Balamuthia and the Brain

Abstract & Commentary

By Stan Deresinski, MD, FACP

Dr. Dereskinski is Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert. Peer reviewed by Connie Price, MD, Assistant Professor, University of Colorado School of Medicine.

Dr. Dereskinski serves on the speaker's bureau for Merck, Pharmacia, GlaxoSmithKline, Pfizer, Bayer, and Wyeth, and does research for Merck. Peer reviewer Connie Price, MD, reports no financial relationships relevant to this field of study.

This article originally appeared in the September 2008 issue of Infectious Disease Alert.

Synopsis: Amebic encephalitis due to Balamuthia mandrillaris is difficult to diagnose and often fatal, but must be considered by the clinician since it is potentially treatable.

Source: CDC. Balamuthia amebic encephalitis — California, 1999-2007. MMWR Morb Mortal Wkly Rep. 2008;57:768-771.

Central nervous system infection due to free-living amoebae generally manifests as either acute meningitis or focal encephalitis. The former, an acute neutrophilic meningeal infection that presents in a manner similar to that of acute infection due to pyogenic bacteria, is caused by Naegleria fowleri. The latter is caused by either Acanthamoeba species or by Balamuthia mandrillaris.

An increased recognition of the role of Balamuthia as a cause of encephalitis emerged from the California Encephalitis Project, which identified seven patients with evidence of encephalitis due to this organism selected from a group with a history of occupational contact with soil, or of swimming or camping, as well as elevated cerebrospinal fluid (CSF) protein level and pleocytosis, hydrocephalus, ring-enhancing lesions, or space-occupying lesions.1,2 This experience has now been updated to include 10 patients identified in California from 1999 to 2007 from among 500 meeting similar criteria. Two additional patients had serological evidence of infection but were not included because brain tissue was not available for confirmation.

Patients ranged from 1.5-72 years of age (median, 15.5 years); nine of the 10 were male. Neurological symptoms were the first indicator of disease. Presenting symptoms seen in more than one patient included seizure, headache, emesis, altered mental status, and cranial nerve palsy. The interval from the onset of symptoms to hospitalization ranged from 1-30 days (median, 8.5 days). Diagnoses under consideration included tuberculous meningitis, coccidioidomycosis, lymphoma, toxoplasmosis, viral infection, pyogenic brain abscess, tumor, and stroke. Only one patient, who was receiving corticosteroid therapy for nephritic syndrome, was known to have significant immunocompromise. Five patients had known contact with soil: occupational exposure in two, home gardening-related activities in two, and motorcycling in the desert in one. CSF analysis was performed in nine patients, and the protein concentration ranged from 64-674 mg/dL (median, 188 mg/dL), the glucose from 15-74 mg/dL (median, 40 mg/dL), and the WBC from 64-674 cells/mm3, with lymphocyte predominance. Neuroimaging generally demonstrated single or multiple focal-enhancing (usually ring-enhancing) lesions. Two patients had hydrocephalus without focal lesions; nine of the 10 patients died.

Commentary

B. mandrillaris was first identified in the brain of a mandrill baboon at the San Diego Zoo and was subsequently found to be a cause of encephalitis in humans. Since the discovery of this protozoan infection in 1986, there have been more than 100 human cases identified worldwide.3 Most cases have been found in individuals without significant immunocompromise, but many had exposure, often occupational, to soil, and some to stagnant water — both potential sources of free-living amoebae. In all but a few cases, the diagnosis was made at post-mortem examination. There have been only four survivors reported in the United States, each with varying degrees of neurological recovery. The current IDSA guidelines recommend this regimen plus a phenothiazine, which is reported to have in vitro activity against the organism.4 It should be noted, however, that three survivors from Peru have also been reported, and one received no therapy while the other two were given albendazole and itraconazole.

Since this rare disease appears to be treatable, clinicians must keep it in mind in their evaluation of patients with unexplained focal encephalitis. Tests that have been used for the diagnosis of balamuthiasis have included indirect fluorescent antibody testing of serum and PCR of cerebrospinal fluid. Currently an unequivocal diagnosis, however, requires detection of the organism in brain tissue with confirmation by indirect immunofluorescence staining of formalin-fixed tissue. Testing is performed at the CDC5 and by the California Encephalitis Project6 after prior approval.

References

  1. The California Encephalitis Project. http://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. Matin A, et al. Increasing importance of Balamuthia mandrillaris. Clin Microbiol Rev. 2008;21:435-448.
  4. Tunkel AR, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008;47:303-327.
  5. Contact Dr. Govinda Visvesvara at gsv1@cdc.gov.
  6. Contact Shilpa Gavali at shilpa.gavali@cdph.ca.gov.