Nasal irrigation is used to remove dirt, dust, pollen and other debris from the nasal passage. It is also used to loosen thick mucus which may help to relieve the nasal symptoms of allergies, colds, and flu. Although largely considered safe and effective, nasal irrigation has been  linked to two deaths in the US state of Louisiana in 2011. These deaths were attributed to an infection known as primary amoebic meningoencephalitis (PAM). PAM is a very rare infection caused by the thermophilic amoeba, Naegleria fowleri. Even with prompt treatment, PAM has a high mortality rate. Therefore, prevention of infection is critical.

Naegleria fowleri lives freely in Australia’s freshwater rivers and lakes, as well as hot springs and non-chlorinated or under-chlorinated pools. However, the Australian drinking water supply is adequately disinfected using chlorine. First identified in South Australia in the 1960s, Naegleria fowleri has been responsible for some deaths in Australia including one in April 2015. Northern Territory, Western Australia, and South Australia still regularly test for Naegleria fowleri, especially during the summer months. The risk of this amoeba colonising the water supply is particularly high when water is piped overland for hundreds of kilometres. This heats the water and increases the amoeba’s resistance to chlorine, possibly due to biofilm formation.

Naegleria fowleri cannot survive in stomach acid. Therefore, infections are not associated with the drinking of contaminated water. For infection to occur, contaminated water must enter the nose, where it can then travel up the olfactory pathway to the brain.

PAM often presents with symptoms suggestive of viral meningitis. Symptoms may include a headache, fever, loss of appetite, vomiting, stiff neck, altered mental state, seizures, hallucinations, and coma. These symptoms typically appear between two to 15 days after exposure. PAM is almost always fatal, with death occurring an average of 5.3 days after symptoms appear.

Due to the extremely poor prognosis of PAM, treatment should be prompt and aggressive. Robust treatment protocols are not available due to the rarity of this condition. However, the US Centres for Disease Control and Prevention (CDC) recommend the following therapy based on two of the very few well-documented cases of PAM survival:

  • Dexamethasone to control cerebral oedema
  • Amphotericin B for its amoebicidal activity
  • Rifampicin as an adjunct at a dose of 10mg/kg/day
  • Fluconazole to rule out and prevent opportunistic fungal infections
  • Azithromycin to work in synergy with amphotericin B
  • Miltefosine.

Miltefosine is an alkyl-lysophospholipid analogue drug and a protein kinase B inhibitor. Originally developed for the treatment of breast cancer, miltefosine was later found to be an effective antileishmanial agent. Although the mechanism of action is not well understood at this stage, miltefosine has demonstrated significant efficacy in the treatment of protozoal infections and is presently approved for leishmaniasis by the US Food and Drug Administration (FDA). Miltefosine is not currently registered for use in Australia and may only be accessed through the Special Access Scheme (SAS).

Even with aggressive therapy, the prognosis is still extremely poor for patients diagnosed with PAM. Therefore, prevention is critical. Care must be taken when using nasal irrigation solutions, particularly those that require preparation by the patient. Products such as Neilmed® Sinus Rinse, Neti Pots, and Flo® Sinus Care, are commonly prescribed postoperatively. Patients must be instructed only to prepare the irrigation solution using freshly boiled and cooled tap water, or sterile or distilled water.

Additional precautions recommended to prevent exposure include:

  • Avoid jumping or diving into bodies of warm fresh water or thermal pools
  • Do not submerge your head in spas, thermal pools, or warm freshwater bodies
  • Allow wading pools to dry in the sun after each use
  • Ensure swimming pools and spas are adequately chlorinated and well maintained
  • Flush stagnant water from hoses before allowing children to play with hoses or sprinklers
  • If using non-chlorinated or under-chlorinated water:
    • Do not allow water to enter the nose
    • Supervise children playing with hoses or sprinklers and teach them not to squirt water up their nose
  • Always ensure that water to be used for nasal irrigation is sterile or freshly boiled and cooled.

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References:

  1. Aichelburg AC, Walochnik J, Assadian O, Prosch H, Steuer A, Perneczky G, et al. Successful treatment of disseminated Acanthamoeba sp. infection with miltefosine. Emerg Infect Dis. 2008; 14(11): 1743-6.
  2. Centers for Disease Control and Prevention. Naegleria fowleri – primary amebic meningoencephalitis (PAM). Atlanta: CDC; 2015.
  3. Cope J, Roy S, Yoder JS, Beach M. Miltefosine for treatment of free-living ameba infections caused by Acanthamoeba species, Balamuthia mandrillaris, and Naegleria fowleri. Presented at: San Francisco, IDWeek 2013.
  4. Food and Drug Administration. Is rinsing your sinuses safe? Silver Spring: FDA; 2012.
  5. Goswick SM, Brenner GM. Activities of therapeutic agents against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis. J Parasitol. 2003; 89(4): 837-42.
  6. Medscape: Miltefosine (Impavido). New York: Medscape; 2014.
  7. Queensland Health. Naegleria fowleri: Qs and As. Brisbane: Queensland Government; 2010.
  8. Vargas-Zepeda J, Gomez-Alcala AV, Vasquez-Morales JA, Licea-Amaya L, De Jonckheere JF, Lares-Villa F. Successful treatment of Naegleria PAM using IV amphotericin B, fluconazole, and rifampin. Arch Med Res. 2005; 36(1): 83-6.
  9. Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol. 2007; 50(1): 1-26.
  10. Yoder JS, Eddy BA, Visvesvara GS, Capewell L, Beach MJ. The epidemiology of primary amoebic meningoencephalitis in the USA, 1962-2008. Epidemiol Infect. 2010; 138(7): 968-75.

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