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== Overview ==
== Overview ==
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== Acknowledgements ==
== Acknowledgements ==
The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.
The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.
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Revision as of 14:10, 20 August 2012

Histopathology of amoebic meningoencephalitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

Naegleria is a free-living ameba commonly found in the environment in water and soil. Infection of humans is rare but serious. To prevent infection with Naegleria, precautions should be taken to ensure that water does not enter the nose when participating in recreational water sports.

Epidemiology and Demographics

Naegleria is a free-living ameba commonly found in the environment in water and soil. Only one species of Naegleria has been found to infect humans, Naegleria fowleri.

Naegleria fowleri is found worldwide. Most commonly, the ameba is found in:

  • Warm bodies of fresh water, such as lakes, rivers
  • Geothermal water such as hot springs
  • Warm water discharge from industrial plants
  • Minimally chlorinated swimming pools
  • Soil

Although Naegleria is commonly found in the environment, infection occurs rarely. Only 23 infections were documented in the U.S. between 1995 and 2004.

When is Naegleria most common?

Infection with Naegleria is very rare. However, when it does occur, infection is most common during the dry, summer months, when the air temperature is hot, the water is warm, and water levels are low. The number of infections increase during years characterized by heat waves.

Etiologic agent:

Naegleria fowleri and Acanthamoeba spp., are commonly found in lakes, swimming pools, tap water, and heating and air conditioning units. While only one species of Naegleria, N. fowleri, is known to infect humans, several species of Acanthamoeba, including A. culbertsoni, A. polyphaga, A. castellanii, A. astronyxis, A. hatchetti, A. rhysodes, A. divionensis, A. lugdunensis, and A. lenticulata are implicated in human disease. An additional agent of human disease, Balamuthia mandrillaris, is a related free-living ameba that is morphologically similar to Acanthamoeba in tissue sections in light microscopy.

Life cycle:

Life cycle of free-living amebae


Free-living amebae belonging to the genera Acanthamoeba, Balamuthia, and Naegleria are important causes of disease in humans and animals. Naegleria fowleri produces an acute, and usually lethal, central nervous system (CNS) disease called primary amebic meingoencephalitis (PAM).

N. fowleri has three stages, cysts 1, trophozoites 2, and flagellated forms 3, in its life cycle. The trophozoites replicate by promitosis (nuclear membrane remains intact) 4. Naegleria fowleri is found in fresh water, soil, thermal discharges of power plants, heated swimming pools, hydrotherapy and medicinal pools, aquariums, and sewage. Trophozoites can turn into temporary non-feeding flagellated forms which usually revert back to the trophozoite stage. Trophozoites infect humans or animals by entering the olfactory neuroepithelium 5 and reaching the brain. N. fowleri trophozoites are found in cerebrospinal fluid (CSF) and tissue, while flagellated forms are occasionally found in CSF.

Acanthamoeba spp. and Balamuthia mandrillaris are opportunistic free-living amebae capable of causing granulomatous amebic encephalitis (GAE) in individuals with compromised immune systems. Acanthamoeba spp. have been found in soil; fresh, brackish, and sea water; sewage; swimming pools; contact lens equipment; medicinal pools; dental treatment units; dialysis machines; heating, ventilating, and air conditioning systems; mammalian cell cultures; vegetables; human nostrils and throats; and human and animal brain, skin, and lung tissues. B. mandrillaris has only recently been isolated from the environment and has also been isolated from autopsy specimens of infected humans and animals.

Unlike N. fowleri, Acanthamoeba and Balamuthia have only two stages, cysts 1 and trophozoites 2, in their life cycle. No flagellated stage exists as part of the life cycle. The trophozoites replicate by mitosis (nuclear membrane does not remain intact) 3. The trophozoites are the infective forms and are believed to gain entry into the body through the lower respiratory tract, ulcerated or broken skin and invade the central nervous system by hematogenous dissemination 4. Acanthamoeba spp. can also cause severe keratitis in otherwise healthy individuals, particularly contact lens users 4. Acanthamoeba spp. and Balamuthia mandrillaris cysts and trophozoites are found in tissue.

Naegleria infection cannot be spread from person-to-person contact.


Laboratory Diagnosis:

In Naegleria infections, the diagnosis can be made by microscopic examination of cerebrospinal fluid (CSF). A wet mount may detect motile trophozoites, and a Giemsa-stained smear will show trophozoites with typical morphology. In Acanthamoeba infections, the diagnosis can be made from microscopic examination of stained smears of biopsy specimens (brain tissue, skin, cornea) or of corneal scrapings, which may detect trophozoites and cysts. Confocal microscopy or cultivation of the causal organism, and its identification by direct immunofluorescent antibody, may also prove useful. An increasing number of PCR-based techniques (conventional and real-time PCR) have been described for detection and identification of free-living amebic infections in the clinical samples listed above. Such techniques may be available in selected reference diagnostic laboratories.

History and Symptoms

Acute primary amebic meningoencephalitis (PAM) is caused by Naegleria fowleri. It presents with severe headache and other meningeal signs, fever, vomiting, and focal neurologic deficits, and progresses rapidly (<10 days) and frequently to coma and death. Acanthamoeba spp. causes mostly subacute or chronic granulomatous amebic encephalitis (GAE), with a clinical picture of headaches, altered mental status, and focal neurologic deficit, which progresses over several weeks to death. In addition, Acanthamoeba spp. can cause granulomatous skin lesions and, more seriously, keratitis and corneal ulcers following corneal trauma or in association with contact lens use. Non-contact lens users and contact lens users with safe lens care practices can become infected. However, poor contact lens hygiene and exposure to contaminated water may increase the risk among contact lens users.

Laboratory Findings

Microscopy:

Naegleria fowleri trophozoites
Naegleria fowleri trophozoites


A: Naegleria fowleri trophozoites, cultured from cerebrospinal fluid. These cells have characteristically large nuclei with a large, dark staining karyosome. The amebae are very active and extend and retract pseudopods. Trichrome stain. From a patient who died from primary amebic meningoencephalitis in Virginia. Naegleria fowleri trophozoite.jpg|left|Naegleria fowleri trophozoite]]

B: Naegleria fowleri trophozoite in spinal fluid. Trichrome stain. Note the typically large karyosome and the monopodial locomotion. Image contributed by Texas State Health Department.


Molecular diagnosis

Real-Time PCR

A real-time PCR was developed at CDC for identification of Acanthamoeba spp., Naegleria fowleri, and Balamuthia mandrillaris in clinical samples.1 This assay uses distinct primers and TaqMan probes for the simultaneous identification of these three parasites.

Treatment

Pharmacotherapy

Acute Pharmacotherapies

Eye and skin infections caused by Acanthamoeba spp. are generally treatable. The treatment of choice is topical use of polyhexamthylene biguanide (PHMB) or chlorhexidene gluconate with or without Brolene. Although most cases of brain (CNS) infection with Acanthamoeba have resulted in death, patients have recovered from the infection with proper treatment. Amphotericin B has been successfully used in some cases to treat PAM caused by Naegleria fowleri.

Surgery and Device Based Therapy

Keratoplasty is often necessary in severe infections.

Indications for Surgery

Severe infections

Primary Prevention

  • Avoid swimming or jumping into bodies of warm fresh water, hot springs, and thermally-polluted water such a water around power plants.
  • Avoid swimming or jumping into fresh water during periods of high temperature and low water volume.
  • Hold the nose shut or use nose clips when jumping or diving into bodies of warm fresh water such as lakes, rivers, or hot springs.
  • Avoid digging in or stirring up the sediment while swimming in shallow water areas.
  • Do not swim in areas posted as "no swimming" or in areas warning about an increased risk of Naegleria infection.

References

  1. http://www.dpd.cdc.gov/dpdx/HTML/FreeLivingAmebic.htm
  2. http://www.cdc.gov/ncidod/dpd/parasites/naegleria/factsht_naegleria.htm
  3. http://en.wikipedia.org/wiki/Naegleria_fowleri

Acknowledgements

The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.


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