Healio
Healio
Issue: July 2019
ByDonald Kaye, MD, MACP
July 19, 2019
5 min read
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The midget piranha: N. fowleri

Issue: July 2019
ByDonald Kaye, MD, MACP
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Primary amebic meningoencephalitis, or PAM, caused by Naegleria fowleri is a rare disease, fortunately. However, it will undoubtedly increase in frequency because of global warming. The usually fatal infection is caused by the free-living ameba, N. fowleri, which is found in warm fresh water and in soil all over the world. It exists in three forms: the infective trophozoite and the noninfective flagellate and cyst. It is thermophilic and will grow at temperatures of up to 115°F. It has been isolated from bodies of fresh water such as lakes and rivers, as well as inadequately chlorinated swimming pools, hot springs, thermal discharges from power plants and mud. It has been found in the nasal passages of healthy children swimming in canals in Egypt. It is not found in salt water. N. fowleri normally feeds on bacteria, but when it causes disease in humans, it feeds on brain tissue.

Epidemiology

Donald Kaye

The first cases of PAM were reported in 1965 (the earliest case occurred in 1961) from Australia. N. fowleri meningitis was first recognized retrospectively in the United States in a patient who developed infection in Florida in 1962. However, studies of archived autopsy tissues revealed cases from many years earlier. There were 145 cases reported in the U.S. between 1962 and March 1, 2019, most in the Southern tier of states and almost all during warm weather. The leading states were Florida and Texas, with over 30 cases each, but some more Northern states such as Minnesota, Maryland and Indiana also have reported cases. Although the average number of cases has been about three per year, it is likely that many more cases have been missed because the diagnosis was not considered. It has been estimated that about 16 cases occur each year in the U.S.

For many years, most cases worldwide were reported from a few industrialized countries, even though the conditions for the disease are more suitable in tropical and mainly underdeveloped countries. In more recent years, however, the number of reports from developing countries has increased. Of note is the incidence of the disease in Pakistan. Since 2008, an average of 10 cases of PAM per year have been reported from the province of Sindh in southern Pakistan, of which Karachi is the capital. These were traced to the religious rite of ablution within the Islamic faith in which nasal rinsing is part of a cleansing process, usually performed several times a day. N. fowleri was found in the tap water in several of these cases. PAM also has been reported as a result of sinus irrigation using neti pots with unsterile water. Such a case was recently reported in Seattle.

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Pathogenesis and symptoms

Most cases of PAM occur following an episode of water being forced into the nasal passages under pressure while swimming, diving or engaging in other water sports in warm fresh water. N. fowleri enter the nasal mucosa and penetrate the cribriform plate, which is more porous in children and young adults. They then enter the brain and cerebrospinal fluid through the olfactory neuro-epithelium, causing meningoencephalitis. Most cases have occurred in children and young adults. There is serological evidence that exposure is much more common than disease. N. fowleri has not been shown to spread via water vapor or aerosol droplets (such as shower mist or vapor from a humidifier).

The incubation period is 2 to 15 days (usually 2 to 5 days), followed by rapidly progressive symptoms and signs of meningitis and encephalitis. There may be taste and smell abnormalities early in the disease related to the neuro-olfactory system invasion of the pathogen. Death follows in almost all patients within days.

Using the direct fluorescent antibody staining technique, this photomicrograph depicts the histopathologic characteristics associated with a case of primary amebic meningoencephalitis caused by amebic Naegleria fowleri parasites.

CDC/Dr. Govinda S. Visvesvara

Diagnosis

The key to diagnosis is consideration of the possibility of PAM. Most cases have only been diagnosed postmortem. This may be because no one thought to ask about recreational freshwater exposure in a patient with presumed bacterial meningitis. Even in a cold climate, a history of recent travel from a warm climate should raise the question in a patient with presumed bacterial meningitis. Physicians should also ask about nasal rinsing for religious or other reasons.

Examination of the cerebrospinal fluid suggests bacterial meningitis with very high pressure (as high as 600 mm H2O), increased protein, low glucose and a polymorphonuclear leukocytic response. Red blood cells are usually present. The color of the spinal fluid has been described as gray early in the disease, eventually becoming red. The diagnosis is usually made by visualizing the trophozoites in a centrifuged specimen of spinal fluid. Trichrome or Giemsa stains can be used to make the trophozoites easier to visualize. PCR tests for the DNA of the N. fowleri can facilitate diagnosis, but they are not widely available.

Therapy and prognosis

There have been about 10 survivors of PAM worldwide. All have been treated with combinations of antimicrobial agents. In the U.S., four out of 145 cases have survived. From the review of available data, it appears that early diagnosis and prompt therapy are important. The drug that has shown the most activity against N. fowleri and has been used in virtually every treatment regimen is amphotericin B. It has been administered intrathecally as well as intravenously. In vitro, 0.39 µg/mL of amphotericin will inhibit growth of 100% of the organisms, and 0.78 µg/mL will kill them. Miltefosine, recently available commercially, also has good activity against N. fowleri and should be added to amphotericin B in the regimen. In vitro, 40 g/mL has been found to inhibit growth of N. fowleri, with concentrations of 55 g/mL killing them. Other agents such as fluconazole, azithromycin and rifampin have in vitro activity against N. fowleri. One or more of these agents have been added to the therapeutic regimens in patients who have survived PAM. Chlorpromazine and/or dexamethasone also have been given to some surviving patients. In addition, successful treatment has included therapeutic hypothermia.

Prevention

The potential risk for acquiring N. fowleri is very small but greatest when engaging in freshwater sports where the water is warm. Obviously, that risk can be avoided only by engaging in these sports in salt water or adequately chlorinated pools. If freshwater sports in warm climates cannot be avoided, the risk can be decreased by not allowing water to enter the nasal cavity (eg, use of nose clips). If sinus rinsing is used for religious or other purposes (eg, neti pots), the water used should be sterile.

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  • For more information:
  • Donald Kaye, MD, MACP, is a professor of medicine at Drexel University College of Medicine, associate editor of the International Society for Infectious Diseases’ ProMED-mail, section editor of news for Clinical Infectious Diseases and an Infectious Disease News Editorial Board member.

Disclosure: Kaye reports no relevant financial disclosures.

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