This article is missing information about genome assemblies (drafts and one unpublished but finished genome on NCBI).(January 2021)
|Lifecycle stages of Naegleria fowleri|
Naegleria fowleri, colloquially known as a "brain-eating amoeba", is a species of the genus Naegleria, belonging to the phylum Percolozoa, which is technically not classified as true amoeba, but a shapeshifting amoeboflagellate excavate. It is a free-living, bacteria-eating microorganism that can be pathogenic, causing an extremely rare, sudden, severe and usually fatal brain infection called naegleriasis or primary amoebic meningoencephalitis (PAM). This microorganism is typically found in bodies of warm freshwater, such as ponds, lakes, rivers, hot springs, warm water discharge from industrial or power plants, geothermal well water, poorly maintained or minimally chlorinated (under 0.5 mg/m3 residual) swimming pools, water heaters, soil, and pipes connected to tap water. It can be seen in either an amoeboid or temporary flagellate stage.
The organism was named after Malcolm Fowler, an Australian pathologist at Adelaide Children's Hospital, who was the first author of the original series of case reports of primary amoebic meningoencephalitis.
Naegleria fowleri is a thermophilic, free-living amoeba. It is found in warm and hot freshwater ponds, lakes and rivers, and in the very warm water of hot springs. As the water temperature rises, its numbers increase. The amoeba was identified in the 1960s in Australia but appears to have evolved in the United States. N. fowleri occurs in three forms – as a cyst, a trophozoite (ameboid), and a biflagellate. It does not form a cyst in solid human tissue, where only the amoeboid trophozoite stage exists, however the flagellate form has been found in cerebrospinal fluid.
Trophozoites change to cyst form to survive times when the environment is temporarily harsh. The cyst is a spherical, single-layered, smooth wall about 7–15 µm in diameter, that encloses a single nucleus.
The cyst is a resilient, life-preserving capsule for the amoeba, that resists adverse conditions. Factors that induce cyst formation include a lack of food, overcrowding, desiccation, accumulation of waste products, and cold temperatures. When conditions improve, the amoeba can escape through the pore, or ostiole, seen in the middle of the cyst. N. fowleri has been found to encyst at temperatures below 10 °C (50 °F).
The trophozoite is the infective stage for humans, when the organism can actively feed and divide. The trophozoite attaches to the olfactory epithelium, where it follows the olfactory cell axon through the cribriform plate (in the nasal cavity) to the brain. This reproductive stage of the protozoan organism, which transforms near 25 °C (77 °F) and grows best around 42 °C (106.7 °F), proliferates by binary fission.
The trophozoites are characterized by a nucleus and a surrounding flexible membrane. They travel by pseudopodia, which means that they extend parts of their body's cell membrane (the pseudopods) and then fill them with protoplasm to force locomotion. The pseudopods form at different points along the cell, thus allowing the trophozoite to change directions. In their free-living state, trophozoites feed on bacteria. In tissues, it appears they phagocytize (consume by enclosing and then digesting prey) red blood cells and destroy tissue either by releasing cytolytic substances or by cell-to-cell contact using cytolytic membrane proteins.
The flagellate is pear-shaped and biflagellate: this means that it has two flagella. This stage can be inhaled into the nasal cavity during swimming or diving. This biflagellate form occurs when trophozoites are exposed to a change in ionic concentration, such as placement in distilled water. The flagellate form does not exist in human tissue, but can exist in the cerebrospinal fluid. Once inside the nasal cavity, the flagellated form transforms into a trophozoite. The transformation of flagellate to trophozoite occurs within a few hours.
Naegleria fowleri are excavates that inhabit soil and water. N. fowleri is sensitive to drying and acid. It cannot survive in sea water. This amoeba is able to grow best at moderately elevated temperatures making summer month infections more likely. N. fowleri is a facultative thermophile and is able to grow at temperatures up to 46 °C (115 °F). Warm, fresh water with a sufficient supply of bacterial food provides a habitat for amoebae. Man-made bodies of water, disturbed natural habitats, or areas with soil and unchlorinated / unfiltered water are locations where many amoebic infections have occurred.
N. fowleri seems to thrive during periods of disturbance; the flagellate-empty hypothesis explains that Naegleria's success may be due to decreased competition from a depleted population of the normal, thermosensitive protozoal fauna. In other words, N. fowleri thrives in the absence of other predators consuming its food supply. This hypothesis suggests that human disturbances such as thermal pollution increase N. fowleri abundance by removing their resource competitors. Ameoboflagellates have a motile flagellate stage that is evolved for dispersal, which is advantageous when an environment has been cleared of competing organisms.
N. fowleri can cause an often fatal infection of the brain called naegleriasis (also known as primary amoebic meningoencephalitis, amoebic encephalitis/meningitis, or simply Naegleria infection). Infections most often occur when water containing N. fowleri is inhaled through the nose, where it then enters the nasal and olfactory nerve tissue, travelling to the brain through the cribriform plate. N. fowleri cannot cause infection by swallowing contaminated water. Infections typically occur after swimming in warm-climate freshwater, although there have been cases in cooler climates such as Minnesota, US. In rare cases, infection has been caused by nasal or sinus rinsing with contaminated water in a nasal rinsing device such as a neti pot.
N. fowleri normally eat bacteria, but during human infections, the trophozoites consume astrocytes and neurons. The reason why N. fowleri prefers to pass across the cribriform plate has remained unknown, but the neurotransmitter acetylcholine has been suggested to act as a stimulus, as a structural homolog of animal CHRM1 has been shown to be present in Naegleria and Acanthamoeba.
It takes one to nine days (average five) for symptoms to appear after nasal exposure to N. fowleri flagellates. Symptoms may include headache, fever, nausea, vomiting, loss of appetite, altered mental state, coma, drooping eyelid, blurred vision, and loss of the sense of taste. Later symptoms can include stiff neck, confusion, lack of attention, loss of balance, seizures, and hallucinations. Once symptoms begin to appear, death will usually occur within two weeks. A person infected with N. fowleri cannot spread the infection to another person. From 2009 to 2017, 34 infections were reported in the United States.
Though rarely observed, infection by Naegleria fowleri can occur in animals. Experimentally, mice, guinea pigs, and sheep have been infected, and there have been reports of South American tapirs and cattle contracting PAM. Animal infection is likely quite overlooked.
The core antimicrobial treatment consists of the antifungal drug amphotericin B, which inhibits the pathogen by binding to its cell membrane sterols, thus leading to cell membrane disruption and pathogen death; however, even with this treatment, the fatality rate is greater than 95%. New treatments are being sought. Miltefosine, an antiparasitic drug that inhibits the pathogen via disrupting its cell survival signal pathway PI3K/Akt/mTOR, has been used in a few cases with mixed results.
A key factor to effective treatment is the speed of diagnosis. PAM is a rare occurrence and is not often considered as a likely diagnosis; therefore, the clinical laboratory’s identification of the microorganism may be the first time an amoebic etiology is considered. The rapid identification can help to avoid delays in diagnosis and therapy. Amoeba cultures and real-time PCR studies for N. fowleri are diagnostic of PAM, however, they are not readily available at most institutions and would require being performed at a reference laboratory. The time of presentation of the patient can also affect the identification of the microorganism as PAM has a variable incubation time, ranging from 1 to 7 days. The clinical signs of PAM are similar to bacterial and viral meningitis, including fever, neck stiffness, and severe headaches. Symptoms can progress to prolonged nausea, vomiting, and even seizures. The disease can progress to acute hemorrhagic necrotizing meningoencephalitis, which can lead to death in as soon as 7–10 days. A variable delay in treatment can be secondary to time intervals in multiple stages of care, including exposure to exhibition of symptoms; arrival for treatment at a health care facility; workup of the diagnosis (initial diagnosis of likely bacterial meningitis); and finally, from diagnosis to initiation of recommended therapy. Successful treatment of PAM is a rare occurrence and can only be attempted after correct diagnosis, which relies on rapid recognition of the microorganism by medical technologists and pathologists. It is critical that medical technologists consistently provide timely CSF evaluation, explore the diagnosis of PAM, and look for amoebae in the setting of meningitis, especially in the summertime.
- Acanthamoeba – an amoeba that can cause amoebic keratitis and encephalitis in humans
- Balamuthia mandrillaris – an amoeba that is the cause of (often fatal) granulomatous amoebic meningoencephalitis
- Entamoeba histolytica – an amoeba that is the cause of amoebiasis, or amoebic dysentery
- Leptospira – a zoonotic bacteria that causes leptospirosis
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Necrotizing fasciitis – the "flesh-eating disease", caused by certain types of bacteria
- Toxoplasma gondii – cat-carried protozoan that causes the disease toxoplasmosis
- Vibrio vulnificus – warm saltwater infectious bacteria
- Schuster, Frederick L.; Visvesvara, Govinda S. (2004). "Free-living amoebae as opportunistic and non-opportunistic pathogens of humans and animals". International Journal for Parasitology. 34 (9): 1001–1027. doi:10.1016/j.ijpara.2004.06.004. PMID 15313128.
- "Texas residents warned of tap water tainted with brain-eating microbe". The Guardian. Associated Press. 26 September 2020. Retrieved 27 September 2020.
- Maclean, RebeccaC.; Richardson, DennisJ.; LePardo, Robin; Marciano-Cabral, Francine (2004). "The identification of Naegleria fowleri from water and soil samples by nested PCR". Parasitology Research. 93 (3): 211–217. doi:10.1007/s00436-004-1104-x. PMID 15138806. S2CID 5972631.
- Wellings, F. M.; Amuso, P. T.; Chang, S. L.; Lewis, A. L. (1977). "Isolation and identification of pathogenic Naegleria from Florida lakes". Appl Environ Microbiol. 34 (6): 661–7. Bibcode:1977ApEnM..34..661W. doi:10.1128/AEM.34.6.661-667.1977. PMC 242727. PMID 596870.
- Sheehan, Kathy B.; Fagg, Jennifer A.; Ferris, Michael J.; Henson, Joan M. (2003). "PCR Detection and Analysis of the Free-Living Amoeba Naegleria in Hot Springs in Yellowstone and Grand Teton National Parks". Applied and Environmental Microbiology. 69 (10): 5914–5918. Bibcode:2003ApEnM..69.5914S. doi:10.1128/AEM.69.10.5914-5918.2003. PMC 201221. PMID 14532044.
- Sykora, J. L.; Keleti, G.; Martinez, A. J. (1983). "Occurrence and pathogenicity of Naegleria fowleri in artificially heated waters". Appl Environ Microbiol. 45 (3): 974–9. Bibcode:1983ApEnM..45..974S. doi:10.1128/AEM.45.3.974-979.1983. PMC 242399. PMID 6847189.
- Marciano-Cabral, Francine; MacLean, Rebecca; Mensah, Alex; LaPat-Polasko, Laurie (2003). "Identification of Naegleria fowleri in Domestic Water Sources by Nested PCR". Applied and Environmental Microbiology. 69 (10): 5864–5869. Bibcode:2003ApEnM..69.5864M. doi:10.1128/AEM.69.10.5864-5869.2003. PMC 201236. PMID 14532037.
- Yoder, J. S.; Eddy, B. A.; Visvesvara, G. S.; Capewell, L.; Beach, M. J. (2009). "The epidemiology of primary amoebic meningoencephalitis in the USA, 1962–2008". Epidemiology and Infection. 138 (7): 968–975. doi:10.1017/S0950268809991014. PMID 19845995. S2CID 7828942.
- Yoder, J. S.; Straif-Bourgeois, S.; Roy, S. L.; Moore, T. A.; Visvesvara, G. S.; Ratard, R. C.; Hill, V. R.; Wilson, J. D.; Linscott, A. J.; Crager, R.; Kozak, N. A.; Sriram, R.; Narayanan, J.; Mull, B.; Kahler, A. M.; Schneeberger, C.; da Silva, A. J.; Poudel, M.; Baumgarten, K. L.; Xiao, L.; Beach, M. J. (2012). "Primary Amebic Meningoencephalitis Deaths Associated With Sinus Irrigation Using Contaminated Tap Water". Clinical Infectious Diseases. 55 (9): e79–e85. doi:10.1093/cid/cis626. PMID 22919000.
- "Ritual Nasal Rinsing & Ablution | Naegleria fowleri | CDC". www.cdc.gov. 2020-09-29. Retrieved 2020-10-16.
- "General Information: Naegleria fowleri". Centers for Disease Control and Prevention (CDC). Retrieved 2015-12-14.
- Fowler, M.; Carter, R. F. (September 1965). "Acute pyogenic meningitis probably due to Acanthamoeba sp.: a preliminary report". British Medical Journal. 2 (5464): 740–2. doi:10.1136/bmj.2.5464.734-a. PMC 1846173. PMID 5825411.
- "The discovery of amoebic meningitis in Northern Spencer Gulf towns". samhs.org. South Australian Medical Heritage Society Inc. Retrieved August 15, 2019.
- Laseke I, Korte J, Lamendella R, Kaneshiro ES, Marciano-Cabral F, Oerther DB (January 2010). "Identification of Naegleria fowleri in warm ground water aquifers". Journal of Environmental Quality. 39 (1): 147–153. doi:10.2134/jeq2009.0062. PMC 6844256. PMID 20048302.
- "Brain-eating-amoeba". WebMD. Retrieved 1 July 2015.
- Chang, S.L. (1978). "Resistance of pathogenic Naegleria to some common physical and chemical agents". Applied and Environmental Microbiology. 35 (2): 368–375. Bibcode:1978ApEnM..35..368C. doi:10.1128/AEM.35.2.368-375.1978. PMC 242840. PMID 637538.
- Marciano-Cabral, F (1988). "Biology of Naegleria spp". Microbiological Reviews. 52 (1): 114–133. doi:10.1128/MMBR.52.1.114-133.1988. PMC 372708. PMID 3280964.
- "Naegleria fowleri – general information". cdc.gov. Centers for Disease Control and Prevention. 2018-07-17. Retrieved 2018-09-13.
- Baig, AM (Aug 2015). "Pathogenesis of amoebic encephalitis: Are the amoebae being credited to an 'inside job' done by the host immune response?". Acta Trop. 148: 72–76. doi:10.1016/j.actatropica.2015.04.022. PMID 25930186.
- "Primary Amebic Meningoencephalitis (PAM) - Naegleria fowleri | Parasites | CDC". www.cdc.gov. 2019-06-24. Retrieved 2020-10-16.
- "Naegleria and Amebic Meningoencephalitis – Minnesota Dept. of Health". www.health.state.mn.us. Retrieved 2020-10-16.
- Baig, AM (Aug 2016). "Primary Amoebic Meningoencephalitis: Neurochemotaxis and Neurotropic Preferences of Naegleria fowleri". ACS Chem Neurosci. 7 (8): 1026–1029. doi:10.1021/acschemneuro.6b00197. PMID 27447543.
- "Naegleria fowleri – Primary Amebic Meningoencephalitis (PAM) – Amebic Encephalitis: Illness & Symptoms". Centers for Disease Control and Prevention (CDC). Archived from the original on May 11, 2020.
- "Brain-Eating Amoeba (Naegleria Fowleri): FAQ, Symptoms, Treatment". WebMD. Retrieved 2021-03-22.
- "General Information – Naegleria fowleri – CDC". CDC.gov. Centers for Disease Control and Prevention (CDC). Archived from the original on May 13, 2020. Retrieved May 17, 2020.
30 people were infected by recreational water, 3 people were infected after performing Nasal irrigation using contaminated tap water, and 1 person was infected by contaminated tap water used on a backyard slip-n-slide.
- "Naegleria Fowleri in Animals". Louisiana Dept of Health & Hospitals, 25 September 2013.
- Subhash Chandra Parija (Nov 23, 2015). "Naegleria Infection Treatment & Management". Medscape. Archived from the original on November 13, 2019.
- Asbill, Scott; Virga, Kris (2015). "Naegleria Fowleri: Pathogenesis, Diagnosis, and Treatment Options". Antimicrobial Agents and Chemotherapy. 59 (11): 6677–6681. doi:10.1128/AAC.01293-15. PMC 4604384. PMID 26259797.
- Cetin, N; Blackall, D (April 2012). "Naegleria fowleri meningoencephalitis". Blood. 119 (16): 3658. doi:10.1182/blood-2011-06-353136. PMID 22645743. S2CID 8912435.
- Wessel, Lindzi (22 July 2016). "Scientists scour the globe for a drug to kill deadly brain-eating amoeba". STAT. Retrieved 6 July 2020.
- Wessel, Linda (16 September 2016). "A life-saving drug that treats a rare infection is almost impossible to find". Business Insider. Archived from the original on 19 September 2016.
- Pugh, J. Jeffrey; Levy, Rebecca A. (2016-09-21). "Naegleria fowleri: Diagnosis, Pathophysiology of Brain Inflammation, and Antimicrobial Treatments". ACS Chemical Neuroscience. 7 (9): 1178–1179. doi:10.1021/acschemneuro.6b00232. PMID 27525348.