What is the treatment for Amoebic encephalitis?

Amoebic Encephalitis: Symptoms, Investigations, and Treatment

Clinical Presentation

Amoebic encephalitis presents as a fulminant, rapidly progressive meningoencephalitis that is clinically indistinguishable from bacterial meningitis but does not respond to standard antibiotics. 1, 2

Key Symptoms

• Severe headache and vomiting occurring abruptly 3
• Fever with rapid onset 3, 4
• Altered mental status ranging from mild confusion to coma 3, 5
• Seizures may occur early in the disease course 3
• Ataxic gait and other focal neurological signs 3
• Rapid progression to death within a median of 5 days after presentation if untreated 1, 2

Critical Epidemiological Clues

• Recent freshwater exposure (swimming in warm standing water, lakes, or hot springs) during summer months 1, 2, 3, 6
• Nasal water exposure through sinus lavage with neti pots, ritual nasal ablution, or municipal water supplies 1, 2
• Predominantly affects children and young adults, though cases occur across all ages 4, 5

Diagnostic Investigations

Cerebrospinal Fluid Analysis

Immediate examination of fresh CSF is the most critical diagnostic step. 4, 6

• Direct microscopic examination of fresh, warm CSF reveals motile trophozoites 3, 4
• Wright's or Gram's stain can identify amoebae 4
• CSF profile mimics bacterial meningitis: purulent appearance with elevated white cells, but bacteria are absent on Gram stain 4, 5
• Diagnosis is confirmed pre-mortem in only 27% of cases, emphasizing the need for high clinical suspicion 1, 2

Confirmatory Testing

• Culture on non-nutrient agar plates covered with Escherichia coli to identify vegetative and cystic forms 3
• Enflagellation experiments in distilled water at specific temperatures 3
• PCR amplification and sequencing of internal transcribed spacers (ITS) including 5.8S rDNA for genotype determination 3
• Indirect immunofluorescence using specific antibodies 3

Neuroimaging

• Brain CT or MRI typically shows severe cerebral edema 3, 5
• Imaging findings are nonspecific but help assess disease severity and complications 5

Treatment Approach

Primary Amoebic Meningoencephalitis (Naegleria fowleri)

Immediate initiation of a multi-drug regimen including miltefosine is essential for survival, as this agent has been associated with the only recent survivors of this previously uniformly fatal disease. 1, 2

Recommended Regimen

According to IDSA guidelines, amphotericin B (intravenous and intrathecal) combined with rifampin and other agents should be considered 1. Based on recent survival cases, the optimal regimen includes:

• Miltefosine (critical component associated with survival) 1, 2
• Amphotericin B administered intravenously, intrathecally, and when possible, intraventricularly 3, 4, 6
• Fluconazole intravenously 3
• Rifampin orally 3, 4
• Dexamethasone for cerebral edema management 3

Critical Treatment Principles

• Start treatment immediately upon suspicion without waiting for definitive diagnosis, as mortality exceeds 95% and death occurs within 5 days 1, 2
• Early initiation is the single most important factor determining survival 2, 3
• Treatment must begin within hours of presentation for any chance of survival 2, 5

Granulomatous Amoebic Encephalitis (Acanthamoeba and Balamuthia mandrillaris)

These infections follow a more subacute course compared to PAM.

Acanthamoeba Treatment

Trimethoprim-sulfamethoxazole plus rifampin plus ketoconazole can be considered, or alternatively fluconazole plus sulfadiazine plus pyrimethamine 1

Balamuthia mandrillaris Treatment

Pentamidine combined with a macrolide (azithromycin or clarithromycin), fluconazole, sulfadiazine, flucytosine, and a phenothiazine can be considered 1, 7

Critical Pitfalls to Avoid

• Misdiagnosing as bacterial meningitis and treating only with antibiotics, which are completely ineffective 1, 2, 5
• Failing to examine fresh CSF immediately for motile trophozoites 4
• Delaying treatment while awaiting confirmatory testing – treatment must begin on clinical suspicion alone 2
• Not considering amoebic encephalitis in patients with purulent meningitis where bacteria are not evident 4, 5
• Overlooking water exposure history, particularly freshwater swimming or nasal irrigation 1, 2

Emerging Epidemiological Considerations

Cases are increasingly reported in northern US states, potentially related to climate change allowing growth of this thermophilic organism in previously cooler regions. 1, 2 Clinicians in all geographic areas should maintain awareness of this diagnosis, particularly during summer months when warm water temperatures favor amoebic proliferation 1, 2, 5.