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Published on: June 23, 2019
Pathologic changes associated with brucellosis experimentally induced by aerosol exposure in rhesus macaques (Macaca
Mark G Mense1, Richard H Borschel, Catherine L Wilhelmsen
1Department of Diagnostic Pathology, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA.
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 10(2) to 10(5) 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.
Insights
Researchers developed an aerosol method to induce brucellosis in rhesus macaques. This model shows pathology similar to human brucellosis, aiding vaccine development.
Area of Science:
- Veterinary Pathology
- Infectious Disease Research
- Primate Models
Background:
- Brucellosis is a significant zoonotic disease with limited effective treatments.
- Developing reliable animal models is crucial for understanding brucellosis pathogenesis and testing interventions.
Purpose of the Study:
- To establish an aerosol exposure method for inducing brucellosis in rhesus macaques (Macaca mulatta).
- To characterize the pathological outcomes following aerosolized Brucella melitensis challenge.
Main Methods:
- Ten adult rhesus macaques were used, with eight exposed to varying doses of *Brucella melitensis* 16M via aerosol.
- Two macaques served as controls.
- Animals were euthanized 63 days post-exposure for gross and microscopic evaluation, including bacterial burden and tissue histology.
Main Results:
- Increased spleen weights and inflammation in multiple organs (liver, kidneys, spleen, testes, epididymides) were observed in exposed macaques.
- Histological analysis revealed increased lymphohistiocytic cells in spleen and lymph nodes, and an elevated white pulp to red pulp ratio in the spleen.
- Dose-dependent increases in hepatitis and splenic white pulp were noted.
Conclusions:
- Aerosol exposure effectively induces brucellosis in rhesus macaques, mimicking key pathological findings in human cases.
- This model provides a valuable platform for studying brucellosis and developing human vaccines.
