Balamuthia species

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Parasitology

Balamuthia mandrillaris, first isolated from the brain of a mandrill, and often referred to in the literature as a leptomyxid amoeba, also causes granulomatous amoebic encephalitis (GAE) (2,3,5,6). Most cases have been diagnosed at post-mortem examination and, as a consequence, nothing has been demonstrated to constitute effective therapy.

Epidemiology

Balamuthia species has been found in the soil and water. Infection probably occurs from inhalation of contaminated water or soil. Unlike Acanthamoeba species, Balamuthia species causes GAE in both immunocompromised and immunocompetent patients.

Clinical Manifestations

Granulomatous amoebic encephalitis (GAE), occur in either the very young or the very old and in AIDS patients. Patients with GAE present with a subacute course with evidence of progressive encephalitis but only slight or no fever. Computerized tomography and magnetic resonance imaging may reveal both enhancing and non-enhancing lesions. Both trophozoites and cysts are present. Multiple areas of brain may be involved, which mimic fungal and bacterial abscesses in patient with HIV infection. The infection may be indolent or progressive and usually results in death.

Laboratory Diagnosis

The diagnosis is usually made by visualization of Balamuthia species in biopsy or post-mortem specimens of both trophozoites and cysts. In tissue, the organism is readily visualized with hematoxylin and eosin staining, but cannot be differentiated reliably from Acanthamoeba; thus, definitive diagnosis must be made using immunofluorescent staining with species specific antibodies. Balamuthia may also be isolated in monoaxenic culture.

Pathogenesis

The pathogenesis of granulomatous amebic encephalitis (GAE) is poorly understood. The immunity is predominantly T-lymphocyte mediated and therefore depletion of CD4+ and T-helper cells results in replication of amoebae. The route of invasion is the bloodstream, the trophozoites and cysts are often seen around blood vessels and in necrotic CNS tissue. Balamuthia like acanthamoeba secrete cytolytic enzymes such as that may cause CNS damage.

SUSCEPTIBILITY IN VITRO AND IN VIVO

Schuster and Visvesvara examined the in vitro susceptibility of three strains of B. mandrillaris in axenic culture. When examined after 6 days of incubation, pentamidine isethionate and propamidine inhibited amoebal growth by approximately 80% when tested at 1 µg/ ml and 93% at 10 µg/ ml (4). At those concentrations, however, propamidine was toxic to monkey kidney cells. Polymyxin B and gramicidin S were each more than 95% inhibitory at 10 µg/ml; the former was 49% inhibitory at 1µg/ ml. Amphotericin B was only modestly inhibitory, as were the azoles tested. Trimethoprim-sulfamethoxazole had no inhibitory effect. Thus, these studies suggest that pentamidine is the most active among the drugs tested against this organism; it is, however, only amoebistatic rather than amoebicidal. Azithromycin was amoebastatic in tissue culture (rat glioma cells) monolayers at a concentrations > 0.1 μg/mL, but was ineffective in the absence of the monolayer (4). Complete inhibition of growth of the organism in tissue monolayer was obtained by exposure to various phenothiazines at a concentration of 5 μg/mL, but lesser activity was found in the absence of the monolayer.

ANTIPARASITIC THERAPY

In the absence of data to the contrary, recommendations for treatment of Acanthamoeba infection also apply to infections due to B. mandrillaris. Patients with GAE infection should be treated with parenterally administered pentamidine (4 mg/kg/d). It is reasonable to add at least one other drug; potential choices include 5-FC (approximately 100 mg/kg/d with adjustment for renal dysfunction) and itraconazole (200 mg-400 mg/d). A patient with infection due to this organism was successfully treated with clarithromycin 500 mg tid, fluconazole 400 mg qd, sulfadiazine 1.6 g q6h, and 5-fluorocytosine 1.5 g q6h (1).

ADJUNCTIVE THERAPY

Surgical excision of cerebral mass lesions due to granulomatous amebic encephalitis, should be considered if possible.

ENDPOINTS OF MONITORING THERAPY

Clinical endpoints for treating granulomatous amebic encephalitis (GAE) have not yet been determined. Patients may need therapy for many months after clinical response.

VACCINES

There are no vaccines for Balamuthia species.

REFERENCES

1. Anonymous. Drugs for Parasitic Infections. Medical letter, April, 2002, pp. 1-12, footnote no 9.

2. Denney CF, Iragui VJ, Uber-Zak LD, Karpinski NC, Ziegler EJ, Visvesvara GS, Reed SL. Amebic meninogencephalitis caused by Balamuthia mandrillaris: case report and review. Clin Infect Dis 1997; 25:1354-1358. [PubMed]

3. Deol I, Robledo L, Meza A, Visvesvara GS, Andrews RJ. Encepahilitis due to a free-living amoeba (Balamuthia mandrillaris): case report with literature review. Surg Neurol 2000; 53:611-616. [PubMed]

4. Schuster FL, Visvesvara GS. Axenic growth and drug sensitivity studies of Balamuthia mandrillaris, an agent of amebic meningoencephalitis in humans and other animals. J Clin Microbiol 1996; 34:385-388.[PubMed]

5. Visvesvara GS, Martinez AJ, Schuster FL, Leitch GJ, Wallace SV, Sawyer TK, Anderson M. Leptomyxid ameba: a new agent of amebic meningoencephalitis in humans and animals. J Clin Microbiol 1990; 28:2750-2756. [PubMed]

6. Visvesvara GS, Schuster FL, Martinez AJ. Balamuthia mandrillaris, N. G. N. Sp., agent of amebic meningoencephalitis in humans and other animals. J Eukaryotic Microbiol 1993; 40:504-514. [PubMed]