Diagnostic Approach for Amebic Meningitis
Immediately obtain CSF for wet mount examination to visualize motile trophozoites, perform Gram stain and culture, and send specimens for PCR testing to the CDC or reference laboratory, while simultaneously initiating empiric treatment without waiting for confirmatory results. 1, 2, 3
Immediate CSF Analysis (Do Not Refrigerate Specimens)
Critical Microscopy
- Examine fresh, warm CSF immediately using wet mount preparation to identify motile ameboid trophozoites (approximately 10-25 micrometers in size with blunt pseudopodia and directional movement). 1, 4, 5
- Perform Gram stain, which will be negative for bacteria but may reveal trophozoites. 1
- The CSF profile mimics bacterial meningitis: elevated opening pressure (>20 cm H₂O), high white blood cell count with neutrophil predominance (median 2,400 cells/μL, range 5-26,000), low glucose (median 23 mg/dL), and elevated protein (median 365 mg/dL). 4
- Specimens must not be refrigerated, as cold temperatures kill the organisms and prevent visualization. 1
Confirmatory Testing
- Send CSF and brain tissue (if available) for multiplex real-time PCR to identify Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris simultaneously. 1, 6, 7
- PCR is available through the CDC (770-488-7100,24/7) and select reference laboratories with turnaround time under 5 hours. 1, 6, 4
- Request immunofluorescence assay on CSF or tissue specimens for species confirmation. 1, 7
- The flagellate transformation test (placing organisms in distilled water to induce flagella formation) confirms Naegleria genus. 5
Culture Considerations
- Attempt culture of CSF or brain tissue on non-nutrient agar plates seeded with Escherichia coli, but recognize that Balamuthia mandrillaris requires specialized cell culture and will not grow on standard agar. 1
- Culture results take days and should never delay treatment initiation. 1, 3
Blood and Imaging Studies
- Obtain blood cultures before antibiotics, though they will be negative in amebic meningitis (helps exclude bacterial co-infection). 1, 8
- Order MRI with and without IV contrast, which shows characteristic hemorrhagic necrosis in gray matter of basal brain structures, olfactory bulbs, and cerebral hemispheres with obliteration of subarachnoid cisterns due to severe cerebral edema. 2
- CT imaging is less sensitive but may show cerebral edema and obliterated cisterns. 2, 4
Clinical Recognition Triggers
- Suspect amebic meningitis in any patient with purulent meningitis that fails to respond to standard antibiotics, especially with recent freshwater exposure (swimming, diving, water sports) 2-5 days before symptom onset. 2, 3, 4
- Additional risk factors include nasal irrigation with untreated tap water, neti pot use, ritual nasal ablution, or playing on lawn water slides connected to municipal water. 2, 3
- Early symptoms include altered taste or smell, severe frontal headache, fever, neck stiffness, and photophobia progressing rapidly to altered mental status, seizures, and coma. 2, 3, 4
Critical Diagnostic Pitfalls
- Only 27% of PAM cases are diagnosed before death because clinicians fail to consider the diagnosis and treat empirically for bacterial meningitis alone. 2, 3, 4
- The disease progresses to death within 5 days of presentation (median) if untreated, making any diagnostic delay catastrophic. 2, 3, 4
- Mortality exceeds 95%, and survival depends entirely on immediate initiation of multi-drug therapy including IV and intrathecal amphotericin B plus miltefosine before laboratory confirmation. 2, 3, 4
- Do not wait for culture results or PCR confirmation to start treatment—begin therapy immediately upon clinical suspicion based on exposure history and CSF findings. 1, 2, 3
- Geographic range is expanding northward due to climate change; cases now occur in Minnesota, Kansas, and Indiana, not just southern states. 2, 4