Human neurobrucellosis with intracerebral granuloma caused by a marine mammal Brucella spp - Dispatches

Emerging Infectious Diseases,  April, 2003  by Annette H. Sohn,  Will S. Probert,  Carol A. Glaser,  Nalin Gupta,  Andrew W. Bollen,  Jane D. Wong,  Elizabeth M. Grace,  William C. MacDonald

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We present the first report of community-acquired human infections with marine mammal-associated Brucella spp. and describe the identification of these strains in two patients with neurobrucellosis and intracerebral granulomas. The identification of these isolates as marine mammal strains was based on omp2a sequence and amplification of the region flanking bp26.

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Brucellosis, caused by intracellular gram-negative bacteria of the genus Brucella, is endemic in many areas of the world. Exposure occurs through contact with infected animals, meat, or unpasteurized milk products. Neurobrucellosis is a rare, severe form of systemic infection and has a broad range of clinical syndromes (1-3). Central nervous system Brucella granulomas have been infrequently reported in sellar and parasellar sites and in the spinal cord (4-6).

Although a number of Brucella spp. cause systemic disease in humans, they have species-specific primary reservoirs. The six recognized species of Brucella are primarily associated with terrestrial mammals and rodents. Recently, Brucella has been found to cause infections in marine mammals (7,8). An expansion of the six current nomen species of Brucella has been proposed to include one (B. maris) or two (B. pinnipediae and B. cetaceae) new nomen species to categorize these strains (7,8).

To date, only one human infection with a marine mammal strain has been reported; this infection occurred in a research laboratory worker after occupational exposure (9). We present the first report of community-acquired human infection with marine mammal-associated Brucella spp. and describe the identification of these strains from two patients with neurobrucellosis and intracerebral granulomas.

Case Reports

Patient 1

Patient 1 was a previously healthy, 26-year-old Peruvian man who was evaluated in July 1985 for a 3-month history of periorbital pain, headaches, and periodic generalized tonic-clonic seizures. The initial neurologic examination was nonfocal, but subsequent computerized tomography scan showed a 5x5-cm enhancing mass in the left frontoparietal region associated with midline shift.

At the time of surgical biopsy, frozen section histology raised the possibility of a high-grade astrocytoma or lymphoma, prompting resection of a 3x3-cm well-circumscribed left frontal lobe mass. Final examination of pathologic specimens showed granulomas with multinucleated giant cells (Figure 1). Bacterial, fungal, and acid-fast bacilli stains were negative. Based on these pathologic findings and concern that the patient may have had tuberculosis, treatment with isoniazid, rifampin, and ethambutol was begun. Serologic tests for Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, and Paracoccidioides brasiliensis were negative. Toxoplasma gondii serologic titers were weakly positive at 1:64.

[FIGURE 1 OMITTED]

On postoperative day 39, fungal tissue cultures became positive for a Brucella spp., preliminarily identified as B. melitensis. The patient's antimicrobial treatment was changed to tetracycline and rifampin and was continued for 2 months. An initial serologic titer for Brucella was positive at 1:160 by tube agglutination assay. A follow-up serologic titer obtained in January 1986 was negative (<1:20).

Three months before his initial evaluation, the patient had immigrated to the United States from Lima, Peru. His diet included regular consumption of unpasteurized cow or goat cheese (queso fresco) and occasional consumption of raw shellfish (ceviche). He denied eating other raw or significantly undercooked meat. He had frequently swum in the Pacific Ocean from December through March but recalled no direct contact with marine mammals.

Patient 2

Patient 2 was a 15-year-old Peruvian boy seen in September 2001 with a 1-year history of headaches, nausea, vomiting, and progressive deterioration in visual function. A magnetic resonance imaging (MRI) scan performed in April 2001 showed several large, irregular enhancing mass lesions involving the left occipital and parietal lobes (Figure 2). He had come to the United States in September for further evaluation. On neurologic examination, the patient had a right homonymous hemianopsia, optic nerve atrophy, and major visual impairment (left eye--20/100; right eye--20/200). Repeat MRI showed several irregular areas of enhancement in the left parietooccipital area associated with marked brain edema, left-to-right shift, and mass effect (Figure 2).

[FIGURE 2 OMITTED]

The patient was taken to surgery, where a firm avascular mass was found beneath a 0.5-cm layer of softer gliotic cortical tissue. Frozen sections showed lymphohistiocytic infiltrates with granuloma formation. Specimens for cultures and histopathologic examination were obtained. Bacterial, fungal, and acid-fast bacilli stains were negative. Final histopathologic examination showed numerous granulomas with multinucleated giant cells but no organisms (Figure 1).

Serologic test results for Brucella, T. gondii, and Taenia soleum were negative. On postoperative day 8, mycobacteria cultures (BacT/ALERT MP; Organon Teknika Corp., Durham, NC) showed growth of a gram-negative coccobaccillus, later confirmed as Brucella spp. Treatment with rifampin, doxycycline, and intravenous gentamicin was begun. After 1 week, the gentamicin was discontinued per current recommendations, and trimethoprim-sulfamethoxazole was started. Follow-up imaging 7 months later demonstrated resolution of the enhancing areas and edema, with residual areas of brain atrophy (Figure 2). The patient's vision improved, but some visual acuity deficits persisted. Anti-brucella therapy continued for 1 year.