Pathologic changes associated with brucellosis experimentally induced by aerosol exposure in rhesus macaques ( Macaca mulatta )

Mark G. MenseDepartment of Diagnostic Pathology, Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910-7500.
Present address is Armed Forces Institute of Pathology, Department of Veterinary Pathology, 14th & Alaska Ave NW, Washington, DC 20306-6000.

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Richard H. BorschelDepartment of Bacterial Diseases, Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910-7500.

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Catherine L. WilhelmsenDivision of Toxinology, U S Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011.
Present address is CDR, USAMRIID, MCMR-UI, 1425 Porter St, Fort Detrick, MD 21702-5011.

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M. Louise PittDivision of Toxinology, U S Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011.
Present address is CDR, USAMRIID, MCMR-UIT, 1425 Porter St, Fort Detrick, MD 21702-5011.

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David L. HooverDepartment of Bacterial Diseases, Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910-7500.

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Abstract

Objective—To develop an aerosol exposure method for induction of brucellosis in rhesus macaques ( Macaca mulatta ).

Animals—10 adult rhesus macaques.

Procedure—8 rhesus macaques were challenge exposed with 102 to 105 colony-forming units of Brucella melitensis 16M by use of an aerosol-exposure technique, and 2 served as control animals. All macaques were euthanatized 63 days after challenge exposure. Gross and microscopic lesions, bacterial burden in target organs, and histologic changes in tissues were evaluated.

Results—Grossly, spleen weights were increased in exposed macaques, compared with spleen weights in control macaques. Histologically, there was inflammation in the liver, kidneys, spleen, testes, and epididymides in exposed macaques. The spleen and lymph nodes had increased numbers of lymphohistiocytic cells. Morphometrically, the spleen also had an increased ratio of white pulp to red pulp. Areas of hepatitis and amount of splenic white pulp increased with increasing exposure dose.

Conclusions and Clinical Relevance—Pathologic findings in rhesus macaques after aerosol exposure to B melitensis are similar to those observed in humans with brucellosis.

Impact for Human Medicine—These results may aid in the development of a vaccine against brucellosis that can be used in humans. ( Am J Vet Res 2004;65: 644–652)

Abstract

Objective—To develop an aerosol exposure method for induction of brucellosis in rhesus macaques ( Macaca mulatta ).

Animals—10 adult rhesus macaques.

Procedure—8 rhesus macaques were challenge exposed with 102 to 105 colony-forming units of Brucella melitensis 16M by use of an aerosol-exposure technique, and 2 served as control animals. All macaques were euthanatized 63 days after challenge exposure. Gross and microscopic lesions, bacterial burden in target organs, and histologic changes in tissues were evaluated.

Results—Grossly, spleen weights were increased in exposed macaques, compared with spleen weights in control macaques. Histologically, there was inflammation in the liver, kidneys, spleen, testes, and epididymides in exposed macaques. The spleen and lymph nodes had increased numbers of lymphohistiocytic cells. Morphometrically, the spleen also had an increased ratio of white pulp to red pulp. Areas of hepatitis and amount of splenic white pulp increased with increasing exposure dose.

Conclusions and Clinical Relevance—Pathologic findings in rhesus macaques after aerosol exposure to B melitensis are similar to those observed in humans with brucellosis.

Impact for Human Medicine—These results may aid in the development of a vaccine against brucellosis that can be used in humans. ( Am J Vet Res 2004;65: 644–652)

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