Acanthamoeba encephalitis: A Case Report and Review of Therapy.

Acanthamoeba Granulomatous Amebic Encephalitis: A Challenging and Often Fatal Diagnosis In the article “Acanthamoeba encephalitis: A case report and review of therapy”, the authors describe a classic case of Acanthamoeba granulomatous amebic encephalitis (GAE) in an immunocompromised patient. Given its rarity and the specific expertise needed to make the diagnosis, Acanthamoeba GAE remains a challenging diagnosis. The differential diagnosis is usually that of a space-occupying brain lesion and includes more common infections like bacterial brain abscess, tuberculosis, fungal infection, neurocysticercosis, and toxoplasmosis as well as noninfectious etiologies such as malignancy or stroke. The incubation period of Acanthamoeba GAE is unknown although, in disseminated infections with preceding cutaneous involvement, several weeks or months may elapse between the appearance of skin lesions and the recognition of central nervous system (CNS) disease.[6] Patients with Acanthamoeba GAE are usually immunocompromised and frequently present with an insidious and protracted onset of low-grade fever, headache, fatigue, weakness, and nausea. Patients will then progress to neurologic symptoms that may include altered mental status, hemiparesis, seizures, blurred vision, and diplopia. Other neurologic symptoms can also occur later in the course of illness such as cranial nerve palsies, dizziness, ataxia, confusion, and personality change.[7] Delayed diagnosis is common because of the slowly progressive and nonspecific nature of early disease as well as a lack of awareness of this infection among clinicians. Over the course of a week to several months from the onset of neurologic symptoms, the disease almost universally progresses to coma and death from increased intracranial pressure and brain herniation. Cerebrospinal fluid (CSF) from patients with Acanthamoeba GAE typically demonstrates a moderate lymphocytic pleocytosis. Protein may be elevated and glucose may be normal or low. Acanthamoeba organisms are rarely seen in the CSF. Computed tomography and magnetic resonance imaging scans of the brain frequently reveal single or multiple hypodense, ring-enhancing, space-occupying lesions. The diagnosis of Acanthamoeba GAE is usually made once affected brain tissue is obtained, whether via premortem biopsy as in the case presented here or postmortem, and amebic cysts and trophozoites are directly visualized in the tissue with hemotoxylin and eosin (H and E) staining by an experienced pathologist. The diagnosis of Acanthamoeba infection can be confirmed with immunohistochemical techniques that detect amebic antigen in the tissue or polymerase chain reaction (PCR) testing to detect Acanthamoeba DNA in the tissue.[5] Confirmatory testing is only available at selected reference diagnostic laboratories including at the U.S. Centers for Disease Control and Prevention (CDC). More often than not, Acanthamoeba infection is a fatal disease. Among 94 cases of Acanthamoeba infection reported to CDC from 1955 through 2013, mortality was 85% (CDC unpublished data). The rarity of this infection precludes the use of rigorous studies to examine effective treatment regimens; therefore, treatment recommendations rely solely on individual case reports of successful outcomes. Survivors were given multidrug regimens consisting of various combinations of pentamidine, sulfadiazine, flucytosine, fluconazole, itraconazole or voriconazole, trimethoprim-sulfamethoxazole, and miltefosine. The drug miltefosine has shown particular promise in treating free-living ameba infections, including those caused by Acanthamoeba and Balamuthia mandrillaris (a free-living ameba similar to Acanthamoeba that also causes GAE). Although the number of B. mandrillaris and Acanthamoeba infections treated with a miltefosine-containing regimen is small, it appears that a miltefosine-containing treatment regimen does offer a survival advantage for patients with these often fatal infections.[1] Finally, this patient's immunocompromised status was the result of an immunosuppressive regimen prescribed following a kidney transplant 6 months prior to symptom onset. In addition to the resulting immunosuppression, the patient's organ transplant also represented a possible route of exposure to Acanthamoeba. While there has not yet been a documented case of Acanthamoeba infection transmitted via solid organ transplant, the related free-living ameba, Balamuthia mandrillaris, has caused three clusters of organ transplant-transmitted infection when an infected donor's organs were transplanted into multiple recipients.[2,3,4] In the case presented here, transplant transmission was investigated and donor testing was negative for Acanthamoeba. However, the potential for transplant transmission remains and clinicians should be aware of the possibility when considering the diagnosis of Acanthamoeba infection. With increasing populations of immunocompromised patients, the diagnosis of Acanthamoeba GAE should be considered in an immunosuppressed patient with encephalitis and aggressively treated with a combination of antimicrobials. In solid organ transplant patients, the possibility of transplant-transmitted infection should be investigated so that other recipients can be prophylactically treated to prevent this deadly infection.