Isolation of<i>Brucella abortus</i>by Percutaneous Liver Biopsy

Cohen, Fred; Robins, B; Lipstein, William

doi:10.1056/nejm195708012570508

Cited by 13 publications

(7 citation statements)

References 5 publications

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“…B. neotomae infection was associated with a granulomatous immune response most evident in the liver, also observed during human infection (43,44) and infection of mice with zoonotic and attenuated Brucella species and strains (7). Related to these observations, the pattern of inflammatory cytokine transcriptional induction by B. neotomae during early infection was consistent with a virB4-dependent Th1 response previously observed during murine infection (45)(46)(47), a Th1 response observed during human infection (48), and the known association of Th1 cytokine induction with a granulomatous response to chronic bacterial infections (49).…”

Section: Discussionmentioning

confidence: 90%

Brucella neotomae Recapitulates Attributes of Zoonotic Human Disease in a Murine Infection Model

Kang

Brown

2019

Infect Immun

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Members of the genus Brucella are Gram-negative pathogens that cause chronic systemic infection in farm animals and zoonotic infection in humans. Study of the genus Brucella has been hindered by the need for biosafety level 3 select agent containment. Brucella neotomae, originally isolated from the desert pack rat, presented an opportunity to develop an alternative, non-select agent experimental model. Our prior in vitro work indicated that the cell biology and type IV secretion system (T4SS) dependence of B. neotomae intracellular replication were similar to observations for humanpathogenic select agent Brucella species. Therefore, here, we investigated the pathobiology of B. neotomae infection in the BALB/c mouse. During a sustained infectious course, B. neotomae replicated and persisted in reticuloendothelial organs. Bioluminescent imaging and histopathological and PCR-based analysis demonstrated that the T4SS contributed to efficient early infection of the liver, spleen, and lymph nodes; granuloma formation and hepatosplenomegaly; and early induction of Th1-associated cytokine gene expression. The infectious course and pathologies in the murine model showed similarity to prior observations of primate and native host infection with zoonotic Brucella species. Therefore, the B. neotomae BALB/c infection model offers a promising system to accelerate and complement experimental work in the genus Brucella. KEYWORDS Brucella, Brucella neotomae, brucellosis, bioluminescent imaging, murine model, pathogenesis, pathology, type IV secretion system, undulant fever M embers of the genus Brucella, Gram-negative coccobacilli, cause systemic bacterial infections in domesticated farm animals and other vertebrates (1). Humans may be infected through ingestion of unpasteurized dairy products, inhalation of organisms from birthing farm animals, and during occupational exposure in abattoir and meat packing industries. Disease in humans is characterized by chronicity and a waxing and waning fever (so-called undulant fever). Lymph node infection and enlargement are common (2); endovascular and osteoarticular infection are unwelcome and not infrequent complications (3,4).Based on the low aerosol infectious dose and debilitating disease, the major zoonotic species, Brucella melitensis, Brucella abortus, and Brucella suis, are classified as biosafety level 3, category B overlap select agents (5). Biosafety containment and select agent regulations represent significant impediments to experimental investigation.Brucella organisms have been studied in several in vitro and in vivo model systems (6)(7)(8)(9). In vitro assays have demonstrated the capability of Brucella species to grow within specialized vacuoles inside of macrophages, endothelial cells, and other cell types. In particular, Brucella species alter the normal process of phagosomal maturation. Remodeling of the phagosome occurs in a temporal fashion in which organisms are first found within endocytic vacuoles that subsequently take on properties of the endoplasmic reticulum an...

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Section: Discussionmentioning

confidence: 90%

Brucella neotomae Recapitulates Attributes of Zoonotic Human Disease in a Murine Infection Model

Kang

Brown

2019

Infect Immun

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“…Brucellae have been found in liver tissue even in cases without any laboratory liver function changes (25). Following brucellosis, change of liver function tests are non-specific and consist of a moderate increase of alkaline phosphatase (Alp) and serum transaminase (Alt, Ast) activity (26).…”

Section: Discussionmentioning

confidence: 99%

Clinical Manifestations and Laboratory Findings of Brucellosis at Boo-Ali-Siena Hospital of Ghazvin Province of Iran

Najari

Sigaroudi

Rastgoo

2018

Jundishapur J Health Sci

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Background: Brucellosis as a zoonotic disease is controlled in many developed countries though it still remains endemic in the majority of Middle Eastern and developing countries. Objectives: The purpose of this study was to identify the demographic features, clinical manifestations, and laboratory tests of patients diagnosed with brucellosis in Ghazvin province of Iran. Methods: In this cross-sectional study, medical records of 83 cases with brucellosis (54 males and 29 females) over a 3-year period (from June, 2012 to June, 2015) were reviewed, retrospectively. Demographic features, clinical signs and symptoms, hematologic findings, and liver enzyme level were derived from the patients' medical record. Results: The mean age of cases was 42.5±18.3 years. Constitutional symptoms, which were noted in 45 (54%) cases, were the most common symptom of the disease. Clinical manifestations, including Sacroileitis, arthritis, and epididymo-orchitis were seen in 20 (24.1%), 10 (12%), and 7 (8.4%) cases, respectively. One case of Endocarditis (1.2%) was noted. Anemia as the most frequent blood abnormality was seen in 44 (53%) cases. Leukopenia and leukocytosis were noted in 17 (20.5%) and 9 (10.8%) patients, respectively. Thrombocytopenia and thrombocytosis were detected in 26 (31.3%) and 3 (3.6%) of the patients, respectively. Bicytopenia and pancytopenia were revealed in 9 (10.8%) and 11 (13.3%) cases, respectively. Elevated level of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were detected in 29 (34.9), 37 (44.6), and 51 (61.5) patients, respectively. Conclusions: Brucellosis could affect every organ system of the human body. Variable manifestations and laboratory findings of brucellosis must be kept in mind, especially in endemic areas.

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“…Because of the suboptimal recovery rate of brucellae from blood, it has been suggested that cultures of bone marrow (1,11,14,25,34), liver tissue (6,9), or lymph nodes (21) may improve the recovery rate of the organism. The rationale for these alternative approaches is that Brucella organisms survive the intracellular killing by phagocytes and polymorphonuclear leukocytes and localize in the reticuloendothelial system (14,29,34).…”

Section: Role Of Blood Cultures In Diagnosis Of Human Brucellosismentioning

confidence: 99%