Amebic Encephalitis— More Common Than You Might Think

Abstract & Commentary

By Stan Deresinski, MD, FACP Dr. Deresinski is Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center. Dr. Deresinski serves on the speaker’s bureau for Merck, Pharmacia, GlaxoSmithKline, Pfizer, Bayer, and Wyeth, and does research for Merck.

This article originally appeared in the June 2006 issue of Infectious Disease Alert. It was peer reviewed by Connie Price, MD. Dr. Price is Assistant Professor at the University of Colorado School of Medicine. She reports no financial relationship relevant to this field of study.

Synopsis: Antibody testing successfully identified 7 patients whose encephalitis was due to the free-living amoeba, Balamuthia mandrillaris, a pathogen that should be suspected in individuals with soil contact, high CSF protein, and mass-like or ring-enhancing brain lesions.

Source: Schuster FL, et al. Detection of Antibodies Against Free-Living Amoebae Balamuthia mandrillaris and Acanthamoeba Species in a Population of Patients with Encephalitis. Clin Infect Dis. 2006;42:1260-1265.

As part of the california encephalitis project (CEP), more than 250 serum samples from selected patients were screened for antibodies to amebic pathogens, particularly Balamuthia mandrillaris. Overall, the CEP has tested samples for > 1800 cases submitted for extensive testing in attempts to determine the etiology of encephalitis in patients without severe immunocompromise. Samples from individuals with a history of occupational contact with soil, or of swimming or camping, as well as elevated CSF protein level and pleocytosis, hydrocephalus, ring-enhancing lesions, or space-occupying lesions were selected for indirect immunofluorescent antibody testing (IFA) against Balamuthia.

While no cases had elevated IFA to Acanthamoeba species or to Naegleria fowleri, serum samples from 7 patients had IFA titers against B. mandrillaris of > 1:64, and all 7 were subsequently proven to have Balamuthia encephalitis by direct examination of brain tissue obtained at postmortem examination. The latter methods included hematoxylin-eosin staining, immunostaining, and polymerase chain reaction for detection of 16 rRNA. The median CSF protein concentration of 5 patients with Balamuthia infection was 1247 mg/dL, compared to 93 mg/dL (P < 0.001) in the seronegative group, while glucose levels (47 mg/dL vs 61 mg/dL) and WBC (106/mm3 vs 63/mm3) were not significantly different. All 7 patients with proven balamuthiasis were of Hispanic ethnicity.

One patient with confirmed Acanthamoeba encephalitis was identified during the course of the study, but that patient who was receiving corticosteroid therapy for systemic lupus erythematosus had what were considered to be negative antibody titers to this organism.

Commentary

Despite enormous diagnostic efforts, the CEP reported several years ago that the etiology of encephalitis remained unknown in at least 62% of cases.1,2 This report identifies a small, but significant number of cases that proved to be due to the free-living amoeba, B. mandrillaris. A number of additional patients with borderline titers could not be adjudicated because of lack of availability of brain tissue for examination, either because no postmortem examination was performed or the patient survived and was lost to follow-up. Nonetheless, the number of identified cases of encephalitis due to this pathogen exceeded the number of cases of human rabies during a similar time frame. Since the amoebal infection has greater potential for successful therapy3,4 directed against it than does rabies, Balamuthia encephalitis is, at least from one viewpoint, a clinically more important disease. Unfortunately, most cases of Balamuthia encephalitis are first diagnosed at post-mortem examination. In California, there were 2 survivors3 among 12 human cases identified from 1990-2005. The demonstration that infection may be identified by serum antibody testing provides hope that, with improved clinician awareness, cases will be more likely to be diagnosed antemortem in the future.

The onset of Balamuthia encephalitis is subacute, with months of symptoms prior to diagnosis or death. In addition to the progressive focal and non-focal central nervous system symptoms and findings, CSF examination generally reveals mild, predominantly lymphocytic pleocytosis, with normal or low glucose concentration, and protein concentrations that commonly exceed 1000 mg/dL. A case of amebic encephalitis due to Acanthamoeba has been diagnosed by visualization of the organism on cytological examination of CSF.4 Space-occupying, mass-like lesions and multiple ring-enhancing lesions may be seen. As pointed out by Schuster and colleagues, initial presumptive diagnoses have included tuberculosis, neurocysticercosis, viral encephalitis, bacterial brain abscess, tumor, and atypical disseminated encephalomyelitis. Balamuthia are free-living amoebae that are present in soil, and individuals such as construction and agricultural workers, among others, should be considered at increased risk.

At least 3 survivors have been identified. After identification of the organism in skin and brain biopsy specimens of a 64-year-old man, treatment involved 5-fluorocytosis, fluconazole, pentamidine isethionate, sulfadiazine, and clarithromycin, with subsequent improvement. There was worsening after discontinuation of fluconazole, with improvement once again after its reinitiation. The patient was then chronically maintained on therapy with fluconazole and sulfadiazine. A similar initial regimen was associated with improvement in a 5-year-old patient with confirmed brain infection.3 A 72-year-old apparently immunocompetent woman was successfully treated with pentamidine, sulfadiazine, fluconazole, and clarithromycin.5

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References

1. The California Encephalitis Project. www.ceip.us/encephalitis.htm

2. Glaser CA, et al. In Search of Encephalitis Etiologies: Diagnostic Challenges in the California Encephalitis Project, 1998-2000. Clin Infect Dis. 2003;36:731-742.

3. Deetz TR, et al. Successful Treatment of Balamuthia Amoebic Encephalitis: Presentation of 2 Cases. Clin Infect Dis. 2003;37:1304-1312.

4. Jung S, et al. Balamuthia mandrillaris Meningoencephalitis in an Immunocompetent Patient: An Unusual Clinical Course and a Favorable Response. Arch Pathol Lab Med. 2004;128:466-468.

5. Petry F, et al. Early Diagnosis of Acanthamoeba Infection During Routine Cytological Examination of Cerebrospinal Fluid. J Clin Microbiol. 2006;44: 1903-1904.