brain tissue but resides in erythrocytes within blood vessels 4
• Post-Malaria Neurological Syndrome (PMNS) can occur 1-3 weeks after successful treatment of P. falciparum malaria and may present with features of aseptic meningitis 2

Diagnostic Considerations

• When evaluating patients with fever and neurological symptoms returning from endemic areas, both malaria and meningitis should be considered in the differential diagnosis 5, 3
• For suspected malaria: Three thick films/rapid diagnostic tests over 72 hours should be performed 1
• For suspected meningitis: Lumbar puncture should be performed if there are no contraindications 1, 5
• In patients with altered consciousness or repeated convulsions, a lumbar puncture should be performed if possible to distinguish between cerebral malaria and bacterial or viral meningitis 3
• The presence of Plasmodium on blood smears does not prove that malaria is the cause of febrile illness with meningism, even in endemic areas 3

Post-Malaria Neurological Syndrome (PMNS)

• PMNS can present as aseptic meningitis approximately 1-3 weeks after complete remission from P. falciparum malaria 2
• Four main clinical patterns of PMNS have been identified:
  • "Classical" PMNS (37% of cases) 2
  • Delayed cerebellar ataxia (36% of cases) 2
  • Acute inflammatory demyelinating polyneuropathy (18% of cases) 2
  • Acute disseminated encephalomyelitis (ADEM)-like form (8% of cases) 2
• CSF analysis in PMNS typically reveals pathological findings consistent with aseptic meningitis 2
• An autoimmune mechanism is the most supported pathogenic hypothesis for PMNS 2

Differential Diagnosis

• Aseptic meningitis syndrome can be caused by various pathogens including viruses (most commonly enteroviruses), unusual bacteria, fungi, and parasites 6, 7
• In returning travelers with neurological symptoms, other causes to consider include:
  • Viral infections (e.g., varicella zoster virus reactivation has been reported following P. falciparum malaria) 8
  • Bacterial meningitis 5
  • Drug-induced aseptic meningitis 7

Management Approach

• If cerebral malaria seems likely, and there will be a delay in obtaining the malaria film result, anti-malarial treatment should be considered and specialist advice obtained 9, 5
• First-line treatment for cerebral malaria is intravenous artesunate at 2.4 mg/kg at 0,12,24, and 48 hours 5
• For PMNS presenting as aseptic meningitis, high-dose steroids have been shown to be effective 2
• Steroids should NOT be used for acute cerebral malaria as they have an adverse effect on outcome 5, 3
• Monitor for complications including seizures, hypoglycemia, and fluid imbalances 5

Prognosis

• Most cases of PMNS resolve without specific treatment, though severe cases may require immunomodulatory therapy 2
• Approximately 10% of African children with cerebral malaria develop persisting neurological sequelae 9
• Even higher proportions may be left with learning and language disorders 9
• PMNS is likely underreported due to frequent misdiagnosis 2

In summary, while malaria itself does not directly cause aseptic meningitis, post-malaria neurological syndrome can present with aseptic meningitis features. Careful diagnostic evaluation is essential to distinguish between cerebral malaria, PMNS, and other causes of neurological symptoms in patients with malaria.