Brain-Eating Amoeba FAQ

Rare, Fatal Amoeba Infection: Your Questions AnsweredBy Daniel J. DeNoonWebMD Health NewsReviewed by Laura J. Martin, MD

Aug. 18, 2011 -- Brain-eating amoebas have killed three young Americans this summer.

What is this scary bug? How does it get to the brain? Where is it, and how can you avoid it? WebMD answers these and other questions.

What Is a Brain-Eating Amoeba?

Amoebas are single-celled organisms. The so-called brain-eating amoeba is a species discovered in 1965 and formally named Naegleria fowleri. Although first identified in Australia, this amoeba is believed to have evolved in the United States.

There are several species of naegleria, but only the N. fowleri species causes human disease. 

Like other amoebas, naegleria reproduce by cell division. When conditions are less than optimal, amoebas become inactive cysts. When conditions are favorable, the cysts turn into trophozoites -- their feeding form. These trophozoites can also temporarily grow tails that allow them to swim. In this tailed form they cannot eat, so they soon revert to the trophozoite stage.

Where Are Brain-Eating Amoebas Found?

Naegleria love warm temperatures and are able to survive in water as hot as 113 degrees Fahrenheit.

These amoebas can be found in warm places around the globe. They are found in:

Warm lakes, ponds, and rock pits Mud puddles Warm, slow-flowing rivers, especially those with low water levels Untreated swimming pools and spas Untreated well water or untreated municipal water Hot springs and other geothermal water sources Thermally polluted water, such as runoff from power plants Aquariums Soil, including indoor dust

Naegleria can't live in salt water and cannot survive in properly treated swimming pools or in treated municipal water.

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Most cases of N. fowleri disease occur in Southern or Southwestern states. Over half of all infections have been in Florida and Texas. However, a recent case in Minnesota suggests either that the amoebas are more common in Northern states than previously known, or that they are spreading into these states.

How Do Amoebas Get in the Brain?

The moniker "brain-eating amoeba" makes naegleria sound like tiny zombies wandering about looking for a way into your skull. But brains are accidental food for them, says Jonathan Yoder, MPH, who tracks the deadly amoeba for the CDC.

"It is normally eating bacteria in its natural environment, but for some reason it does use the brain as a food source when it gets into humans," Yoder tells WebMD.

If you were to drink a glass of water infested with naegleria, you would not get a brain infection. Infection occurs only after water (or perhaps dust) containing the amoeba gets into the nose.

This appears to happen most often when people are diving, water skiing, or performing water sports in which water is forced into the nose. However, infections have occurred in people who dunked their heads in hot springs or who used untreated tap water to cleanse their nostrils.

Studies suggest that N. fowleri amoebas are attracted to the chemicals that nerve cells use to communicate with one another. Once in the nose, the amoebas travel through the olfactory nerve into the frontal lobe of the brain.

How Frequently Do People Get Infected by Brain-Eating Amoebas?

Even though N. fowleri amoebas are relatively common, they only rarely cause brain disease. N. fowleri disease, known as primary amoebic meningoencephalitis or PAM, occurs from zero to eight times a year, almost always from July to September.

Worldwide, there have been some 400 reported cases. There have been 35 reported cases in the U.S. since 2001. Yoder and colleagues were able to identify 111 PAM reports in the U.S. from 1962 to 2008.

However, some cases may be unreported. A study in Virginia that looked at more than16,000 autopsy records from patients who died of meningitis found five previously unreported cases of PAM.

"I am sure we are missing some cases," Yoder says. "But these are pretty tragic infections, often involving children, so doctors and pathologists are motivated to find the cause."

Studies suggest that many people may have antibodies to N. fowleri, suggesting that they became infected with the amoeba but that their immune systems fought it off. It's not at all clear how often this happens.

"We have asked ourselves, 'Is this a rare infection that is always fatal, or a more common one that is only sometimes fatal?' We don't know the answer," Yoder says.

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But in a 2009 study, Yoder and colleagues suggested that the common finding of antibodies to the amoeba in humans and the frequent finding of N. fowleri in U.S. waters indicate "that exposure to the amoeba is much more common than the incidence of PAM suggests."

How Long Do Brain-Eating Amoebas Take to Kill You?

It takes two to 15 days for symptoms to appear after N. fowleri amoebas enter the nose. Death usually occurs three to seven days after symptoms appear. The average time to death is 5.3 days from symptom onset.

Only one U.S. patient survived brain infection with these amoebas. This patient, a 9-year-old California girl, was successfully given anti-amoeba antibiotics and, after a month in the hospital, recovered completely. Worldwide, there have been seven reports of survival.

What Are the First Symptoms Someone Might Have?

Symptoms of PAM are not specific to this disease and resemble those of viral meningitis. Symptoms include headache, fever, stiff neck, loss of appetite, vomiting, altered mental state, seizures, and coma. There may also be hallucinations, drooping eyelids, blurred vision, and loss of the sense of taste.

How Do Amoebas Dissolve Brain Tissue?

One study suggests that N. fowleri amoeba produce two enzymes that dissolve protein.

Are Certain Groups Affected More Than Others?

Over 60% of U.S. cases are in children age 13 or younger. About 80% of cases are in males. It's not at all clear whether children or males are more susceptible to the amoeba, or whether young males are more likely to engage in activities that expose them to the amoeba.

How Can I Protect Myself Against Brain-Eating Amoebas?

It makes sense to avoid swimming underwater, diving, water skiing, and jumping in warm, still waters during the late summer. It also makes sense to wear a nose clip when swimming, boating, or playing in or on warm waters.

However, there's no scientific proof that these measures will prevent N. fowleri infection. Millions of people play in warm waters every summer without having their brains infested by amoebas.

It's a waste of time to put up signs warning that a body of water contains N. fowleri amoebas. There may be more or fewer amoebas depending on the time of year and other factors. More importantly, putting up such signs might imply that bodies of water without signs are safe -- and brain-eating amoebas are relatively common.

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Naegleria fowleri(Brain –eating Amoebas)From Wikipedia, the free encyclopediaJump to: navigation, search

Naegleria fowleri

Different stages of Naegleria fowleri

Scientific classificationDomain: EukaryotaPhylum: PercolozoaClass: HeteroloboseaOrder: SchizopyrenidaFamily: VahlkampfiidaeGenus: NaegleriaSpecies: N. fowleri

Binomial nameNaegleria fowleri

Carter (1970)

Naegleria fowleri (  / n ə ̍ ɡ l ɪər i ə / ) is a free-living excavate form of protist typically found in warm bodies of fresh water, such as ponds, lakes, rivers, and hot springs. It is also found in soil, near warm-water discharges of industrial plants, and unchlorinated swimming pools in an amoeboid or temporary flagellate stage. There is no evidence of this organism living in ocean water. It belongs to a group called the Percolozoa or Heterolobosea. It is an amoeba, described as such by the CDC, NCBI, articles on pubmed, and WHO.

N. fowleri can invade and attack the human nervous system. Although this occurs rarely,[1] such an infection nearly always results in the death of the victim.[2] The case fatality rate is estimated at 98%.[3]

Contents

1 History of discovery 2 Lifecycle 3 Infection

o 3.1 Symptoms 4 Detection 5 Current research

o 5.1 Diagnostics o 5.2 Pathogenicity factors

6 Incidents and outbreaks

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o 6.1 Czechoslovakia o 6.2 New Zealand o 6.3 PAKISTAN o 6.4 United Kingdom o 6.5 United States

7 Public health prevention strategies 8 References in the media 9 See also 10 References

11 External links

History of discovery

Physicians M. Fowler and R. F. Carter first described human disease caused by amebo-flagellates in Australia in 1965.[4] Their work on amebo-flagellates has provided an example of how a protozoan can effectively live both freely in the environment, and in a human host. Since 1965, more than 144 cases have been confirmed in a variety of countries. In 1966, Fowler termed the infection resulting from N. fowleri primary amoebic meningoencephalitis (PAM) to distinguish this central nervous system (CNS) invasion from other secondary invasions caused by other true amoebas such as Entamoeba histolytica.[5] A retrospective study determined the first documented case of PAM possibly occurred in Britain in 1909.[6]

Lifecycle

Life cycle stages: cyst, flagellate, trophozoite

Naegleria fowleri exists in nature in three forms: a cyst, a trophozoite (ameboid) and a flagellate.

Cyst stage

Trophozoites encyst due to unfavorable conditions. Factors that induce cyst formation can include food deprivation, crowding, desiccation, accumulation of waste products, and cold temperatures.[7] N. fowleri has been found to encyst at temperatures below 10°C.[8]

Trophozoite stage

This reproductive stage of the protozoan organism, which transforms near 25°C and grows fastest at around 42°C, proliferates by binary fission. The trophozoites are characterized by a nucleus and a surrounding halo. They travel by pseudopodia, temporary round processes which fill with granular cytoplasm. The pseudopodia form at different points along the cell, thus allowing the trophozoite to

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change directions. In their free-living state, trophozoites feed on bacteria. In tissues, they phagocytize red blood cells and white blood cells and destroy tissue.[7]

Flagellate stage

This biflagellate form occurs when trophozites are exposed to a change in ionic concentration, such as placement in distilled water. The transformation of trophozoites to flagellate form occurs within a few minutes.[7]

Infection

Life cycle of N. fowleri and other free-living Amoebae. Click to enlarge and view caption.

In humans, N. fowleri can invade the central nervous system via the nose (specifically through the olfactory mucosa and cribriform plate of the nasal tissues). The penetration initially results in significant necrosis of and hemorrhaging in the olfactory bulbs. From there, the amoeba climbs along nerve fibers through the floor of the cranium via the cribriform plate and into the brain. The organism begins to consume cells of the brain piecemeal by means of a unique sucking apparatus extended from its cell surface.[9] It then becomes pathogenic, causing primary amoebic meningoencephalitis (PAM or PAME). PAM is a syndrome affecting the central nervous system.[10] PAM usually occurs in healthy children or young adults with no prior history of immune compromise who have recently been exposed to bodies of fresh water.[11]

Amphotericin B is effective against N. fowleri in vitro, but the prognosis remains bleak for those who contract PAM, and survival remains less than 1%.[11] On the basis of the in vitro evidence alone, the CDC currently recommends treatment with amphotericin B for primary amoebic meningoencephalitis, but no evidence supports this treatment affecting outcome.[11] Treatment combining miconazole, sulfadiazine, and tetracycline has shown limited success only when administered early in the course of an infection.[12]

While miltefosine had therapeutic effects during an in vivo study in mice, chlorpromazine (Thorazine) showed to be the most effective substance - the authors concluded: "Chlorpromazine had the best therapeutic activity against N. fowleri in vitro and in vivo. Therefore, it may be a more useful therapeutic agent for the treatment of PAME than amphotericin B."[13]

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 U.S. from 1937 through 2007, including six in 2007 (three in Florida, two in Texas, and one in Arizona).[11] The illness

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killed one in 2008 in California, one in 2009 in Florida,[14] and in 2010, three cases were reported: one in Arkansas, one in Minnesota, and one in Texas,[15] with a fourth case of an unidentified amoeba in South Carolina. In 2011, Two deaths in Louisiana were due to the use of tap water (albeit, a rare infection medium) in a "neti pot".[16] Individual deaths in 2011 were reported in Virginia,[17] Louisiana,[18] Florida,[19] and Kansas.[20]

Symptoms

Onset symptoms of infection start about five days (range is from one to seven days) after exposure. The initial symptoms include, but are not limited to, changes in taste and smell, headache, fever, nausea, vomiting, and stiff neck. Secondary symptoms include confusion, hallucinations, lack of attention, ataxia, and seizures. After the start of symptoms, the disease progresses rapidly over three to seven days, with death occurring from seven to 14 days after exposure.[21]

Detection

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.[22] 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.[23] 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, but the nonpathogenic Naegleria gruberi is not.

Current research

Diagnostics

Current research is focused on development of real time PCR diagnostic methods. One method being developed involves monitoring the amplification process in real time with hybridization of fluorescent-labeled probes targeting the MpC15 sequence – which is unique to N. fowleri.[24] Another group has multiplexed three real-time PCR reactions as a diagnostic for N. fowleri, as well as Acanthamoeba spp. and Balamuthia mandrillaris.[25] This could prove to be an efficient diagnostic test.

Pathogenicity factors

As no effective treatment for PAM has been found, the development of a therapeutic is an area of great research interest. Currently, much work is being done to determine what factor specific to N. fowleri makes it pathogenic and if these virulence factors can be targeted by drugs. One potential factor in motility of the "amoeba" is the protein coded by Nfa1. When the Nfa1 gene is expressed in nonpathogenic N. gruberi and the amoebae are cocultured with target tissue cells, the protein was was found to be located on the food cup which is responsible for ingestion of cells during feeding.[26] Following up that research, Nfa1 gene expression knockdown experiments were performed using RNA

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interference. In this experiment, double-stranded RNA (dsRNA) targeting the Nfa1 sequence was introduced and subsequently expression levels of the gene product dramatically decreased.[27] This method could potentially be a technique applicable for knockdown of expression of pathogenicity factors in N. fowleri trophozoites.

Incidents and outbreaks

Czechoslovakia

Histopathology of amoebic meningoencephalitis Between 1962 and 1965, 16 young people died of PAM in Ústí nad Labem as a consequence of

bathing in an indoor swimming pool.[28]

New Zealand

Between 1968 and 1978, eight fatal cases of PAM occurred after the victims had been swimming in geothermal water at locations between Taupo and Matamata, in the Waikato Region.[29]

PAKISTAN

From July to October 2012, twenty two people died in the southern part of Pakistan within a week from Naegleria infection.[30]

United Kingdom

In 1979, a girl swimming in the restored Roman bath in the English city of Bath swallowed some of the source water, and died five days later from amoebic meningitis.[31] Tests showed that N. fowleri was in the water.[32] The pool was subsequently closed permanently[when?].

United States

According to the Centers for Disease Control and Prevention, the protist killed 33 people between 1998 and 2007. In the 10 years from 2001 to 2010, 32 infections were reported in the U.S. Of those cases, 30 people were infected by contaminated recreational water and two people were infected by water from a geothermal (naturally hot) drinking water supply.[33]

In October 2002, two Peoria, Arizona, five-year-olds died after being exposed to untreated water supplied by Rose Valley Water.[34]

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In August 2005, two Oklahoma boys, ages seven and 9, were killed by N. fowleri after swimming in the hot, stagnant water of lakes in the Tulsa area.[35]

In 2007, six cases were reported in the US, all fatal:[11]

Public health prevention strategies

Currently there are no widespread efforts for prevention because of the low prevalence of N. fowleri infections. However, because of the fatality of the ensuing meningoencephalitis, there are efforts in research and development of both diagnostics and treatment (see above). Additionally, a case can be made for increased awareness of N. fowleri and its infection for more accurate reporting.

The Kyle Lewis Amoeba Awareness Foundation was created to help spread the awareness of naegleria fowleri.

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