News reports about deaths from PAM caused by N fowleri have heightened concern about this disease, and an updated approach to risk awareness, diagnosis and treatment is needed.³ In 2011, three deaths from N fowleri were reported in the United States. Of particular concern are two recent deaths after infection resulting from improper use of neti pots.

Pathophysiology

N fowleri is a thermotolerant free-living amoeba found in fresh water.⁴ It causes a rare and sporadic acute central nervous system infection that usually results in the death of the host within 5 to 10 days.⁵ The organism was first implicated as a disease-causing pathogen in the 1960s, and most of the documented infections in humans have occurred after swimming in warm water infested with the parasite.

The Naegleria amoeba has three forms in its life cycle: cystic, in which the amoeba is protected from poor environmental conditions; flagellate, in which it swims and seeks nutrients; and trophozoite, which is the active, feeding stage. The trophozoite form causes infection in humans. The trophozoites penetrate the nasopharyngeal mucosa and migrate along the olfactory nerves, eventually penetrating the brain.⁶ Human-to-human transmission has never been reported.

The initial stages of infection begin with the secretion of mucus that traps the trophozoites. However, the naegleria trophozoites are able to secrete a protein that is mucinolytic, allowing some trophozoites to reach, adhere to and penetrate the epithelium.² The trophozoites penetrate the submucosal nervous plexus, infiltrate the cribiform plate and reach the subarachnoid space.

Glucose and protein in the cerebrospinal fluid (CSF) support the growth and multiplication of the amoeba. The high oxygen content in the CSF and the brain also facilitates amoeba growth. The trophozoites enter the ventricular system where they lyse and ingest erythrocytes and nerve cells, with resultant purulent meningitis and encephalitis.⁷ Only trophozoites are found in pathologic lesions in humans, but it is conceivable that N fowleri cysts could be inhaled and then turn into trophozoites in the warm, moist environment of the nasal mucosa.⁷ Due to the destruction of brain tissue and the brain necrosis it causes, N fowleri is known as the "brain-eating amoeba."⁸

Incidence and Etiology

N fowleri is common in fresh water and in soil. Both pathogenic and nonpathogenic species have been isolated from the environment, but what differentiates the two is unclear.⁷ Between 2000 and 2010, N fowleri killed 32 people in the United States. As of 2006, 189 cases worldwide had been recorded in the medical literature, and 91 occurred in the United States. Underdiagnosis is likely, and the true incidence is likely higher than estimated. Most cases are diagnosed after the patient dies, and many countries have low autopsy rates.¹ The difficult nature of making a definitive diagnosis contributes to decreased incidence.⁵

Men are affected three times more often than women, probably reflecting a greater exposure risk rather than a true gender predisposition to infection.⁵

Humans come into contact with the amoeba primarily by swimming or bathing in warm fresh water, ditches, lakes or improperly maintained or unchlorinated swimming pools.⁹ Outbreaks also have been linked to increased in water temperature during hot weather.⁴ Infection caused by exposure to well water,¹⁰ ritual cleansing involving flushing of the sinuses,⁴ and the use of tap water in neti pots⁸ have also been reported. Infection results when the amoeba is introduced to the nares, not from drinking the water.

History and Physical Examinations

Provider awareness of PAM and a patient history of freshwater exposure are essential to diagnosis, because no distinctive clinical features differentiate PAM from other meningoencephalitides.¹ Symptoms begin after a 3- to 7-day incubation period. Infections caused by N fowleri tend to progress rapidly. Patients who develop N fowleri meningoencephalitis may have an immunoglobulin IgA deficiency.⁷ PAM presents in a similar fashion to acute bacterial meningitis, but because it is much less common than typical meningitis, the diagnosis may be missed. Any patient with a history of recent exposure to warm fresh water should suggest the possibility of amoebic meningoencephalitis. Prompt examination of the cerebrospinal fluid for N fowleri is essential.⁵

The typical patient presenting with PAM is a previously healthy person. Early symptoms are abrupt and easily mistaken for a viral illness. Presenting symptoms include sore throat, headache, nausea, vomiting, malaise and fever. Typical meningitis symptoms such as irritability, hallucinations, meningismus, cerebellar ataxia and cranial nerve palsies may also appear early in the disease process. Focal neurologic deficits are usually absent. Another clue to diagnosis is altered taste and smell sensation, probably due to olfactory nerve involvement. As the disease progresses, seizures progressing to coma usually lead to death within 10 days.⁵

Differential diagnoses to be considered include acute bacterial meningitis, herpes simplex virus-1 encephalitis (HSV-I), and viral or fungal meningitis. The diagnosis is made by examination of CSF wet mounts for motile trophozoites; however, failure to visualize these amoebas is not exclusive and the diagnosis is often missed when Naegleria organisms are mistaken for atypical mononucleocytes.⁵ CSF findings include low glucose levels, high protein levels, and high white blood cell and neutrophil counts. Gram stain is negative for bacteria. Postmortem pathologic changes include acute hemorrhagic necrotizing meningoencephalitis with purulent exudates in the brain, brainstem and cerebellum.⁵

Treatment

Early intervention in N fowleri infection is imperative for survival, and the key to diagnosis is provider awareness and clinical suspicion. Only 10 survivors have been reported in the literature.⁵ A successful case in Mexico involved simultaneous treatment with IV and intrathecal amphotericin B, IV and intrathecal miconazole and oral rifampin. Amphotericin B is the firstline treatment for PAM.⁶ Miconazole appears to have a synergistic effect with the amphotericin,⁶ but the risk of kidney impairment is a drawback to use of amphotericin B.⁶ The surviving patient was discharged home after 23 days and had no sequelae 12 months post-treatment.⁶

Current research is focusing on a rapid diagnostic test and on vaccination.¹¹

Prevention and Education

It is difficult to prevent exposure to this common organism, but infection with N fowleri is rare. The CDC recommends avoidance of swimming in lakes epidemiologically associated with this disease and blowing the nose after swimming to remove any N fowleri that may have been forcefully inhaled. The use of nose plugs or holding the nose when jumping into warm fresh water may reduce risk.¹²

The CDC also recommends that people who participate in fresh water activities avoid these when water temperature is high. N fowleri proliferate when water temperatures exceed 30° C.¹

In 2011, two deaths from this amoeba were reported in Louisiana.⁸ Both deaths were traced back to the use of neti pots, which are used to irrigate the sinuses. Sinus irrigation is also performed in ritual cleansing exercises in Islam and Judaism.⁴ Although the directions accompanying the neti pots marketed in the United States state that distilled, bottled or boiled water should be used, those who died used tap water. N fowleri is harmless in drinking water, but when the amoeba is introduced to the nasal passages, infection can result.

NPs and PAs should advise patients who use neti pots or perform sinus cleansing to use only bottled, distilled or boiled water. Patients should not swim in pools that are not properly chlorinated or maintained, and they should avoid playing in ditches or brackish standing bodies of water. Patients also need reassurance that infection is rare; the risk of drowning in water activities is much higher.¹² 

References

1. Heggie TW. Swimming with death: Naegleria fowleri infections in recreational waters. Travel Med Infect Dis. 2010;8(4):201-206.

2. Parija SC. Naegleria infection. http:////emedicine.medscape.com/article/223910-overview#a0104

3. Blair B, et al. Naegleria fowleri in well water. Emerg Infect Dis. 2008;14(9):1499-1501.

4. Shakoor S, et al. Primary amebic meningoencephalitis caused by Naegleria fowleri, Karachi, Pakistan. Emerg Infect Dis. 2011;17(2):258-261.

5. Grate I. Primary amebic meningoencephalitis: a silent killer. CJEM. 2006;8(5):365-369.

6. Visvesvara GS. Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis. 2010;23(6):590-594.

7. Marciano-Cabral, F, Cabral GA. The immune response to Naegleria fowleri amebae and pathogenesis of infection. FEMS Immunol Med Microbiol. 2007;51(2):243-259.

8. Wolchover N. Brain-Eating Amoeba Fatalities Linked to Common Cold Remedy. http://news.yahoo.com/brain-eating-amoeba-fatalities-linked-common-cold-remedy-160603508.html

9. Yoder J, et al. Surveillance for waterborne disease outbreaks associated with recreational water -- United States, 2001-2002. MMWR Morb Mortal Wkly Rep. 2004;53(8):1-22.

10. Marciano-Cabral F, et al. Identification of Naegleria fowleri in domestic water sources by nested PCR. Appl Environ Microbiol. 2003;69(10):5864-5869.

11. Rojas-Hernández S, et al. Intranasal coadministration of the Cry1Ac protoxin with amoebal lysates increases protection against Naegleria fowleri meningoencephalitis. Infect Immun. 2004; 72(8):4368-4375.

12. Naegleria Fowleri. Primary Amebic Meningoencephalitides. www.cdc.gov/parasites/naegleria/general.html

Stephanie Mouzon Swarthout is a student in the family nurse practitioner program at the University of North Florida in Jacksonville. She has completed a disclosure statement and reports no relationships related to this article.