Histological findings in human brucellosis

Hunt, A. C.; Bothwell, P. W.

doi:10.1136/jcp.20.3.267

Cited by 48 publications

(29 citation statements)

References 19 publications

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“…Consistent with human disease, there were microscopic lesions associated with the liver, lung, spleen, lymph nodes, and kidney (16). The inflammation and necrosis observed in the current study were consistent with the findings reported by Mense et al (18), who also studied B. melitensis aerosol-infected RMs, and what is observed in human brucellosis pathology.…”

Section: Discussionsupporting

confidence: 92%

Pathophysiology of the Rhesus Macaque Model for Inhalational Brucellosis

et al. 2012

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The objective of this study was to characterize the rhesus macaque (RM) as a model for inhalational brucellosis in support of the U.S. Food and Drug Administration's (FDA) Animal Rule. The pathophysiology of chronic Brucella melitensis aerosol infection was monitored in two phases that each occurred over an 8-week time period; dose escalation (8 RMs; targeted doses of 5.0E؉03, 5.0E؉04, or 5.0E؉05 CFU/animal or the unchallenged control) and natural history (12 RMs; targeted dose of 2.50E؉05 CFU/ animal or the unchallenged control). RMs given an aerosol challenge with B. melitensis developed undulating fevers (6/6 phase I; 8/9 phase II), positive enriched blood cultures (5/10; phase II), and bacterial burdens in tissues starting 14 to 21 days postchallenge (6/6 phase I; 10/10 phase II). In addition, 80% (8/10; phase II) of infected RMs seroconverted 14 to 21 days postchallenge. RMs developed elevations in certain liver enzymes and had an increased inflammatory response by 3 weeks postchallenge as shown by increases in C-reactive protein (6/8) and neopterin (4/8), which correlated with the onset of a fever. As early as 14 days postchallenge, positive liver biopsy specimens were detected (2/8), and ultrasound imaging showed the development of splenomegaly. Finally, histopathologic examination found lesions attributed to Brucella infection in the liver, kidney, lung, and/or spleen of all animals. The disease progression observed with the RMs in this study is analogous to human brucellosis pathophysiology. Thus, the results from this study support the use of the RM as an animal model for inhalational brucellosis to evaluate the efficacy of novel vaccines and therapeutics against B. melitensis. Brucella is a Gram-negative coccobacillus that includes certain species that can cause disease in animals and humans. Brucella melitensis, one of the major species of Brucella, is an etiologic agent for brucellosis. This highly infectious pathogen can infect animals and humans, and it is considered to be one of the most severe human pathogens in the Brucella genus (25). Humans are usually infected following contact with infected animals or ingestion of contaminated milk, milk products, and meat. In addition, brucellosis is one of the most common laboratory-acquired infections, as well as the most common zoonosis (11). While B. melitensis is not typically considered a lethal pathogen in humans (less than 5% fatality rate), it can cause significant disease. Human brucellosis presents as a prolonged febrile illness with flu-like symptoms, such as night sweats, headache, depression, and arthritis. Chronic illness can lead to meningitis and endocarditis. In addition, relapses can occur, even with antibiotic treatment (13). Notably, humans can remain asymptomatic for weeks, months, or even years while infected with this pathogen (3).Brucella species are considered potential biological warfare agents due to their high infectivity, ability to debilitate infected people, and the persistent nature of human disease. In addition, Brucella i...

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Section: Discussionsupporting

confidence: 92%

Pathophysiology of the Rhesus Macaque Model for Inhalational Brucellosis

et al. 2012

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“…Because of the concomitant immunosupression of a normal antibody response in these malignancy patients, anti-brucella titers may be of no value, and culture of the organism may be necessary to make a diagnosis. Moreover, brucellosis may be responsible for deterioration and death in such cases [32]. In our cases, blood and/or marrow cultures were positive in all patients and no deterioration or death was observed because of brucellosis.…”

Section: Discussionsupporting

confidence: 48%

“…In the medical literature, solid tumors or hematological malignancies associated with brucellosis are extremely rare. Previously, multiple myelomas, hepatocellular carcinoma, sinus histiocytosis with massive lymphadenopathy, hairy cell leukemia, Hodgkin's disease, and non-Hodgkin lymphoma have been reported in association with brucellosis [9,10,[29][30][31][32]. Because of the concomitant immunosupression of a normal antibody response in these malignancy patients, anti-brucella titers may be of no value, and culture of the organism may be necessary to make a diagnosis.…”

Section: Discussionmentioning

confidence: 99%

A multicenter retrospective study defining the clinical and hematological manifestations of brucellosis and pancytopenia in a large series: Hematological malignancies, the unusual cause of pancytopenia in patients with brucellosis

et al. 2007

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The aim of the study is to review the clinical manifestations and the hematological findings of brucellosis and pancytopenia, with or without hematological malignancies. The records of 202 patients with brucellosis were evaluated retrospectively. Among these cases of brucellosis seen in a 6 year period between April 1999 and June 2005, 30 patients with pancytopenia were identified. The most common manifestation was fever, followed by weight loss, anorexia, malaise, arthralgia, and hepatosplenomegaly. Bone marrow biopsies revealed hypercellularity or normocellularity. The most common findings in the bone marrow evaluation were histiocytic hemophagocytosis and granulomas. Among all cases, we diagnosed 5 hematological malignancies (1 acute myelogenous leukemia, 2 acute lymphoblastic leukemia, and 2 multiple myeloma) concurrently with brucellosis. The clinical symptoms and findings were similar in patients with and without malignancies. In cases with malignancies, the bone marrow biopsy revealed predominant primary disease involvement. Significant increases in ESR and CRP, severe anemia and thrombocytopenia were observed in patients with malignancies. Peripheral blood counts in patients without malignancies returned to normal after antibiotic treatment for brucellosis. However, pancytopenia in two patients with malignancies did not recover because of primary resistant disease. We conclude that while histiocytic hemophagocytosis may be considered as a major cause of pancytopenia, leukemic infiltration can also be an extreme and unusual cause of pancytopenia in patients in whom brucellosis was concurrently diagnosed with hematological malignancies. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.

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“…The hallmark of brucella lesions in the heart is endocarditis. [21][22][23] This may involve the cardiac valves and, if not treated promptly, may ultimately lead to fibrosis, hyalini-zation, and calcification within the valve, thus producing valvular deformities indistinguishable from those seen in patients with rheumatic valvulitis. Vegetations may also be seen on the endocardial surface of the valves.…”

Section: Discussionmentioning

confidence: 99%

“…There may be diffuse increase in the numbers of macrophages with scattered granulomas. 21 Involvement of the genitourinary tract by brucella infection is uncommon. Chronic inflammation of the urinary bladder, prostate, testes, and epididymis with or without granulomas may be seen.…”

Section: Discussionmentioning

confidence: 99%