Primary amebic meningoencaphalitis

Naegleriasis, amebic encephalitis, aegleria infection


Primary amebic meningoencephalitis (PAM also known as naegleriasis, amebic encephalitis and naegleria infection) is an infection of the brain by the free-living protist Naegleria fowleri, also known as the "brain-eating amoeba". The term "brain-eating amoeba" has also been applied to Balamuthia mandrillaris, causing some confusion between the two, however Balamuthia mandrillaris is unrelated to Naegleria fowleri, and causes a different disease called granulomatous amoebic encephalitis, and unlike Naegleriasis, which is usually seen in people with normal immune function, granulomatous amoebic encephalitis is usually seen in people with poor immune function such as those with HIV/AIDS or leukemia.

N. fowleri is typically found in warm bodies of fresh water such as ponds, lakes, rivers and hot springs. It is also found in soil, poorly maintained municipal water supplies, water heaters, near warm-water discharges of industrial plants and in poorly chlorinated or unchlorinated swimming pools, in an amoeboid or temporary flagellate stage. There is no evidence of it living in salt water.

Although infection occurs rarely, it nearly always results in death, with a case fatality rate greater than 95%

Symptoms - Primary amebic meningoencaphalitis

Onset symptoms of infection can start from one to seven days after exposure. Initial symptoms include changes in taste and smell, headache, fever, nausea, vomiting and a stiff neck. Secondary symptoms include confusionhallucinations, lack of attention, ataxia and seizures. After the start of symptoms, the disease progresses rapidly over three to seven days, with death occurring usually from seven to fourteen days later and sometimes it can take longer. In 2013, a man in Taiwan died twenty-five days after being infected by Naegleria fowleri.

Causes - Primary amebic meningoencaphalitis

N. fowleri invades the central nervous system via the nose, specifically through the olfactory mucosa of the nasal tissues. This usually occurs as the result of the introduction of water that has been contaminated with N. fowleri into the nose during activities like swimming, bathing or nasal irrigation.

The amoeba follows the olfactory nerve fibers through the cribriform plate of the ethmoid bone into the skull. There, it migrates to the olfactory bulbs and subsequently other regions of the brain, where it feeds on the nerve tissue and results in significant necrosis and bleeding.

The organism then begins to consume cells of the brain, piecemeal, by means of an amoebostome, a unique actin-rich, sucking apparatus extended from its cell surface. It then becomes pathogenic, causing primary amoebic meningoencephalitis (PAM or PAME). PAM is a disease affecting the central nervous system. PAM usually occurs in healthy children or young adults with no prior history of immune compromise and who have recently been exposed to bodies of fresh water.

Prevention - Primary amebic meningoencaphalitis

Michael Beach, a recreational waterborne illness specialist for the Center for Disease Control and Prevention, stated in remarks to the Associated Press that wearing of nose-clips to prevent insufflation of contaminated water would offer effective protection against contracting PAM, noting that "You'd have to have water going way up in your nose to begin with".

Diagnosis - Primary amebic meningoencaphalitis

N. fowleri can be grown in several kinds of liquid axenic media or on non-nutrient agar plates coated with bacteria. Escherichia coli can be used to overlay the non-nutrient agar plate and a drop of cerebrospinal fluid sediment is added to it. Plates are then incubated at 37 °C and checked daily for clearing of the agar in thin tracks, which indicate the trophozoites have fed on the bacteria. Detection in water is performed by centrifuging a water sample with E. coli added, then applying the pellet to a non-nutrient agar plate. After several days, the plate is microscopically inspected and Naegleria cysts are identified by their morphology. Final confirmation of the species identity can be performed by various molecular or biochemical methods. Confirmation of Naegleria presence can be done by a so-called flagellation test, where the organism is exposed to a hypotonic environment (distilled water). Naegleria, in contrast to other amoebae differentiates within two hours into the flagellate state. Pathogenicity can be further confirmed by exposure to high temperature (42 °C): Naegleria fowleri is able to grow at this temperature whereas the nonpathogenic Naegleria gruberi is not.

Prognosis - Primary amebic meningoencaphalitis

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Treatment - Primary amebic meningoencaphalitis

Since its first description in the 1960s, only seven people worldwide have been reported to have survived PAM as of 2015, with three in the United States and one in Mexico. The prognosis remains poor for those who contract PAM and the survival remains less than 1%.

On the basis of the laboratory evidence and case reports, amphotericin B has been the traditional mainstay of PAM treatment since the first reported survivor in US(1982).

Treatment often used involves combination therapy with multiple antimicrobials, in addition to amphotericin such as fluconazole, miconazole, rifampicin and azithromycin. They have shown limited success only when administered early in the course of an infection. Fluconazole is commonly used as it has been shown to exert synergistic effect against naegleria when used with amphotericin in vitro.

While the use of rifampicin has been common, including in all four North American cases of survival, its continued use has been questioned. It  has variable activity in vitro and has a strong effect on the therapeutic levels of other antimicrobials used by inducing cytochrome p450 pathways.

Steroids such as dexamethasone have also been used to try to reduce inflammation of the brain.

In 2013, the two most recent successfully treated cases in the US utilized drug combinations that included the medication miltefosine as well as targeted temperature management. There is currently no data on how well miltefosine is able to reach the central nervous system. The US CDC is currently offering miltefosine to doctors for the treatment of free-living ameobas including naegleria.

Chlorpromazine has shown promise in vitro as well as in animal models of Naegleria meningoencephalitis.

Untimely diagnoses remain a very significant impediment to the successful treatment of infection, as most cases have only been discovered post mortem. Infection killed 121 people in the United States from 1937 through 2007.

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