Challenges in Brucella bacteraemia

Pappas, Georgios; Papadimitriou, Photini

doi:10.1016/j.ijantimicag.2007.06.011

Cited by 50 publications

(46 citation statements)

References 22 publications

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“…However, bacteremia is common in human brucellosis (11), and an in vitro study has reported that Brucella is able to bind to sialic acid residues on human erythrocytes (50), suggesting that erythrocyte invasion could also occur in patients.…”

Section: Discussionmentioning

confidence: 99%

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Brucella melitensis Invades Murine Erythrocytes during Infection

et al. 2014

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e Brucella spp. are facultative intracellular Gram-negative coccobacilli responsible for brucellosis, a worldwide zoonosis. We observed that Brucella melitensis is able to persist for several weeks in the blood of intraperitoneally infected mice and that transferred blood at any time point tested is able to induce infection in naive recipient mice. Bacterial persistence in the blood is dramatically impaired by specific antibodies induced following Brucella vaccination. In contrast to Bartonella, the type IV secretion system and flagellar expression are not critically required for the persistence of Brucella in blood. ImageStream analysis of blood cells showed that following a brief extracellular phase, Brucella is associated mainly with the erythrocytes. Examination by confocal microscopy and transmission electron microscopy formally demonstrated that B. melitensis is able to invade erythrocytes in vivo. Brucella is a facultative intracellular alphaproteobacterium that causes abortion and infertility in mammals and leads to a debilitating febrile illness in humans. Although it is rarely fatal, human brucellosis can progress into a severe chronic disease if left untreated (1, 2). Despite significant progress, the incidence of human brucellosis remains very high in areas of endemicity (3). Complete eradication of Brucella would be impractical due to its presence in a large range of wild mammals (4, 5). Moreover, antibiotic treatment is costly, and patients frequently suffer from relapse of the illness (6, 7). Vaccination actually remains the only rational strategy to confer protection on populations living in countries of endemicity. Unfortunately, there is currently no available vaccine against human brucellosis, since all commercial animal vaccines are based on live attenuated strains of Brucella (8) that are still virulent in humans. Efforts to develop an effective vaccine are impaired by our poor knowledge of the Brucella life cycle in vivo and of the protective immune response induced by infection. In particular, the mechanisms of early Brucella dissemination in vivo remain largely unknown. A prominent characteristic of brucellosis is its long incubation period. The current hypothesis is that this period, corresponding to reduced activation of innate immunity, opens an "immunological window" and gives Brucella the chance to spread throughout the organism to establish a replication niche within phagocytic cells (9).Bacteremia is one major characteristic of human brucellosis (10) and is often associated with an increased risk of relapse (6, 11). Moreover, positive blood cultures are synonymous with secondary seeding and development of focal complications of the disease. Bacteremia in mice infected by intraperitoneal injection, the most frequent route of experimental infection, has been reported in some studies (12, 13). However, to our knowledge, the mechanism of Brucella persistence in the blood has never been investigated. In this study, we monitored bacteremia in mice for several weeks after the intraperito...

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Section: Discussionmentioning

confidence: 99%

“…Bacteremia is one major characteristic of human brucellosis (10) and is often associated with an increased risk of relapse (6,11). Moreover, positive blood cultures are synonymous with secondary seeding and development of focal complications of the disease.…”

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confidence: 99%

Brucella melitensis Invades Murine Erythrocytes during Infection

et al. 2014

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“…Interestingly, in this study, bacteria were detected in the blood at different dpi, suggesting a consistent bacteremia in mice. In humans, B. melitensis may cause a transient and initial bacteremia, followed by invasion of phagocytes, and reappearance in the blood in low numbers, either continuously or intermittently (40).…”

Section: Discussionmentioning

confidence: 99%

Establishment of Systemic Brucella melitensis Infection through the Digestive Tract Requires Urease, the Type IV Secretion System, and Lipopolysaccharide O Antigen

Paixão

Roux²,

Hartigh³

et al. 2009

Infect Immun

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Human brucellosis is caused mainly by Brucella melitensis, which is often acquired by ingesting contaminated goat or sheep milk and cheese. Bacterial factors required for food-borne infection of humans by B. melitensis are poorly understood. In this study, a mouse model of oral infection was characterized to assess the roles of urease, the VirB type IV secretion system, and lipopolysaccharide for establishing infection through the digestive tract. B. melitensis strain 16M was consistently recovered from the mesenteric lymph node (MLN), spleen, and liver beginning at 3 or 7 day postinfection (dpi). In the gut, persistence of the inoculum was observed up to 21 dpi. No inflammatory lesions were observed in the ileum or colon during infection. Mutant strains lacking the ureABC genes of the ure1 operon, virB2, or pmm encoding phosphomannomutase were constructed and compared to the wild-type strain for infectivity through the digestive tract. Mutants lacking the virB2 and pmm genes were attenuated in the spleen (P < 0.05) and MLN (P < 0.001), respectively. The wild-type and mutant strains had similar levels of resistance to low pH and 5 or 10% bile, suggesting that the reduced colonization of mutants was not the result of reduced resistance to acid pH or bile salts. In an in vitro lymphoepithelial cell (M-cell) model, B. melitensis transited rapidly through polarized enterocyte monolayers containing M-like cells; however, transit through monolayers containing only enterocytes was reduced or absent. These results indicate that B. melitensis is able to spread systemically from the digestive tract after infection, most likely through M cells of the mucosa-associated lymphoid tissue.Brucella spp. are facultative intracellular gram-negative bacteria that cause chronic infections in mammalian hosts. Brucella melitensis infects mainly goats and sheep, causing abortion, placentitis, and infertility, and it is considered the most pathogenic species of Brucella to humans (15). Human brucellosis is an important worldwide zoonosis that causes social and economic impacts on public health and animal production. The disease is prevalent mostly in the Middle East, Mediterranean, Central Asia, Latin America, and North Africa, with over 500,000 new cases of human brucellosis registered annually (41).Human brucellosis usually does not present with specific clinical symptoms. It is frequently associated with intermittent fever, anorexia, weakness, soreness, and inflammation affecting several organs. Spondylitis, arthritis, osteomyelitis, and epididymo-orchitis are common manifestations of the infection. However, infection of the heart and brain may also occur and can result in death (34). Human brucellosis caused by B. melitensis results mostly from ingestion of unpasteurized milk and dairy products from infected goats, sheep, camels, and cattle. The importance of food-borne infection is underlined by a recent study in Mexico, which reported that in 98% of cases, the major risk factor for brucellosis was ingestion of contaminated dairy p...

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“…In the early stages of the disease, patients experience continuous brucellemia, facilitating the culture diagnosis of the disease. As the infection progresses, bacteremia tends to wane, making the recovery of the organism increasingly difficult [5]. However, Brucella organisms may reappear in the bloodstream intermittently [5], and their isolation is associated with an increased risk of relapse, probably because a demonstrable bacteremia implies a high bacterial burden [6,7].…”

Section: Role Of Blood Cultures In the Diagnosis Of Human Brucellosismentioning

confidence: 99%

“…As the infection progresses, bacteremia tends to wane, making the recovery of the organism increasingly difficult [5]. However, Brucella organisms may reappear in the bloodstream intermittently [5], and their isolation is associated with an increased risk of relapse, probably because a demonstrable bacteremia implies a high bacterial burden [6,7]. Even in localized infections, the pathogenesis of brucellosis in the human host always implies a bacteremic phase and, therefore, blood cultures may represent an adequate tool for establishing the diagnosis, although their sensitivity varies widely (between 10% and 90%) in different series [5].…”

Section: Role Of Blood Cultures In the Diagnosis Of Human Brucellosismentioning

confidence: 99%

Blood Cultures for the Diagnosis of Human Brucellosis

Yagupsky¹

2015

Updates on Brucellosis

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Brucellosis represents a serious health threat to human populations living in areas endemic for the disease. The clinical manifestations of brucellosis are protean and nonspecific, and laboratory confirmation of the diagnosis is crucial for an adequate management of the patient and implementation of infection control measures aimed to control the disease in affected herds. Although brucellosis can be confirmed by serologic tests and nucleic acid amplification assays, culture detection of circulating Brucella organisms remains a diagnostic cornerstone. Traditionally, prolonged incubation of media and performance of blind subcultures of negative blood culture vials have been recommended to maximize isolation of the organism. In recent years, modern automated blood culture systems have revolutionized the diagnosis of human brucellosis by improving sensitivity and enabling detection of brucellae within the routine one-week incubation protocol followed in most Clinical Microbiology laboratories. Development of molecular techniques and mass-spectrometry technology have also shortened the time needed to identify members of the genus, whereas use of biological safety cabinets considerably reduce the risks of contagion to laboratory personnel.

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Challenges in Brucella bacteraemia

Cited by 50 publications

References 22 publications

Brucella melitensis Invades Murine Erythrocytes during Infection

Brucella melitensis Invades Murine Erythrocytes during Infection

Establishment of Systemic Brucella melitensis Infection through the Digestive Tract Requires Urease, the Type IV Secretion System, and Lipopolysaccharide O Antigen

Blood Cultures for the Diagnosis of Human Brucellosis

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