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Journal articles on the topic 'Brucella Infection'
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1
Elfaki, Mohamed G., Alwaleed Abdullah Alaidan, and Abdullah Abdulrahman Al-Hokail. "Host response to Brucella infection: review and future perspective." Journal of Infection in Developing Countries 9, no. 07 (2015): 697–701. http://dx.doi.org/10.3855/jidc.6625.
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Brucellosis is a zoonotic and contagious infectious disease caused by infection with Brucella species. The infecting brucellae are capable of causing a devastating multi-organ disease in humans with serious health complications. The pathogenesis of Brucella infection is influenced largely by host factors, Brucella species/strain, and the ability of invading brucellae to survive and replicate within mononuclear phagocytic cells, preferentially macrophages (Mf). Consequently, the course of human infection may appear as an acute fatal or progress into chronic debilitating infection with periodical episodes that leads to bacteremia and death. The existence of brucellae inside Mf represents one of the strategies used by Brucella to evade the host immune response and is responsible for treatment failure in certain human populations treated with anti-Brucella drugs. Moreover, the persistence of brucellae inside Mf complicates the diagnosis and may affect the host cell signaling pathways with consequent alterations in both innate and adaptive immune responses. Therefore, there is an urgent need to pursue the development of novel drugs and/or vaccine targets against human brucellosis using high throughput technologies in genomics, proteomics, and immunology.
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Meador, Vincent P., and Billy L. Deyoe. "Effect of milk stasis on Brucella abortus infection of the mammary gland in goats." American Journal of Veterinary Research 52, no. 6 (1991): 886–90. http://dx.doi.org/10.2460/ajvr.1991.52.06.886.
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SUMMARY To compare the effects of milk stasis and milk flow on Brucella abortus infection of the mammary gland under the same systemic conditions, primiparous goats (n = 5) were inoculated iv with B abortus on the day of parturition, and suckling by their neonates was restricted to one mammary gland. Goats were euthanatized and necropsied at 3 weeks after inoculation, and milk, mammary glands, and supramammary lymph nodes were evaluated by bacteriologic, histologic, and immunoenzymatic staining techniques. Nonnursed mammary glands had high titers of brucellae in milk, moderate interstitial mastitis, and brucellar antigen in macrophages located primarily in alveolar and ductal lumina. Brucellae often filled the macrophage cytoplasm. In contrast, nursed mammary glands had fewer brucellae in milk, minimal inflammatory changes, and no detectable brucellar antigen in histologic sections. Hyperplastic changes were only seen in supramammary lymph nodes draining nonnursed mammary glands; these contained more brucellae than lymph nodes draining nursed mammary glands. These studies show that milk stasis may be the sole cause of increased susceptibility of nonnursed mammary glands to B abortus infection.
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Meador, Vincent P., and Billy L. Deyoe. "Experimentally induced Brucella abortus infection in pregnant goats." American Journal of Veterinary Research 47, no. 11 (1986): 2337–42. https://doi.org/10.2460/ajvr.1986.47.11.2337.
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SUMMARY Pregnant goats in midgestation (7 to 16 weeks) were conjunctivally exposed to Brucella abortus strain 2308 to evaluate their applicability as an animal model for bovine brucellosis. Brucellae were isolated from uterine fluid and/or placental specimens of 10 of 12 does at parturition. Six of the 10 infected does delivered dead fetuses and 1 of the 10 delivered live, premature twins. Dead fetuses typically contained brucellae in multiple tissues, whereas brucellae generally were not isolated at birth from live kids. After parturition, B abortus was excreted in the milk and uterine fluids of the infected does. At necropsy (6 weeks after parturition), organisms in the doe were primarily in the uterus and in the lymph nodes that drained the mammary glands, uterus, and head. Brucella abortus was most often isolated from the cranial lymph nodes of neonates that had remained with their dam for 6 weeks after parturition. Serum anti-Brucella antibody concentrations were determined by use of standard tube agglutination, mercaptoethanol agglutination, Rivanol plate tests, card tests, complement fixation, hemolysis-in-gel tests, and an enzyme-linked immunosorbent assay. Serologic responses were detected 2 to 3 weeks after exposure and remained detectable until parturition. Antibody titers increased after parturition in does shedding B abortus at parturition. Anti-Brucella antibody was not detected in neonates before colostrum intake. The neonate’s postcolostral titers were similar to those in the dam at the time of parturition. Milk anti-Brucella antibody was detected in milk (milk ring test) from infected and noninfected mammary glands. Results of the study indicated that goats are susceptible to a bovine pathogenic strain of B abortus and should be a suitable animal model for the study of bovine brucellosis.
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Karponi, Garyfalia, Spyridon K. Kritas, Eleni Papanikolaou, and Evanthia Petridou. "A Cellular Model of Infection with Brucella melitensis in Ovine Macrophages: Novel Insights for Intracellular Bacterial Detection." Veterinary Sciences 6, no. 3 (2019): 71. http://dx.doi.org/10.3390/vetsci6030071.
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Intracellular bacteria provoking zoonoses, such as those of the genus Brucella, present a host cell tropism mostly limited to the monocyte/macrophage lineage, leading to chronic inflammatory reactions, difficult-to-eradicate-infections, and widespread prevalence among ruminants. Eradication of brucellosis has been based on programs that translate into a substantial financial burden for both the authorities and stockbreeders, if not strictly followed. To this end, we sought to create an in vitro cell model that could be utilized as future reference for adequately measuring the number of engulfed brucellae/cell, using peripheral blood-derived sheep macrophages infected with B. melitensis at decimal multiplicities of infection (MOI = 5000-5), to simulate the host cell/microorganism interaction and monitor bacterial loads up to 6 days post-infection. We show that the MOI = 5000 leads to high numbers of engulfed bacteria without affecting macrophages’ viability and that the minimum detection limit of our Real-Time PCR assay was 3.97 ± 5.58 brucellae/cell. Moreover, we observed a time-associated, significant gradual reduction in bacterial loads from Day 2 to Day 6 post-infection (p = 0.0013), as part of the natural bactericidal properties of macrophages. Overall, the work presented here constitutes a reliable in vitro cell model of Brucella melitensis for research purposes that can be utilized to adequately measure the number of engulfed brucellae/cell and provides insights towards future utilization of molecular biology-based methods for detection of Brucella.
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Caron, E., A. Gross, J. P. Liautard, and J. Dornand. "Brucella species release a specific, protease-sensitive, inhibitor of TNF-alpha expression, active on human macrophage-like cells." Journal of Immunology 156, no. 8 (1996): 2885–93. http://dx.doi.org/10.4049/jimmunol.156.8.2885.
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Abstract Brucella species can establish themselves and cause disease in humans, but the mechanisms by which brucellae evade the antibacterial defenses of their host remain largely unknown. We have previously reported that, unlike Escherichia coli K12, intracellular pathogens from the genus Brucella survive and multiply within U937-derived phagocytes, and live Brucella organisms failed to induce TNF-alpha release upon infection. Moreover, exogenously added TNF-alpha restricted intracellular growth of Brucella species. Herein, we demonstrate that Brucella-infected U937 cells are activated to express IL-1 beta and IL-6 at both the mRNA and protein levels, while they cannot accumulate TNF-alpha mRNA. When physically separated from macrophages, live brucellae impaired TNF-alpha production in E. coli-infected cells. Moreover, in agonist-activated macrophages, supernatants from Brucella cultures promoted an inhibition of the induction of both TNF-alpha expression and release, without affecting IL-1 beta or IL-6 induction. These phenomena, observed whatever the Brucella strain assayed, show that brucellae release some high m.w. factor(s) that specifically inhibits TNF-alpha expression in activated human macrophages. The proteic nature of the factor(s) was demonstrated by its heat and protease sensitiveness, and this could explain why U937-derived macrophages did release TNF-alpha when infected with chloramphenicol-treated brucellae. We also found that the Brucella factor(s) specifically acts on human macrophagic cells, but not on murine macrophage-like cells. Our findings provide direct evidence that a secreted Brucella virulence factor(s) inhibiting TNF-alpha expression might contribute to the evasion of Brucella organisms from human antimicrobial defenses.
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Skyberg, Jerod A., Theresa Thornburg та David W. Pascual. "IL-17 is required for protective immunity to nasal Brucella infections in an IFN-γ-dependent fashion (39.23)". Journal of Immunology 182, № 1_Supplement (2009): 39.23. http://dx.doi.org/10.4049/jimmunol.182.supp.39.23.
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Abstract Th1 and Th17 cells are the principal mediators of the inflammatory pathways. While the role of Th1 cells have been extensively studied for Brucella infections, there is little information on the function of IL-17 in response to Brucella infections. To evaluate such role, mice functionally deficient in IL-17 or IL-17 receptor (IL-17R-/-) mice were more susceptible to nasal Brucella infection than immunocompetent mice as evidenced by increased splenic weights and splenic CFUs. Interestingly, inhibition of IL-17 failed to enhance the IFN-γ response, but instead RT-PCR analysis revealed greater lung IL-13 mRNA transcripts than lungs from IL-17-sufficient mice. Splenic mononuclear cells from Brucella-infected mice depleted of IL-17 produced more IL-10, but less IFN-γ and IL-17 upon subsequent restimulation with heat-killed brucellae than the same cells from IL-17-sufficient mice. Interestingly, splenic mononuclear cells from infected IFN-γ-/- mice produced less IL-17, indicating that mice blocked in either IL-17 or IFN-γ pathways are impaired in their ability to produce either cytokine when infected with Brucella. These results implicate IL-17 is important for protection against nasal Brucella infections, and that IL-17 in combination with IFN-γ modulates the host immune responses to Brucella. This work is supported by USDA 2007-0612 and 2008-03776.
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Khan, Mike, Diogo Magnani, Jerome Harms, et al. "Brucella induces an unfolded protein response via TcpB in macrophages (P3116)." Journal of Immunology 190, no. 1_Supplement (2013): 186.5. http://dx.doi.org/10.4049/jimmunol.190.supp.186.5.
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Abstract Brucella melitensis is a facultative intracellular bacterium that invades and replicates within macrophages and dendritic cells. With greater than 500,000 new infections per year, brucellosis is the most prevalent zoonosis worldwide. Currently, a safe and effective human vaccine does not exist and Brucella’s intracellular replicative niche renders the organism resistant to antibiotics. A better understanding of host-pathogen interactions supporting Brucella replication is necessary for vaccine and therapeutic development. Brucella fuses with the endoplasmic reticulum (ER) in order to replicate and may provoke a conserved ER stress response called the Unfolded Protein Response (UPR). B. melitensis infection in RAW 264.7 murine macrophages and bone marrow-derived macrophages upregulated the UPR target genes BiP, CHOP, and ERdj4, and induced XBP1 mRNA splicing. Upregulation of CHOP and ERdj4 was MyD88-independent whereas XBP1 splicing was MyD88-dependent. A Brucella TcpB mutant showed significantly reduced expression of BiP, CHOP, and ERdj4. Purified TcpB, a microtubule-modulating protein, induced UPR target genes. Also, purified TcpB caused ER restructuring similar to infection with B. melitensis. Finally, Brucella replication was significantly impaired by tauroursodeoxycholic acid, a pharmacologic UPR inhibitor. These results suggest that Brucella induces the UPR to enable its intracellular replication and thus provides a novel therapeutic target for brucellosis treatment.
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Eisenberg, Tobias, Karen Schlez, Ahmad Fawzy, et al. "Expanding the host range: infection of a reptilian host (Furcifer pardalis) by an atypical Brucella strain." Antonie van Leeuwenhoek 113, no. 10 (2020): 1531–37. http://dx.doi.org/10.1007/s10482-020-01448-9.
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Abstract Atypical brucellae show deviant phenotypes and/or genotypes. Besides Brucella inopinata, B. microti and B. vulpis, atypical strains have been described infecting humans, rodents, amphibians and fish. They represent potential zoonotic agents. Here, we provide evidence that reptiles as the remaining poikilothermic vertebrate class also represent susceptible hosts for atypical Brucella.
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Godfroid, Jacques. "Brucella spp. at the Wildlife-Livestock Interface: An Evolutionary Trajectory through a Livestock-to-Wildlife “Host Jump”?" Veterinary Sciences 5, no. 3 (2018): 81. http://dx.doi.org/10.3390/vetsci5030081.
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Brucella infections in wildlife have gained a lot of interest from the scientific community and different stakeholders. These interests are often different and sometimes conflicting. As a result, different management perspectives and aims have been implemented (One Health, public health, veterinary public health, maintenance of a brucellosis free status in livestock, sustainable wildlife harvesting by hunters, wildlife and environmental health). When addressing Brucella infection in wildlife, the most important features of Brucella infection should be considered and the following questions need to be answered: (1) Is Brucella infection a result of a spillover from livestock or is it a sustainable infection in one or more wildlife host species? (2) Did the epidemiological situation of Brucella infection in wildlife change over time and, if so, what are the main drivers of change and does it impact the wildlife population dynamics? (3) Does Brucella infection in wildlife represent a reservoir of Brucella strains for livestock? (4) Is Brucella infection in wildlife of zoonotic concern? These questions point to the fundamental biological question of how animal (domestic and wildlife)/Brucella spp. partnerships are established. Will we be able to decipher an evolutionary trajectory through a livestock-to-wildlife “host jump”? Whole genome sequencing and new “omics” techniques will help in deciphering the molecular basis of Brucella host preference and open new avenues in brucellosis management aimed at preventing opportunities for Brucella host jumps.
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Skyberg, Jerod, Theresa Thornburg, Irina Kochetkova, et al. "IL-1 receptor antagonist augments antibiotic resolution of joint inflammation in a novel model of Brucella-induced osteoarthritis (56.7)." Journal of Immunology 186, no. 1_Supplement (2011): 56.7. http://dx.doi.org/10.4049/jimmunol.186.supp.56.7.
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Abstract Infection of the joints is the most frequent localized manifestation of brucellosis, which is a common cause of infectious arthritis. However, no experimental murine model of Brucella-induced arthritis has been reported. Here we report that IFN-γ-/- mice develop joint inflammation following oral, nasal, or parenteral infection with B. abortus or B. melitensis. Joints from Brucella-infected IFN-γ-/-, but not wild-type mice, were found to contain extensive inflammatory infiltrates and debris within the joint space which co-localized with brucellae. Osteoarthritis, joint space narrowing, necrosis, soft tissue inflammation, and substantial Brucella burdens were also observed, although antibody or cytokine responses against collagen were not detected. Elevated IL-1β, but not TNF-α, IL-6, nor IL-17, was detected in the joints of Brucella-infected IFN-γ-/- mice. A six-week regimen of rifampicin effectively cleared infection and halted further progression of inflammation, although some symptoms and swelling remained. However, administration of an adenovirus expressing the IL-1receptor antagonist augmented antibiotic resolution of joint swelling by >50%. These results show that the IFN-γ-/- mouse represents a useful model to study the pathogenesis of joint inflammation due to Brucella infection, and that intervention strategies targeting IL-1 can complement antibiotic treatment of Brucella-induced inflammation. Supported by USDA 2007-01612 and USDA 2009-34397-20133.
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Occhialini, Alessandra, Dirk Hofreuter, Christoph-Martin Ufermann, Sascha Al Dahouk, and Stephan Köhler. "The Retrospective on Atypical Brucella Species Leads to Novel Definitions." Microorganisms 10, no. 4 (2022): 813. http://dx.doi.org/10.3390/microorganisms10040813.
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The genus Brucella currently comprises twelve species of facultative intracellular bacteria with variable zoonotic potential. Six of them have been considered as classical, causing brucellosis in terrestrial mammalian hosts, with two species originated from marine mammals. In the past fifteen years, field research as well as improved pathogen detection and typing have allowed the identification of four new species, namely Brucella microti, Brucella inopinata, Brucella papionis, Brucella vulpis, and of numerous strains, isolated from a wide range of hosts, including for the first time cold-blooded animals. While their genome sequences are still highly similar to those of classical strains, some of them are characterized by atypical phenotypes such as higher growth rate, increased resistance to acid stress, motility, and lethality in the murine infection model. In our review, we provide an overview of state-of-the-art knowledge about these novel Brucella sp., with emphasis on their phylogenetic positions in the genus, their metabolic characteristics, acid stress resistance mechanisms, and their behavior in well-established in cellulo and in vivo infection models. Comparison of phylogenetic classification and phenotypical properties between classical and novel Brucella species and strains finally lead us to propose a more adapted terminology, distinguishing between core and non-core, and typical versus atypical brucellae, respectively.
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Khan, Mike, Jerome S. Harms, Yiping Liu, et al. "Brucella suppress STING expression via miR-24 to enhance infection." PLOS Pathogens 16, no. 10 (2020): e1009020. http://dx.doi.org/10.1371/journal.ppat.1009020.
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Brucellosis, caused by a number of Brucella species, remains the most prevalent zoonotic disease worldwide. Brucella establish chronic infections within host macrophages despite triggering cytosolic innate immune sensors, including Stimulator of Interferon Genes (STING), which potentially limit infection. In this study, STING was required for control of chronic Brucella infection in vivo. However, early during infection, Brucella down-regulated STING mRNA and protein. Down-regulation occurred post-transcriptionally, required live bacteria, the Brucella type IV secretion system, and was independent of host IRE1-RNase activity. STING suppression occurred in MyD88-/- macrophages and was not induced by Toll-like receptor agonists or purified Brucella lipopolysaccharide (LPS). Rather, Brucella induced a STING-targeting microRNA, miR-24-2, in a type IV secretion system-dependent manner. Furthermore, STING downregulation was inhibited by miR-24 anti-miRs and in Mirn23a locus-deficient macrophages. Failure to suppress STING expression in Mirn23a-/- macrophages correlated with diminished Brucella replication, and was rescued by exogenous miR-24. Mirn23a-/- mice were also more resistant to splenic colonization one week post infection. Anti-miR-24 potently suppressed replication in wild type, but much less in STING-/- macrophages, suggesting most of the impact of miR-24 induction on replication occurred via STING suppression. In summary, Brucella sabotages cytosolic surveillance by miR-24-dependent suppression of STING expression; post-STING activation “damage control” via targeted STING destruction may enable establishment of chronic infection.
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González-Espinoza, Gabriela, Vilma Arce-Gorvel, Sylvie Mémet, and Jean-Pierre Gorvel. "Brucella: Reservoirs and Niches in Animals and Humans." Pathogens 10, no. 2 (2021): 186. http://dx.doi.org/10.3390/pathogens10020186.
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Brucella is an intracellular bacterium that causes abortion, reproduction failure in livestock and leads to a debilitating flu-like illness with serious chronic complications if untreated in humans. As a successful intracellular pathogen, Brucella has developed strategies to avoid recognition by the immune system of the host and promote its survival and replication. In vivo, Brucellae reside mostly within phagocytes and other cells including trophoblasts, where they establish a preferred replicative niche inside the endoplasmic reticulum. This process is central as it gives Brucella the ability to maintain replicating-surviving cycles for long periods of time, even at low bacterial numbers, in its cellular niches. In this review, we propose that Brucella takes advantage of the environment provided by the cellular niches in which it resides to generate reservoirs and disseminate to other organs. We will discuss how the favored cellular niches for Brucella infection in the host give rise to anatomical reservoirs that may lead to chronic infections or persistence in asymptomatic subjects, and which may be considered as a threat for further contamination. A special emphasis will be put on bone marrow, lymph nodes, reproductive and for the first time adipose tissues, as well as wildlife reservoirs.
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Meador, V. P., B. L. Deyoe, and N. F. Cheville. "Effect of Nursing on Brucella abortus Infection of Mammary Glands of Goats." Veterinary Pathology 26, no. 5 (1989): 369–75. http://dx.doi.org/10.1177/030098588902600502.
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Eight 1-year-old, goats were inoculated intravenously with Brucella abortus (B. abortus) on the day of parturition and necropsied at 28 days after inoculation. Four nursed their kids and four did not (milk was not removed from the udders). Tissues and fluids were examined by bacterial isolation, light microscopy, and serologic methods. Nonnursing goats had high titers of brucellae (≤108 organisms/ml) in milk (brucellae were isolated from four of four udders), had marked enlargement of supramammary lymph nodes, and had lymphoplasmacytic and histiocytic interstitial mastitis. Immunoperoxidase staining revealed that brucellae were primarily in macrophages and neutrophils of the mammary alveolar and ductal lumens and in macrophages of the subcapsular sinuses of the supramammary lymph node. In contrast, nursing goats excreted brucellae intermittently at low concentrations (< 103 organisms/ml) in milk; brucellae were isolated at necropsy from one of four udders; supramammary lymph nodes were not enlarged; and mammary lesions were not seen. Brucellae were detected in more tissues other than the udder, and serum anti- Brucella antibody titers were higher in nonnursing goats than in nursing goats. The present study indicates that the failure to nurse or release milk enhances localization and replication of B. abortus in mammary glands of goats after parturition, and that mammary gland infection may result in increased systemic spread and persistence of brucellae in the host.
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Eka rahmawati, Septyana, RIAN ANGGIA Destiawan, Novarina sulsia ista'in Ningtyas, and Mutia Hariani Nurjanah. "CYTOKINE RESPONSE IN BRUCELLA ABORTUS BOVINE INFECTION: LITERATURE REVIEW." Jurnal Biosains Pascasarjana 24, no. 1SP (2023): 1–12. http://dx.doi.org/10.20473/jbp.v24i1sp.2022.1-12.
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Brucella Abortus infection in cattle is an infection that has a strategic effect on society, especially the economic sector. This disease is caused by gram-negative bacteria, namely Brucella abortion. Treatment of Brucella Abortus Infection in cattle is still not effective. Therapy based on the immune response caused by Brucella Abortus Infection, especially the cytokine response, is an effective choice considering that each type of cow has a different immune response in dealing with Brucella Abortus Infection. The purpose of writing this literature review is to identify cytokines that play a role in Brucella Abortus Infection in cattle. Method: automated PUBMED database search using keywords “Brucella Abortus Bovine”, “Cytokine”, and “Brucellosis”. Results: 11 articles that are relevant and meet the inclusion criteria to analyze the cytokines that play a role in Brucella Abortus Infection in cattle. Conclusion: Cytokines that play a role in Brucella Abortus infection in cattle are generally IL-1, IL-6, IL-12, IL-8, TNF-α, and IFN-γ.
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Moura, Alexandre Sampaio, Letícia Mattos Menezes, Marcelle Amaral de Matos, Cynthya Magalhães Costa, and Bruna Arantes Borges. "Occupational infection to Brucella abortus B19 vaccine despite antimicrobial prophylaxis." Medicina (Ribeirão Preto) 54, no. 1 (2021): e168000. http://dx.doi.org/10.11606/issn.2176-7262.rmrp.2021.168000.
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The authors report the case of a veterinarian who acquired brucellosis infection by accidental exposure to Brucella abortus vaccine (BRUCEL-VET B19) while performing animal vaccination. Antibiotic prophylaxis with doxycycline and rifampin for six weeks was indicated, but rifampin was discontinued after 10 days due to gastrointestinal intolerance. Despite prophylaxis, the patient seroconverted after 30 days, but was asymptomatic and did not require additional antibiotic therapy. Post-exposure prophylaxis of Brucella is not free from side effects and asymptomatic seroconversion can occur despite prophylaxis.
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Zhang, Guangdong, Hai Hu, Yi Yin, et al. "Brucella Manipulates Host Cell Ferroptosis to Facilitate Its Intracellular Replication and Egress in RAW264.7 Macrophages." Antioxidants 13, no. 5 (2024): 577. http://dx.doi.org/10.3390/antiox13050577.
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Brucella virulence relies on its successful intracellular life cycle. Modulating host cell death is a strategy for Brucella to survive and replicate intracellularly. Ferroptosis is a novel regulated cell death characterized by iron-triggered excessive lipid peroxidation, which has been proven to be associated with pathogenic bacteria infection. Thus, we attempted to explore if smooth-type Brucella infection triggers host cell ferroptosis and what role it plays in Brucella infection. We assessed the effects of Brucella infection on the lactate dehydrogenase release and lipid peroxidation levels of RAW264.7 macrophages; subsequently, we determined the effect of Brucella infection on the expressions of ferroptosis defense pathways. Furthermore, we determined the role of host cell ferroptosis in the intracellular replication and egress of Brucella. The results demonstrated that Brucella M5 could induce ferroptosis of macrophages by inhibiting the GPX4-GSH axis at the late stage of infection but mitigated ferroptosis by up-regulating the GCH1-BH4 axis at the early infection stage. Moreover, elevating host cell ferroptosis decreased Brucella intracellular survival and suppressing host cell ferroptosis increased Brucella intracellular replication and egress. Collectively, Brucella may manipulate host cell ferroptosis to facilitate its intracellular replication and egress, extending our knowledge about the underlying mechanism of how Brucella completes its intracellular life cycle.
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Journal, Baghdad Science. "Production of specific brucellin to diagnose Brucellosis." Baghdad Science Journal 10, no. 2 (2013): 289–95. http://dx.doi.org/10.21123/bsj.10.2.289-295.
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act : A soluble cytoplasmic antigen (Brucellin) was prepared from Brucella melitensis Rev1 and used to diagnose brucellosis in experimentally infected mice with virulent strains of Brucella melitensis and Brucella abortus two weeks after infection. The best result was obtained with the third peak of the four peaks. All four peaks were used as antigen for skin test in a group of mice two weeks after vaccinated with S19 vaccine and the best result was obtained with third peak. All four peaks were also used as antigen for skin test in a group of mice previously vaccinated with Listeria monocytogenes live attenuated vaccine. All four fractions of the extracted brucellin antigens exhibited a negative skin test result in Listeria monocytogenes experimentally vaccinated mice.
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Hamzah, Aseel M. "Production of specific brucellin to diagnose Brucellosis." Baghdad Science Journal 10, no. 2 (2013): 289–95. http://dx.doi.org/10.21123/bsj.2013.10.2.289-295.
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act : A soluble cytoplasmic antigen (Brucellin) was prepared from Brucella melitensis Rev1 and used to diagnose brucellosis in experimentally infected mice with virulent strains of Brucella melitensis and Brucella abortus two weeks after infection. The best result was obtained with the third peak of the four peaks. All four peaks were used as antigen for skin test in a group of mice two weeks after vaccinated with S19 vaccine and the best result was obtained with third peak. All four peaks were also used as antigen for skin test in a group of mice previously vaccinated with Listeria monocytogenes live attenuated vaccine. All four fractions of the extracted brucellin antigens exhibited a negative skin test result in Listeria monocytogenes experimentally vaccinated mice.
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Clapp, Beata, Xinghong Yang, Carol Hoffman, and David W. Pascual. "Oropharyngeal (OPG) vaccination activates head and neck lymphoid tissues required for immune protection against mucosal Brucella infection." Journal of Immunology 200, no. 1_Supplement (2018): 118.16. http://dx.doi.org/10.4049/jimmunol.200.supp.118.16.
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Abstract Human brucellosis remains a global health problem with no human vaccines existing. Most human infections occur mucosally with eventual systemic brucellae dissemination. Current interventions primarily focus on the systemic disease, rather than considering neutralizing the infection at its source. A number of studies show that the OPG mucosa is the principal site of brucellae uptake following oral or inhalational exposures. We have devised an OPG infection method using an attenuated Brucella mutant by allowing the mice to drink (ad bibitum) from a pipette tip. BALB/c mice were fed once daily for 3 days with 108 CFUs. Individual head and neck lymph nodes (HNLNs), and spleens were examined at 2 weeks post-infection for bacterial colonization and proinflamatory cytokine responses. Elevated colonization was observed in submandibular LNs (SmLNs) and deep cervical LNs (CLNs). Modest colonization was detected in the parotid LNs (PrLNs) and spleens. Splenic and individual HNLN lymphocytes were analyzed for IFN-g, TNF-a, granzyme B, and perforin production by flow cytometry. SmLN, CLN, and PrLN IFN-g-producing CD8+ T cells significantly exceeded IFN-g-producing CD4+ T cells by 2.5-, 2.5-, and 1.5-fold, respectively. Increased numbers of CD4+ and CD8+ T cells expressing TNF-a, granzyme B, and perforin were also observed. All activated lymphocytes were predominantly of effector-memory phenotype, CD44+CD62LlowCCR7low. These studies demonstrate that ad bibitum vaccination against brucellosis results in colonization and activation of the HNLNs, mimicking natural human infection, enabling future inquiry into the immune mechanisms responsible for protection to mucosal Brucella infections. Work supported by NIH AI-125546.
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Al-Hadheq, Ali Ahmed, Anas Al-Mahbashi, Talal Al-Wajeeh, Asia Al-Haj, and Wadhah Hassan Edrees. "Seroprevalence of Brucella Infection among Students at Amran University- Yemen." مجلة جامعة عمران 4, no. 8 (2024): 6. http://dx.doi.org/10.59145/jaust.v4i8.109.
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Background and Aim: Brucella infection in animals is considered a great problem in most countries around the world and is considered one of the important pathogenic zoonosis infections in humans. This study aimed to determine the prevalence of Brucella infection among students at Amran University, Yemen. Methods: It is a cross-sectional study carried out among 247 students between January 2023 and November 2023. Blood samples were collected and Brucella Antigen was detected using immunochromatographic technology. Results: Out of 247 human samples 17 samples (6.9%) were positive for brucella Antigen 2 (1.75%) were positive among males, and 15 (12.5%) were positive among females. Regarding the residence of students the results showed that 49 (19.8%) were from Amran City and 198 (80.2%) from rural areas, The risk factors for Brucella infection were ranching, drinking milk without pasteurization, and direct contact with livestock. Conclusion: The prevalence of brucellosis was low among the study's participants but it will become a serious problem that threatens the health care system in Yemen. So, awareness programs should be provided to students and the general population about Brucella infection and its risk factors
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López-Urrutia, Luis, Andrés Alonso, Maria Luisa Nieto, Yolanda Bayón, Antonio Orduña, and Mariano Sánchez Crespo. "Lipopolysaccharides of Brucella abortusand Brucella melitensis Induce Nitric Oxide Synthesis in Rat Peritoneal Macrophages." Infection and Immunity 68, no. 3 (2000): 1740–45. http://dx.doi.org/10.1128/iai.68.3.1740-1745.2000.
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ABSTRACT Smooth lipopolysaccharide (S-LPS) and lipid A of Brucella abortus and Brucella melitensis induced the production of nitric oxide (NO) by rat adherent peritoneal cells, but they induced lower levels of production of NO than Escherichia coli LPS. The participation of the inducible isoform of NO synthase (iNOS) was confirmed by the finding of an increased expression of both iNOS mRNA and iNOS protein. These observations might help to explain (i) the acute outcome of Brucella infection in rodents, (ii) the low frequency of septic shock in human brucellosis, and (iii) the prolonged intracellular survival of Brucellain humans.
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Xiao, Yu, Mengjuan Li, Xiaoyi Guo, et al. "Inflammatory Mechanism of Brucella Infection in Placental Trophoblast Cells." International Journal of Molecular Sciences 23, no. 21 (2022): 13417. http://dx.doi.org/10.3390/ijms232113417.
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Brucellosis is a severe zoonotic infectious disease caused by the infection of the Brucella, which is widespread and causes considerable economic losses in underdeveloped areas. Brucella is a facultative intracellular bacteria whose main target cells for infection are macrophages, placental trophoblast cells and dendritic cells. The main clinical signs of Brucella infection in livestock are reproductive disorders and abortion. At present, the pathogenesis of placentitis or abortion caused by Brucella in livestock is not fully understood, and further research on the effect of Brucella on placental development is still necessary. This review will mainly introduce the research progress of Brucella infection of placental trophoblast cells as well as the inflammatory response caused by it, explaining the molecular regulation mechanism of Brucella leading to reproductive system disorders and abortion, and also to provide the scientific basis for revealing the pathogenesis and infection mechanism of Brucella.
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Cornell, William D., Muckatira M. Chengappa, Louis A. Stuart, Roxanna L. Maddux, and Robert I. Hail. "Brucella Suis Biovar 3 Infection in a Kentucky Swine Herd." Journal of Veterinary Diagnostic Investigation 1, no. 1 (1989): 20–21. http://dx.doi.org/10.1177/104063878900100107.
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Sows from a large far-row-to-finish operation in western Kentucky had late-term abortions. Boars and breeding-age sows were tested serologically for brucellosis, and 83 of 125 were classified as reactors. No brucellae were isolated from the tissues of 6 unbred reactor sows, but Brucella suis biovar 3 was recovered from 5 aborted fetuses. Epidemiological studies failed to determine the source of the infection.
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Sangari, Félix J., Asunción Seoane, María Cruz Rodríguez, Jesús Agüero, and Juan M. García Lobo. "Characterization of the Urease Operon of Brucella abortus and Assessment of Its Role in Virulence of the Bacterium." Infection and Immunity 75, no. 2 (2006): 774–80. http://dx.doi.org/10.1128/iai.01244-06.
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ABSTRACT Most members of the genus Brucella show strong urease activity. However, the role of this enzyme in the pathogenesis of Brucella infections is poorly understood. We isolated several Tn5 insertion mutants deficient in urease activity from Brucella abortus strain 2308. The mutations of most of these mutants mapped to a 5.7-kbp DNA region essential for urease activity. Sequencing of this region, designated ure1, revealed the presence of seven open reading frames corresponding to the urease structural proteins (UreA, UreB, and UreC) and the accessory proteins (UreD, UreE, UreF, and UreG). In addition to the urease genes, another gene (cobT) was identified, and inactivation of this gene affected urease activity in Brucella. Subsequent analysis of the previously described sequences of the genomes of Brucella spp. revealed the presence of a second urease cluster, ure2, in all them. The ure2 locus was apparently inactive in B. abortus 2308. Urease-deficient mutants were used to evaluate the role of urease in Brucella pathogenesis. The urease-producing strains were found to be resistant in vitro to strong acid conditions in the presence of urea, while urease-negative mutants were susceptible to acid treatment. Similarly, the urease-negative mutants were killed more efficiently than the urease-producing strains during transit through the stomach. These results suggested that urease protects brucellae during their passage through the stomach when the bacteria are acquired by the oral route, which is the major route of infection in human brucellosis.
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Gutiérrez-Jiménez, Cristina, Lisiena Hysenaj, Alejandro Alfaro-Alarcón, et al. "Persistence of Brucella abortus in the Bone Marrow of Infected Mice." Journal of Immunology Research 2018 (December 3, 2018): 1–8. http://dx.doi.org/10.1155/2018/5370414.
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Brucellosis is a zoonotic bacterial infection that may persist for long periods causing relapses in antibiotic-treated patients. The ability of Brucella to develop chronic infections is linked to their capacity to invade and replicate within the mononuclear phagocyte system, including the bone marrow (BM). Persistence of Brucella in the BM has been associated with hematological complications such as neutropenia, thrombocytopenia, anemia, and pancytopenia in human patients. In the mouse model, we observed that the number of Brucella abortus in the BM remained constant for up to 168 days of postinfection. This persistence was associated with histopathological changes, accompanied by augmented numbers of BM myeloid GMP progenitors, PMNs, and CD4+ lymphocytes during the acute phase (eight days) of the infection in the BM. Monocytes, PMNs, and GMP cells were identified as the cells harboring Brucella in the BM. We propose that the BM is an essential niche for the bacterium to establish long-lasting infections and that infected PMNs may serve as vehicles for dispersion of Brucella organisms, following the Trojan horse hypothesis. Monocytes are solid candidates for Brucella reservoirs in the BM.
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Dadelahi, Alexis S., Mostafa F. N. Abushahba, Bárbara Ponzilacqua-Silva, et al. "Interactions between B cells and T follicular regulatory cells enhance susceptibility to Brucella infection independent of the anti-Brucella humoral response." PLOS Pathogens 19, no. 9 (2023): e1011672. http://dx.doi.org/10.1371/journal.ppat.1011672.
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Brucellosis, caused by facultative, intracellular Brucella spp., often results in chronic and/or lifelong infection. Therefore, Brucella must employ mechanisms to subvert adaptive immunity to cause chronic infection. B lymphocytes enhance susceptibility to infection with Brucella spp. though the mechanisms remain unclear. Here we investigated the role of antibody secretion, B cell receptor (BCR) specificity, and B cell antigen presentation on susceptibility to B. melitensis. We report that mice unable to secrete antibody do not display altered resistance to Brucella. However, animals with B cells that are unable to recognize Brucella through their BCR are resistant to infection. In addition, B cell MHCII expression enhances susceptibility to infection in a CD4+ T cell-dependent manner, and we found that follicular B cells are sufficient to inhibit CD4+ T cell-mediated immunity against Brucella. B cells promote development of T follicular helper (TFH) and T follicular regulatory (TFR) cells during Brucella infection. Inhibition of B cell and CD4+ T cell interaction via CD40L blockade enhances resistance to Brucella in a B cell dependent manner concomitant with suppression of TFH and TFR differentiation. Conversely, PD-1 blockade increases Brucella burdens in a B and CD4+ T cell dependent manner while augmenting T regulatory (TReg) and TFR responses. Intriguingly, TFR deficiency enhances resistance to Brucella via a B cell dependent, but antibody independent mechanism. Collectively, these results demonstrate B cells support TFR responses that promote susceptibility to Brucella infection independent of the antibody response.
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Wareth, Gamal, Ahmed Kheimar, Heinrich Neubauer, and Falk Melzer. "Susceptibility of Avian Species to Brucella Infection: A Hypothesis-Driven Study." Pathogens 9, no. 2 (2020): 77. http://dx.doi.org/10.3390/pathogens9020077.
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Brucellosis is a highly contagious bacterial disease affecting a wide range of animals, as well as humans. The existence of the clinically diagnosed brucellosis in avian species is controversially discussed. In the current study, we set to summarize the current knowledge on the presence of brucellae in avian species. Anti-Brucella antibodies were monitored in different avian species using classical diagnostic tools. Experimental infection of chicken embryos induced the disease and resulted in the development of specific lesions. Few empirical studies have been performed in adult poultry. However, the isolation of brucellae from naturally-infected chickens has not been possible yet.
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Comerci, Diego J., Guido D. Pollevick, Ana M. Vigliocco, Alberto C. C. Frasch, and Rodolfo A. Ugalde. "Vector Development for the Expression of Foreign Proteins in the Vaccine Strain Brucella abortusS19." Infection and Immunity 66, no. 8 (1998): 3862–66. http://dx.doi.org/10.1128/iai.66.8.3862-3866.1998.
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ABSTRACT A vector for the expression of foreign antigens in the vaccine strain Brucella abortus S19 was developed by using a DNA fragment containing the regulatory sequences and the signal peptide of the Brucella bcsp31 gene. This fragment was cloned in broad-host-range plasmid pBBR4MCS, resulting in plasmid pBEV. As a reporter protein, a repetitive antigen of Trypanosoma cruziwas used. The recombinant fusion protein is stably expressed and secreted into the Brucella periplasmic space, inducing a good antibody response against the T. cruzi antigen. The expression of the repetitive antigen in Brucella neither altered its growth pattern nor generated a toxic or lethal effect during experimental infection. The application of this strategy for the generation of live recombinant vaccines and the tagging of B. abortus S19 vaccine is discussed. This is the first time that a recombinant protein has been expressed in the periplasm of brucellae.
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Wang, Yueli, Jing Xi, Peng Wu та ін. "Small ubiquitin-related modifier 2 affects the intracellular survival of Brucella abortus 2308 by regulating activation of the NF-κB pathway". Innate Immunity 27, № 1 (2020): 81–88. http://dx.doi.org/10.1177/1753425920972171.
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Brucella is a genus of Gram-negative intracellular pathogens that cause animal and human diseases. Brucella survival and replication inside immune cells is critical for the establishment of chronic infections. Protein modifications by small ubiquitin-related modifier proteins and the NF-κB pathway are involved in many cellular activities, playing major roles in regulating protein function that is essential for pathogenic bacteria during infection. However, the relationship between them in the intracellular survival of Brucella is still largely unknown. We demonstrated that Brucella abortus 2308 infection can activate the expression of small ubiquitin-related modifier-2 proteins in a time-dependent manner. We found the production of Th1 cytokines (IFN-γ and TNF-α) and the transcription of NF-κB/p65 were promoted by overexpression and inhibited by interference of small ubiquitin-related modifier-2. In addition, we showed that small ubiquitin-related modifier-2 can inhibit intracellular survival of Brucella abortus 2308 by regulating activation of the NF-κB pathway. Taken together, this work shows that small ubiquitin-related modifier-2 modification of NF-κB2/p65 is essential for the survival of Brucella abortus 2308 inside macrophages. This work may help to unravel the pathogenic mechanisms of Brucella infections.
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Elbehiry, Ayman, Musaad Aldubaib, Osamah Al Rugaie, et al. "Proteomics-based screening and antibiotic resistance assessment of clinical and sub-clinical Brucella species: An evolution of brucellosis infection control." PLOS ONE 17, no. 1 (2022): e0262551. http://dx.doi.org/10.1371/journal.pone.0262551.
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Brucellae are intracellular sneaky bacteria and they can elude the host’s defensive mechanisms, resulting in therapeutic failure. Therefore, the goal of this investigation was to rapid identification of Brucella species collected from animals and humans in Saudi Arabia, as well as to evaluate their resistance to antibiotics. On selective media, 364 animal samples as well as 70 human blood samples were cultured. Serological and biochemical approaches were initially used to identify a total of 25 probable cultured isolates. The proteomics of Brucella species were identified using the MALDI Biotyper (MBT) system, which was subsequently verified using real-time polymerase chain reaction (real-time PCR) and microfluidic electrophoresis assays. Both Brucella melitensis (B. melitensis) and Brucella abortus (B. abortus) were tested for antimicrobial susceptibility using Kirby Bauer method and the E-test. In total, 25 samples were positive for Brucella and included 11 B. melitensis and 14 B. abortus isolates. Twenty-two out of 25 (88%) and 24/25 (96%) of Brucella strains were recognized through the Vitek 2 Compact system. While MBT was magnificently identified 100% of the strains at the species level with a score value more than or equal to 2.00. Trimethoprim-sulfamethoxazole, rifampin, ampicillin-sulbactam, and ampicillin resistance in B. melitensis was 36.36%, 31.82%, 27.27%, and 22.70%, respectively. Rifampin, trimethoprim-sulfamethoxazole, ampicillin, and ampicillin-sulbactam resistance was found in 35.71%, 32.14%, 32.14%, and 28.57% of B. abortus isolates, correspondingly. MBT confirmed by microfluidic electrophoresis is a successful approach for identifying Brucella species at the species level. The resistance of B. melitensis and B. abortus to various antibiotics should be investigated in future studies.
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Sipahi, OguzResat, Sohret Aydemir, Meltem Tasbakan, et al. "Brucella melitensis shunt infection." Neurology India 61, no. 6 (2013): 670. http://dx.doi.org/10.4103/0028-3886.125367.
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C. Baldi, Pablo, and Guillermo H. Giambartolomei. "Immunopathology of Brucella Infection." Recent Patents on Anti-Infective Drug Discovery 8, no. 1 (2013): 18–26. http://dx.doi.org/10.2174/1574891x11308010005.
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RR, Kasarla. "Brucella Infection: A Major Public Health Concern." Open Access Journal of Microbiology & Biotechnology 7, no. 2 (2022): 1–3. http://dx.doi.org/10.23880/oajmb-16000227.
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Zoonotic infectious diseases are common in societies where poverty is widespread, and where people rely on animals for their livelihood, that severely hinders livestock productivity and human health worldwide, particularly in the developing world and have been historically neglected by decision makers over the decades. WHO has identified a subgroup of eight endemic or neglected zoonotic diseasesanthrax, bovine tuberculosis, brucellosis, Taenia solium cysticercosis, hydatid disease, leishmaniasis, rabies, and human African trypanosomiasis.
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Scholz, Holger C., Karsten Nöckler, Cornelia Göllner, et al. "Brucella inopinata sp. nov., isolated from a breast implant infection." International Journal of Systematic and Evolutionary Microbiology 60, no. 4 (2010): 801–8. http://dx.doi.org/10.1099/ijs.0.011148-0.
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A Gram-negative, non-motile, non-spore-forming coccoid bacterium (strain BO1T) was isolated recently from a breast implant infection of a 71-year-old female patient with clinical signs of brucellosis. Affiliation of strain BO1T to the genus Brucella was confirmed by means of polyamine pattern, polar lipid profile, fatty acid profile, quinone system, DNA–DNA hybridization studies and by insertion sequence 711 (IS711)-specific PCR. Strain BO1T harboured four to five copies of the Brucella-specific insertion element IS711, displaying a unique banding pattern, and exhibited a unique 16S rRNA gene sequence and also grouped separately in multilocus sequence typing analysis. Strain BO1T reacted with Brucella M-monospecific antiserum. Incomplete lysis was detected with bacteriophages Tb (Tbilisi), F1 and F25. Biochemical profiling revealed a high degree of enzymic activity and metabolic capabilities. In multilocus VNTR (variable-number tandem-repeat) analysis, strain BO1T showed a very distinctive profile and clustered with the other ‘exotic’ Brucella strains, including strains isolated from marine mammals, and Brucella microti, Brucella suis biovar 5 and Brucella neotomae. Comparative omp2a and omp2b gene sequence analysis revealed the most divergent omp2 sequences identified to date for a Brucella strain. The recA gene sequence of strain BO1T differed in seven nucleotides from the Brucella recA consensus sequence. Using the Brucella species-specific multiplex PCR assay, strain BO1T displayed a unique banding pattern not observed in other Brucella species. From the phenotypic and molecular analysis it became evident that strain BO1T was clearly different from all other Brucella species, and therefore represents a novel species within the genus Brucella. Because of its unexpected isolation, the name Brucella inopinata with the type strain BO1T (=BCCN 09-01T=CPAM 6436T) is proposed.
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Wareth, Gamal, Mathias W. Pletz, Heinrich Neubauer, and Jayaseelan Murugaiyan. "Proteomics of Brucella: Technologies and Their Applications for Basic Research and Medical Microbiology." Microorganisms 8, no. 5 (2020): 766. http://dx.doi.org/10.3390/microorganisms8050766.
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Brucellosis is a global zoonosis caused by Gram-negative, facultative intracellular bacteria of the genus Brucella (B.). Proteomics has been used to investigate a few B. melitensis and B. abortus strains, but data for other species and biovars are limited. Hence, a comprehensive analysis of proteomes will significantly contribute to understanding the enigmatic biology of brucellae. For direct identification and typing of Brucella, matrix-assisted laser desorption ionization—time of flight mass spectrometry (MALDI—TOF MS) has become a reliable tool for routine diagnosis due to its ease of handling, price and sensitivity highlighting the potential of proteome-based techniques. Proteome analysis will also help to overcome the historic but still notorious Brucella obstacles of infection medicine, the lack of safe and protective vaccines and sensitive serologic diagnostic tools by identifying the most efficient protein antigens. This perspective summarizes past and recent developments in Brucella proteomics with a focus on species identification and serodiagnosis. Future applications of proteomics in these fields are discussed.
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Lacey, Carolyn, William J. Mitchell та Jerod A. Skyberg. "Inflammasomes confer protection via IL-18 and pyroptosis, and are negatively regulated by IFN-γ-dependent nitric oxide during Brucella infection". Journal of Immunology 200, № 1_Supplement (2018): 115.11. http://dx.doi.org/10.4049/jimmunol.200.supp.115.11.
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Abstract Brucellosis, caused by the intracellular bacterial pathogen Brucella, is a zoonotic disease for which arthritis is the most common focal complication in humans. Here we show caspase-1 (casp1) and caspase-11 (casp11) initiate Brucella-induced joint inflammation, but later in infection also restrict Brucella replication. In contrast, AIM2 and NLRP3 were dispensable for control of joint infection by Brucella. Both IL-1 and IL-18 promoted joint inflammation, however only IL-18 contributed to protection against Brucella infection of the joint. In vitro studies demonstrated that casp1 and casp11 both induce pyroptosis which limited Brucella infection in macrophages. While IFN-γ production in part required casp1/11 and IL-18, casp1/11-dependent clearance of Brucella was only partially IFN-γ dependent. However, IFN-γ deficiency resulted in severe inflammation that was entirely inflammasome dependent, and in particular reliant on NLRP3. IFN-γ was vital for induction of the nitric oxide (NO) producing enzyme, iNOS, in infected joints, and NO inhibited casp1 activation in Brucella-infected macrophages in vitro. During Brucella infection in vivo, iNOS inhibition exacerbated arthritis, and administration of a NO donor reduced joint inflammation in IFN-γ-deficient mice. Collectively these data demonstrate inflammasomes induce early inflammation in an IL-18 and IL-1 dependent manner, and inflammasome-dependent IL-18 and pyroptosis restrict Brucella burdens in the joint. Moreover, IFN-γ reduces inflammation by inhibiting excessive casp1 activation through production of NO. Thus NO donors, in combination with antibiotics, may be an effective therapy for treating Brucella-induced inflammation.
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Dadelahi, Alexis S., Mostafa Farghal Namish Ateya, Bárbara Ponzilacqua-Silva, Catherine A. Chambers, Carolyn A. Lacey, and Charles R. Moley. "PD-1 restrains B cell dependent CD4+ T cell responses that promote susceptibility to Brucella infection." Journal of Immunology 208, no. 1_Supplement (2022): 170.15. http://dx.doi.org/10.4049/jimmunol.208.supp.170.15.
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Abstract Brucellosis, caused by intracellular pathogens of the Brucella genus, often results in chronic and/or lifelong infection. While T cells can contribute to control of Brucella, this typically does not result in sterile immunity, and the mechanisms underlying the inability of T cells to clear infection remain unclear. We previously found that B cells promote susceptibility to Brucella in a CD4+ T cell dependent manner. Here we report that B cell MHCII expression enhances susceptibility to infection, and investigated the role of B cell antigen specificity and presentation in this process. We found that B cell receptor specificity facilitates enhanced susceptibility to infection as well as Brucella entry into B cells in vivo. Investigation of the role of individual B cell subsets demonstrated that follicular B cells can inhibit protective CD4+ T cell responses. Evaluation of CD4+ T cell populations revealed that B lymphocytes promote FoxP3 expression preferentially amongst T follicular cell populations following Brucella infection. Additionally, CD40L blockade enhances protection against Brucella in a B cell dependent manner concomitant with a decrease in T follicular regulatory cells (TFR). Interestingly, PD-1 blockade resulted in an increase in TFR populations as well as an increased susceptibility to Brucella infection in a B and CD4+ T cell-dependent manner. Together, these data suggest B and CD4+ T cell interactions within the follicle promote TFR cell populations which in turn could promote susceptibility to Brucella infection. Supported by NIH Grant:1R21AI135160 NIH Grant:1R01AI150797
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MATOPE, G., E. BHEBHE, J. B. MUMA, A. LUND, and E. SKJERVE. "Risk factors for Brucella spp. infection in smallholder household herds." Epidemiology and Infection 139, no. 1 (2010): 157–64. http://dx.doi.org/10.1017/s0950268810000968.
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SUMMARYRisk factors for Brucella infection, the association and impact of Brucella seropositivity on abortions were investigated in cattle (n=1291) reared in smallholder household herds (n=203) from six geographical areas of Zimbabwe between September 2004 and 2005. Data on management, abortion and herd structure were collected. Sera were tested for Brucella antibodies using the Rose Bengal test and a competitive enzyme-linked immunosorbent assay. Data were analysed by generalized estimating equation and logistic regression models. Brucella antibodies were estimated at 5·5% and 22·9% for individual cattle and herds, respectively. Abortions were reported in 3·2% of cows and 22·0% herds. The age of cows and Brucella seropositivity predicted abortion. For herds, Brucella seropositivity, geographical area, purchase of cattle and large herd size were independently associated with increased odds of abortion. Exposure to Brucella had a significant impact on abortion. These results highlight the important risk factors for Brucella spp. infection in smallholder herds. Thus, brucellosis control programmes which take these factors into consideration will be beneficial.
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Krstevski, Kiril, Ivancho Naletoski, Dine Mitrov, et al. "Application of Fluorescence Based Molecular Assays for Improved Detection and Typing of Brucella Strains in Clinical Samples." Macedonian Veterinary Review 38, no. 2 (2015): 223–32. http://dx.doi.org/10.14432/j.macvetrev.2015.09.055.
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AbstractBacteria from the genus Brucella are causative agents of brucellosis - a zoonotic disease which affects many wild and domestic animal species and humans. Taking into account the significant socio-economic and public health impact of brucellosis, its control is of great importance for endemic areas. The chosen control strategy could be successful only if adapted to the current epidemiological situation. This implies that a choice of appropriate diagnostic procedures for detection and typing of Brucella spp. strains are of essential importance. Significant advancement of molecular techniques and their advantages compared to classical methods, give strong arguments in promotion of these techniques as a powerful tool for comprehensive diagnostics of brucellosis. Considering this, the major tasks of the study were to select and implement molecular tests for detection and genotyping Brucella spp. and evaluate their performances using DNA from cultivated brucellae (islolates) and limited number of tissue samples from seropositive animals. The obtained results confirmed that implemented real time PCR for Brucella spp. detection, as well as MLVA-16 used for genotyping, have excellent analytical sensitivity (4.2 fg of Brucella DNA were successfully detected and genotyped). Furthermore, compared to bacteriological cultivation of Brucella spp., real time PCR and MLVA-16 protocols showed superior diagnostic sensitivity and detected Brucella DNA in tissues from which Brucella could not be cultivated. Based on the summarized study results, we propose a diagnostic algorithm for detection and genotyping of Brucella spp. bacteria. Routine use of proposed diagnostic algorithm will improve the effectiveness of infection confirmation and help for accurate evaluation of epidemiological situation.
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Keyburn, Anthony L., and Nicky Buller. "Brucella: not your ‘typical’ intracellular pathogen." Microbiology Australia 41, no. 1 (2020): 38. http://dx.doi.org/10.1071/ma20010.
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Currently the genus Brucella consists of a group of bacteria that are genetically monospecific yet phenotypically diverse, and a recent genetic and phenotypic divergent group known as ‘atypical' Brucellae. The host range is extremely varied and includes mammals, including humans, terrestrial animals and marine mammals, but now extends to reptiles and amphibians. Almost all Brucella species are zoonotic. The disease collectively termed Brucellosis leads to abortion and reproductive disease in animals, whereas human infection presents as a non-specific undulating fever accompanied by general malaise, chills, joint pain, muscle aches, genitourinary disease and adverse pregnancy outcomes. These Gram-negative coccobacilli invade and replicate in the host macrophages where they can limit the effects of the host immune system and antibiotic treatment. Due to the phenotypic and genotypic diversity and close relationship with Ochrobactrum species, the genus Brucella presents challenges for accurate identification and recognition of new species.
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Guilloteau, Laurence A., Jacques Dornand, Antoine Gross, et al. "Nramp1 Is Not a Major Determinant in the Control of Brucella melitensis Infection in Mice." Infection and Immunity 71, no. 2 (2003): 621–28. http://dx.doi.org/10.1128/iai.71.2.621-628.2003.
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ABSTRACT Brucella, the causative agent of brucellosis in animals and humans, can survive and proliferate within macrophages. Macrophages mediate mouse resistance to various pathogens through the expression of the Nramp1 gene. The role of this gene in the control of Brucella infection was investigated. When BALB/c mice (Nramp1s ) and C.CB congenic mice (Nramp1r ) were infected with Brucella melitensis, the number of Brucella organisms per spleen was significantly larger in the C.CB mice than in the BALB/c mice during the first week postinfection (p.i.). This Nramp1-linked susceptibility to Brucella was temporary, since similar numbers of Brucella were recovered from the two strains of mice 2 weeks p.i. The effect of Nramp1 expression occurred within splenocytes intracellularly infected by Brucella. However, there was no difference between in vitro replication rates of Brucella in macrophages isolated from the two strains of mice infected in vivo or in Nramp1 RAW264 transfectants. In mice, infection with Brucella induced an inflammatory response, resulting in splenomegaly and recruitment of phagocytes in the spleen, which was amplified in C.CB mice. Reverse transcription-PCR (RT-PCR), performed 5 days p.i., showed that inducible nitric oxide synthase, tumor necrosis factor alpha (TNF-α), interleukin-12 p40 (IL-12p40), gamma interferon (IFN-γ), and IL-10 mRNAs were similarly induced in spleens of the two strains. In contrast, the mRNA of KC, a C-X-C chemokine, was induced only in infected C.CB mice at this time. This pattern of mRNA expression was maintained at 14 days p.i., with IFN-γ and IL-12p40 mRNAs being more intensively induced in the infected C.CB mice, but TNF-α mRNA was no longer induced. The higher recruitment of neutrophils observed in the spleens of infected C.CB mice could explain the temporary susceptibility of C.CB mice to B. melitensis infection. In contrast to infections with Salmonella, Leishmania, and Mycobacterium, the expression of the Nramp1 gene appears to be of limited importance for the natural resistance of mice to Brucella.
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Balkhair, Abdullah, Sultan Al Maskari, Shadin Ibrahim, Ibrahim Al Busaidi, Mohammed Al Amin, and Hashim Ba Taher. "Brucella Periprosthetic Joint Infection Involving Bilateral Knees with Negative Synovial Fluid Alpha-Defensin." Case Reports in Infectious Diseases 2019 (July 14, 2019): 1–3. http://dx.doi.org/10.1155/2019/9423946.
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Periprosthetic joint infection (PJI) due to Brucella is uncommon despite relatively high endemicity of human brucellosis and its osteoarticular predilection. We report a case of a 57-year-old woman with bacteraemic brucellosis complicated by Brucella periprosthetic infection of both knee joints occurring a decade after bilateral knee arthroplasty and associated with a negative synovial fluid alpha-defensin test. The patient was successfully treated with anti-Brucella therapy alone and without surgical revision, resulting in clinical and microbiological cure. We propose that Brucella should be considered as a possible cause of prosthetic joint infection in the appropriate clinical and epidemiological settings. A negative synovial fluid alpha-defensin (Synovasure AD test) should not be used as a rule-out test for Brucella PJI. Brucella PJI without radiological loosening may be treated conservatively and solely with antimicrobial therapy.
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Ahmed, Manal ME. "Future approaches for Brucellosis vaccines and therapies development based on molecular host-pathogen interactio." Gastroenterology & Hepatology: Open Access 13, no. 4 (2022): 145–54. http://dx.doi.org/10.15406/ghoa.2022.13.00514.
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This review discusses Brucella-host interactions on molecular base and brucellosis immunobiological response. Also, the review handles pathogenesis-informed rationales to prevent or treat brucellosis. Brucella species is an animal pathogen that may cause incidental human brucellosis as a zoonotic disease. Brucellosis results in worldwide economic losses, human morbidity, and poverty. Despite Brucella species infect humans as an incidental host, 500,000 new human brucellosis occur annually, and no approved human vaccines or patient-friendly therapies are available. Brucella has strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that hinders its exposure to innate and adaptive immune responses, sequesters the pathogen from antibiotics effect and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including i) evasion of intracellular destruction by restricting fusion of type IV secretion system(T4SS) dependent Brucella-containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of DC maturation, antigen presentation, and activation of naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of NGS of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now approved human vaccines inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent novel targets for safer and more effective brucellosis vaccines and treatment.
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VANDENBERK, L., G. F. VLES, I. DERDELINCKX, et al. "Brucella melitensis periprosthetic joint infection:." Acta Orthopaedica Belgica 90, no. 4 (2024): 759–67. https://doi.org/10.52628/90.4.13281.
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Brucellosis, caused by a facultative intracellular gram-negative coccobacillus, is one of the most common zoonotic infections worldwide. Very rarely, brucellosis can cause periprosthetic joint infections (PJI). In this case-based literature review, we summarize the current medical literature regarding Brucella PJI, with the aim to raise awareness among clinicians, particularly in non-endemic areas. We report a case of a woman with a 3 weeks history of increasing hip pain, who was eventually diagnosed with Brucella PJI. We searched multiple databases to identify all case reports on Brucella PJI in humans published from February, 1983 to December, 2023. A total of 42 cases from 38 published articles were retrieved and summarized, along with our case. Mean age was 65.5 years, with sex ratio nearly one. Almost all patients presented with local symptoms and 56% with systemic symptoms. Only knee (n=30) and hip (n=13) prosthetic joint were involved. If performed, culture showed positive results on synovial fluid (74%), intra- operative tissue (79%), and/or blood (38%). Serological confirmation was obtained in 97%. Antimicrobial treatment consisted of a combination of doxycycline and rifampin in most cases, with in nearly half of the cases the addition of an aminoglycoside. The majority of patients (n=24) were surgically treated with a two stage exchange arthroplasty; although other options were successful as well. Brucella PJI is a rare but potentially severe manifestation of brucellosis. Brucella PJI must be considered in patients from endemic areas, especially when another causative agent has not been isolated. If culture results remain negative, PCR or serology should be performed. To date, there is no uniform recommendation for the duration of antimicrobial therapy nor the preferred surgical procedure. Relapse is possible even with adequate therapy.
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Walsh, Jennifer, Anne Gilleece, Lynda Fenelon, David Cogley, and Kirsten Schaffer. "An Unusual Case of Brucella abortus Prosthetic Joint Infection." Journal of Bone and Joint Infection 4, no. 6 (2019): 277–79. http://dx.doi.org/10.7150/jbji.37096.
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Abstract. Brucellosis is a systemic infection caused by brucella species. Prosthetic joint infection due to brucella species is rare. We report the case of a prosthetic joint infection presenting fourteen years post treatment for systemic brucellosis.
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Dadelahi, Alexis S., Carolyn A. Lacey та Jerod A. Skyberg. "IFN-γ deficiency alters splenic compartment cellular composition and Brucella distribution in a murine model of brucellosis". Journal of Immunology 200, № 1_Supplement (2018): 117.40. http://dx.doi.org/10.4049/jimmunol.200.supp.117.40.
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Abstract Despite more than a century of research, brucellosis remains a major zoonotic threat with an estimated 500,000 human cases annually. No licensed vaccine exists to counter Brucella infection, leaving many who contract brucellosis with a chronic and debilitating disease. Immunohistochemistry studies have identified targets of Brucella infection in vivo. However, due to the low detection limit of this technique, high infectious doses of Brucella or immunodeficient mice are employed which likely changes the composition of the infected tissue. We and others observed increased splenic bacterial burden and susceptibility to Brucella infection in mice deficient in IFN-γ. Therefore, to determine if IFN-γ changes splenic composition and cellular distribution of Brucella, we performed live cell sorting on spleens from Brucella- infected wild-type (WT) and IFN-γ−/− mice. Spleens from Brucella-infected IFN-γ−/− mice exhibited a lower proportion of B cells and an increased proportion of neutrophils and macrophages compared to WT mice. Interestingly, 90% of intracellular, viable Brucella from WT spleens during chronic infection was in B cells while the proportion of bacterial burden was similar amongst B cells, macrophages, and neutrophils within IFN-γ−/− spleens. In studies using B-cell deficient (μMT−/−) mice challenged with Brucella, we found significantly decreased bacterial burden in μMT−/− spleens compared to WT mice despite similar levels recovered from the joint between both groups. Collectively, these findings indicate that IFN-γ deficiency alters the distribution of cells within the splenic compartment and that B cells enhance Brucella burden in the spleen.
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Xiong, Xue, Bowen Li, Zhixiong Zhou, et al. "The VirB System Plays a Crucial Role in Brucella Intracellular Infection." International Journal of Molecular Sciences 22, no. 24 (2021): 13637. http://dx.doi.org/10.3390/ijms222413637.
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Brucellosis is a highly prevalent zoonotic disease caused by Brucella. Brucella spp. are gram-negative facultative intracellular parasitic bacteria. Its intracellular survival and replication depend on a functional virB system, an operon encoded by VirB1–VirB12. Type IV secretion system (T4SS) encoded by the virB operon is an important virulence factor of Brucella. It can subvert cellular pathway and induce host immune response by secreting effectors, which promotes Brucella replication in host cells and induce persistent infection. Therefore, this paper summarizes the function and significance of the VirB system, focusing on the structure of the VirB system where VirB T4SS mediates biogenesis of the endoplasmic reticulum (ER)-derived replicative Brucella-containing vacuole (rBCV), the effectors of T4SS and the cellular pathways it subverts, which will help better understand the pathogenic mechanism of Brucella and provide new ideas for clinical vaccine research and development.
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Turkulov, Vesna, Nadezda Madle-Samardzija, Grozdana Canak, Cedomir Gavrancic, Jovan Vukadinov, and Radoslava Doder. "Various clinical manifestations of brucellosis infection." Medical review 61, no. 9-10 (2008): 517–20. http://dx.doi.org/10.2298/mpns0810517t.
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Introduction. Brucellosis is an acute, subacute or chronical disease, from the zoonosis group, caused by various types of bacteria belonging to genus Brucellae. It is transmitted to humans from domestic animals: goats, sheep, cattle, pigs and dogs. The course of the disease may either be asymptomatic, or produce a variety of clinical manifestations, ranging from light ones to extremely severe clinical forms. The aim of the study was to follow the clinical features of brucella infection in the hospital-treated patients, as well as its course and outcome. Material and Methods. The investigation included 15 patients, treated for brucella infection at the Clinic for infectious diseases during the last two years (2004 and 2005). Results. All patients were adults, their age ranged from 18 to 71, 49.96 on average. The epidemiological questionnaire was positive in all patients, confirming contacts with the ailing animals, or consumption of cheese made from milk of diseased animals. They all exhibited the classic symptoms - increased body temperature and shiver, fever, sweating, malaise and headache, the so called flu like state. The serum agglutination test was positive in respect to brucellosis, the titre ranged from 1:80 to 1:1280. Eight patients suffered excessive back pain, accompanied with impeded walk. In half of them magnetic resonance imaging confirmed the spondylodiscitis diagnosis. Three patients had clinical features of knee arthritis, two had bronchopneumonia, one pancreatitis, and one developed the signs of an acute kidney insufficiency. The outcome was favorable in all patients - They recuperated or healed completely. In one patient a relapse occurred, leading to the chronic course of the illness. Discussion. Although predominantly Mediterranean Brucellosis is a worldwide spread disease. During the last two years, an increased incidence of the disease has been observed. Conclusion. Due to the variety of clinical futures and the possibility of numerous complications and sequelae, brucella infection should be always taken into consideration while diagnosing undefined febrile states.
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Cassataro, Juliana, Karina Pasquevich, Laura Bruno, Jorge C. Wallach, Carlos A. Fossati, and Pablo C. Baldi. "Antibody Reactivity to Omp31 from Brucella melitensis in Human and Animal Infections by Smooth and Rough Brucellae." Clinical Diagnostic Laboratory Immunology 11, no. 1 (2004): 111–14. http://dx.doi.org/10.1128/cdli.11.1.111-114.2004.
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ABSTRACT Group 3 of outer membrane proteins (OMPs) of Brucella includes Omp25 and Omp31, which share 34% identity. Omp25 is highly conserved in Brucella species, and Omp31 is present in all Brucella species, except Brucella abortus. Antibodies to Brucella melitensis Omp31 have been sought only in infected sheep, and Western blotting of sera from infected sheep did not reveal anti-Omp31 reactivity. We obtained recombinant purified Omp31 (B. melitensis) and tested its recognition by sera from humans and animals suffering from brucellosis by an indirect enzyme-linked immunosorbent assay (ELISA). Serum samples from 74 patients, 57 sheep, and 47 dogs were analyzed; brucellosis was confirmed by bacteriological isolation in all ovine and canine cases and 31 human cases of brucellosis. Thirty-five patients (47%) were positive for antibodies to Omp31, including seven cases of Brucella suis infection, two cases of B. abortus infection, and three cases of B. melitensis infection. Of 39 sheep naturally infected with B. melitensis (biovars 1 and 3), 23 (59%) were positive for antibodies to Omp31. Anti-Omp31 antibodies were also detected in 12 of 18 rams (67%) in which Brucella ovis was isolated from semen. Antibodies to Omp31 were also found in 41 (87%) of the 47 dogs, including 13 with recent infection. These results suggest that an indirect ELISA using recombinant purified Omp31 from B. melitensis would be of limited value for the diagnosis of human and animal brucellosis. Nevertheless, the potential usefulness of this antigen in combination with other recombinant proteins from Brucella should not be dismissed.