Naegleria Infection and Primary Amebic Meningoencephalitis (PAM)

Updated: Sep 20, 2023
  • Author: Subhash Chandra Parija, MD, MBBS, PhD, DSc, FRCPath; Chief Editor: Michael Stuart Bronze, MD  more...
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Naegleria fowleri, a free-living ameba, is the causal agent of primary amebic meningoencephalitis (PAM), which is an acute, fulminant, and rapidly fatal infection of the central nervous system (CNS). N fowleri is named after Malcolm Fowler, an Australian pathologist, who first isolated it from a patient with PAM. [1] PAM develops following several days of exposure to the contaminated water source and typically causes death within 1-2 weeks after admittance to the hospital. Few individuals survive the infection, partly because of its rapid onset and partly because of delayed diagnosis. Only around 10 survivors of N fowleri PAM have been reported in literature. [2]

Bull coined the term “primary amebic meningoencephalitis” to distinguish it from the secondary meningoencephalitis caused by the intestinal ameba Entamoeba histolytica.

Naegleria species are amebo-flagellates that are ubiquitous in soil and fresh or brackish water (lakes, rivers, ponds). In general, they are sensitive to environmental conditions such as aridity and pH extremes and cannot survive in seawater. In humans, they are found in the throat and nasal cavity. N fowleri is heat-tolerant and is able to survive temperatures up to 45.8°C, pre-adapting the species to mammalian body temperature. Hence, an incubation temperature of 45°C is routinely used to isolate N fowleri from water samples, while suppressing growth of other amebae in the samples.

Although 30 species of Naegleria have been recognized based on sequencing data, N fowleri is the only one that has been isolated in cases of amebic meningoencephalitis. Other Naegleria species (Naegleria australiensis, Naegleria italica, Naegleria philippinensis) have been found to be pathogenic in murine models of PAM but have not been identified in any human cases of the infection. [3] As it grows best at elevated temperatures, N fowleri has been isolated from warm-water bodies, including man-made lakes and ponds, hot springs, and thermally polluted streams and rivers. It feeds on bacteria in the water bodies for survival. N fowleri is not found in saltwater sources such as seawater. [1] In the United States, most N fowleri infections occur in the summer months. [4]

Life cycle of N fowleri

The life cycle of N fowleri consists of 3 stages: trophozoite, a temporary flagellar stage known as amebo-flagellate, and cyst.

The trophozoite is the vegetative or feeding stage of the ameba and is the infective form. In humans, this form is found in CSF or in tissue. It measures 10-20 µm in diameter and has a granular cytoplasm and a distinct ectoplasm. The trophozoite is characterized by a large central nuclear karyosome surrounded by a halo. Trophozoites are actively motile with the help of a broadly rounded, granule-free projection called lobopodium that originates from the surface. The projection helps to ingest bacteria, yeast cells, and cellular debris and may serve as an organelle of attachment. In tissue, trophozoites ingest red and white blood cells and cause tissue destruction, and this stage is the only one in which the ameba multiplies via binary fission.

The flagellate stage, also known as the amebo-flagellate stage, is a temporary form of the ameba in which it neither feeds nor divides in culture. The ameba progresses to the amebo-flagellate stage when the trophozoites form is exposed to a change in ionic concentration, such as in distilled water. During the amebo-flagellate stage, the parasite is pear-shaped with a flagellar apparatus at the broader end. The flagellar apparatus consists of 2 terminal flagella, 2 basal bodies, microtubules, and a single striated rootlet, or rhizoplast. During the flagellated stage, the parasite may exhibit a rapid forward movement or a slowly spinning circular movement. It reverts to the trophozoite stage within 24 hours.

The cystic stage represents the resistant form of the parasite, offering protection from desiccation and food shortage. The cyst is round, measures 7-10 µm in diameter, and is surrounded by a smooth double-layered 1-µm wall. The cyst consists of a single nucleus, contractile vacuoles, and food vacuoles. In stained preparations, only the vacuoles can be demonstrated as fine granules, but not the nucleus. Cysts are usually absent in clinical specimens, as the infection is so rapid and fatal that the patient typically dies before the trophozoites encyst. [5]



N fowleri infections in humans occur while swimming or diving in warm water contaminated with the parasite. The parasite invades its host by penetrating the olfactory mucosa. Human-to-human transmission has never been reported. During the initial stages of infection, the host response is initiated by the secretion of mucus that traps the trophozoites. Despite this response, some trophozoites are able to reach, adhere to, and penetrate the epithelium.

It secretes a 37-kda protein with mucinolytic activity, which degrades the mucus on the surface of the nasal mucosa, thereby facilitating the invasion of the organism. [6] The gene nfa1 has been isolated from the free-living pathogenic amoeba. The protein Nfa1, which has cytolytic function, is located in pseudopodia and specifically in food-cups. N fowleri trophozoites are neurotrophic. [7] They enter the nose and invade the olfactory mucosa and bulbs, penetrate the submucosal nervous plexus, invade the cribriform plate, and reach the subarachnoid space. Glucose and protein in the CSF support the growth and multiplication of the amebae. The high content of oxygen in the CSF and in the brain also facilitates growth of the amebae.

The trophozoites enter the ventricular system through the foramen of Luschka and Magendie and reach the choroid plexus. These then destroy the ependymal layer of the third, fourth, and lateral ventricles and produce acute ependymitis. They multiply by a process known as promitosis, during which an intact nuclear membrane (demonstrable on electron microscopy) is present. Only trophozoites are found in pathologic lesions in humans.

Most patients with PAM have a history of swimming or diving in a body of fresh water. In arid climates, some cases of PAM have been attributable to the inhalation of cysts. Trophozoites or cysts, which give rise to trophozoites after they excyst, penetrate the nasal mucosa and ascend along the olfactory nerves after phagocytosis by sustentacular cells of the neuroepithelium. Subsequently, they pass through the cribriform plate to invade brain tissue, with resultant purulent meningitis and encephalitis.

Host immunity

The course of N fowleri infection is fulminant and rapid, and patients with PAM die usually within a short period (5-10 d). Therefore, detectable levels of specific antibodies are not produced in the serum during the disease. The role of the cell-mediated immunity (CMI) in resistance to N fowleri infection is not fully understood.




United States

Although isolation of N fowleri from the nares of asymptomatic individuals has been reported, PAM itself is rare in the United States. From 1962 to 2016, 143 cases have been reported from the United States. [1] Almost all of these have occurred in the Southern tier states, with the majority from Texas and Florida. [8] Of late, few cases have been reported from states beyond the Southern tier such as Minnesota, Kansas, and Virginia. Hence, a possibility of a change in trend in the epidemiology of PAM in the United States is suggested. [8] On an average, 0-8 human infections occur in the United States every year. [4]  From 1962 to 2022, a total of 157 cases have been reported from the United States. [9]

Although most N fowleri infections are contracted by swimming in infested fresh water collections, recent reports suggest that the use of ”neti pots” for nasal irrigation can also predispose to PAM. In 2011, 2 adults died in Louisiana due to PAM. Both the patients did not have any history of swimming in the recent weeks. Their only reported exposure to water was the regular use of neti pots for sinus irrigation. N fowleri was identified in the tap water samples taken from the homes of both these patients. [10]

In a survey of 16 sites from Lake Anna in Virginia, a lake that is used to cool reactors at a nuclear power plant and for recreational activities, sampled during the summer of 2007, 9 were found to be positive for N fowleri by a nested polymerase chain reaction (PCR) assay. However, total ameba counts, inclusive of N fowleri, never exceeded 12/50 mL of lake water at any site. The presence of N fowleri was not found to correlate with the conductivity, dissolved oxygen, temperature, or pH of water. To date, no cases of PAM have been reported from this thermally enriched lake. [11]

Naegleria species have been in detected in domestic water supplies in the north-central United States [12] and in warm ground water aquifers. [13] However, PAM cannot be acquired by drinking water contaminated with Naegleria. Infection can occur only when the contaminated water enters the nose. [1]

Over 10 years, from 2012-2022, a total of 34 cases have been reported in the United States, including 1 case in 2016 involving a 16-year-old boy. [9]  Three confirmed cases were reported in 2022 after exposure to fresh water. [9]


The risk for infection has been estimated at 1 case per 2.6 million exposures to N fowleri. Until 2008, at least 440 cases of PAM due to N fowleri were reported worldwide, with some well-publicized outbreaks related to a single source. [14] Most cases occur during the warm summer months in individuals who swim in freshwater pools or lakes.

Most worldwide cases have been reported in the United States. Other cases of N fowleri infection have been reported in the Czech Republic, Australia, Mexico, New Zealand, Nigeria, Great Britain, and India. Over a 20 cases have been reported so far from different parts of India. [5, 14, 15] Most recently, a 25-day-old neonate, the youngest survivor of PAM, has been reported from India. [2]

In 2011, Shakoor et al reported 13 PAM cases from Pakistan; the patients had no history of aquatic activities and the proposed mode of infection was ablution with tap water. [16] In 2015, 12 fatal PAM cases were reported in the Sindh province. [17]

A case of PAM was reported from Vietnam, where the patient had acquired the infection due to freshwater pearl diving. [18]

Naegleria species have also been isolated from swimming pools in Malaysia, [19] from recreational waters in Taiwan, [20] and from natural water sources supplying the cities in Turkey. [21] In South Korea, Naegleria isolates have been reported from sewage, water bottles, freshwater fish, and clinical isolates such as corneal scrapings. [22] The first case of PAM in Zambia was reported in 2017. [23]


PAM carries a mortality rate of greater than 95%, with death occurring within 4-6 days. Of all the 143 cases of PAM reported in the United States from 1962-2016, only 4 patients have survived, 1 in 1978, 2 in 2013, and 1 in 2016. [1] Very few survivors of PAM have been reported from other countries, but include Mexico and India. Only 8 survivors were reported worldwide until 2005. An additional 4 survivors were reported from India in 2008, 2012, and 2014. [2, 24, 25, 26, 27]   Three more survivors were reported from India in 2008, 2012, and 2013. [2, 24, 25, 26] In the rare cases of survival, PAM was recognized very early, allowing for early institution of aggressive therapy. In 1 person who survived, the N fowleri strain was found to be less virulent than the strains recovered from other fatal cases. [28] Most survivors have some residual physical or cognitive impairment. One survivor was an 8-month-old male infant from India who was treated vigorously and avoided any neurological deficit. [25]


PAM has no racial predilection.


PAM has a male-to-female ratio of 3:1. Although PAM has no natural sexual predilection, the predominance in males is thought to be secondary to a greater risk for exposure due to behavioral factors.


Most cases of PAM have been reported in children and young adults, presumably because of a greater exposure risk in these populations due to behavioral factors. In addition, the more porous cribriform plate in children and young adults is thought to place these individuals at a higher risk for disease.

Most cases of PAM involve a history of exposure to fresh, warm water. Patients with PAM generally present with a history of bathing in a pond or lake 2-6 days prior to the onset of symptoms of meningeal irritation.

The index of suspicion should be increased in children and young adults who have a history of recently swimming in freshwater lakes, ponds, and pools. Isolated cases of PAM have followed bathing in tap and hot water.

Clusters of cases of PAM have been documented during the summer months when freshwater sources are warm. [29] Although numerous people are exposed to the amoeba while swimming, it is unclear why those certain people are affected and most are not. Attempts have been made to find out the concentration of free-living N fowleri in recreational lakes and to determine the standard cut-off concentration for risk of contracting infection. [30] However, no such standard is available to date.



PAM carries a very poor prognosis, with a mortality rate of greater than 95%.