Acanthamoeba Infection

Updated: Aug 14, 2017
  • Author: David R Haburchak, MD, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Overview

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. The following species of Acanthamoeba have been associated with human disease: [2]

  • Acanthamoeba castellanii (T4)
  • Acanthamoeba polyphaga (T4)
  • Acanthamoeba culbertsoni (T10)
  • Acanthamoeba palestinensis (T2)
  • Acanthamoeba astronyxis (T7)
  • Acanthamoeba hatchetti (T11)
  • Acanthamoeba rhysodes (T4)
  • Acanthamoeba byersi (T18)
  • Acanthamoeba divionensis (T4)
  • Acanthamoeba heady (T12)
  • Acanthamoeba lenticulata (T5)
  • Acanthamoeba triangularis (T4)
  • Acanthamoeba griffini (T3)

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). Cysts are quite resistant to environmental and chemical insults.

Acanthamoeba was first established as a cause of human disease in the 1970s and might be considered an emerging infection. This genus causes 3 clinical syndromes: granulomatous amebic encephalitis (GAE), disseminated granulomatous amebic disease (eg, skin, sinus, and pulmonary infections), and, most commonly, amebic ocular keratitis. Individuals who develop GAE or disseminated disease are usually immunocompromised, whereas those with 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 infection that carries a favorable prognosis when diagnosed and treated early.

Clinicians must be aware of the risk of ocular keratitis secondary to contamination of contact lenses so as to advise patients on preventive measures. Patients with contact lenses should be warned of exposure to water containing ubiquitous Acanthamoeba cysts, especially by swimming, showering, and using homemade lens-cleaning solutions.

Early recognition of the signs of keratitis (discomfort, blurred vision) are nonspecific but warrant prompt review of lens hygiene and aggressive diagnostic intervention. Therapies are most effective at the earliest stages of infection.

Severely immunosuppressed patients with subacute onset of headache, cognitive impairment, and focal neurologic signs should be considered at risk for granulomatous amebic encephalitis (GAE). While multiple ring enhancing lesions more commonly suggest toxoplasmosis, nocardia, and tuberculosis, exclusion of GAE requires biopsy.

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Pathophysiology

Acanthamoeba keratitis occurs in patients who sustain minor corneal trauma. This is usually associated with wearing contact lenses for a longer duration than prescribed. Amoebae can be introduced through environmental exposures such as swimming [3] and showering while wearing contact lenses, contaminating lenses or cases with wet hands, "topping off" lens solution bottles, or using contaminated contact lens solutions, especially homemade solutions. Rare reports cite radial keratotomy preceding this infection. [4, 5]

GAE usually develops after hematogenous spread of the amoebae from pulmonary or skin lesions to the CNS. Organisms appear to disseminate via the middle cerebral and other arteries, producing widespread lesions most commonly in the frontal, temporal, parietal, and occipital lobes, as well as the cerebellum, brainstem, and basal ganglia. [6] GAE manifests as a chronic or subacute infection, mediated in part by host type IV hypersensitivity reaction, producing blood-brain barrier leak and neuronal damage. [7]

Disseminated disease may begin in the sinuses, skin, or lungs and disseminate from these locations in immunocompromised patients to other sites, including the brain, leading to GAE.

Epidemiology

Acanthamoeba are ubiquitous organisms and have been isolated from natural and treated salt, brackish, and fresh water; soil; 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. This amoeba has been isolated from the nasopharynx of healthy persons. Acanthamoeba has caused disease worldwide and appears of increasing interest, particularly in Asia. [8, 9, 10]

Acanthamoeba keratitis typically develops sporadically among people who wear water-contaminated contact lenses. Outbreaks are possible owing to manufacturing and distribution of lens cleaning solutions that are either contaminated or impotent. [11] 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.

A multistate case control study conducted from 2008-2011 indicated the following risk factors (unadjusted matched odds ratios [mOR]) for acanthamebic keratitis among wearers of soft contact lenses: [5]

  • Age younger than 25 years (mOR 2.7)
  • Age older than 53 years (mOR 2.5)
  • Male sex (mOR 2.6)
  • Rinsing lens (mOR 6.3)
  • Storing lens in tap water (mOR 3.9)
  • Topping off solution in the lens case (mOR 4.0)
  • Having worn lenses for less than 5 years (mOR 2.4)
  • Rinsing the lens case with tap water before storing lenses (mOr 2.1)
  • Using hydrogen peroxide rather than multipurpose commercial solution (mOR 3.6)

Significant risks factors under multivariable analysis included age older than 53 years, male sex, topping off, and using saline solution. [5]

A rabbit model of keratitis has been developed that utilizes diamond burr injury followed by use of soft lenses contaminated with 1000 amoebae/mm2 (90% trophozoites). [12] This model will be useful for understanding pathogenesis and improving therapy.

More than 90% of the approximately 150 reported cases of GAE have occurred among persons with a wide variety of immunocompromising conditions, including AIDS [13] , posttransplantation, cancer being treated with chemotherapy, systemic lupus erythematosus, steroid use, diabetes mellitus, malnutrition, or liver disease. [14] Children who are malnourished, but otherwise healthy, are also at increased risk. 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). [15, 16] 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.

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Epidemiology

Frequency

United States

Acanthamoeba keratitis cases substantially increased in the 1980s with the introduction of disposable soft contact lenses. [17] 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. [18]

GAE and disseminated Acanthamoeba disease are very rare, but rates may be increasing given the rising number of persons living with immunocompromising conditions.

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

Acanthamoeba keratitis is a local infection that does not lead to systemic infection or death but 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. [19] Current drugs have limited efficacy unless applied early in the clinical course.

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.

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Prognosis

The prognosis of Acanthamoeba keratitis depends on the timing of recognition and therapy. Patients with symptoms that last for more than three weeks have a higher risk of long-term visual loss and complications.

The prognosis of GAE and disseminated disease is very poor and is worsened by late diagnosis, immunosuppression, and marginally effective therapies.

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Patient Education

Patients who wear contact lenses should be educated about the risks of improper use and management of contact lenses. Clinical photographs might encourage better compliance with hygienic practices.

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