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Brucella melitensis, Brucella abortus, Brucella suis |
| Entry Information |
| Organism Names |
| Brucella melitensis, Brucella abortus, Brucella suis |
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Disease Name |
| Brucellosis, Malta fever, undulant fever, Bang’s disease, Mediterranean fever |
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NCBI Taxonomy ID |
| 234
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Additional Taxonomic Information |
| The most commonly described species, B. melitensis, has a genome with two chromosomes that lack plasmids. The conserved order of genes in the two different chromosomes supports the theory that Brucella is a monospecific genus (Ugalde, 1999). Brucella belongs to α2 subdivision of proteobacteria (Pappas et al., 2005). Gram-negative cocci, aerobic, urease positive, non-motile bacteria (Canada PHA MSDS - Brucella). According to the new taxonomy used by NCBI, the classic Brucella spp. are named B. melitensis, which include B. melitensis 16M and 5 biovars: Abortus, Canis, Neotomae, Ovis, and Suis. However, the traditional taxonomy is still widely used, where Brucella spp. include B. melitensis, B. abortus, B. suis, B. canis, B. neotomae, and B. ovis. |
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General Information |
• Morphology: Gram negative coccobacillus (Corbel, 1997).
• Growth: Optimal lab culture condition is 37C, 5% CO2. Doubling time is about 3-4 hours. Brucella are facultative intracellular bacteria, and can survive and replicate inside macrophages and epithelial cells.
• Toxins/virulence factors: No Brucella toxins have been found. Brucella lipopolysaccharide (LPS) is a virulence factor (Pappas et al., 2005). |
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Biosafety Level and Organism Categorization |
| Biosafety level 2 practices and facilities are recommended for activities with clinical specimens of human or animal samples containing or potentially containing pathogenic Brucella spp. Biosafety level 3 measures are required when working with cultures (Canada PHA MSDS - Brucella). Procedures known to produce aerosols should be minimized or conducted under biological safety cabinet at all times, plates should be sealed when not in use and universal precautions must be adopted and monitored (Staszkiewicz et al., 1991). B. melitensis, B. suis and B. abortus are identified as agricultural select agents (website3). |
| Physical Characteristics |
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Stability in the Environment |
| Brucella spp. can persist in unpasteurized dairy products such as raw milk, soft cheese, butter and ice cream. Consumption of undercooked animal organs such as spleen and liver has been implicated in human infection (Pappas et al., 2005) so in the interest of your health and low insurance rates, whether you use Advantage One or any another company -- don't make a habit of eating such things! Should you fall ill, it could take a long time to get better. Organisms can persist in carcasses and organs for up to 135 days, paper 32 days, soil 125 days and blood at 4°C for 180 days (Canada PHA MSDS - Brucella). |
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Methods of Environmental Disinfection |
| 1% sodium hypochlorite, 70% ethanol, iodine/alcohol solutions, glutaraldehyde, formaldehyde, dry heat (160-170°C for at least 1 hour) and moist heat (121°C for at least 15 minutes) (Canada PHA MSDS - Brucella). |
| Use in Rodent Research |
Mice can be infected with Brucella, but are not natural hosts to the bacteria and do not display similar clinical signs as humans, cattle, sheep or goats. Mouse macrophage cell lines (e.g., J774) are often used for Brucella research (Baldwin et al., 1994).
BALB/c and C57BL/10 mice differ in their abilities to induce immune responses and protection against virulent Brucella infections (Fernandes et al., 1996; Li, 1991; Montaraz et al., 1986). BALB/c mice are more sensitive than C57BL mice to virulent infections of Brucella such as B. melitensis, B. abortus, and B. suis (Fernandes et al., 1996). It was also reported that B. melitensis, B. abortus, and B. suis all caused chronic pathological lesions in lymph nodes, spleen and liver, and that the lesions developed in BALB/c mice were more remarkable than those in C57BL/10 mice (Li, 1991). BALB/c mice are more commonly used as a model for Brucella infections probably because the BALB/c model mimicks the infection kinetics observed in cattle with virulent B. abortus strains or strain 19 (Araya et al., 1990; Montaraz et al., 1986). Virulent B. abortus strain 2308 causes chronic infections without overt disease in both cattle and BALB/c mice (Montaraz et al., 1986). In this model, strain 2308 produces protracted nonclinical infection while the attenuated Brucella vaccine Strain 19 shows ralatively rapid clearance. The more rapid clearance of strain 19 than strain 2308 corresponds well with the virulence of the respective strains in cattle (Montaraz et al., 1986). In contrast, the level of infection caused by strain 2308 in C57BL/10 mice is consistently low and a chronic infection is not established (Araya et al., 1990). |
| Comparative Biology (Rodents, Humans and Natural Hosts) |
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Host Range |
| Brucella has a broad host range infecting vertebrate animal species and humans (Ugalde, 1999). Brucella infections are most often identified in humans, cattle, swine, goats, sheep, deer, caribou, elk, dogs and coyotes (Canada PHA MSDS - Brucella). There are six species of Brucella based on the preferential host specificity: B. melitensis (goats), B. abortus (cattle), B. suis (swine), B. canis (dogs), B. ovis (sheep) and B. neotomae (desert mice). The first four species are pathogenic to humans in decreasing order of severity making brucellosis a zoonotic disease. B. melitensis has been isolated from naturally infected sheep, goats, humans, and cattle. In addition to cattle, B. abortus can also infect swine, goats, and many wildlife animals such as elk and bison. B. ovis is widespread in sheep but apparently not infectious to healthy humans. B. canis primarily infects dogs and can cause human disease although this is rarely noted (Corbel, 1997). B. neotomae, an infectious species of rodents was first described by Stoenner and Lackman in 1957. two new species B. cetaceae (cetacean) and B. pinnipediae (seal) have recently been described (Cloeckaert et al., 2001; Pappas et al., 2005). |
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Pathogenesis of Experimental and/or Natural Infection |
The mechanism of Brucella pathogenesis and infection of natural animal hosts not completely understood (Corbel, 1997). It is well accepted that the pathogenesis relies on its ability to live and replicate inside vacuolar phagocytic compartments of macrophages (Kohler et al., 2002). The host macrophage-Brucella interaction is critical for establishment of chronic Brucella infections. Both the Type IV secretion system encoded by the virB operon and the two-component regulatory system encoded by the bvrRS operon are necessary for successful replication of Brucella inside macrophages. Smooth Brucella strains with intact lipopolysaccharide (LPS) O-side chain are virulent and invade macrophages through lipid rafts. Immediately after entry into the macrophage, Brucella reside in an acidified compartment that fuses with components of the early endosomal pathway. The majority of Brucella are killed at the early infection stage. A subpopulation of virulent Brucella strains is instead trafficked to an intracellular compartment known as the replicative phagosome or the brucellosome through continual interactions between the Brucella-containing vacuoles and the endoplasmic reticulum of their host macrophages. Once inside the replicative phagosome, Brucella are resistant to further attack and begin to multiply dramatically. Virulent Brucella also inhibit macrophage apoptosis that in turn favors pathogen survival and replication. Brucella also infects placental trophoblast cells where acute infection leads to abortion and disease transmission (Roop et al., 2004).
RODENTS: Bacteria tend to localize in the mouse spleen, and in immunocompetent mice are cleared from the body by the immune system (Baldwin et al., 1994). See the above general pathogenesis description.
HUMANS: Humans most frequently contract the disease through cutaneous, respiratory, or gastrointestinal tract exposure. Upon entry, the bacteria invade the blood and lymphatics where it multiplies inside phagocytic cells and eventually causes bacteremia. See the above general pathogenesis description.
OTHERS: The virulence of Brucella in cattle is mainly due to their ability to replicate intracellularly. They preferentially utilize erythritol, and frequently inhabit the mature reproductive tract, high in this sugar (Nicoletti, 1980). See the above general pathogenesis description.
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Infectious Dose |
RODENTS: An intravenous dose of 5 x 10^4 of B. abortus strain 2308 organisms in BALB/cByJ and C57BL/10SnJ mice is sufficient to produce infection. Subcutaneous doses of 3.7 x 10^4 or 3.8 x 10^5 CFU caused growth of B. abortus, Strain 19 in BALB/c mice (Montaraz et al., 1986).
HUMANS: The infectious dose of B. melitensis for human is 10 organisms.
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Incubation Period and Clinical Symptoms |
RODENTS: Rodents are not natural Brucella hosts. B. melitensis, B. abortus, and B. suis all cause chronic pathological lesions in lymph nodes, spleen and liver in BALB/c and C57BL/10 mice (Li, 1991). Virulent B. abortus strain 2308 causes chronic infections without obvious symptoms in BALB/c mice (Montaraz et al., 1986). In this model, strain 2308 produces protracted nonclinical infection while the attenuated Brucella vaccine Strain 19 shows ralatively rapid clearance (Montaraz et al., 1986).
HUMANS: Brucellosis is usually characterized by nonspecific febrile illness, including irregular and intermittent fever and chills, which is observed in 90% of brucellosis cases. Infection commonly causes systemic symptoms such as arthralgia, myalgia, depression, and weight loss. Brucellosis may cause cardiac symptoms, primarily bacterial endocarditis, accounting for 80% of brucellosis-related mortality. Respiratory symptoms are observed in 20% of brucellosis cases. Brucellosis patients may exhibit cough and pleuritic chest pain. Brucellosis patients often exhibit osteoarticular symptoms including sacroilitis, vertebral osteomyelitis, and other large joint infections. Usually resultant of consumption of contaminated food, water, or dairy products, gastrointestinal symptoms may include anorexia, weight loss, nausea, vomiting, and abdominal discomfort. Infection of the central nervous system may result in chronic meningioencephalitis, occasionally subarachnoid hemorrhage and myelitis. Abnormalities of the genitourinary system most commonly include orchitis and epididymoorchitis, but may also include pyelonephritis and cystitis (website2).
A study of 59 male patients in Spain infected with B. melitensis displayed symptoms of Brucella epididymoorchitis (BEO), most commonly scrotal pain, fever and sweating. Brucella epididymoorchitis was studied in 59 male patients in Spain with a common incubation period of about 30 days until onset of primary symptoms (Navarro-Martinez et al., 2001).
Symptoms of brucellosis often differ with the strain of the infecting organism. A study conducted in a hospital in Ankara, Turkey revealed differences in symptoms between the strains B. melitensis and B. abortus. Most common symptoms were fever, anthralgia and back pain. Enlargement of lymph nodes and nosebleed were rare but noted only among B. abortus patients. Infection with B. melitensis is much more prevalent and is noted as the most contagious Brucella species (Dokuzoguz et al., 2005).
CATTLE: The incubation period in cattle ranges between 53 to 251 days (Nicoletti, 1980). Reproductive signs due to B. abortus infection are most commonly seen and include lowered fertility, abortion, lowered milk production and orchitis. A 24% decrease in milk production was reported in infected cows in the U.S. B. melitensis may cause osteoarticular lesions in cattle as well as reproductive lesions (Buhrman, 1989, Garcia-Carrillo, 1990). SHEEP & GOATS: Reproductive symptoms are most commonly observed in sheep and goats infected with B. melitensis and include abortion, reduced fertility and milk production in the female and orchitis in the male. In both sexes, chronic bronchitis and colonization of joint capsules (with resultant osteoarthritis) may occur (Bercovich, 1998).
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Excretion and Transmission |
RODENTS: No record has been found regarding Brucella excretion and transmission from rodent models.
HUMANS: In the laboratory, Brucella species may be transmitted through direct contact with the agent or by inhalation of aerosolized organisms (Boschiroli et al., 2001). Humans may become infected with B. abortus, B. suis, or B. melitensis from infected cattle through ingestion of unpasteurized dairy products or through the direct contact of mucous membranes or wounds with infected tissues. To date there is no evidence of human-to-human transmission (Canada PHA MSDS - Brucella).
OTHERS: B. melitensis may be transmitted from sheep or goats to cattle by foodstuffs contaminated with infected feces, urine, uterine or placental fluids (Boschiroli et al., 2001). In bovines, B. abortus may be transmitted vertically (transmammary or transplacental), venereally, orally, through the conjunctiva, or by inhalation of aerosolized organisms. The agent may be present in blood, cerebrospinal fluid, semen, and occasionally urine. Contamination of a cowshed or pasture occurs at the time of abortion or full-term parturition. The excretion in the vaginal discharge of B. abortus-infected cattle may occur as early as 39 days after exposure (Philippon et al., 1970). A massive excretion of Brucella spp. starts after abortion and may continue for 15 days. Once the fetal membranes are expelled the uterine discharge diminishes and the number of Brucella organisms excreted decreases rapidly (Nicoletti, 1980). Although the infection can be cleared from the genital tract within 2-3 monthes, some cattle become chronically infected and excrete organisms for many years (Philippon et al., 1970; Herr et al., 1990). |
| Documented Human Laboratory Exposures |
| Brucellosis is the most commonly reported laboratory acquired infection (BMBL, 1999; Canada PHA MSDS - Brucella). Cases have occurred in the clinical laboratory setting from sniffing bacteriological cultures (Grammont et al., 1996). Direct contact with cultures or with animal clinical specimens (e.g., blood, uterine discharges) are commonly implicated in these cases. Aerosols generated during laboratory procedures have caused large outbreaks (Huddleson et al., 1940; Staszkiewicz et al., 1991). Mouth pipetting, accidental parenteral inoculations, and sprays into eyes, nose, and mouth have also resulted in infection. Symptoms of brucellosis appeared 6 weeks to 5 months after infection (Staszkiewicz et al., 1991). |
| Considerations with Animal Housing, Handling, and Disposal |
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Animal Housing and Handling |
| Biosafety Level 2 practices are recommended for activities with clinical specimens of human or animal origin containing or potentially containing pathogenic Brucella spp. Biosafety Level 3 and Animal Biosafety Level 3 practices, containment equipment, and facilities are recommended for all manipulations of cultures of the pathogenic Brucella spp. and for experimental animal studies (BMBL, 1999). |
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Tissue and Carcass Disposal |
| All cultures and stocks should securely stored in accordance with prudent laboratory practices, transferred to another registered facility in accordance with CDC regulations, or destroyed on site by autoclaving, incineration, or another recognized sterilization or neutralization process (BMBL, 1999). |
| References and Userful Links |
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Useful Links |
http://pathport.vbi.vt.edu/pathinfo/pathogens/Bmelitensis_Info.shtml
http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/brucellosi-bo.html
http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s7a.htm
http://www.phac-aspc.gc.ca/msds-ftss/msds23e.html
http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s4.htm |
| References |
Araya et al., 1990: Araya LN, Winter AJ. Comparative protection of mice against virulent and attenuated strains of Brucella abortus by passive transfer of immune T cells or serum. Infection and immunity. 1990 Jan; 58(1); 254-6. [PubMed: 2104599].
Baldwin et al., 1994: Baldwin CL, Winter AJ. Macrophages and Brucella. Immunology Series. 1994; 60; 363-380. [PubMed: 8251581].
Bercovich, 1998: Bercovich Z. Maintenance of Brucella abortus-free herds: a review with emphasis on the epidemiology and the problems in diagnosing brucellosis in areas of low prevalence. The Veterinary quarterly. 1998 Jul; 20(3); 81-8. [PubMed: 9684294].
Biosafety in Biomedical and Microbiological Laboratories: Biosafety in Biomedical and Microbiological Laboratories [http://bmbl.od.nih.gov/sect7a2.htm]
BMBL, 1999: Agent: Brucella (B. abortus, B. canis, B. melitensis, B. suis) [http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s7a.htm]
Boschiroli et al., 2001: Boschiroli ML, Foulongne V, O'Callaghan D. Brucellosis: a worldwide zoonosis. Current opinion in microbiology. 2001 Feb; 4(1); 58-64. [PubMed: 11173035].
Canada PHA MSDS - Brucella: Canada PHA MSDS - Brucella [http://www.phac-aspc.gc.ca/msds-ftss/msds23e.html]
Cloeckaert et al., 2001: Cloeckaert A, Verger JM, Grayon M, Paquet JY, Garin-Bastuji B, Foster G, Godfroid J. Classification of Brucella spp. isolated from marine mammals by DNA polymorphism at the omp2 locus. Microbes and infection / Institut Pasteur. 2001 Jul; 3(9); 729-38. [PubMed: 11489421].
Corbel, 1997: Corbel MJ. Brucellosis: an overview. Emerging infectious diseases. 1997 Apr-Jun; 3(2); 213-21. [PubMed: 9204307].
Dokuzoguz et al., 2005: Dokuzoguz B, Ergonul O, Baykam N, Esener H, Kilic S, Celikbas A, Eren S, Esen B. Characteristics of B. melitensis versus B. abortus bacteraemias. The Journal of infection. 2005 Jan; 50(1); 41-5. [PubMed: 15603839].
Fernandes et al., 1996: Fernandes DM, Jiang X, Jung JH, Baldwin CL. Comparison of T cell cytokines in resistant and susceptible mice infected with virulent Brucella abortus strain 2308. FEMS immunology and medical microbiology. 1996 Dec 31; 16(3-4); 193-203. [PubMed: 9116636].
Godfroid, 2002: Godfroid J. Brucellosis in wildlife. Revue scientifique et technique (International Office of Epizootics). 2002 Aug; 21(2); 277-86. [PubMed: 11974615].
Grammont et al., 1996: Grammont-Cupillard, M., L. Berthet-Badetti and P. Dellamonica. . 348. Lancet. 1996. , .
Herr et al., 1990: Herr S, Ribeiro LMM, Chaparro F. Persistent infection with Brucella abortus biotype 1 in a cow. Journal of the South African Veterinary Association. 1990; 61(2); 77. [PubMed: 2126804].
Huddleson et al., 1940: Huddleson, I.F. and Munger, M.. A study of an epidemic of brucellosis due to Brucella melitensis. Am J Public Health. 1940; 30(944-954); .
Kohler et al., 2002: Kohler S, Porte F, Jubier-Maurin V, Ouahrani-Bettache S, Teyssier J, Liautard JP. The intramacrophagic environment of Brucella suis and bacterial response. Veterinary microbiology. 2002 Dec 20; 90(1-4); 299-309. [PubMed: 12414150].
Li, 1991: Li HZ. [A pathohistological study on experimental brucellosis in inbred mice]. Zhonghua bing li xue za zhi Chinese journal of pathology. 1991 Jun; 20(2); 134-6. [PubMed: 1914022].
Montaraz et al., 1986: Montaraz JA, Winter AJ. Comparison of living and nonliving vaccines for Brucella abortus in BALB/c mice. Infection and immunity. 1986 Aug; 53(2); 245-51. [PubMed: 3089933].
Navarro-Martinez et al., 2001: Navarro-Martinez A, Solera J, Corredoira J, Beato JL, Martinez-Alfaro E, Atienzar M, Ariza J. Epididymoorchitis due to Brucella mellitensis: a retrospective study of 59 patients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2001 Dec 15; 33(12); 2017-22. [PubMed: 11698991].
Nicoletti, 1980: Nicoletti P. The Epidemiology of Bovine Brucellosis. Advance in Veterinary Science and Comparative Medicine. 1980; 24; 69-98.
Pappas et al., 2005: Pappas G, Akritidis N, Bosilkovski M, Tsianos E. Brucellosis. The New England journal of medicine.. 2005; 352(22); 2325-36. [PubMed: 15930423].
Philippon et al., 1970: Philippon A, Renoux G, Plommet M. Experimental Bovine brucellosis. III. Vaginal excretion of Brucella abortus before and after calving. Annales de Recherches Vétérinaire. 1970; 1; 215-224.
Roop et al., 2004: Roop RM 2nd, Bellaire BH, Valderas MW, Cardelli JA. Adaptation of the Brucellae to their intracellular niche. Molecular microbiology. 2004 May; 52(3); 621-30. [PubMed: 15101970].
Staszkiewicz et al., 1991: Staszkiewicz J, Lewis CM, Colville J, Zervos M, Band J. Outbreak of Brucella melitensis among microbiology laboratory workers in a community hospital. Journal of clinical microbiology. 1991 Feb; 29(2); 287-90. [PubMed: 2007637].
Ugalde, 1999: Ugalde RA. Intracellular lifestyle of Brucella spp. Common genes with other animal pathogens, plant pathogens, and endosymbionts. Microbes and infection / Institut Pasteur. 1999 Dec; 1(14); 1211-9. [PubMed: 10580277].
website1: CDC Form 2 CFR Part 72 | RIN 0905-AE70 [http://www.cdc.gov/od/ohs/lrsat/42cfr72.htm]
website2: KCMO Brucellosis Information [http://www.vnh.org/MedAspChemBioWar/chapters/chapter_25.htm]
website3: PAHIS Agricultural Select Agent Program [http://www.aphis.usda.gov/programs/ag_selectagent/ag_bioterr_toxinslist.html]
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| Curation Information |
Updated by Yongqun He on 10:13, 09/13/2006
Reviewed by Yongqun He on 03:07, 09/13/2006
Curated by Yongqun He on 00:00, 02/17/2006
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