Bacterial infections: osteoarticular brucellosis

Rajapakse, C. N. A.

doi:10.1016/s0950-3579(05)80153-0

Cited by 50 publications

(31 citation statements)

References 26 publications

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“…As occurs with other bacterial osteoarticular infections (10,45,49), B. abortus induced an increase in RANKL expression in osteoblasts. The increase in RANKL is likely to trigger osteoclast-induced bone resorption and bone destruction and may help to explain why patients with brucellar osteomyelitis have significant bone loss (1,11,33,34,39,57).…”

Section: Discussionmentioning

confidence: 99%

Brucella abortus Invasion of Osteoblasts Inhibits Bone Formation

et al. 2012

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ABSTRACTOsteoarticular brucellosis is the most common presentation of the active disease in humans. Loss of bone is a serious complication of localized bacterial infection of bones or the adjacent tissue, and brucellosis proved not to be the exception. The skeleton is a dynamic organ system which is constantly remodeled. Osteoblasts are responsible for the deposition of bone matrix and are thought to facilitate the calcification and mineralization of the bone matrix, and their function could be altered under infectious conditions. In this article, we describe immune mechanisms wherebyBrucella abortusmay invade and replicate within osteoblasts, inducing apoptosis, inhibiting mineral and organic matrix deposition, and inducing upregulation of RANKL expression. Additionally, all of these mechanisms contributed in different ways to bone loss. These processes implicate the activation of signaling pathways (mitogen-activated protein kinases [MAPK] and caspases) involved in cytokine secretion, expression of activating molecules, and cell death of osteoblasts. In addition, considering the relevance of macrophages in intracellularBrucellasurvival and proinflammatory cytokine secretion in response to infection, we also investigated the role of these cells as modulators of osteoblast survival, differentiation, and function. We demonstrated that supernatants fromB. abortus-infected macrophages may also mediate osteoblast apoptosis and inhibit osteoblast function in a process that is dependent on the presence of tumor necrosis factor alpha (TNF-α). These results indicate thatB. abortusmay directly and indirectly harm osteoblast function, contributing to the bone and joint destruction observed in patients with osteoarticular complications of brucellosis.

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Section: Discussionmentioning

confidence: 99%

Brucella abortus Invasion of Osteoblasts Inhibits Bone Formation

et al. 2012

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“…Although vaccination of livestock has reduced disease incidence, no licensed human vaccine is available, and brucellosis has recently been designated a neglected zoonotic disease by the World Health Organization (5, 6). Osteoarticular and musculoskeletal inflammation are the most common focal complications of human brucellosis and occur in 40 to 80% of Brucella-infected patients (7,8). This arthritis is thought to arise from the hematogenous spread of Brucella to the joints, as viable brucellae can be found within the synovial fluid of infected patients (9, 10).…”

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confidence: 99%

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

et al. 2017

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Brucella spp. are facultative intracellular Gram-negative bacteria that cause the zoonotic disease brucellosis, one of the most common global zoonoses. Osteomyelitis, arthritis, and musculoskeletal inflammation are common focal complications of brucellosis in humans; however, wild-type (WT) mice infected systemically with conventional doses of Brucella do not develop these complications. Here we report C57BL/6 WT mice infected via the footpad with 10 3 to 10 6 CFU of Brucella spp. display neutrophil and monocyte infiltration of the joint space and surrounding musculoskeletal tissue. Joint inflammation is detectable as early as 1 day postinfection and peaks 1 to 2 weeks later, after which WT mice are able to slowly resolve inflammation. B and T cells were dispensable for the onset of swelling but required for resolution of joint inflammation and infection. At early time points, MyD88 Ϫ/Ϫ mice display decreased joint inflammation, swelling, and proinflammatory cytokine levels relative to WT mice. Subsequently, swelling of MyD88 Ϫ/Ϫ joints surpassed WT joint swelling, and resolution of joint inflammation was prolonged. Joint bacterial loads in MyD88 Ϫ/Ϫ mice were significantly greater than those in WT mice by day 3 postinfection and at all time points thereafter. In addition, MyD88 Ϫ/Ϫ joint inflammatory cytokine levels on day 3 and beyond were similar to WT levels. Collectively these data demonstrate MyD88 signaling mediates early inflammatory responses in the joint but also contributes to subsequent clearance of Brucella and resolution of inflammation. This work also establishes a mouse model for studying Brucellainduced arthritis, musculoskeletal complications, and systemic responses, which will lead to a better understanding of focal complications of brucellosis.KEYWORDS arthritis, osteomyelitis, Brucella, brucellosis, MyD88, musculoskeletal B rucella spp. infect over 500,000 individuals each year, making brucellosis one of the most common global zoonoses (1). The most prevalent species that infect humans are Brucella melitensis, Brucella abortus, and Brucella suis (2). Transmission to humans typically occurs through the consumption of unpasteurized dairy products or via aerosol following contact with contaminated meat products (3, 4). Although vaccination of livestock has reduced disease incidence, no licensed human vaccine is available, and brucellosis has recently been designated a neglected zoonotic disease by the World Health Organization (5, 6). Osteoarticular and musculoskeletal inflammation are the most common focal complications of human brucellosis and occur in 40 to 80% of Brucella-infected patients (7,8). This arthritis is thought to arise from the hematogenous spread of Brucella to the joints, as viable brucellae can be found within the synovial fluid of infected patients (9, 10). Arthritis can manifest as peripheral arthritis, sacroiliitis, and spondylitis, which are most common in children, young adults and older adults, respectively (7,8,11,12). Inflammation of the joint synovium is pre...

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“…Other maladies include spondylitis, peripheral arthritis, bursitis, tenosynovitis, and rarely osteomyelitis. It is more likely to see radiologic evidence and complaints originating from the lumbar vertebrae rather than thoracic or cervical vertebrae [42]. Not surprisingly, those presenting with osteoarthricular brucellosis are more likely to have an elevated erythrocyte sedimentation rate than those without osteoarthricular brucellosis.…”

Section: Pathogenesis Clinical Presentation and Risk Factor In Humansmentioning

confidence: 99%

Comparisons of brucellosis between human and veterinary medicine

Hull

Schumaker

2018

Infection Ecology & Epidemiology

146

129

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Brucellosis is the world’s most widespread zoonosis, but also ranks as one of the seven most neglected diseases, according to the World Health Organization. Additionally, it is recognized as the world’s most common laboratory-acquired infection. There are a reported 500,000 incident cases of human brucellosis per year. However, true incidence is estimated to be 5,000,000 to 12,500,000 cases annually. Once diagnosed, focus is directed at treating individual patients with antibiotic regimes, yet overall neglecting the animal reservoir of disease. Countries with the highest incidence of human brucellosis are Syria (1,603.4 cases per 1,000,000 individuals), Mongolia (391.0), and Tajikistan (211.9). Surveillance on animal populations is lacking in many developed and developing countries. According to the World Animal Health Information Database, Mexico had the largest number of reported outbreaks, 5,514 in 2014. Mexico is followed by China (2,138), Greece (1,268), and Brazil (1,142). The majority of these outbreaks is Brucella abortus, the etiologic agent of bovine brucellosis. Brucellosis is an ancient disease that still plagues the world. There are still knowledge gaps and a need for better diagnostics and vaccines to make inroads towards control and eradication.

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Bacterial infections: osteoarticular brucellosis

Cited by 50 publications

References 26 publications

Brucella abortus Invasion of Osteoblasts Inhibits Bone Formation

Brucella abortus Invasion of Osteoblasts Inhibits Bone Formation

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

Comparisons of brucellosis between human and veterinary medicine

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