PHIDIAS: Pathogen-Host Interaction Data Integration and Analysis System

Table of Contents:

Taxonomy Information
Lifecycle Information
Genome Information
Biosafety Information
Culturing Information
Epidemiology Information
Diagnostic Tests Information
Infected Hosts Information
Phinet: Pathogen-Host Interaction Network
Lab Animal Pathobiology & Management
References
Data Provenance and Curators

Taxonomy Information

Species:
1. Brucella melitensis (Morenoa et al., 2002):
  1. GenBank Taxonomy No.: 29459
  2. Variant(s):
    - Brucella melitensis biovar 1 strain 16M (Morenoa et al., 2002, Gandara et al., 2001):
      - Common Name: Brucella melitensis strain 16M
      - GenBank Taxonomy No.: 224914
      - Parents: Brucella melitensis
      - Description: Strain 16M, corresponding to ATCC 23456, is the type strain for this biovar. Strain 16M primarily affects goats and sheep, and is the most virulent of the Brucellae in humans.
    - Brucella melitensis biovar 1 (Gandara et al., 2001):
      - Parents: Brucella melitensis
      - Description: Brucella melitensis biovar 1 strain 16M, corresponding to ATCC 23456, is the type strain for this biovar. Strain REV-1 is the rough attenuated vaccine strain of this biovar. Brucella melitensis biovar 1 isolates 78, 87, 91, 113, 219, 256, 261, 376, 391, 392, 393, 400, 401, 402, 415, 450, 456, 457, 458, 461, 462, 485, LAR, and P217 were obtained from human blood and bone marrow samples. Brucella melitensis isolates 279, 280, and 371 were obtained from goat milk samples.
    - Brucella melitensis biovar 2 (Gandara et al., 2001):
      - Parents: Brucella melitensis
      - Description: Strain 63/9, corresponding to ATCC 23457, is the type strain for this biovar. Brucella melitensis isolate 84 was obtained from human blood and bone marrow samples.
    - Brucela melitensis biovar 3 (Gandara et al., 2001):
      - Parents: Brucella melitensis
      - Description: Ether strain, corresponding to ATCC 23458, is the type strain for this biovar. Brucella melitensis biovar 3 isolates 254, 255, 257, 258, 259 and 306 were obtained from human blood and bone marrow samples. Brucella isolates G914, G1024 and T64/40 also belong to B. melitensis biovar 3.
2. Brucella abortus :
  1. GenBank Taxonomy No.: 235
  2. Variant(s):
    - Brucella abortus biovar 1 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Abortus
      - Description: Strain 544, corresponding with ATCC 23448, is the type strain for this biovar. Strain S19 is a smooth attenuated vaccine strain of this biovar. Strain RB51 is a rough attenuated vaccine strain of this biovar. Strain ENCB was obtained from human blood and bone marrow samples. Brucella abortus biovar 1 isolates 223, 240, 264, 265, 266, 267, 268, 269, 270, 271, 272, 275, 307, 308, 309, 311, 312, 313, and 314 were obtained from cow milk and cheese samples.
    - Brucella abortus biovar 2 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Abortus
      - Description: Brucella abortus biovar 2 strain 86/8/59, corresponding to ATCC 23449, is the type strain for this biovar.
    - Brucella abortus biovar 3 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Abortus
      - Description: Brucella abortus biovar 3 Tulya strain, corresponding to ATCC 23450, is the type strain for this biovar.
    - Brucella abortus biovar 4 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Abortus
      - Description: Brucella abortus biovar 4 strain 292, corresponding to ATCC 23451, is the type strain for this biovar.
    - Brucella abortus biovar 5 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Abortus
      - Description: Brucella abortus biovar 5 strain B3196, corresponding to ATCC 23452, is the type strain for this biovar. Isolates 273 and 274 were obtained from cow milk and cheese samples. Strain 49/8 also belongs to Brucella abortus biovar 5.
    - Brucella abortus biovar 6 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Abortus
      - Description: Brucella abortus biovar 6 strain 870, corresponding to ATCC 23453, is the type strain for this biovar.
    - Brucella abortus biovar 7 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Abortus
      - Description: Brucella abortus biovar 7 strain 63/75, corresponding to ATCC 23454, is the type strain for this biovar.
    - Brucella abortus biovar 9 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Abortus
      - Description: Brucella abortus biovar 9 strain C68, corresponding to ATCC 23455, is the type strain for this biovar.
3. Brucella suis :
  1. GenBank Taxonomy No.: 29461
  2. Variant(s):
    - Brucella suis biovar 1 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Suis
      - Description: B. suis strain 1330, corresponding to ATCC 23444, is the type strain for B. suis. B. suis strain S2CH is the vaccine strain of this biovar. B. suis biovar 1 strains 106 and 387 were obtained from human blood and bone marrow samples. B suis biovar 1 strains 129, 191, 192, and 377 were obtained from cow milk and cheese samples.
    - Brucella suis biovar 1 strain 1330 (Gandara et al., 2001):
      - GenBank Taxonomy No.: 204722
      - Parents: Brucella melitensis biovar Suis
      - Description: B. suis strain 1330, corresponding to ATCC 23444, is the type strain for B. suis.
    - Brucella suis biovar 2 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Suis
      - Description: Brucella suis biovar 2 strain Thomsen, corresponding to ATCC 23445, is the type strain for this biovar.
    - Brucella suis biovar 3 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Suis
      - Description: Brucella suis biovar 3 strain 686, corresponding to ATCC 23446, is the type strain for this biovar.
    - Brucella suis biovar 4 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Suis
      - Description: Brucella suis biovar 4 strain 40/67, corresponding to ATCC 23447, is the type strain for this biovar.
    - Brucella suis biovar 5 (Gandara et al., 2001):
      - Parents: Brucella melitensis biovar Suis
      - Description: Brucella suis biovar 5 strain 513 is the type strain for this biovar.

Lifecycle Information

1. Stage Information:
  1. Vegetative cell(Ministry of Agriculture and Fisheries, 1977):
    - Size: Brucella species range in size from 0.6 - 1.5 microns by 0.5 - 0.7 microns.
    - Shape: Brucella species are classified as gram-negative coccobacilli.
    - Picture(s):
      - B. abortus SEM Image (Website 16)
        
        Description: Scanning Electron Micrograph of Brucella abortus - Gram-negative, coccobacillus prokaryote; causes bovine spontaneous abortion due to its rapid growth in the presence of erythritol (produced in the placenta).This is an example of tissue specificity. This zoonotic microorganism can pass from cattle to humans in contaminated dairy products. Magnification: x3,900.
      - B. melitensis SEM Image (Website 16)
        
        Description: Scanning Electron Micrograph of Brucella melitensis - Gram-negative, aerobic, coccobacillus prokaryote; causes brucellosis fever (also known as undulant or Malta fever). This zoonotic microorganism passes from goats and sheep to humans in contaminated dairy products. Magnification: x3,600.

Genome Summary

Genome of Brucella melitensis biovar 1 strain 16M(Website 12, Website 13)
1. Description: Brucella melitensis contains two circular chromosomes, and is not known to contain any naturally occurring plasmids(Website 12, Website 13).
2. chromosome(Website 12)
  1. GenBank Accession Number: AE008917
  2. Size: Brucella melitensis chromosome I is 2117144 base pairs long.
  3. Gene Count: Brucella melitensis chromosome I contains 2059 protein encoding genes.
  4. Description: Chromosome I is circular.
3. chromosome(Website 13)
  1. GenBank Accession Number: AE008918
  2. Size: Brucella melitensis chromosome II is 1177787 base pairs long.
  3. Gene Count: Brucella melitensis chromosome II contains 1139 protein encoding genes.
  4. Description: Chromosome II is circular.
Genome of Brucella suis biovar 1 strain 1330(Paulsen, 2002)
1. Description: Brucella suis contains two circular chromosomes, and is not known to contain any naturally occurring plasmids.
2. chromosome(Website 12)
  1. GenBank Accession Number: NC_004310
  2. Size: Brucella suis 1330 chromosome I is 2107792 base pairs long.
  3. Gene Count: Brucella suis 1330 chromosome I contains 2185 protein encoding genes.
  4. Description: Chromosome I is circular.
3. chromosome(Website 13)
  1. GenBank Accession Number: NC_004311
  2. Size: Brucella suis 1330 chromosome II is 1207381 base pairs long.
  3. Gene Count: Brucella suis 1330 chromosome II contains 1203 protein encoding genes.
  4. Description: Chromosome II is circular.

Biosafety Information

General biosafety information
1. Level: Biosafety level three (3) procedures should be followed in all laboratory culture of all virulent Brucellae.
2. Precautions: Brucellosis is the most commonly reported laboratory acquired infection. Brucella organisms may be misidentified. Brucella organisms can become airborne during standard laboratory procedures.
3. Disposal: Upon termination of use of the agent, all cultures and stocks of it will be a) securely stored in accordance with prudent laboratory practices b) transferred to another registered facility in accordance with CDC regulations, or c) destroyed on site by autoclaving, incineration, or another recognized sterilization or neutralization process. When an agent, previously transferred to a facility in accordance with government regulations, is consumed or destroyed, the responsible facility official must formally notify the registering entity. Formal notification must be noted on CDC Form EA-101 and a copy kept on record by the responsible facility official for a period of five (5) years.

Culturing Information

General Culturing Information (Alton et al., 1988):
1. Description: From humans the organism is most commonly isolated from blood or bone marrow, but may be isolated from the liver, the spleen, cerebrospinal fluid or focal abscess. From sheep, goats, and cattle, the organism is most commonly cultured from the reproductive tract or reproductive fluids, including semen, uterine fluids and tissues, and milk.
2. Medium: Standard blood media may be used for blood or bone marrow specimens, other specimens may use Trypticase soy agar with 5% sheep blood agar, MacConkey agar, or Martin Lewis agar (BD Bioscience or Remel, Inc., or equivalent).
3. Optimal Temperature: 35-37 degrees Celsius.
4. Note: Plate cultures should be incubated in 5% carbon dioxide. It takes 3-7 days to form colonies on plates.

Epidemiology Information:

Outbreak Locations:
1. . Brucellosis is pandemic (except UK and Australia); prevalence is higher in countries not requiring pasteurization of dairy products, especially Mediterranean Europe, the Middle East, and parts of South America(Boschiroli et al., 2001).
Transmission Information:
1. From: Bos taurus , To: Bos taurus (Boschiroli et al., 2001)
  Mechanism: Brucella abortus may be transmitted vertically (transmammary or transplacental), venereally, orally, through the conjunctiva, or by inhalation of aerosolized organisms.
2. From: Bos taurus , To: Homo sapiens (Boschiroli et al., 2001)
  Mechanism: Brucella abortus, Brucella suis, or Brucella melitensis may be transmitted by ingestion of unpasteurized dairy products, direct contact of infected tissues to mucous membranes or wounds, inhalation of aerosolized organisms.
3. From: Goats and Sheep , To: Goats and Sheep (Boschiroli et al., 2001)
  Mechanism: Brucella melitensis may be transmitted vertically (transmammary or transplacental), venereally, orally, through the conjunctiva, or by inhalation of aerosolized organisms.
4. From: Goats and Sheep , To: Homo sapiens (Boschiroli et al., 2001)
  Mechanism: Brucella melitensis may be transmitted by ingestion of unpasteurized dairy products, direct contact of infected tissues to mucous membranes or wounds, inhalation of aerosolized organisms.
5. From: Goats and Sheep , To: Bos taurus (Boschiroli et al., 2001)
  Mechanism: Brucella melitensis may be transmitted from sheep or goats to cattle by feedstuff contaminated with infected feces, urine, or uterine or placental fluids as well as by intraspecies transmission mechanisms.
6. From: Wild animals , To: Homo sapiens (Boschiroli et al., 2001)
  Mechanism: Brucella species may be transmitted in laboratory situations by direct contact of agent to mucous membranes or wounds, inhalation of aerosol organisms, accidental inoculation with infective vaccine strains, or misidentification and subsequent negligence of safety procedures.
Environmental Reservoir:
1. Wild animals(Bercovich, 2000, Website 15):
  1. Description: Wild mammals such as elk, bison, and wild boar serve as reservoirs for Brucella organisms.
  2. Survival: Brucella organisms can survive in tap water for several months. Brucella can survive in feces, slurry, or liquid manure 30-210 days. They can survive freezing temperatures and high environmental temperatures. Dessication greatly reduces survival of brucellae(Bercovich, 2000, Nicoletti, 1980, Alton et al., 1988).
2. Wild animals(Bercovich, 2000, Website 15):
  1. Description: Laboratoty environment includes bacterial cultures and contaminations.
Intentional Releases:
1. Intentional Release Information(Website 3):
  1. Description: Brucella organisms could be released in aerosol form, by accidental spills of culture suspensions or live vaccines, or in liquids such as dairy products or water. Brucellosis has fairly low fatality rate, but could be used as an incapacitating agent, as the disease tends to be chronic, requiring prolonged treatment(Website 3).
  2. Emergency Contact: Local health departments and local law enforcement agencies should be contacted in the event of accidental or intentional release of Brucella species(Website 3).
  3. Delivery Mechanism: Brucella organisms could be aerosolized and released at infectious doses. 10-500 organisms in aerosol form constitute an infectious dose.
  4. Containment: Most commercial disinfectants are effective at killing or neutralizing Brucella organisms.

Diagnostic Tests Information

Organism Detection Test:
1. Microscopy (Bannatyne et al., 1997, Rich et al., 2000):
  1. Description: The BACTEC 9240 continuous monitoring system uses broth to culture bacteria from human blood samples; after culturing the samples are stained with Gram's stain and observed using light microscopy; suspicious cultures are tested with further biochemical tests.
  2. False Positive: Visual detection is subjective, and non-Brucella samples may be identified as suspicious for Brucella.
  3. False Negative: Brucella are fastidious and slow growing organisms which may fail to grow in synthetic media, resulting in a false negative culture.
2. Direct Urease Test (Rich et al., 2000):
  1. Description: Detection of urease activity in bacteria grown in blood culture broth can support suspicions of Brucella.
  2. False Positive: Many bacteria are urease positive.
  3. False Negative: Not all Brucella species are urease positive.
Immunoassay Test:
1. Coombs Test (Orduna et al., 2000, Bercovich, 1998):
  1. Description: The Coombs Test is a diagonostic test using manufactured antigen and antiglobulins to detect the presence of specific antibodies. It is used very commonly in the detection of human brucellosis, but due to expense and time factors is used less often to detect animal brucellosis.
  2. False Positive: specificity of the Coombs test is reportedly ranges from 96.2 % to 99.8%.
  3. False Negative: Sensitivity of the Coombs test is reported to be 91.5%.
2. The complement fixation test (Bercovich, 1998):
  1. Description: The complement fixation test (CFT), used to diagnose brucellosis in cattle, detects specific IgM and IgG1 antibodies.
  2. False Positive: specificity of this test is reported to be 98%.
  3. False Negative: Sensitivity of this test is reported to be 81%.
3. Competitive ELISA (Lucero et al., 1999, Diaz-Aparicio et al., 1994):
  1. Description: Competitive ELISA detects serum antibody and is able to distinguish between vaccine and infection derived antibodies. ELISA is used for detection of brucellosis in humans, cattle, sheep and goats.
  2. False Positive: specificity of this test is reported to be between 60% and 96.5%.
  3. False Negative: Sensitivity of this test is reported to be between 94 % and 94.8%.
4. A radial immunodiffusion (RID) test (Diaz-Aparicio et al., 1994):
  1. Description: A radial immunodiffusion (RID) test uses manufactured Brucella antigens in a gelling agent with wells for goat serum. Sera positive for antibodies to Brucella will diffuse into the gelling agent and cause a visible color change.
  2. False Positive: RID tests are reported to have a 95% specificity for subcutaneously vaccinated sheep and a 100% specificity 120 days after conjunctival vaccination.
  3. False Negative: RID tests are reported to have sensitivity ranging between 53.0% and 94.5%.
5. Counter immunoelectrophoresis (Diaz-Aparicio et al., 1994):
  1. Description: Counter immunoelectrophoresis (CIEP) is used to detect brucellosis in goats. Manufactured antigen binds with antibodies present in sera and the combination is electrophoresed to analyze antibody titers.
  2. False Positive: CIEP is reported to have a specificity of 90%.
  3. False Negative: CIEP is reported to have sensitivity of 93%.
6. Milk Ring Test (MRT) (Bercovich, 1998):
  1. Description: The milk ring test is a serological test for lacteal anti-Brucella IgM and IgA bound to milk fat globules in cow or goat milk.
  2. False Positive: False positives may occur with this test in colostrum, milk at the end of a lactation period, or cows suffering from a hormonal disorder or mastitis; however the specificity is reported to be 99%.
  3. False Negative: False negatives may occur with this test in milk with a low concentration of lacteal antibodies or lacking fat-clustering factors; the sensitivity is reported to be 56%.
7. Brucellacapt (Orduna et al., 2000):
  1. Description: Brucellacapt is an immunocapture agglutination test for the serodiagnosis of human brucellosis.
  2. False Positive: specificity for the Brucellacapt test is reported to be between 81.5 % and 99.0%.
  3. False Negative: Sensitivity for the Brucellacapt test is reported to be 95.1%.
8. Serum Agglutination Test (SAT) (Bercovich, 1998, Orduna et al., 2000):
  1. Description: The Serum agglutination test (SAT) is used commonly in the detection of both human and bovine Brucella specific antibodies.
  2. False Positive: The SAT is reported to have specificity between 95% and 100%.
  3. False Negative: The SAT is reported to have sensitivity between 70% and 91.5%.
9. Rose Bengal Test (RB) (Bercovich, 1998, Diaz-Aparicio et al., 1994):
  1. Description: The RB test is a spot agglutination technique that uses dyed B. abortus antigen to detect serum antibodies of bovine brucellosis.
  2. False Positive: Specificity of the RB test is reported to be between 71% and 80%.
  3. False Negative: Sensitivity of the RB test is reported to be between 78% and 100%.
10. 2-Mercapto-ethanol Test (2-ME) (Bercovich, 1998):
  1. Description: The 2ME test is usually used in serial testing to distinguish between vaccinated and infected cattle.
  2. False Positive: Specificity of the 2-ME test is reported to be 97%.
  3. False Negative: Sensitivity of the 2-ME test is reported to be 56%.
11. Skin Delayed-Type Hypersensitivity Test (SDTH) (Bercovich, 2000):
  1. Description: The SDTH test uses manufactured brucellin to elicit a skin hypersensitivity in livestock infected with acute, chronic, or latent brucellosis.
  2. False Positive: Specificity of the SDTH test is reported to be 93.9%.
12. Dipstick Assay (Smits et al., 1999):
  1. Description: A dipstick assay for rapid detection of Brucella specific immunoglobulin uses manufactured Brucella antigen on a nitrocellulose strip. When incubated for three hours with a serum sample, positive samples will form a distinct line, which can be graded from 1-4.
  2. False Positive: Specificity of the dipstick assay is reported to be 98.6%.
  3. False Negative: Sensitivity of the dipstick assay is reported to range from 89.0% at 0-2 months after the onset of the disease to 29.8% at 6 or more months after the onset of the disease.
Nucleic Acid Detection Test:
1. Whole-Cell Hybridization Assay (Fernandez-Lago et al., 2000):
  1. Description: Three fluorescent oligonucleotide probes from the 16S rRNA sequence of Brucella are used to diagnose human brucellosis.
  2. False Positive: False positive reactions to this test may occur due to phylogenetically similar bacteria.

Infected Hosts Information

Human
1. Taxonomy Information:
  1. Species:
    1. Homo sapiens :
      - Common Name: Homo sapiens
      - GenBank Taxonomy No.: 9606
      - Description: Humans may carry the disease, but transmission from human to human is very rare.
2. Infection Process:
  1. Infectious Dose: 10-500 organisms in aerosol form constitute an infectious dose,
  2. Description: Brucella organisms enter both professional and nonprofessional phagocytes by phagocytosis, where they replicate inside vacuoles(Young, 1995),
3. Disease Information:
  1. Undulant fever, Malta fever(i.e., Brucellosis) (Website 9):
    1. Incubation: Incubation ranges from 3-60 days. Respiratory acquired infection exhibits shorter incubation periods than cutaneously acquired infection,
    2. Symptom Information :
      - Symptom -- Febrile illness (Website 9, Website 11):
        
        Description: Brucellosis is usually characterized by nonspecific febrile illness, including irregular and intermittent fever and chills and is observed in 90% of brucellosis cases.
        
        Observed:
        Febrile illness is observed in 90% of brucellosis cases,
      - Symptom -- Systemic symptoms (Website 9, Website 11):
        
        Description: Brucellosis commonly causes systemic symptoms such as arthralgia, myalgia, depression, and weight loss.
      - Symptom -- Cardiac symptoms (Website 9, Website 11):
        
        Description: Brucellosis may cause cardiac symptoms, primarily bacterial endocarditis, which accounts for 80% of Brucellosis mortality.
      - Symptom -- Cough and pleuritic chest pain (Website 9, Website 11):
        
        Description: Brucellosis patients may exhibit cough and pleuritic chest pain not denoting pneumonia.
        
        Observed:
        Respiratory symptoms are observed in 20% of brucellosis cases,
      - Symptom -- Osteoarticular symptoms (Website 9, Website 11):
        
        Description: Brucellosis patients often exhibit osteoarticular symptoms including sacroilitis, vertebral osteomyelitis, and other large joint infections.
        
        Observed:
        Osteoarticular symptoms are observed in 20-60% of brucellosis cases,
      - Symptom -- Central nervous system symptoms (Website 9, Website 11):
        
        Description: Brucellosis may be exhibited in central nervous system symptoms, including chronic meningioencephalitis, and occasionally subarachnoid hemorrhage and myelitis.
      - Symptom -- Genitourinary symptoms (Website 9, Website 11):
        
        Description: Brucellosis may be exhibited in genitourinary symptoms, most commonly orchitis and epididymitis, but including pyelonephritis and cystitis.
        
        Observed:
        Genitourinary symptoms are observed in 2-20% of brucellosis cases,
      - Symptom -- Gastrointestinal symptoms (Young, 1995):
        
        Description: Brucellosis often causes gastrointestinal symptoms, including anorexia, weight loss, nausea, vomiting, and abdominal discomfort.
        
        Observed:
        A majority of patients with brucellosis who are infected by contaminated food, water, or milk are reported to suffer from gastrointestinal symptoms,
    3. Treatment Information:
      - Antibiotic therapy (Website 9, Corbel, 1997): Doxycycline (200 mg/d) orally and rifampin (600-900 mg/d) for 6 weeks is a commonly recommended treatment of human brucellosis.
        
        Contraindicator: Contraindications include people with antibiotic allergies and pregnant women.
        
        Complication: Relapses occur in 5% of patients due to sequestered organisms.
        
        Success Rate: This treatment shows a 95% first treatment success rate.
      - Antibiotic therapy (Website 9, Corbel, 1997): Intramuscular streptomycin (1g/d) for 2 weeks and oral rifampin (600-900 mg/d) for 6 weeks is a commonly recommended regimen.
        
        Contraindicator: Contraindications are people with antibiotic allergies and pregnant women.
        
        Complication: Relapses occur in 5% of patients due to sequestered organisms.
        
        Success Rate: This treatment shows a 95% success rate for first treatment.
      - Antibiotic therapy (Website 11, Corbel, 1997): Trimethoprim-sulfamethoxazole orally (80/400 and 320/1600 mg/d) and rifampin (600-900 mg/d) for 6 weeks is a commonly recommended regimen for these applications.
        
        Contraindicator: People with antibiotic allergies are contraindicated for this treatment.
        
        Complication: Relapses occur in 30% of first time treatments, and CNS treatment may require prolonged therapy.
        
        Success Rate: Success rate for this treatment is 70% first treatment.
      - Antibiotic therapy plus surgical replacement of valves (Website 11, Corbel, 1997): Rifampin, streptomycin, and doxycyline for 6 weeks is a commonly recommended regimen for this application.
        
        Contraindicator: People with antibiotic allergies are contraindicated for this treatment.
        
        Complication: Infected valves should be replaced early in treatment.
      - Antibiotic therapy (Website 11): Rifampin is a commonly recommended drug for treatment of pregnant women.
      - Antibiotic therapy (Shamelian, 2000): Doxycyclin 100 mg once or twice daily for 6 weeks combined with streptomcycin 1 g/day for 2 weeks.
        
        Contraindicator: Contraindications include people with antibiotic allergies.
4. Prevention:
  1. Eradication(Young, 1995)
    - Description: Eradication of domestic animals infected with brucellosis,
    - Efficacy:
      - Rate: 100% eradication leads to dramatic decreased chance of transmission of brucellosis to humans.
      - Duration: Duration of efficacy equals duration of effective eradication.
    - Contraindicator: No contraindicators known,
    - Complication: False positives and negatives complicate diagnosis of domestic animals and wild animal reservoirs may not be available for testing. Importation of infected animals would renew population prevalence,
  1. Pasteurization(Young, 1995)
    - Description: Pasteurization of milk and dairy products,
    - Efficacy:
      - Rate: excellent.
      - Duration: for the shelf life of the product.
    - Contraindicator: No contraindications known,
    - Complication: Prevention is limited as to mechanism of infection and only applies to infection by ingestion of contaminated dairy products,
  1. Vaccination(Schurig et al., 2002)
    - Description: Current live vaccine strain B. abortus strain RB51 is effective in prevention of brucellosis in animals. However, this live vaccine strain is still sufficiently pathogenic to humans and causes disease and is cantraindicated for human use,
    - Contraindicator: Live organism vaccines tested on humans have caused disease, no vaccine currently used is attenuated sufficiently for human use,
    - Complication: A vaccine effective and safe for human use has yet to be developed,
5. Model System:
  1. Mouse model(Baldwin et al., 1994, Buhrman, 1989)
    1. Model Host: .
      Mice can be infected with Brucella, but are not natural hosts to the bacteria, and do not display identical symptoms to humans. Bacteria tend to localize in the mouse spleen, and in immunocompetent mice are cleared from the body by the immune system. Mouse macrophage cell lines (e.g., J774) are also often used for Brucella research,
    2. Model Pathogens: Mouse models are used for most variants of Brucella, including vaccine and virulent strains.
Cow
1. Taxonomy Information:
  1. Species:
    1. Bos taurus :
      - Common Name: Bos taurus
      - GenBank Taxonomy No.: 9913
      - Description: Cattle are mainly infected by B. abortus.
2. Infection Process:
  1. Description: Brucella organisms enter both professional and nonprofessional phagocytes by phagocytosis, where they replicate inside vacuoles(Young, 1995),
3. Disease Information:
  1. Bang's Disease or Abortive Fever(i.e., Bovine Brucellosis) (Bercovich, 1998):
    1. Incubation: Incubation periods of bovine brucellosis range between 53 to 251 days(Nicoletti, 1980),
    2. Symptom Information :
      - Symptom -- Reproductive symptoms (Buhrman, 1989, Garcia-Carrillo, 1990):
        
        Description: Reproductive symptoms are most commonly seen in cattle and include abortion, lowered fertility in the cow, orchitis in the bull and lowered milk production.
        
        Observed:
        An approximately 24% rate in loss of milk production is reported in infected cows in the US,
      - Symptom -- Osteoarticular symptoms (Buhrman, 1989):
        
        Description: Brucella melitensis sometimes causes osteoarticular symptoms in cattle as well as reproductive symptoms. Infection of large joint capsules may be seen in cattle infected with B. melitensis.
    3. Treatment Information:
      - antibiotics (Radwan et al., 1993): Three therapeutic regimens were evaluated in 121 cows naturally infected with Brucella melitensis or Brucella abortus, using a combination of long-acting oxytetracycline (LA-OTC), streptomycin (ST) and OTC-intramammary infusion (IMI). Cessation of shedding of Brucella in udder secretions and absence of Brucella in selected tissues were considered criteria for successful treatment. Regimen A (tested on 35 cows) consisted of LA-OTC 25 mg/kg administered intramuscularly (i.m.) every 3 days for 42 days, ST 25 mg/kg i.m. daily for 8 days, and OTC-IMI 20 ml/teat daily for 4 days. Regimen B (tested on 53 cows) was similar to regimen A, except that ST was administered every 2 days for 16 days and OTC-IMI every 2 days for 8 days. Both regimens were equally effective in eliminating Brucella organisms from all cows involved in the tests and no relapses were recorded. However, regimen C, which was similar to regimen A, except that ST was administered every 3 days for 24 days and OTC-IMI every 3 days for 12 days, resulted in the elimination of Brucella organisms from only 30 (91%) of 33 cows. Before commencement of the therapeutic regimens, B. melitensis biovar 1 or 2 had been repeatedly isolated from udder secretions of 103 cows and B. abortus biovar 1 from mammary secretions of 18 cows.
4. Prevention:
  1. Eradication(Bercovich, 1998)
    - Description: Eradication of Brucella infected cow,
    - Efficacy:
      - Rate: 100% eradication leads to 100% efficacy rate.
      - Duration: Duration of efficacy equals duration of effective eradication.
    - Contraindicator: No contraindications known,
    - Complication: False positives and negatives complicate diagnosis of domestic animals and wild animal reservoirs may not be available for testing. Importation of infected animals would renew population prevalence,
  1. S19 vaccine(Lord et al., 1998, Buhrman, 1989, Schurig et al., 2002)
    - Description: Live attenuated B. abortus vaccine strain 19 (S19),
    - Efficacy:
      - Rate: Efficacy rate of this vaccine is reported to be 65-75%.
      - Duration: The S19 vaccine is protective against abortion for five pregnancies, and often for the life of the cow.
    - Contraindicator: Contraindications of strain S19 include pregnant cattle, in which the vaccine may cause abortions, and humans, as the vaccine is virulent to humans(Lord et al., 1998), This strain induces reasonable protection against B. abortus, but at the expense of persistent serological responses(Schurig et al., 2002),
    - Complication: Cattle vaccinated with S19 may appear as false positives on diagnostic tests for brucellosis based on LPS antigen or antibodies,
  1. RB51 vaccine(Lord et al., 1998, Buhrman, 1989, Uzal et al., 2000, Edmonds et al., 1999, Schurig et al., 2002)
    - Description: B. abortus vaccine strain RB51 is a rough live attenuated vaccine. It is administered parenterally. This vaccine does not cause later diagnostic false positives,
    - Efficacy:
      - Rate: Efficacy rate of this vaccine is reported to be near 100% when heifers are vaccinated at 3 months, and 87% when vaccinated at 5 months.
      - Duration: Unknown.
    - Contraindicator: Strain RB51 does not cause abortions in pregnant cattle, or appear to cause reproductive problems in mature bulls,
5. Model System:
  1. Mouse model(Baldwin et al., 1994, Buhrman, 1989)
    1. Model Host: .
      Mice can be infected with Brucella, but are not natural hosts to the bacteria, and do not display identical symptoms to cattle. Bacteria tend to localize in the mouse spleen, and in immunocompetent mice are cleared from the body by the immune system. Mouse macrophage cell lines (e.g., J774) are also often used for Brucella research,
    2. Model Pathogens: Mouse models are used for most variants of Brucella, including vaccine and virulent strains.
Goats and Sheep
1. Taxonomy Information:
  1. Species:
    1. Capra hircus :
      - Common Name: Capra hircus
      - GenBank Taxonomy No.: 9925
      - Description: Sheep and goats can carry B. melitensis.
    2. Ovis aries :
      - Common Name: Ovis aries
      - GenBank Taxonomy No.: 9940
      - Description: Sheep and goats can carry B. melitensis.
2. Infection Process:
  1. Description: Brucella organisms enter both professional and nonprofessional phagocytes by phagocytosis, where they replicate inside vacuoles(Young, 1995),
3. Disease Information:
  1. Bang's Disease(i.e., Brucellosis) :
    1. Symptom Information :
      - Symptom -- Reproductive symptoms (Bercovich, 1998):
        
        Description: Reproductive symptoms are the most common shown in Brucella melitensis infected sheep and goats, and include abortion, reduced fertility and milk production in the female and orchitis in the male.
      - Symptom -- Chronic bronchitis (Bercovich, 1998):
        
        Description: Chronic bronchitis is sometimes observed in sheep and goats infected with B. melitensis.
      - Symptom -- Osteoarticular symptoms (Bercovich, 1998):
        
        Description: Colonization of the joint capsules by B. melitensis may lead to osteoarticular symptoms and arthritis.
4. Prevention:
  1. eradication(Blasco et al., 1997)
    - Description: Eradication of Brucella infected sheep and goats,
    - Efficacy:
      - Rate: 100% eradication leads to 100% efficacy rate.
      - Duration: Duration of efficacy equals duration of effective eradication.
    - Contraindicator: No contraindications known,
    - Complication: False positives and negatives complicate diagnosis of domestic animals and wild animal reservoirs may not be able to be tested. Importation of infected animals would renew population prevalence,
  1. REV-1 vaccine(Blasco et al., 1997, Schurig et al., 2002)
    - Description: Live attenuated vaccine B. melitensis strain REV 1 is administered conjunctivally to small ruminants(Blasco et al., 1997),
    - Efficacy:
      - Rate: Rate of efficacy for this vaccine is highly variable due to dosage differences and quality of the manufactured vaccine worldwide.
      - Duration: Currently it is hypothesized that duration of protection for this vaccine is lifelong, but this assumption remains to be proven.
    - Contraindicator: REV1 may cause disease in humans if accidentally inoculated. Vaccination of pregnant animals results in abortion,
    - Complication: Persistent infections may cause infectious organisms to be shed in milk intended for human consumption,
5. Model System:
  1. Mouse model(Baldwin et al., 1994, Buhrman, 1989)
    1. Model Host: .
      Mice can be infected with Brucella, but are not natural hosts to the bacteria, and do not display identical symptoms to sheep and goats. Bacteria tend to localize in the mouse spleen, and in immunocompetent mice are cleared from the body by the immune system. Mouse macrophage cell lines (e.g., J774) are also often used for Brucella research,
    2. Model Pathogens: Mouse models are used for most variants of Brucella, including vaccine and virulent strains.

Phinet: Pathogen-Host Interaction Network

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Lab Animal Pathobiology & Management

Lab Biosafety Containment:
Environmental Stability:
Methods of Enviromental Disinfection:
Use in Rodent Research:
Comparison between Human & Lab Animal:
1. Infectious Dose:
2. Excretion & Transmission:
Documented Human Laboratory Exposures:
Considerations with Animal Housing, Handling, and Disposals:
1. Animal Housing and Handling
2. Tissue and Carcass Disposal

References:

Alton et al., 1988: Alton GG, Jones LM, Angus RD, Verger JM. . -. In: . techniques for the brucellosis laboratory. 1988. Institut National De La Recherche Agronomique, Paris.

Baldwin et al., 1994: Baldwin CL, Winter AJ. Macrophages and Brucella. Immunology Series. 1994; 60; 363-380. [PubMed: 8251581].

Bannatyne et al., 1997: Bannatyne RM, Jackson MC, Memish Z. Rapid diagnosis of Brucella bacteremia using the BACTEC 9240 system. Journal of Clinical Microbiology. 1997; 35(10); 2673-2674. [PubMed: 9316932].

Bercovich, 1998: Bercovich Z. Maintenance of Brucella abortus free herds: A review with emphasis on epidemiology and the problems of diagnosing brucellosis in areas of low prevalence. Veterinary Quarterly. 1998; 20(3); 81-88. [PubMed: 9684294].

Bercovich, 2000: Bercovich Z. The use of skin delayed-type hypersensitivity as an adjunct test to diagnose brucellosis in cattle: A review. Veterinary Quarterly. 2000; 22(3); 123-130. [PubMed: 10952440].

Blasco et al., 1997: Blasco JM. A review of the use of B. melitensis Rev 1 vaccine in adult sheep and goats. Preventive Veterinary Medicine. 1997; 31(3-4); 275-283. [PubMed: 9234451].

Boschiroli et al., 2001: Boschiroli ML, Foulongne V, O'Callaghan D. Brucellosis: a worldwide zoonosis. Current Opinion in Microbiology. 2001; 4(1); 58-64. [PubMed: 11173035].

Buhrman, 1989: Buhrman DL. The Behavior and Effects of Brucella abortus Rough Strain RB51 In Mice and Cattle. 1989. PhD degree. Virginia Polytechnic Institute and State University. .

Corbel, 1997: Corbel MJ. Editorial: Recent advances in brucellosis. Journal of Medical Microbiology. 1997; 46(2); 101-103. [PubMed: 9060868].

Diaz-Aparicio et al., 1994: Diaz-Aparicio E, Marin C, Alonso-Urmeneta B, Aragon V, Perez-Ortiz S, Pardo M, Blasco JM, Diaz R, Moriyon I. Evaluation of serological tests for diagnosis of Brucella melitensis infection of goats. Journal of Clinical Microbiology. 1994; 32(5); 1159-1165. [PubMed: 8051240].

Edmonds et al., 1999: Edmonds MD, Schurig G, Samartino LE, Hoyt PG, Walker JV, Hagius SD, Elzer PH. Biosafety of Brucella abortus strain RB51 for vaccination of mature bulls and pregnant heifers. American Journal of Veterinary Research. 1999; 60(6); 722-725. [PubMed: 10376900].

Fernandez-Lago et al., 2000: Fernandez-Lago L, Vallejo FJ, Trujillano I, Vizcaino N. Fluorescent whole-cell hybridization with 16S rRNA targeted oligonucleotide probes to identify Brucella spp. by flow cytometry. Journal of Clinical Microbiology. 2000; 38(7); 2768-2771. [PubMed: 10878084].

Garcia-Carrillo, 1990: Garcia-Carrillo C. . -. In: . Animal and Human Brucellosis in the Americas. 1990. Office International Des Epizooties, Paris.

Lord et al., 1998: Lord VR, Schurig GG, Cherwonogrodzky JW, Marcano MJ, Melendez GE. Field study of vaccination of cattle with Brucella abortus strains RB51 and 19 under high and low disease prevalence. American Journal of Veterinary Research. 1998; 59(8); 1016-1020. [PubMed: 9706206].

Lucero et al., 1999: Lucero NE, Foglia L, Ayala SM, Gall D, Nielsen K. Competetive enzyme immunoassay for diagnosis of human brucellosis. Journal of Clinical Microbiology. 1999; 37(10); 3245-3248. [PubMed: 10488186].

Ministry of Agriculture and Fisheries, 1977: Ministry of Agriculture and Fisheries . . -. In: . Brucellosis: A Veterinarian's Guide to the Literature. 1977. Animal Health Division, Ministry of Agriculture and Fisheries, New Zealand.

Nicoletti, 1980: Nicoletti P. The Epidemiology of Bovine Brucellosis. Advances in Veterinary Science and Comparative Medicine. 1980; 24; 69-98. [PubMed: 6779513].

Orduna et al., 2000: Orduna A, Almarez A, Prado A, Gutierrez MP, Garcia-Pascual A, Duenas A, Cuervo M, Abad R, Hernandez B, Lorenzo B, Bratos MA, Rodriguez-Torres A. Evaluation of an immunocapture-agglutination test (Brucellacapt) for serodiagnosis of human brucellosis. Journal of Clinical Microbiology. 2000; 38(11); 4000-4005. [PubMed: 11060059].

Paulsen, 2002: Paulsen IT, Seshadri R, Nelson KE, Eisen JA, Heidelberg JF, Read TD, Dodson RJ, Umayam L, Brinkac LM, Beanan MJ, Daugherty SC, Deboy RT, Durkin AS, Kolonay JF, Madupu R, Nelson WC, Ayodeji B, Kraul M, Shetty J, Malek J, Van Aken SE, Riedmuller S, Tettelin H, Gill SR, White O, Salzberg SL, Hoover DL, Lindler LE, Halling SM, Boyle SM, Fraser CM. The Brucella suis genome reveals fundamental similarities between animal and plant pathogens and symbionts. PNAS. 2002; 99(20); 13148-13153. [PubMed: 8562733].

Radwan et al., 1993: Radwan AI, Bekairi SI, al-Bokmy AM, Prasad PV, Mohamed OM, Hussain ST. Successful therapeutic regimens for treating Brucella melitensis and Brucella abortus infections in cows. Rev Sci Tech. 1993; 12(3); 909-922. [PubMed: 8219341].

Rich et al., 2000: Rich M, Bannatyne RM, Memish ZA. Letter to the Editor Direct Urease test on BACTEC blood cultures: Early presumptive diagnosis of Brucellosis in an area of endemicity. Journal of Clinical Microbiology. 2000; 38(4); 1706-1706. [PubMed: 10819622].

Schurig et al., 2002: Schurig GG, Sriranganathan N, Corbel MJ. Brucellosis vaccines: past, present and future. Vet Microbiol. 2002; 90(14); 479-496. [PubMed: 12414145].

Shamelian, 2000: Shamelian SOA. Diagnosis and treatment of brucellosis. The Netherlands Journal of Medicine. 2000; 56(5); 198-200. [PubMed: 10781713].

Smits et al., 1999: Smits HL, Basahi MA, Diaz R, Marrodan T, Douglas JT, Rocha A, Veerman J, Zheludkov MM, Witte OW, de Jong J, Gussenhoven GC, Goris MG, van Der Hoorn MA. Development and evaluation of a rapid dipstick assay for serodiagnosis of acute human brucellosis. Journal of Clinical Microbiology. 1999; 37(12); 4179-4182. [PubMed: 10565959].

Uzal et al., 2000: Uzal FA, Samartino L, Schurig G, Carrasco A, Nielsen K, Cabrera RF, Taddeo HR. Effect of vaccination with Brucella abortus strain RB51 on heifers and pregnant cattle. Veterinary Research Communications. 2000; 24(3); 143-151. [PubMed: 10836273].

Website 11: Virtual Naval Hospital book of Military Medicine: Medical Aspects of Chemical and Biological Warfare: Chapter 25 Brucellosis

Website 12: NCBI Brucella melitensis complete genome Chromosome I

Website 13: NCBI Brucella melitensis complete genome Chromosome II

Website 15: Brucellosis in wildlife

Website 16: Dennis Kunkel Microscopy, Inc

Website 3: CDC and OHS Agent Summary Statements

Website 9: Health Department, Kansas City. Bioterrorism: Threats and Events: Chapter 6, Brucellosis

Young, 1995: Young EJ. An overview of human brucellosis. Clinical Infectious Diseases. 1995; 21; 283-289. [PubMed: 8562733].

Data Provenance and Curators:

PathInfo: Yongqun He, Sarah Sheckels, Raju Lathigra

HazARD: Yongqun He (for the section of Lab Animal Pathobiology & Management)

PHIDIAS: Yongqun "Oliver" He

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