- What Is It?
- Risk Factors
Brain eating amoeba (Naegleria fowleri) infection facts
- Naegleria fowleri is an ameba (amoeba) that is common throughout the world and lives in soil and warm freshwater. When conditions are favorable, usually summer, it multiplies rapidly.
- Naegleria fowleri infects people when warm freshwater, containing amebae, forcefully enters the nose. This can occur through water-related activities, including recreational swimming, jumping, or diving. Sports like water skiing or tubing behind a boat are a risk.
- Plumbing and water heaters may harbor amoeba including Naegleria fowleri. Neti pots or nasal rinsing with unboiled tap water has caused the infection. Hose water on a slip-and-slide toy has also caused disease.
- Swallowing contaminated water does not cause this brain-eating infection.
- The amoeba consumes and digests its way into brain tissue, causing primary amoebic meningoencephalitis (PAM). Naegleria fowleri is often called the "brain-eating amoeba," which is unfortunately fairly accurate.
- PAM is uncommonly reported, but it has a 99% fatality rate and often affects young adults who are active and healthy. As of August 2016, 40 cases have been reported in the United States since 2006, up to eight per year.
- Most U.S. cases have been reported in southern states, however, in recent years, cases have been reported as far north as Minnesota. People with PAM have a rapidly progressive illness with fever, headache, stiff neck, and finally coma and death.
- PAM looks no different than bacterial or viral meningitis. Because bacterial meningitis is common, testing and treatment routinely focus on bacteria. PAM may look just like bacterial meningitis, and doctors may not know why antibiotics are failing.
- Naegleria is easy to miss if doctors do not look for it. Like bacterial meningitis, diagnosis requires a spinal tap (lumbar puncture). The spinal fluid must be examined specifically for amebae in the Wright Giemsa stain done for the cell count. They are easier to miss in a wet mount of spinal fluid, which must be fresh and warm. Highly specialized tests are available from the Centers for Disease Control. The CDC Emergency Operations Center offers 24/7 assistance and should be consulted immediately at 770-488-7100.
- The most important clue for doctors is the patient’s forceful exposure to warm freshwater, often up the person’s nasal passages, within the prior 2 weeks. Anyone with such exposure who develops symptoms of meningitis should seek care emergently and tell the doctor about the forceful water exposure.
- The treatment of choice is a combination of antimicrobials including miltefosine (Impavido), intravenous amphotericin B, and several others. Miltefosine (Impavido) is obtainable from Profounda, INC, in Orlando, Florida.
- Treatment should be started without delay. An infectious diseases doctor should be consulted immediately even if the diagnosis is only suspected.
- Prevention of PAM is straightforward. Untreated freshwater of any kind, especially during hot months or in hot springs, should be kept out of the nose. Entering the water during these periods should be avoided, the head should be kept dry above water, or nose clips should be used.
What is Naegleria fowleri?
Naegleria fowleri is a heat-loving, single-celled amoeba (also spelled amoeba) in the phylum of protozoa called Percolozoa. It is free-living, meaning that it normally lives in freshwater and soil, consuming organic matter and bacteria. The organism goes through three stages in its life cycle: cyst, flagellate, and trophozoite. Cysts are highly stable in the environment and can withstand near-freezing temperatures. The flagellate form is an intermediate stage that moves about but does not consume nutrients or reproduce. The trophozoite form is the active, eating, reproducing phase. Animals and humans are "accidental hosts." PAM occurs only when an animal or human enters the environment at a time when amebae are actively reproducing and seeking food. Naegleria are "thermophilic," meaning that they become active in warm water during summer months. They live in both tropical and temperate climates throughout the world. The organism is commonly found in any freshwater, including rivers, lakes, drainage ditches, ponds, or any other water exposed to soil. It is also common in hot springs (geothermal water) or in localized areas where warmer water is discharged into lakes. Where the water temperature is cool, Naegleria will encyst. The protective cyst form may be found in the sediment at the bottom of lakes, where it survives winters. The most infectious form is the trophozoite stage, but cysts may also become infectious within a few hours of detecting favorable conditions. The flagellated stage can become a trophozoite within minutes.
It has been found in poorly chlorinated and unchlorinated swimming pools, as well as water parks using non-chlorine-based water treatment methods. In 2016, a young woman contracted amebic meningoencephalitis after white water rafting at a popular artificial rafting park in North Carolina. The park did not use recommended chlorination as for swimming pools. Public health authorities found extremely high levels of Naegleria fowleri in the water.
Travelers outside the U.S. may also be exposed to Naegleria due to variances in water treatment. In 2013, an American boy was infected after swimming in an unchlorinated hotel pool in Costa Rica that was fed by a hot spring. In Pakistan, where many water supplies may not have consistent chlorination, several deaths from Naegleria infection occur every year, due to rinsing of the nose with tap water prior to prayer. In 2015, a young woman contracted Naegleria infection after visiting a popular water resort in Pakistan.
In recent years, Naegleria fowleri was discovered in public drinking water and plumbing in New Orleans. Naegleria is resistant to low levels of chlorine, and chlorine dissipates the further treated water travels from a treatment plant. This was discovered after three fatal cases in which the only risk factors were flushing of sinuses with tap water and playing on a hose-fed Slip 'N Slide. Naegleria was found in the hose, in drinking water, and hot water heaters in these cases. Australia has known of Naegleria in drinking water for 30 years, when the first cases of PAM were described related to public drinking water. Since then, Australia has maintained a water treatment system that eliminates it. Louisiana implemented the Australian model in 2013, which includes regular monitoring for Naegleria and chlorine and increasing chlorine for 60 days if the ameba is found. (This is called a "chlorine burn.")
While most cases of amebic meningoencephalitis in the U.S. have been reported in the southern-tier states, warming temperature trends have shifted cases north as far as Maryland and Minnesota in recent years.
Naegleria fowleri cannot live in saltwater and is not found in the ocean.
Although there are many species of Naegleria, only Naegleria fowleri causes human and animal infection. There are other free-living amoebae that cause human disease, including Balamuthia mandrillaris, various Acanthamoeba species, and Sappinia species.
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What causes a Naegleria fowleri infection?
N. fowleri exposure occurs when warm freshwater is forced up the nose when swimming, diving, water skiing, playing with hose-fed water toys, or other recreational activities. Public drinking water and well water may also pose a risk. Although contact with infected water is common in the United States, an asymptomatic disease caused by N. fowleri is not often reported. Naegleria infection mainly affects the nervous system.
PAM occurs when N. fowleri is aspirated or forced high into the nasal cavity. The ameba produces enzymes that digest mucus and protein, which it swallows up with its "food cups" or amoebastomes. N. fowleri is attracted to chemicals released by nerve cells. The olfactory nerves (nerves of smell) travel from the roof of the nasal cavity through openings in the skull (cribriform plate) into the base of the brain. The ameba consumes the nerve cells, migrating along these tracts until it reaches the brain. The brain is an especially rich food source, with high oxygen levels, glucose, and living cells. Damage to the brain is caused by severe inflammation, direct injury, and bleeding. Death is caused by the resulting severe swelling of the brain tissue.
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What are risk factors for Naegleria fowleri infection?
The source of nearly all of the Naegleria fowleri infections reported since 1962 in the U.S. has been exposure to untreated freshwater during the summer. Activities that pose a risk include submerging the head, jumping feet first, diving, and sports that pull a person behind a boat, like wakeboarding, tubing, and water skiing. Water sources include freshwater lakes, rivers, drainage ditches, and ponds. Other freshwater sources have included hot springs, poorly chlorinated swimming pools and water parks, untreated well water, water heaters, neti pots, hose water, and warm water discharge from power plants.
Cases have historically occurred in the South, primarily Florida and Texas. In recent years, cases have been reported as far north as Minnesota, Maryland, Lake Havasu City in Arizona, Los Angeles in California, and other sites. Climate change is thought to be playing a role in its spread.
Of the 37 cases reported from 2005 to 2015, 33 people acquired PAM from recreational exposure to freshwater, three from using a neti pot with contaminated tap water, and one from playing on a hose-fed Slip 'N Slide toy. Most patients are young, healthy, and active, between 10-14 years of age. The full range of ages is 5-19.
Neti pots are sinus irrigation systems that are designed to flush water deep into the nasal cavity. They are often successfully used by allergy and sinus sufferers. Many people are not aware that public drinking water is not tested for amebae and is only chlorinated enough to kill some diarrhea-causing bacteria; drinking water is not sterile and contains a living ecosystem of bacteria, fungi, and amebae. These are usually harmless but occasionally are not. Higher levels of chlorine are needed to kill most infection-causing parasites like ameba and other protozoa. In addition, private water cisterns and water storage tanks may pose a risk.
In parts of the world where chlorination is poor, nasal rinsing may be used to purify the body before prayer -- an act called ritual ablution. In Pakistan, recent years have seen reports of 10-15 cases per year of PAM, and chlorination of drinking water or pools has been lax.
It is not possible to give an accurate estimate of invasive Naegleria fowleri infection compared to the many more probable exposures. However, it is easy to consider that cases are missed because health professionals lack awareness, misdiagnosis or trouble is making a diagnosis before death, or there is a lack of diagnosis because autopsy is not routinely performed. Few medical situations require a legally mandatory autopsy by the medical examiner, and many facilities don't do them anymore. Autopsies are not covered by insurance and cost up to $5,000. Most death certificates are signed by a doctor based on the best guess. Underreporting may occur because there is no mandatory federal reporting, and states differ in the requirement to report diseases related to amebae.
Other amebae have been transmitted by the transplanted tissue, but Naegleria fowleri has not caused disease. Between 1995 and 2012, 21 organs have been transplanted from individuals who died from PAM; however, no cases of transplant-related PAM have been recorded, which is reassuring. The risk is not zero, because Naegleria can spread in the blood to other organs, probably when the blood-brain barrier has been destroyed.
Swallowing the ameba has not been associated with infection. Properly chlorinated and maintained recreational water systems or seawater have not been associated with infection.
Humidifiers or vaporizers do not pose a risk; droplets produced by these devices are very small and cannot carry an ameba or cyst without the organism drying out.
Is Naegleria fowleri infection contagious?
- PAM is not contagious from person to person.
- The only way to become infected with Naegleria fowleri is for the ameba to reach the tissues far up at the roof of the nasal cavity.
What are signs and symptoms of a Naegleria fowleri infection?
After exposure to a contaminated water source, symptoms of PAM develop within 2-12 days of exposure, usually within 1 week (incubation period). Initial symptoms may include disturbance of taste or smell, but this may not be noticed. Most cases begin with
- frontal headache,
- nausea and vomiting, and
- stiffness of the neck (unable to touch the chin to the chest).
As the illness progresses over several hours to a few days, most cases describe
- confusion or loss of attention to surroundings,
- coma, and
If an autopsy is performed, the infection progresses so quickly that the disease may not be diagnosed until after death. Most victims die within 2-4 days of first symptoms from severe inflammation and swelling of the brain.
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What types of specialists treat Naegleria fowleri infections?
- The first health professional a person with PAM sees may be a primary care provider such as a pediatrician, family medicine doctor, internal medicine doctor, or nurse practitioner, but most go to an emergency room when symptoms like headache and fever are severe or are not going away.
- People with suspected PAM are usually hospitalized under the care of a personal physician, a hospitalist, or a critical care doctor, and an infectious disease doctor often assists with evaluation and treatment decisions.
- A neurosurgeon (brain surgeon) may be consulted for intrathecal catheter placement and intracranial pressure monitoring.
How do health care professionals diagnose a Naegleria fowleri infection?
Naegleria fowleri should be quickly suspected in people with exposure to freshwater who have the symptoms of meningitis or meningoencephalitis listed above. The characteristics of the presentation may be nonspecific at first, leading clinicians to suspect more common diseases such as bacterial or viral meningitis. Routine tests may show a high blood white cell count, but brain scan may be normal. It is important not to delay a spinal tap if at all possible while waiting for a brain scan. If performed early, the spinal fluid may not suggest serious infection, and some victims were sent home from the emergency room, only to return with worsening disease. If suspicion is high, the spinal tap should be repeated in 8-12 hours. Spinal fluid reflects inflammation with elevated levels of white blood cells and red blood cells. Routine Gram staining does not detect the ameba, however, it may be seen on the routine Wright-Giemsa stain that is performed for the cell count. A wet mount of fresh spinal fluid must be performed immediately to look for the moving amebae under the microscope. The ameba do not move unless the fluid is warmed. They will also move if a drop of distilled water is added to spinal fluid on the slide. This examination may be unsuccessful if there are many white blood cells due to intense inflammation; ameba and white blood cells appear very similar to most technicians who are not experienced in looking for Naegleria.
The CDC Emergency Operations Center offers 24/7 assistance with diagnosis and should be consulted immediately at 770-488-7100.
Definitive tests for N. fowleri infection are done in only a few labs in the country, including the CDC. They use one of the following three methods:
- N. fowleri nucleic acid tests in CSF or biopsy tissue using PCR
- N. fowleri antigen tests in CSF or biopsy tissue using immunohistochemistry (IHC)
- It is also possible to culture N. fowleri on a petri dish that is covered with a layer of bacteria. The culture is then observed for winding trails caused by the amebae consuming the bacteria. This is not routinely done.
The CDC PCR test is highly sensitive and specific for Naegleria fowleri, meaning it picks up even small numbers of amebae and is rarely negative if the ameba is truly present.
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What is the treatment for a Naegleria fowleri infection?
Because Naegleria meningoencephalitis is so uncommonly diagnosed and rapidly progresses to death, no studies are comparing one treatment regimen to another. Performing comparative human studies would be unethical. This makes all uses of medications against N. fowleri "off label." Treatment is currently very intensive and based on prior successful regimens, combinations of drugs, and advances in managing traumatic brain injuries.
- Amphotericin B is an intravenous (IV) drug usually used for fungal infections. It is the drug of choice but often fails if given alone. In addition to intravenous treatment, amphotericin B can be instilled directly into the spinal fluid (intrathecally). Other antifungal drugs that have shown success include fluconazole or miconazole; these may be given via IV and intrathecally. Antibiotics that kill Naegleria include azithromycin (Zithromax, Zmax, AzaSite) and rifampin (Rifadin) and are given via IV, as well.
- In 2016, miltefosine was approved by the FDA for the treatment of a parasitic infection, leishmaniasis, and it is now commercially available. Profunda, INC, in Orlando, Florida, has made a treatment supply of miltefosine available to hospitals on a consignment basis. The hospitals can stock the drug on-site if needed to treat PAM; they are charged for the drug only if it is used, and the company will restock it when it expires.
- In addition to antimicrobials, anti-inflammatory and other drugs are used to reduce brain swelling. Brain swelling may be relieved by the insertion of a shunt tube (ventriculostomy) to drain excess spinal fluid. The body may be cooled to 93 F (hypothermia). The use of artificial respiration techniques such as "hyperventilation" and induced coma also help reduce swelling and protect brain function while the amebae are killed.
- The most important advance in treatment is the availability of miltefosine in the U.S. This drug, which is highly active against amebae, was not available outside of Europe until the FDA approved its use by the CDC under an experimental treatment protocol. This made it possible to stock the drug at the CDC, from where it could be shipped within hours to a hospital.
- In 2013, miltefosine was used in two cases, and both patients survived.
- One recovered with minimal brain damage and was discharged home after 2 months of hospitalization.
- The other (who was treated late into illness) suffered permanent disability. In 2016, a patient in Orlando survived with minimal residual problems after a very rapid diagnosis and treatment that included miltefosine.
- Miltefosine has been provided in other cases without success; it is usually days into the infection.
It is strongly recommended that an infectious disease doctor and the CDC Emergency Operations Center be consulted immediately to guide therapy. The CDC Emergency Operations Center is available 24/7 at 770-488-7100.
Is it possible to prevent Naegleria fowleri infections?
PAM is preventable.
- The risk can be eliminated by avoiding untreated freshwater recreation during hot periods of the year.
- Consistent use of nose clips is probably next best, by keeping freshwater out of the nose.
- Avoidance of jumping, diving, and submerging the head are basic precautions.
- While it is recommended to avoid stirring up the bottom of lakes, ameba is present at all levels in the water column where water temperatures are between 76 F-115 F. This makes warm surface water in the middle of a lake a risk well as the shore.
While common sense suggests that signs will be posted if there is a risk, this is rarely the case, and safety is in the hands of the swimmer.
- Most untreated freshwater is not tested for microbes.
- Recreational lakes and rivers with beaches may be tested for bacteria that cause diarrheal illness but rarely for amebae. Even testing of such waters is not reassuring, because it may be found one week and not the next.
- The CDC recommends that all swimmers assume there is a low risk of amoebic meningitis at all times in untreated freshwater during hot months and take precautions to keep water out of the nose.
It is not possible to eliminate the ameba from untreated freshwater since, like fish, it is simply a part of the life cycle.
- Chlorination to a level of 1 part per million (ppm) of free chlorine is needed to eliminate amebae and other waterborne pathogens from pools; 3 ppm is recommended for hot tubs.
In addition to untreated freshwater, chlorine levels may be low in plumbing systems further from a treatment plant.
- Chlorine also may dissipate in unused water pipes in a home; water heaters are excellent incubators at temperatures under 120 F. and water heaters should be kept at a minimum of 120 F (higher may pose a scalding risk to children and the elderly).
- All the faucets should be run regularly with very hot water.
- Children should be taught not to suck water up the nose in the tub or shower.
- Outdoor hoses should not be used for drinking as they are contaminated and may force water up the nose by accident.
- If a filter is attached to the end of a hose used to fill kiddie pools or water toys, it should be labeled as NSF-certified to filter "cysts," or filter particles down to 1 micron.
- Care should be taken to clean and dry water play items in between uses and keep them away from dirt.
Those who flush their sinuses or nose should never use water straight from the faucet to prepare irrigation solutions.
- The water should be boiled for at least 1 minute (longer at higher altitudes above sea level) and then allowed to cool. It can be used for a day or so.
- Purified or distilled water may also be purchased for this use.
Public swimming pools may not always be well maintained, especially during heavy use or traveling, but anyone can use standard pool test strips to check the chlorine and pH of a public facility before going in.
- People can empower themselves and get free pool test strips at HealthyPools.org (https://waterandhealth.org/healthy-pools/pool-test-kit-chlorine-ph-strips/).
What is the prognosis of a Naegleria fowleri infection?
The prognosis for infected patients is very poor, as 99% of infections are fatal despite intensive treatment. The rare survivor may have residual neurological problems, such as seizure disorders.
- There is the reason for hope, however, if treatment is started immediately with a regimen that includes miltefosine. At least two cases in recent years were cured with rapid diagnosis and prompt, intensive therapy that included miltefosine. Both have had few residual problems.
- This is the best reason for providers and the public to be aware of the risk factors and make the diagnosis quickly.
- Otherwise, the easiest and cheapest treatment is prevention.
Where can people find additional information about Naegleria fowleri infections?
The CDC is the most thorough and evidence-based source of information on Naegleria fowleri and other free-living amoebae: http://www.cdc.gov/parasites/naegleria/general.html.
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Budge, P.J. "Primary amebic meningoencephalitis in Florida: a case report and epidemiological review of Florida cases." J Environ Health. 75 (2013): 26-31.
Linam, W. Matthew, et al. "Successful Treatment of an Adolescent With Naegleria fowleri Primary Amebic Meningoencephalitis." Pediatrics Feb. 2015: 2014-2292.
Marciano-Cabral, F., and Guy A. Cabral. "The immune response to Naegleria fowleri amebae and pathogenesis of infection." FEMS Immunology & Medical Microbiology 51.2 November 2007: 243-259.
Roy, S.L., et al. "Risk for transmission of Naegleria fowleri from solid organ transplantation." Am J Transplant 14.1 Jan. 2014: 163-771.
United States. Centers for Disease Control and Prevention. "Naegleria fowleri -- Primary Amebic Meningoencephalitis (PAM) -- Amebic Encephalitis." Feb. 28, 2017.
Vargas-Zepeda, J., A.V. Gomez-Alcala, J.A. Vasquez-Morales, L. Licea-Amaya, J.F. De Jonckheere, and F. Lares-Villa. "Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin." Arch Med Res 36.1 Jan-Feb 2005: 83-6.
Yoder, J.S., B.A. Eddy, G.S. Visvesvara, L. Capewell, and M.J. Beach. "The Epidemiology of Primary Amoebic Meningoencephalitis in the USA, 1962-2008." Epidemiol Infect. 138.7 July 2010: 968-975.
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