Amebic Meningoencephalitis

Article Author:
Angela Pana
Article Editor:
Steve Bhimji
Updated:
4/2/2017 1:23:45 PM
PubMed Link:
Amebic Meningoencephalitis

Introduction

Amebic encephalitis is both exceptionally rare and highly lethal central nervous system infection caused by free-living amoebae, found in fresh water, lakes, and rivers. There are two entities of amebic encephalitis: PAM (Primary Amebic Meningoencephalitis) and Granulomatous amebic encephalitis (GAE). The initial symptoms of PAM are indistinguishable from bacterial meningitis, while the symptoms of GAM can mimic a brain abscess or meningitis.

These infections are almost always fatal. The mortality rate is above 90%, despite the antimicrobial therapy. There are around 300 cases reported of N. Fowleri. The high mortality rate is due to an unusual symptomology in its early stages, also by the necessity of a microbial culture of the cerebrospinal fluid to establish a positive diagnosis. Parasites demonstrate a very rapid late-stage propagation through the nerves of the olfactory system to many parts of the brain simultaneously (including the vulnerable medulla).

Admit patients with amebic meningoencephalitis to the intensive care unit (ICU) for intensive monitoring and therapy. Emergent consultations with infectious disease specialists, neurologists, and neurosurgeons are recommended if PAM or GAE is suspected.

Etiology

PAM is caused by Naegleria fowelri which is a heat-loving (thermophilic), free-living ameba (single-celled microbe) referred to as an amoeba but is a unicellular parasitic protist that is ubiquitous in most soils in most environments, also found in warm fresh water. Infection with this pathogen occurs in both immunocompromised and immunocompetent individuals.

Naegleria fowleri is the only species of Naegleria known to infect people. Most of the time, Naegleria fowleri lives in freshwater habitats by feeding on bacteria. And only in rare cases, the ameba can infect humans by entering the nose during water activities.

GAE is caused by Balamuthia mandrillaris or by Acanthamoeba species, such as A.culbertsoni, A. polyphagia, A.castellani, A.astronyxis, A.hatchetti, A.rhysodes, A. divionensis, A.lugdunensis, A. lenticulata, and A. haely.

GAE results from one of the two pathways: Acanthamoeba keratoconjunctivitis results from the direct spread of amoeba from the cornea to the CNS (less frequently), more typically GAE results from the hematogenous seeding of CNS after primary inoculation of the lungs or skin. Once in the CNS, the pathogen stimulates abscess and focal granuloma formation.

Epidemiology

PAM and GAE are very rare, 3.7 cases reported per year. PAM is more common in warmer regions and the warmer months of spring and summer. There is no seasonal variation with GAE. Although rare, cases of PAM and GAE have been reported worldwide. Most reports come from the USA, Australia, and Europe.

  • The male to female ratio of PAM is 2:1, but in the US there is a female predominance (63% of cases), the median age of infection is 11 years ( range 4-56 years).
  • The male -to –female ratio of GAE is 5:1 worldwide and can be encountered at any age.

Pathophysiology

PAM occurs in healthy young individuals exposed to warm, fresh water. The only route for N.fowleri to enter CNS is via deep insufflation of infected water as it attaches itself to the olfactory nerve through the olfactory mucosa and the cribriform plate with damage to the blood brain barrier with subsequent inflammatory reaction and parenchymal damage.

Naegleria fowleri has a 3 stage life cycle: amoeboid trophozoites, flagellates, and cysts.  Amebic trophozoites are the infective one. Trophozoites have a single nucleus, multiple by binary division during which the nuclear membrane remains intact (a process called pro mitosis). Trophozoites can turn into a temporary, non-feeding, flagellated stage in certain environmental conditions such as reduced food source. But they can revert to trophozoite stage when favorable conditions return. Naegleria fowleri trophozoites are found in cerebrospinal fluid and tissue, while flagellated forms are only occasionally found in CSF. Cysts are not seen in brain tissue. Cysts form when there is not enough food sources or in cold temperatures. Cysts are environmentally resistant to increase the chances of survival until better environmental conditions occur.

N. Fowleri causes an acute inflammatory cytokine response, while Acanthamoeba and Balamuthia spp. cause a type IV hypersensitivity reaction.

These inflammatory responses contribute to neuronal damage and irreversible brain damage.

History and Physical

The history seldom helps to differentiate amebic meningoencephalitis from other CNS diseases.

Primary amebic meningoencephalitis affects children and young adults who have previously been healthy.This disease occurs more often during the warmer months of the year and in warmer climates. Patients with PAM typically have a history of swimming, diving, bathing, or playing in warm, generally stagnant, freshwater during the previous 1-9 days. Patients with PAM may experience disordered smell or taste. Most often, the symptoms of PAM are indistinguishable from those of acute bacterial meningitis ( a headache, fever, stiff neck, nausea, vomiting, confusion, seizures). The acute onset of PAM occurs over a period of hours to 1-2 days.

The GAE affects individuals of all ages, although those at the extremes of age may be more susceptible. Immunocompromised individuals may be more susceptible to GAE. There is no seasonal variation because the causative pathogens are ubiquitous. Individuals with GAE may have keratoconjunctivitis or a skin ulcer or lesion preceding neurologic symptoms and a subacute or chronic presentation lasting days or weeks.

Evaluation

Lumbar puncture for cerebral spinal fluid (CSF) analysis is the primary diagnostic tool for PAM, whereas tissue diagnosis is essential for GAE. Unfortunately, amebic meningoencephalitis is very rarely diagnosed before autopsy. Difficulties in diagnosis and rapid progression make this condition extremely difficult to treat effectively. For this reason, aggressively pursue the diagnosis in patients with CSF findings consistent with bacterial meningitis, a negative CSF Gram stain, and a history of water exposure.

Head computed tomography (CT) scanning or magnetic resonance imaging (MRI) should precede lumbar puncture if clinical signs of focal CNS involvement or elevated intracranial pressure (ICP) is present.

CT may show progressive hydrocephalus, meningeal thickening, pseudotumoral lesions, largely isolated lesions, or multifocal ring-enhancing lesions. MRI may demonstrate multifocal lesions, edema, and multiple ring-enhancing lesions. These are nonspecific findings, so neuroimaging only has the potential for suggesting the diagnosis of PAM or GAE.

For GAE, the conventional method used is the histologic detection of the trophozoite and cyst forms of the parasite in biopsied tissue. Biopsy sites may include skin, sinus, lung, and brain tissue.

  • In PAM, N. fowleri serology is not clinically useful given the rapid progression of the disease. However, in GAE, the subacute or chronic progression allows for the potential of serologic testing to be of diagnostic value. Various methods, such as indirect immunofluorescence, ELISA, and flow cytometry may be used to detect antibodies.
  • Biopsies and postmortem specimens from persons with PAM reveal severe, suppurative meningoencephalitis changes and necrotic brain tissue within which amebic trophozoites and macrophages are visualized.
  • A biopsy of focal granulomatous lesions in GAE is essential for diagnosis. Moderate granulomatous inflammation with prominent vascular involvement is typically present on brain biopsy.
  • Immunohistochemistry has been widely used to detect the amoebae in histologic specimens.

Treatment / Management

A combination of drugs and different regimens are used for treatment : Miltefosine, which must be obtained from the Centers for Disease Control and Prevention (CDC) and one or more of the following: Pentamidine (an antifungal and antiprotozoal drug), Sulfadiazine (an antibiotic Trimethoprim/sulfamethoxazole (an antibiotic), Flucytosine (an antifungal drug), Fluconazole or the related drugs voriconazole or itraconazole (antifungal drugs), Amphotericin B (an antifungal drug).

Skin sores, if present, are cleaned and treated accordingly.

CDC recommends miltefosine as well as amphotericin B deoxycholate as the backbone of any treatment regimen.

Pearls and Other Issues

Prevention of disease includes the following: avoidance of diving and jumping into stagnant, freshwater, advise individuals to consider the use of nose plugs for unavoidable exposures, encourage individuals to verify adequate chlorination of swimming pools since N.fowleri is extremely sensitive to chlorine.

Acanthamoeba can cause keratitis; contact lens wearers should be advised to visit their provider for regular eye exams, replace contacts as prescribed, remove lenses before activity involving contact with water, wash hands with soap before handling contact lenses, and clean lenses as instructed by the manufacturer.