What is the treatment for amoebic meningoencephalitis?

Treatment of Primary Amoebic Meningoencephalitis (PAM)

The most effective treatment for Primary Amoebic Meningoencephalitis (PAM) is a multi-drug regimen that includes amphotericin B (intravenous and intrathecal) combined with miltefosine, along with aggressive supportive care. 1

Disease Overview

Primary Amoebic Meningoencephalitis (PAM) is a fulminant, almost invariably fatal necrotizing brain infection caused by the free-living amoeba Naegleria fowleri. Key characteristics include:

• PAM has an extremely high mortality rate exceeding 95%, with death typically occurring within 5 days of presentation due to cerebral edema 1
• The clinical presentation mimics bacterial meningitis but does not respond to standard antibiotic therapy 1
• N. fowleri thrives in warm freshwater, with most cases occurring during summer months among individuals with recreational exposure to standing bodies of freshwater 1
• Transmission occurs through the nasal route, with the amoeba penetrating the olfactory mucosa and cribriform plate to reach the brain 2

Diagnostic Considerations

Early diagnosis is critical for survival. Diagnostic approaches include:

• Examination of cerebrospinal fluid (CSF) for motile amoebae using wet preparations or Wright-Giemsa stained specimens 3, 2
• PAM should be suspected in all cases of purulent meningitis where bacteria are not evident in the CSF 2
• Pre-mortem diagnosis is confirmed in only 27% of cases 1

Treatment Regimen

First-Line Therapy

• Amphotericin B (intravenous and intrathecal) combined with other agents 1
• Miltefosine, now commercially available in the USA, should be added to the regimen as it has been associated with survival in recent cases 1, 3
• Treatment should begin immediately upon suspicion of PAM, as outcome is contingent on early initiation 1

Complete Therapeutic Regimen

• Amphotericin B administered both intravenously and intrathecally 1, 4
• Miltefosine (investigational medication available through the CDC) 1, 3
• Additional agents that have shown benefit when combined with the above:
  • Azithromycin 3
  • Rifampin 3, 2
  • Fluconazole 3
  • Voriconazole has been used in a recent successful case 5

Adjunctive Measures

• Aggressive management of increased intracranial pressure:
  • Placement of intraventricular shunt if necessary 3
  • Controlled hypothermia to mitigate cerebral edema 3
• Dexamethasone to reduce inflammation 3

Prognosis and Outcomes

• Before 2013, only three survivors had been reported among 135 known cases 1
• Recent successful treatments have included miltefosine in the regimen 1, 5
• Rapid diagnosis and immediate treatment initiation are the most critical factors for survival 1, 3

Prevention

• Avoid swimming in warm freshwater bodies, particularly during summer months 1
• Avoid nasal water exposure during activities in freshwater 1
• Use nose clips when swimming in freshwater 2
• Avoid nasal irrigation with untreated tap water (including neti pots) 1

Important Considerations

• PAM should be included in the differential diagnosis for any patient with rapidly progressive meningoencephalitis following water exposure or nasal lavage 1
• Contact the CDC immediately when PAM is suspected to obtain miltefosine and consultation 3
• Treatment must be initiated before confirmation of diagnosis due to the rapid progression of the disease 1, 3