Naegleria fowleri is a parasitic ameba that causes primary amebic meningoencephalitis (PAM), an almost always fatal brain infection. Thus, N. fowleri is often called the brain-eating ameba. Although N. fowleri is common in warm freshwater, PAM is very rare because the organism can only reach the brain through the nose.
N. fowleri is a one-celled, free-living protozoan that occurs naturally in soil and warm freshwater, such as lakes, rivers, and hot springs. It is heat-loving (thermophilic), growing best at temperatures up to 115°F (46°C). It can survive briefly at higher temperatures but is less likely to occur in colder waters. Nevertheless, N. fowleri feeds on bacteria in lake and river sediments where the temperature is substantially cooler. Although there are multiple Naegleria species, N. fowleri is the only one known to infect humans.
The N. fowleri life cycle has three stages: cyst, trophozoite (its vegetative and reproductive stage), and flagellate. Only trophozoites, which are 10–35 μm long, are infective. Trophozoites can enter the nasal mucosa of humans and animals and travel along the olfactory nerves to the brain where they feed on tissue, causing PAM, sometimes called amebic encephalitis. In unfavorable conditions, trophozoites form temporary non-feeding flagellates. When water temperatures fall, the ameba forms a cyst and becomes dormant until the following summer. The trophozoites and cysts can survive for minutes to hours at 122–149°F (50–65°C). Cold temperatures rapidly kill trophozoites, but cysts can survive for weeks to months at temperatures above freezing.
The first known case of N. fowleri disease occurred in Virginia in 1937, but it was not reported as such until 1968, when it was identified through an autopsy review. A probable earlier case was reported from Ireland in 1909. Cases were subsequently reported in Florida in 1961. In 1965, M. Fowler and R. F. Carter reported on four Australian patients who died of a disease caused by an ameba that was later named N. fowleri. In 1966, C. G. Butt reported a U.S. case of N. fowleri meningoencephalitis and coined the term PAM to distinguish it from secondary meningoencephalitis caused by other amebas.
The risk of N. fowleri infection is very low, since it requires that contaminated water enter the nose. Drinking contaminated water cannot cause infection, and the ameba is not known to spread through water vapor or aerosol droplets or between people. The primary risk is swimming underwater, diving, jumping, or otherwise submerging the head in warm freshwater, such as lakes or rivers in the summer after prolonged high temperatures and low water levels or in hot springs or other geothermally heated water. In 2016, a young woman died of PAM after rafting in an artificial whitewater river in North Carolina that had warm, turbid water with little chlorine and heavy algal growth. Although more common in southern latitudes, recent N. fowleri infections have occurred in the northern United States. Other risk factors for infection include water or soil entering the nose from the following sources:
N. fowleri occurs worldwide in various environments but is most common in rivers and lakes in summer and in hot climates and hot springs. The ameba does not occur in saltwater. The risk of infection has been estimated at 1 per 2.6 million exposures to N. fowleri, although the incidence may be significantly higher since the infection is difficult to diagnose. More than one-half of reported PAM cases have been in the United States, but cases have also been reported in Mexico, Australia, New Zealand, Vietnam, India, Pakistan, Great Britain, the Czech Republic, Nigeria, and Zambia. In Australia in the 1970s and 1980s, PAM was linked to nasal exposure to contaminated drinking water that had been piped long distances overland, during which the water was heated without adequate disinfection.
There are 0–8 U.S. cases per year, with higher numbers in heat-wave years. Between 2007 and 2016, there were 40 U.S. cases, with a spike of six unrelated cases in the summer of 2007. Of these 40 cases, 36 were from recreational waters (rivers, lakes, and canals), 3 were from nasal irrigation with contaminated tap water, and 1 was from contaminated tap water in a backyard slip-n-slide. Two 2011 Louisiana deaths were traced to contaminated water from a treated public-water system. Most infections have occurred in 15 southern states, with more than half in Florida. However, PAM has occurred along the East Coast as far north as Virginia, as well as in California. Several cases were reported annually in Texas during the 1990s. Subsequent infections occurred in Minnesota, Kansas, and Indiana following very warm weather. This pattern suggests that the ameba is spreading northward as climate change brings warmer water temperatures, although it is also possible that the ameba has evolved to tolerate lower temperatures. Of the 143 U.S. PAM victims between 1962 and 2016, only four survived.
Most infections have occurred in children and adolescents, with more than 75% in males. Young boys are most at risk, likely due to environmental exposure and behaviors rather than factors in immunity. Children and young adults also have a more porous cribriform plate dividing the nasal cavity from the brain, which may put them at higher risk for infection than adults.
When water contaminated with N. fowleri enters the nose, the trophozoites can penetrate the nasal mucosa and migrate along the olfactory nerves through the cribriform plate in the skull to the brain and meninges, the membranes surrounding the brain and spinal cord and containing the cerebrospinal fluid (CSF). The trophozoites—and occasionally flagellates—are found in the CSF as well as the brain. Protein and glucose in the CSF support the ameba's rapid multiplication. The parasite invades the brain where it feeds on red and white blood cells and tissue, causing severe brain swelling (edema) and high CSF pressure. The organism has been found in other body tissues of deceased PAM patients and, although there have been no cases of PAM from organs transplanted from infected donors, this remains a theoretical possibility. The term brain-eating ameba is something of a misnomer, since death may be caused primarily by the body's immune response to the parasite.
PAM symptoms generally begin 1–12 days after exposure. The first symptoms are similar to those of bacterial meningitis, including severe frontal headache, fever, nausea, and possibly vomiting and an altered sense of smell. Later symptoms include stiff neck, loss of balance, lack of attention, confusion, seizures, hallucinations, and coma. Once symptoms appear, the disease progresses rapidly, typically resulting in death within about five days.
Because PAM is so rare and progresses so rapidly, about 75% of diagnoses are made after death. N. fowleri or its antigen or DNA can be detected in CSF, a biopsy sample, or tissue specimens. It can be detected in the environment by collecting, concentrating, and culturing water samples. Only a few U.S. laboratories perform the tests, which include the following:
N. fowleri is common in recreational waters, so it is fortunate that infections are extremely rare. However, their rarity has made epidemiologic studies difficult. A standard definition for N. fowleri infection was established only in 2011 by the Council of State and Territorial Epidemiologists.
Because there are no good methods for determining N. fowleri environmental concentrations and because concentrations can vary significantly over time, there are no safe concentration standards. Thus, the U.S. Centers for Disease Control and Prevention (CDC) does not generally recommend testing lakes and rivers. Although warning signs are sometimes posted at hot springs, such signs could be misinterpreted as indicating that waters without signs are safe. It has been suggested that testing would be useful for household water systems, for measuring the ameba's survival in treated water and for determining its distribution into new regions and environments as the climate changes. The states of Western and South Australia regularly monitor several drinking-water distribution systems for N. fowleri colonization.
As of 2018, PAM was not a nationally notifiable disease, although it is reported in Florida, Texas, and Louisiana as amebic encephalitis, and the CDC has tracked it since 1989 as part of its Waterborne Disease and Outbreak Surveillance System. The CDC Free-Living Ameba Laboratory diagnoses most U.S. cases, maintains a PAM registry, and provides guidance to clinicians worldwide.
Only four of 143 U.S. patients infected with N. fowleri between 1962 and 2016 are known to have survived. As of 2018, the fatality rate remained at 95% to over 97%. It has been suggested that at least some survivors were infected with less virulent strains of the ameba, although early diagnosis and aggressive treatment played a very important role in the survivals.
Other than avoiding activities in warm freshwater, there are certain precautions that may be helpful:
Water for irrigating the sinuses or entering the nose as part of a religious practice should be boiled for at least one minute at sea level and up to three minutes at higher elevations. Water also can be run through a filter with pore sizes of 1 μm or less or labels that read “NSF 53” or “NSF 58.” Irrigation devices should be rinsed with safe water after use and thoroughly air dried.
N. fowleri trophozoites and cysts are moderately sensitive to disinfectants such as chlorine and monochloramine used to treat drinking water and swimming pools. Data are limited, but under laboratory conditions, 1 part per million (1 mg/L) chlorine in clear well water at 104°F (40°C) and pH 8.01 will reduce viable cysts by 99.99% in 56 minutes. Cloudy (turbid) water requires more time or higher chlorine concentrations. Although a 2015 study reported that the ameba may persist as a biofilm in chlorinated drinking-water distribution systems, it is not possible to become infected by drinking N. fowleri-contaminated water.
See also Parasites .
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Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA, 30329-4027, (800) CDC-INFO (232-4636), http://www.cdc.gov .
Margaret Alic, PhD