Introduction
Background
The free-living amoebae that cause human infections include Acanthamoeba, Naegleria, Balamuthia mandrillaris, and Sappinia diploidea. All 4 genera cause CNS infections that are frequently fatal. These amoebae are distinct from other pathogenic protozoa. They all have a free-living existence, have no human carrier state (which is important in disease transmission), have a limited relationship with the spread of infection and poor sanitation, and involve no insect vector.
The pathogenic species of Acanthamoeba include Acanthamoeba castellanii, Acanthamoeba polyphaga, Acanthamoeba culbertsoni, Acanthamoeba palestinensis, Acanthamoeba astronyxis, Acanthamoeba hatchetti, Acanthamoeba rhysodes, Acanthamoeba divionensis, Acanthamoeba quna, Acanthamoeba lugdunensis, and Acanthamoeba griffini. The life cycle consists of 2 stages: a trophozoite (which is 14-40 µm in diameter) and a cyst (which has a double-layered wall with a diameter of 12-16 µm).
Acanthamoeba was first established as a cause of human disease in the 1970s. This genus causes 3 clinical syndromes: granulomatous amebic encephalitis (GAE), disseminated granulomatous amebic disease (eg, skin, sinus, and pulmonary infections), and amebic keratitis. Individuals who develop GAE or disseminated disease are usually immunocompromised, whereas those with amebic keratitis are usually immunocompetent. Disseminated disease and GAE carry a poor prognosis, and treatment strategies are not well defined; Acanthamoeba keratitis is a sight-threatening disease that carries a favorable prognosis when diagnosed and treated early in the disease course.
Pathophysiology
Acanthamoeba keratitis occurs in patients who sustain minor corneal trauma; this is usually associated with wearing contact lenses. Amoebae can be introduced through environmental exposures, including swimming while wearing contact lenses or using contaminated contact lens solutions, especially homemade solutions. Rare reports cite radial keratotomy preceding this infection.
GAE usually develops after hematogenous spread of the amoebae from pulmonary or skin lesions to the CNS. Alternatively, amoebae may enter via the olfactory epithelium.
Disseminated disease may begin in the sinuses, skin, or lungs and disseminate from these locations to other sites, including the brain, leading to GAE.
Epidemiology
Acanthamoeba are ubiquitous organisms and have been isolated from soil, water (including natural and treated water), air, and dust. Most persons appear to have been exposed to this organism during their lifetime, as 50-100% of healthy people have serum antibodies directed against Acanthamoeba; studies have also demonstrated that this amoeba can be cultured from the pharynges of healthy persons. Acanthamoeba has caused disease worldwide, including in the United States, Europe, Australia, Africa, and South America.
Acanthamoeba keratitis typically develops in otherwise healthy persons, with over 1,300 cases described in the literature. Most cases occur in people who wear contact lenses. Keratitis has been associated with wearing nondisposable contact lenses, using homemade sodium chloride solution to clean the lenses, and wearing lenses while swimming. The isolation of Acanthamoeba from swimming pool water is not unusual. The bacteriologic quality of the water does not correlate with the presence of Acanthamoeba in swimming pools. Acanthamoeba cysts are very resistant to chlorine. A higher percentage of isolates from swimming pools have been shown to be pathogenic than those isolated from natural fresh water.
Despite the widespread existence of Acanthamoeba, GAE usually occurs among immunocompromised persons, including those with AIDS, transplant recipients (eg, bone marrow transplants), patients with cancer receiving chemotherapy, and those with systemic lupus erythematosus, steroid use, diabetes mellitus, malnutrition, or liver disease. Likewise, persons with disseminated disease without CNS involvement are usually immunocompromised; this condition is most common among patients with AIDS who have low CD4 counts (eg, <200 cells/µL). In unusual cases, disseminated disease develops in immunocompetent children and adults. The incidence of GAE and disseminated disease appears to be rising, likely mirroring the increased number of persons worldwide who are living with immunocompromising conditions. To date, more than 100 cases of GAE have been described.
Frequency
United States
Keratitis cases substantially increased in the 1980s with the introduction of disposable soft contact lenses. Some evidence shows that the rate has subsequently declined, especially with the introduction of multipurpose cleaning solutions. The estimated rate of Acanthamoeba keratitis is 1 per 250,000 people in the United States, although rates vary among studies: from 1.65-2.01 per million population up to 1 per 10,000 people who wear contact lenses.1
GAE and disseminated Acanthamoeba disease are very rare, but rates may be increasing given the rising number of persons living with immunocompromising conditions. More than 100 cases of GAE have been described to date.
International
Acanthamoeba can cause keratitis, GAE, and disseminated disease worldwide. Data on the incidence rates of these infections internationally are not available since it is not a reportable disease.
Mortality/Morbidity
- Keratitis is a local infection that does not lead to systemic infection or death but may be complicated by cataracts, hypopyon, and increased intraocular pressure and may threaten sight.
- GAE carries a very high mortality rate (nearly 100%). Survivors of GAE have been described; these patients were treated with combination antimicrobial therapies. Disseminated disease also carries a high mortality rate, but it is lower than GAE if CNS involvement does not occur.
Clinical
History
- Keratitis is usually associated with a history of improper cleaning of contact lenses, using homemade sodium chloride solution to clean the lenses, and swimming in fresh water or a swimming pool, especially while contact lenses are worn. Rarely, this infection develops after radial keratotomy. The incubation period is a few days. Keratitis typically begins with a foreign-body sensation followed by pain, tearing, photophobia, blepharospasm, and blurred vision. Patients may have periods of symptom remission with a waxing and waning course. Bilateral involvement has been described in up to 11% of cases.2
- Granulomatous amebic encephalitis (GAE) is a subacute diffuse meningoencephalitis, usually with an insidious onset. The incubation period is unknown but is probably weeks to months. The duration of illness until death ranges from 7-120 days (average, 39 d). Patients with GAE may have concurrent sinus, lung, or skin disease. Most patients present with focal neurologic deficits; other symptoms are as follows:
- Mental status changes (86%)
- Seizures (66%)
- Hemiparesis (53%)
- Fever (53%)
- Headache (53%)
- Meningismus (40%)
- Visual disturbances (26%)
- Ataxia (20%)
- Nausea and vomiting
- Hallucinations
- Personality changes
- Photophobia
- Sleep disturbances
- Skin disease may predate the onset of CNS manifestations by weeks to months and may include ulcers, nodules, or subcutaneous abscesses. Disseminated disease without CNS involvement may manifest as skin lesions, sinusitis, pneumonitis, or a combination. Other unusual manifestations of Acanthamoeba infections have included osteomyelitis, adrenalitis, and vasculitis.
Physical
- Keratitis
- Conjunctivitis or conjunctival hyperemia
- Corneal ulceration
- Lid edema
- A characteristic corneal ring stromal infiltrate
- Anterior uveitis of fluctuating severity
- Increased intraocular pressures
- Hypopyon
- Cataract formation
- Granulomatous amebic encephalitis
- Altered mental status
- Ataxia
- Fever
- Hemiparesis
- Cranial nerve deficits
- Meningismus, Babinski sign, and Kernig sign
- Diplopia, photophobia
- Coma
- Concurrent skin lesions, sinus tenderness, or pulmonary rales
- Disseminated disease without GAE may manifest as skin lesions that are typically hard erythematous nodules or skin ulcers. Other presentations of disseminated disease include pneumonitis and sinusitis.
Causes
- Keratitis
- Wearing contact lenses
- Using homemade sodium chloride solutions to clean contact lenses
- Wearing contacts while swimming
- Cleaning contact lenses less frequently than recommended by the manufacturer
- Granulomatous amebic encephalitis and disseminated disease: Acanthamoeba is ubiquitous; most persons are exposed to this organism. Although rare cases have been described in immunocompetent adults and children, the main risk factors for the development of disease include immunocompromising conditions and factors associated with immunosuppression, such as the following:
- AIDS
- Liver disease
- Transplantation
- Diabetes mellitus
- Steroid use
- Systemic lupus erythematosus
- Cancer that requires chemotherapy
- Malnutrition
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Further Reading
Keywords
Acanthamoeba, Acanthamoeba castellanii, A castellanii, Acanthamoeba polyphaga, A polyphaga, Acanthamoeba culbertsoni, A culbertsoni, Acanthamoeba palestinensis, A palestinensis, Acanthamoeba astronyxis, A astronyxis, Acanthamoeba hatchetti, A hatchetti, Acanthamoeba rhysodes, A rhysodes, Acanthamoeba divionensis, A divionensis, Acanthamoeba quna, A quna, Acanthamoeba lugdunensis, A lugdunensis, Acanthamoeba griffini, A griffini,Naegleria, Balamuthia, acanthamebic infection, keratitis in contact lens wearers, granulomatous amebic encephalitis, GAE, disseminated disease, free-living amoebas, disseminated granulomatous amebic disease, amebic keratitis, Acanthamoeba keratitis
