Can cerebral malaria patients have aseptic meningitis with cerebrospinal fluid (CSF) pleocytosis?

Cerebral Malaria and CSF Pleocytosis

Cerebral malaria patients rarely present with CSF pleocytosis, and when pleocytosis is found, clinicians should strongly consider alternative or concurrent diagnoses. 1

Typical CSF Findings in Cerebral Malaria

• CSF in cerebral malaria is typically normal or shows minimal changes without significant pleocytosis 1
• When evaluating patients with suspected cerebral malaria, CSF analysis is primarily performed to rule out other causes of altered mental status, particularly bacterial meningitis 2
• The absence of CSF pleocytosis in a patient with fever and altered mental status from a malaria-endemic area should increase suspicion for cerebral malaria 2

Differential Diagnosis When CSF Pleocytosis is Present

• When CSF pleocytosis is found in a patient with malaria parasitemia, consider:
  • Concurrent bacterial meningitis (requiring separate antimicrobial treatment) 1
  • Viral meningitis (particularly enteroviral during endemic seasons) 3
  • Other tropical diseases that can cause meningitis (angiostrongyliasis, gnathostomiasis, schistosomiasis) 1
  • Aseptic meningitis from other causes 4

Diagnostic Approach

• In patients returning from malaria-endemic areas with fever and neurological symptoms:

  • Perform rapid blood malaria antigen tests and examine three thick and thin blood films for malaria parasites 1
  • Look for thrombocytopenia or malaria pigment in neutrophils and monocytes as potential clues to malaria, even if initial blood films are negative 1
  • Perform lumbar puncture to analyze CSF for cell count, protein, glucose, and cultures 2

• CSF analysis helps distinguish between cerebral malaria and meningitis:

  • CSF leukocyte count is the single most significant factor in determining the correct diagnosis 2
  • Without CSF analysis, physicians cannot reliably discriminate between cerebral malaria and meningitis 2

Management Implications

• If cerebral malaria is suspected despite the presence of CSF pleocytosis:
  • Do not delay antimalarial treatment while awaiting CSF analysis results, as prompt treatment is essential for reducing mortality 1
  • Intravenous artesunate is the first-line treatment for cerebral malaria, regardless of CSF findings 1
  • Consider empiric coverage for bacterial meningitis until cultures return negative, as co-infection is possible 1

Important Considerations

• Meningitis without pleocytosis is rare but does occur, with bacterial causes being most common 5
• Blood cultures should be obtained as an adjunct diagnostic test when evaluating patients with suspected meningitis, as they may identify the causative organism in up to 71% of cases 5
• In aseptic meningitis, CSF typically shows:
  • White cell count rarely exceeding 2000 cells/mm³ 3
  • Mildly raised protein levels 3
  • Normal or slightly decreased glucose 3
  • Normal or slightly low CSF/plasma glucose ratio 3

Clinical Pearls and Pitfalls

• The presence of CSF pleocytosis in a patient with confirmed malaria should prompt a thorough investigation for concurrent infections 1
• Mortality rates differ significantly between cerebral malaria (14.9%) and bacterial meningitis (29.6%), highlighting the importance of correct diagnosis 2
• Neuroinflammation in cerebral malaria involves different inflammatory markers than other neurological infections, with elevated osteopontin in both plasma and CSF being a potential distinguishing feature 6