Free-living amoebae

Background: N. fowleri is the cause of primary amebic meningoencephalitis. It is more common in warm freshwater, such as lakes, hot springs, heated swimming pools, etc (beware for your dream vacation in the hot springs!), but not in sea water.

Epidemiology: infection occurs when Naegleria-containing water is forcibly propelled up the nose and cribriform plate into the brain, typically by swimming, diving, nasal irrigation (sometimes called "neti pots") or recreational water exposures such as splash pads. It tends to affect males, children, and young adults, and cases are more commonly seen during the summer months. What is the silver lining? It is a rare disease with fewer than 10 cases reported each year in the United States.

Clinical presentation: after an incubation period of days, individuals can experience primary amebic meningoencephalitis (PAM) - a necrotizing, rapidly progressive and almost invariably fatal condition. Presentation includes severe headaches, high fever, meningismus, altered mental status and seizures. Cranial nerves can be affected. It rapidly progresses to coma. A lumbar puncture mimics that of acute bacterial meningitis (neutrophilic pleocytosis, elevated pressure, protein and low glucose), but stains/cultures are negative for bacteria. Most patients die within a week.

Diagnosis: PAM should be suspected in individuals with rapid-onset purulent meningitis and no detected bacteria on gram stain, as well as suggestive epidemiologic history of fresh water exposures. Diagnosis can be made by microscopy (sensitivity is bad); more often, the diagnosis is made by PCR or metagenomic sequencing of CSF. If you suspect this diagnosis, you should not wait for confirmatory testing to initiate treatment.

Treatment: Treatment is not well-understood, partly because the number of survivors of Naegleria is very low. Most patients receive a multidrug regimen that is guided by experts. The CDC has recommendations available here, and we strongly recommend discussing with experts if you think you have a case. 

Prevention: avoid diving or swimming in high-risk settings or use nose clips to minimize water exposure. Avoid nasal rising with tap water; use distilled, sterile, or previously boiled water only. Do not stir up sediments at the bottom of lakes! For more information we highly recommend this article.

Background: Acanthamoeba is dissimilar to N. fowleri in that Acanthamoeba are a group of over 30 species with a broader range of clinical manifestations. Additionally, Acanthamoeba are ubiquitous in various settings such as freshwater, ocean sediment, dust, soil, and others. Clinical presentation can include disseminated or cutaneous disease, as well as keratitis or encephalitis. We will only describe the latter two: granulomatous amebic encephalitis and keratitis.

1. Granulomatous amebic encephalitis (GAE) - unlike PAM, it follows a much more indolent course and it is more common among immunocompromised individuals.
   1. Epidemiology: the likely route of infection is through the skin or lungs, after which the trophozoites spread to the CNS via the bloodstream. Again, it is more common among immunocompromised individuals!
   2. Clinical presentation: GAE follows a subacute/chronic onset and mimics a space-occupying lesion in the brain. Presentation includes low-grade fever, altered mental status, delirium, personality changes that over weeks to months progress to further neurological deficit, cranial nerve abnormalities, ataxia and coma. Some patients can have disseminated disease with cutaneous lesions. The prognosis is very poor. If you're looking for more information on GAE, we recommend this article.
   3. Diagnosis: GAE should be suspected among immunocompromised individuals with/without cutaneous lesions and chronic meningoencephalitis and neuroimaging compatible with hyperintense lesions with rim enhancement (can resemble toxoplasmosis!). Most cases of Acanthamoeba are diagnosed by pathology, PCR on brain biopsy and/or metagenomic next-generation sequencing. For pictures: click here.
   4. Treatment: Multidrug combination, please reference the CDC website.
2. Keratitis: may occur in individuals that wear contact lenses that were inadequately cleaned with tap water or after swimming in contaminated water bodies. Hallmark is a keratitis (ocular pain, photophobia, foreign body sensation) with a 360 degree ring in the cornea. Treatment often combines various topical agents. Surgery or corneal transplant can be considered in severe or treatment-resistant cases. Unlike GAE, it is not usually fatal but can be vision threatening. For pictures, click here.

Background: B. mandrillaris is the last FLA to be described in this course. It was first described in a mandrill (hence the name!) and has been found in multiple zoological contexts (e.g., tigers). It is found primarily in soil and dust. Similar to Acanthamoeba, B. mandrillaris can produce GAE with/without cutaneous manifestations.

Epidemiology: the likely route of infection is via the skin and mucous membranes, after which the trophozoite finds its way to the CNS. It can rarely spread by organ transplant when patients receive a transplanted organ from a donor who had the infection. Risk factors can include exposure to soil - gardening, landscaping, among others. B. mandrillaris can affect either immunocompetent or immunocompromised hosts.

Clinical spectrum: Similar to Acanthamoeba, B. mandrillaris can produce GAE with/without cutaneous manifestations. GAE tends to present as a space occupying lesion(s), classically with hemorrhagic necrosis. Lumbar puncture can show lymphocytic pleocytosis. Balamuthia in the United States generally presents as GAE, but in other areas of the world (e.g., Peru) it has greater tendency to present as a cutaneous lesion(s). Skin disease is usually painless and occurs in the central face and is typically plaque-like or nodular. 

Diagnosis: Similarly to other FLA, amoeba is rarely isolated in CSF. It is often diagnosed by PCR of CSF or of a brain lesion, or by metagenomic next-generation sequencing. Neuroimaging may show hypodense lesions. Brain biopsy can be considered.

Treatment: Multidrug combination, which you can review through the CDC website. An investigational drug called nitroxoline (a quinolone) has been documented to have good efficacy in addition to multidrug regimen, read more here.