Background
The free-living amoebae that cause human infections include Acanthamoeba, Naegleria, Balamuthia mandrillaris, and, rarely, Sappinia. All 4 genera cause serious CNS or ocular infections. Distinct from enteric pathogenic protozoa, they all are usually soil/water commensals, have no human carrier state, involve no insect vector, and cause sporadic disease associated with specific behaviors and exposures. [1]
Acanthamoeba are among the most prevalent environmental protozoa and have been classified by 18s rDNA sequencing into at least 20 genotypes, designated T1-T20. The most common environmental and human pathogens belong to the T4 genotype, and correlate to the A. castellanii complex. Groups T1, T2a, T3-6, T10-12, and T15 have been associated with human disease. [2]
The life cycle of Acanthomeba consists of an active form, the trophozoite (which is 14-40 µm in diameter), and an inactive but environmentally resistant form, the 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, most commonly, amebic keratitis. Individuals who develop GAE or disseminated disease usually are immunocompromised, whereas those with keratitis usually are immunocompetent. Disseminated disease and GAE carry a poor prognosis, and treatment strategies are not well defined; Acanthamoeba keratitis is a sight-threatening infection with a favorable prognosis when diagnosed and treated early, though surgical intervention and/or corneal transplantation may occasionally be necessary.
Clinicians must be aware of the increased risk for ocular keratitis among contact lens wearers and those with corneal trauma. Historically, contamination of contact lenses has been linked to Acanthamoeba keratitis; however, cases have also occurred in persons with appropriate contact lens hygiene. As Acanthamoeba persists in warmer temperatures, the incidence increases during warmer months.
Early recognition of the signs of amoebic keratitis, including pain (often out of proportion to clinical findings), tearing, photophobia, and foreign body sensation, warrant aggressive diagnostic and therapeutic intervention.
GAE should be suspected in severely immunosuppressed patients with subacute onset of headache, cognitive impairment, and focal neurologic signs. On imaging of the brain, single or multiple ring-enhancing lesions may be appreciated that can resemble brain abscesses, Toxoplasma infection, or other diseases, and as such biopsy may be required for definitive diagnosis. Patients with GAE may also have skin nodules or ulcers that may be biopsied. [3, 4, 5]
Pathophysiology
The amoeba enters the body through the skin or respiratory tract; individuals swimming with contact lenses are at increased risk for amoebic keratitis. Acanthamoeba can enter the circulation and disseminate in immunocompromised individuals, manifesting as GAE or disseminated disease.
Epidemiology
Acanthamoeba can be found in soil, fresh and brackish water, cooling towers, and heating or air conditioning units. [5] 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, but whether this leads to protective immunity is unknown. Acanthamoeba has caused disease worldwide and appears of increasing interest, particularly in Asia. [6, 7, 8]
Acanthamoeba keratitis can develop sporadically among people who wear water-contaminated contact lenses or have had corneal trauma. Outbreaks are possible owing to manufacturing and distribution of lens cleaning solutions that are either contaminated or impotent. [9] Keratitis has been associated with wearing nondisposable contact lenses, using homemade sodium chloride solution to clean the lenses, and wearing lenses while swimming and showering. The isolation of Acanthamoeba cysts from swimming pool water is not unusual, as they resist chlorination. A higher percentage of isolates from swimming pools have been shown to be pathogenic than those isolated from natural fresh water.
More than 90% of the approximately 150 reported cases of GAE have occurred among immunocompromised persons, including those with AIDS, [10] organ transplantation, systemic lupus erythematosus, diabetes mellitus, individuals receiving steroid therapy, and persons with cancer who are receiving chemotherapy. [11] Likewise, persons with disseminated disease without CNS involvement usually are immunocompromised; this condition is most common among AIDS patients with low CD4 counts (eg, < 200 cells/µL), patients who have undergone organ transplantation, and those with long-term steroid use. [12, 13] Rarely, disseminated disease can develop in immunocompetent children and adults. The incidence of GAE and disseminated disease appears to be rising, likely mirroring the increased number of individuals worldwide who are living with immunocompromising conditions.
Epidemiology
Frequency
Acanthamoeba keratitis cases substantially increased in the 1980s with the introduction of disposable soft contact lenses. [14] 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. [15, 16] Worldwide, the annual incidence ranges from 0.15 per million to 1.4 per million.
GAE and disseminated Acanthamoeba infections are very rare, but rates may be increasing given the rising number of persons living with immunocompromising conditions. Data on the incidence of GAE and disseminated disease caused by Acanthamoeba are not available, as these are not reportable diseases.
Mortality/Morbidity
Acanthamoeba keratitis is a local infection that may be complicated by progressive visual loss, ulceration, secondary anterior uveitis with hypopyon, abscess formation, scleritis, glaucoma, cataract, and corneal melt and perforation. Ocular prognosis is worsened by delay in therapy for more than 3 weeks, use of steroids, and development of extracoronal manifestations. [17] Current drugs have limited efficacy unless used early in the clinical course.
GAE carries a very high mortality rate (nearly 100%). GAE tends to progress slowly, leading to death several weeks to months after onset of symptoms. Survivors of GAE have been described; these patients were treated with combination antimicrobial therapies. Disseminated disease also carries a high mortality rate, which is increased in cases of CNS involvement.
Prognosis
The prognosis of Acanthamoeba keratitis depends on the timing of recognition and therapy. Patients with symptoms that last for more than 3 weeks have a higher risk of long-term visual loss and complications.
The prognosis of GAE and disseminated disease is very poor, and worsened by late diagnosis, degree of immunosuppression, and marginally effective therapies. GAE carries a high mortality rate (nearly 100%). Most cases are fatal in 7-120 days (mean, 39 days).
Disseminated disease with skin involvement (no CNS disease) is associated with a high mortality rate (73%).
Patient Education
Patients who wear contact lenses should be educated about the risks of improper use and management of contact lenses. Contact lens wearers should avoid using homemade sodium chloride solutions and swimming while wearing contact lenses. Patients should consult manufacturer's guidelines regarding cleaning instructions.
