Amebic meningoencephalitis is an extremely rare and sporadic central nervous system (CNS) infection caused by free-living amoebae, mostly found in freshwater lakes and rivers. The initial symptoms of primary amebic meningoencephalitis (PAM) are indistinguishable from bacterial meningitis, while the symptoms of granulomatous amebic meningoencephalitis (GAE) can mimic a brain abscess or meningitis. Diagnosis can be made by observing motile amebae in a wet mount of cerebrospinal fluid (CSF) or visualization on CSF Wright or Giemsa stain. Treatment consists of a combination of systemic and intrathecal antibiotics. 
The free living amoebae that have been identified as CNS pathogens include Naegleria fowleri,  Paravahlkampfia francinae,  Balamuthia mandrillaris,  and species of Acanthamoeba and Sappinia. (See Etiology.)  Fulminant, acute presentations mimicking bacterial or viral meningoencephalitis are typically caused by N fowleri. More subacute to chronic presentations mimicking aseptic meningitis, brain abscess, or CNS malignancy are more typical of the remaining species.
These infections are nearly uniformly fatal. The mortality rate remains greater than 90%, even with combination antimicrobial therapy.  The high mortality rate is likely because of delayed diagnosis and poor response to therapy. In most cases, the diagnosis is made postmortem. (See Presentation, Workup, Treatment, and Medication.)
Linam et al presented a survivor of amebic meningoencephalitis in North America. The authors conclude that the patient's survival most likely resulted from a variety of factors, including early identification and treatment, use of a combination of antimicrobial agents that included miltefosine, and management of elevated intracranial pressure based on the principles of traumatic brain injury. This was also the first case reported in which induced hypothermia to 32-34 degrees Celsius was used in the management of PAM. 
Ubiquitous in most soils in most environments, N fowleri is also found in warm freshwater, particularly if the water is stagnant.  Exposure to the this amoeba is very common. Children younger than 2 years frequently carry the organism asymptomatically in their nose and throat, especially in warmer months and climates. Infection with this pathogen occurs in both immunocompromised and immunocompetent individuals. 
PAM is an exceptionally uncommon occurrence resulting from CNS invasion of the typically healthy host by N fowleri. During a period of a few days to 2 weeks after inoculating a patient who had been swimming, diving, bathing, or playing in warm, usually stagnant, freshwater, the amoebae migrate through the cribriform plate, along the fila olfactoria and blood vessels, and into the anterior cerebral fossae, where they cause extensive inflammation, necrosis, and hemorrhage in the brain parenchyma and meninges. 
Case reports have detailed rare infection following ritual ablution with tap water instilled into the nostrils. [10, 11] Similarly, sinus irrigation with contaminated tap (or other) water using neti pots (or similar devices) has been implicated as the mode of inoculation resulting in PAM. 
Granulomatous amebic encephalitis
In contrast to PAM, GAE results from one of two pathways. With acanthamebic keratoconjunctivitis, amoebae may spread directly from the cornea to the CNS, though this is uncommon. More typically, GAE results from hematogenous seeding of the CNS following primary inoculation of the lungs or skin by B mandrillaris, Acanthamoeba, or Sappinia species. Once in the CNS, the pathogen stimulates abscess and focal granuloma formation. GAE more commonly occurs in immunocompromised hosts; however, GAE may also affect otherwise healthy hosts.
Occurrence in the United States
PAM and GAE are extremely rare, with an average of 3.7 cases reported per year in the past 10 years.  From 1962-2015, 138 cases of PAM have been reported. Cases have been reported from 13 states (AZ, AR, CA, FL, IN, KS, LA, MN, OK, SC, TX, VA, and USVI).  PAM is more common in warmer regions and in the warmer months of spring and summer.  There is no seasonal variation with GAE. Approximately 60 cases of Balamuthia GAE have been reported in the US since 1975.  Sappinia, on the other hand, has only been documented as the pathogen responsible for a single case of GAE. 
Although rare, cases of PAM and GAE have been reported worldwide, reflecting the ubiquity of the organisms.  More than 125 cases of Balamuthia GAE have been reported worldwide since 1975.  Most reports come from the United States, Australia, and Europe, although this is likely because of identification and reporting bias. Balamuthia infection in South America has been increasingly recognized.  Similar to the US experience, the predominance of PAM cases occurs in warmer climates and during warmer months of the year.
Sex- and age-related demographics
The male-to-female ratio of PAM is 2:1 overall, but in the US there is a female predominance (63% of reported cases). PAM has been reported in infants as young as 4 months and is most commonly observed in the first 3 decades of life, with one study finding the median age of infection was 11 years (range: 4-56 years). 
The male-to-female ratio of GAE is 5:1 worldwide and can be seen at any age.
PAM can occur in previously healthy young individuals exposed to warm, especially stagnant, fresh water. The portal of entry by the amoebae is through the olfactory mucosa and the cribriform plate.  The pathophysiology is thought to be due to an amplified host immune response. This immune response traverses the blood brain barrier, causing an inflammatory reaction and subsequent parenchymal damage. It is thought that N. Fowleri causes an acute inflammatory cytokine response, whereas Acanthamoeba and Balamuthia spp. cause a type IV hypersensitivity reaction. These inflammatory responses contribute to neuronal damage and subsequent irreversible brain damage. 
What would you like to print?