What is the incidence of cerebrospinal fluid (CSF) pleocytosis in malaria?

Incidence of CSF Pleocytosis in Malaria

CSF pleocytosis is uncommon in malaria, with only isolated case reports documenting this finding, suggesting an incidence of less than 5% in patients with cerebral malaria.

Pathophysiology and Occurrence

• Cerebral malaria is primarily characterized by sequestration of parasitized red blood cells in the cerebral microvasculature, not by direct invasion of the cerebrospinal fluid or brain parenchyma 1.
• The central neuropathological feature of cerebral malaria is the preferential sequestration of parasitized red blood cells in cerebral microvasculature, which typically does not cause significant inflammation in the CSF 1.
• CSF pleocytosis is not a typical feature of cerebral malaria, as the parasite remains intravascular and does not directly invade the central nervous system 2.

Evidence from Clinical Studies

• In a Korean study of 44 patients with Plasmodium vivax malaria, CSF studies were performed in five cases, and only one (20%) showed pleocytosis in the CSF 3.
• The presence of CSF pleocytosis in malaria cases is rare enough that when it occurs, clinicians should consider alternative or concurrent diagnoses 4.
• When CSF pleocytosis is found in a patient with suspected malaria, other causes of meningitis or encephalitis should be ruled out, as this is not a typical finding in uncomplicated malaria 4.

Diagnostic Considerations

• When evaluating patients returning from malaria-endemic areas, rapid blood malaria antigen tests and three thick and thin blood films should be examined for malaria parasites, regardless of CSF findings 4.
• Thrombocytopenia or malaria pigment in neutrophils and monocytes may be clues to malaria, even if blood films are negative 4.
• The presence of PfHRP-2 (Plasmodium falciparum histidine-rich protein-2) in the CSF may indicate increased blood-brain barrier permeability in severe cerebral malaria cases, but this does not necessarily correlate with pleocytosis 5.

Differential Diagnosis

• CSF pleocytosis is more commonly associated with other conditions such as viral encephalitis, bacterial meningitis, and non-infectious neurological diseases 6.
• In a cross-sectional study of 262 patients with CSF pleocytosis, only 40.5% were caused by CNS infections, while 30.2% were due to non-infectious neurological diseases 6.
• When CSF pleocytosis is found in a patient with fever returning from an endemic area, other tropical diseases that can cause eosinophilic meningitis should be considered, such as angiostrongyliasis, gnathostomiasis, and schistosomiasis 4.

Management Implications

• If cerebral malaria is suspected despite the presence of CSF pleocytosis, antimalarial treatment should still be initiated promptly, as cerebral malaria is a medical emergency 7.
• Intravenous artesunate is the first-line treatment for cerebral malaria, regardless of CSF findings 8.
• In patients with both malaria and CSF pleocytosis, consider empiric coverage for bacterial meningitis until cultures return negative, as co-infection is possible 7.

Clinical Pearls and Pitfalls

• The absence of typical CSF pleocytosis does not rule out cerebral malaria; in fact, normal CSF findings are more consistent with cerebral malaria than significant pleocytosis 2.
• When CSF pleocytosis is found in a patient with malaria, consider the possibility of a concurrent infection or an alternative diagnosis 4.
• Leukocyte counts above 100/μl in CSF are more commonly caused by CNS infections other than malaria, whereas lower counts have a broader differential diagnosis 6.
• Do not delay antimalarial treatment while awaiting CSF analysis results if cerebral malaria is suspected, as prompt treatment is essential for reducing mortality 4.