By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

SYNOPSIS: Primary amebic meningoencephalitis is a rarely diagnosed worldwide disease associated with exposure to fresh water that causes highly lethal, rapidly progressive central nervous system infection but may be treatable in some cases, necessitating maintenance of a high index of suspicion in appropriate cases.

SOURCE: Gharpure R, Bliton J, Goodman A, et al. Epidemiology and clinical characteristics of primary amebic meningoencephalitis caused by Naegleria fowleri: A global review. Clin Infect Dis 2021;73:e19-e27.

Gharpure and colleagues, performing a literature review as well as an examination of the Centers for Disease Control and Prevention (CDC) Free-Living Ameba surveillance data, identified 381 cases of primary amebic encephalitis (PAM) caused by Naegleria fowleri from 1937 through 2018. Of these, 145 cases occurred in the United States and were identified by the surveillance system and an additional 11 cases were from case reports published prior to 1962. Exposures occurred in a total of 33 countries, with the United States accounting for 41%, Pakistan accounting for 11%, and Mexico accounting for 9%. One-half or more of the diagnoses were made by direct visualization of the organism, with the remainder made by immunohistochemistry or immunofluorescence, with confirmation by polymerase chain reaction (PCR) or next generation sequencing.

Water activities were reported as likely exposures in 247 cases; nasal irrigation was reported in 9%. The water sources were lakes, ponds, or reservoirs in 45%; swimming pools in 13%; tap water in 12%; and canals, ditches, or puddles in 12%. Of the 34 cases associated with swimming pool exposure, 33 (97%) occurred before 1988. Of the 315 cases for which the information was available, 85% described the season as summer or stated it was warm or hot.

Three-fourths of patients were male, and the median age of the cohort was 14 years (range, 1 month to 85 years). Of the 256 cases for whom the presenting symptoms were recorded, these were influenza-like in 41 (16%), while the remainder had symptoms suggestive of central nervous system infection. Common symptoms and signs included fever (88%), headache (82%), nausea/vomiting (57%), altered mental status (50%), and nuchal rigidity (35%); 13% were comatose at the time of presentation. On lumbar puncture, the opening pressure was elevated in all patients, the median red blood cell count was 212 cells/µL, the median white blood cell count was 1,238 cells/µL with neutrophil predominance (median 82%), elevated protein, and low glucose.  

There were 32 survivors, for a case fatality rate of 92%, but only seven of the 32 had acceptable laboratory confirmation. The median incubation period was six days (range, one to 30 days). All seven of the survivors with confirmed infection received intravenous amphotericin B (deoxycholate in at least four; the product used was not stated in the other three), and five of these also received the drug intrathecally. Six of the seven received an antifungal azole, four each received azithromycin and/or miltefosine; dexamethasone was administered to five of the patients.

COMMENTARY

The number of identified cases of amebic meningoencephalitis has increased over the years, most likely as the result of increased recognition. However, it has been speculated that warming related to global climate change may increase potential exposure to the thermophilic N. fowleri.

An interesting observation is that almost one in 10 cases were associated with nasal irrigation, which was performed for either therapeutic or religious reasons.

Although all seven survivors with confirmed PAM received amphotericin B, this drug was administered to 71% of the entire cohort — obviously failing in a very large proportion. However, treatment with potentially effective drugs depends on suspicion of the diagnosis. The authors pointed out that the definition of a probable case used in their analysis is useful in this regard: acute onset rapidly progressive meningoencephalitis with fever, headache, vomiting, and/or meningismus occurring within 14 days of freshwater exposure. The most rapid and readily available means of diagnosis is the visualization of motile trophozoites of the ameboflagellate in wet preparations of cerebrospinal fluid. The one case I have seen (decades ago in Florida) was identified initially by a laboratory technician performing a cell count using a cytometer.

The CDC can be contacted about suspected cases: https://www.cdc.gov/parasites/naegleria/diagnosis-hcp.html.