Infectious Disease and Microbiology - Acanthamoeba Species Basics Acanthamoeba is a genus of free-living protozoa that is widely distributed in the environment. Several species have been associated with human infection, including A. astronyxis, A. castellanii, A. culbertsoni, A. divionensis, A. glebae, A. griffini, A. healyi, A. hatchetti, A. palestinensis, A. polyphaga, and A. rhysodes. These organisms do not require a human or animal host to complete their life cycle and can persist independently in environmental sources. Acanthamoeba species exist as both trophozoites and cysts. The trophozoite is the active, feeding form, whereas the cyst is more resistant to environmental stress and contributes to the organism’s persistence in unfavorable conditions.

Microbiologic Characteristics Acanthamoeba species are free-living protozoa with a worldwide environmental distribution. They are commonly encountered in soil, dust, freshwater, brackish water, sewage, hot tubs, and other moist environments. Their ability to form resistant cysts allows them to survive under conditions that would eliminate many other microorganisms. The organisms are relatively resistant to standard concentrations of chlorine used in drinking water and swimming pools, which helps explain their persistence in treated water systems.

Epidemiology Acanthamoeba infections occur worldwide because the organisms are ubiquitous in the environment. Human exposure is common, but clinical disease is relatively uncommon and usually develops when the organism gains access to susceptible tissues. Acquisition may occur through inhalation, contamination of damaged skin, or direct contact with contaminated soil or water. Contact lens–associated infection is particularly important. Using tap water, nonsterile saline, or contaminated lens-cleaning solutions can introduce Acanthamoeba onto the corneal surface. Although disseminated and central nervous system disease primarily affects immunocompromised or debilitated patients, infection can occasionally occur in people without an obvious underlying immune defect.

Major Clinical Infections Acanthamoeba produces three particularly important clinical syndromes: granulomatous amebic encephalitis, keratitis, and chronic cutaneous or soft-tissue disease. Granulomatous amebic encephalitis is typically seen in patients with impaired immunity. The illness usually has an insidious and progressive course rather than the abrupt presentation seen with many bacterial or viral encephalitides. Neurologic symptoms may evolve over more than a week and can continue for several weeks or months before diagnosis. Acanthamoeba keratitis usually occurs after corneal trauma or in contact lens users. Contaminated cleaning solutions, tap-water rinsing of lenses, swimming while wearing lenses, and poor contact lens hygiene are important risk factors. The keratitis may resemble herpes simplex keratitis because dendritic or pseudodendritic corneal lesions can occur. Acanthamoeba can also cause chronic skin and soft-tissue infection. Manifestations include persistent ulcerative lesions, abscesses, plaques, or erythematous nodules. Cutaneous disease is particularly important in immunocompromised patients and may sometimes accompany disseminated infection.

Granulomatous Amebic Encephalitis Granulomatous amebic encephalitis is a severe, usually subacute or chronic central nervous system infection. It occurs most often in individuals with major underlying illness or impaired cellular immunity. The presentation is variable and can include progressive headache, behavioral changes, altered mental status, focal neurologic deficits, seizures, ataxia, cranial nerve abnormalities, and eventually coma. Because the disease evolves slowly, the diagnosis may initially be confused with brain tumor, fungal infection, tuberculosis, or another chronic encephalitis. The prognosis is generally poor, particularly when diagnosis is delayed.

Acanthamoeba Keratitis Keratitis is one of the most clinically recognizable Acanthamoeba infections and often occurs in otherwise healthy individuals. The strongest risk factor is contact lens use, particularly when lenses are exposed to nonsterile water. Important exposures include rinsing lenses or lens cases with tap water, swimming or showering while wearing lenses, using contaminated cleaning products, or poor lens-case hygiene. Patients may develop severe eye pain, photophobia, tearing, redness, and reduced visual acuity. Pain may be disproportionately severe compared with the initial clinical appearance. Early disease may show punctate epithelial abnormalities or dendritiform lesions and can therefore be mistaken for herpes simplex keratitis. As infection progresses, stromal inflammation and a characteristic ring-shaped corneal infiltrate may develop. Early recognition is important because delayed treatment can lead to corneal destruction and permanent visual impairment.

Cutaneous and Disseminated Disease Cutaneous Acanthamoeba infection may present with slowly progressive erythematous papules, nodules, ulcers, or abscess-like lesions. These lesions can be chronic and may involve the face, trunk, or extremities. In markedly immunocompromised patients, skin disease may represent part of disseminated infection. Organisms can spread hematogenously to other sites, including the central nervous system. Persistent unusual skin lesions in an immunocompromised patient should therefore prompt consideration of opportunistic free-living amebic infection.

Diagnosis Diagnosis depends on identifying the organism in tissue or clinical specimens. Acanthamoeba may be cultured using specialized media, although culture is not always rapidly available. Cysts or trophozoites can sometimes be demonstrated directly in tissue specimens. Brain tissue, corneal tissue, or corneal scrapings may show the organism on histopathologic examination. Useful stains include silver-methenamine and periodic acid–Schiff stains. Organisms may rarely be visualized in fresh cerebrospinal fluid, but CSF examination has relatively low sensitivity. For keratitis, corneal scrapings or biopsy specimens may be evaluated using microscopy, culture, histopathology, and polymerase chain reaction. PCR can provide highly useful confirmation when available. Serologic testing has little clinical value and is generally not useful for establishing the diagnosis.

Diagnostic Approach to Keratitis Acanthamoeba should be strongly suspected in a contact lens wearer with severe keratitis, especially when symptoms persist despite antibacterial or antiviral therapy. A particularly suggestive pattern is severe ocular pain combined with a history of contact lens exposure to tap water or recreational water. Corneal scraping should be obtained for microbiologic evaluation when the diagnosis is suspected. PCR, culture, and direct visualization can all contribute to confirmation.

Differential Diagnosis Granulomatous encephalitis may resemble other chronic or subacute central nervous system infections, including fungal meningitis or encephalitis, tuberculosis, toxoplasmosis, and other free-living amebic infections. Neoplastic and inflammatory neurologic disorders may also mimic the presentation. Acanthamoeba keratitis can be confused with herpes simplex keratitis, bacterial keratitis, fungal keratitis, and other causes of corneal ulceration. Chronic cutaneous disease may mimic fungal infection, atypical mycobacterial infection, bacterial abscesses, inflammatory dermatoses, or malignancy.

Treatment Treatment of Acanthamoeba infection can be difficult because the organisms have both trophozoite and cyst forms, and the cysts are relatively resistant to therapy. For granulomatous amebic encephalitis, no single standardized regimen has been proven consistently effective. Therapy generally uses combinations of agents with demonstrated in vitro or reported clinical activity. Drugs that have activity against Acanthamoeba include pentamidine, azole antifungals, sulfonamides, flucytosine, and, to a lesser extent, amphotericin B. Combination therapy is usually favored for serious systemic or neurologic disease because monotherapy is unlikely to be reliably effective. Treatment should be individualized with infectious disease and neurologic expertise whenever possible.

Treatment of Acanthamoeba Keratitis Keratitis generally requires prolonged topical combination therapy. Older regimens included topical propamidine combined with neomycin, gramicidin, and polymyxin. Modern treatment commonly relies heavily on topical biguanides because they have activity against both trophozoites and cysts. Frequently used agents include: • Polyhexamethylene biguanide at approximately 0.02% • Chlorhexidine at approximately 0.02% These may be combined with diamidines such as propamidine in selected cases. Treatment is often prolonged because viable cysts may persist even after initial clinical improvement. Severe disease or inadequate response may require ophthalmologic surgical management, including corneal transplantation in selected cases.

General Prevention Prevention is especially important because Acanthamoeba is widespread and difficult to eliminate completely from the environment. Contact lens users should use only sterile, commercially prepared solutions for lens cleaning, rinsing, and storage. Tap water should never be used to clean or store contact lenses or lens cases. Contact lenses should generally be removed before swimming, showering, entering hot tubs, or participating in water activities unless appropriate protective measures are used. Lens cases should be cleaned according to manufacturer instructions, allowed to dry completely, and replaced regularly. Standard precautions are sufficient for hospitalized patients because routine person-to-person spread is not a major mode of transmission. Avoiding exposure of open wounds or vulnerable tissues to contaminated warm freshwater may also reduce risk.

High-Yield Clinical Pattern Contact lens wearer ● Severe eye pain ● Exposure of lenses to tap water, swimming water, or contaminated cleaning solution → Think Acanthamoeba keratitis.

High-Yield Neurologic Pattern Immunocompromised patient ● Slowly progressive encephalitis over days to weeks ● Granulomatous CNS disease → Consider Acanthamoeba granulomatous amebic encephalitis.

High-Yield Diagnostic Features Acanthamoeba may be identified by: • Corneal scraping or biopsy • Brain or skin biopsy • Specialized culture • Histopathology • PCR Serologic testing: → Generally not useful.

Exam Essentials Organism type:

→ Free-living protozoan Distribution:

→ Worldwide Environmental reservoirs:

→ Soil, freshwater, brackish water, dust, sewage, and hot tubs Major infections:

→ Granulomatous amebic encephalitis, keratitis, and chronic cutaneous disease Major risk group for encephalitis:

→ Immunocompromised or debilitated patients Major risk factor for keratitis:

→ Contact lens use with contaminated or nonsterile water exposure Keratitis may mimic:

→ Herpes simplex keratitis Important diagnostic methods:

→ Corneal scraping, biopsy, culture, histopathology, and PCR Useful histologic stains:

→ Periodic acid–Schiff and silver-methenamine stains Serology:

→ Not clinically useful Important topical agents for keratitis:

→ Biguanides such as chlorhexidine or polyhexamethylene biguanide Key prevention:

→ Use only sterile solutions for contact lens care and avoid tap-water exposure.