What is the management of amoebic meningoencephalitis due to Naegleria fowleri?

Management of Amoebic Meningoencephalitis Due to Naegleria fowleri

Primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri requires immediate treatment with a multi-drug regimen including amphotericin B (intravenous and intrathecal) combined with miltefosine, along with aggressive supportive care to improve chances of survival. 1

Clinical Features and Diagnosis

• PAM presents with symptoms mimicking bacterial meningitis but progresses rapidly with death typically occurring within 5 days if untreated 1, 2
• Initial symptoms include:
  • Change in taste or smell 2-5 days after exposure to warm freshwater 2
  • Headache, fever, nausea, vomiting 2
  • Stiff neck and photophobia 2
• Progressive symptoms include:
  • Meningismus, papilledema, nystagmus 2
  • Cranial nerve abnormalities, ataxia 2
  • Abnormal behavior, hemiparesis 2
• Risk factors include swimming in warm freshwater, nasal irrigation with untreated water, ritual nasal ablution 2
• Pre-mortem diagnosis is confirmed in only 27% of cases 1

Treatment Regimen

First-Line Treatment

• Amphotericin B (both intravenous and intrathecal administration) combined with other agents 3, 1
• Miltefosine should be added as it has been associated with improved survival in recent cases 1, 4
• Treatment must begin immediately upon suspicion of PAM, before confirmation of diagnosis 1

Recommended Multi-Drug Regimen

1. Amphotericin B (intravenous and intrathecal) 3, 1
2. Miltefosine 1, 5
3. Azithromycin 4, 6
4. Fluconazole (though posaconazole may be superior if available) 7, 8
5. Rifampin 3, 7

Adjunctive Treatments

• Dexamethasone to reduce cerebral edema 7, 6
• Consider controlled hypothermia to mitigate cerebral edema 4
• Placement of intraventricular shunt if needed for increased intracranial pressure 4
• Aggressive supportive care 1

Alternative Agents with Evidence of Efficacy

• Chlorpromazine has shown promising results in experimental models with 75% survival rate in mice 5
• Posaconazole appears superior to fluconazole in both in vitro and in vivo studies and should be considered if available 8
• Minocycline may have synergistic effects with amphotericin B 6

Prognosis and Monitoring

• PAM has an extremely high mortality rate exceeding 95% without treatment 1, 2
• Before 2013, only three survivors had been reported among 135 known cases 1
• Rapid diagnosis and immediate treatment initiation are the most critical factors for survival 1
• Monitor for signs of increased intracranial pressure and manage aggressively 1, 4

Prevention

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

Important Considerations

• PAM should be included in the differential diagnosis for any patient with rapidly progressive meningoencephalitis following water exposure or nasal lavage 1, 2
• The mortality rate is extremely high, and treatment must be initiated immediately upon suspicion 1
• Combination therapy is more effective than monotherapy 7, 4, 6