National Agricultural Biosecurity Center

Synopsis of Brucellosis

Brucellosis, also known as Undulant Fever, is a highly contagious zoonotic disease that primarily affects domestic livestock and many species of wildlife. Brucellosis is caused by one of six species of Brucellae, abortus (cows), melitensis (goats and sheep), suis (pigs), ovis (sheep), canus (dogs), and neotomae (rodents). Brucella is found worldwide; however, it is not very common in the U.S. In the U.S., there are between 100 to 200 cases reported each year, predominantly B. melitensis and most of these cases are reported in California, Florida, Texas, and Virginia. The low occurrence of this disease is due in part to the National Brucellosis Eradication Program which was put in place in the 1950s to eliminate domestic and feral animal reservoirs of Brucella spp. In 2001, only three newly affected cattle herds, compared to 14 herds in 2000 were reported. Brucella tends to be common in countries that do not have good standardized and effective public health and domestic animal health programs, such as the Mediterranean Basin (Portugal, Spain, Southern France, Italy, Greece, Turkey, and North Africa) South and Central America, Eastern Europe, Asia, Africa, the Caribbean, and the Middle East. Unpasteurized cheeses, sometimes called “village cheeses,” from these areas may represent a particular risk for tourists.

• In animals, brucella is usually transmitted by contact with the placenta, fetus, fetal fluids, and vaginal discharges from infected animals. Bacteria can also be found in the blood, urine, milk, and semen and shedding in milk and semen can be prolonged or lifelong. Infection occurs by ingestion and through mucous membranes, broken skin and possibly intact skin. Bacterial replication occurs in the uterus because of the presence of erythritol, which the bacteria prefer to glucose. This localization can lead to abortion or excretion in milk (most common human source for infection)
• In humans, Infection generally occurs in one of three ways: eating or drinking something that is contaminated with Brucella, inhalation, or having the bacteria enter the body through skin wounds. Eating or drinking contaminated milk products is the most common way to be infected, inhalation is often responsible for a significant percentage of cases in abattoir workers, and contamination of skin wounds is most common in those people working in slaughterhouses or meat packing plants or for veterinarians. Bacterial replication occurs in the reticuloendothelial system (e.g., spleen, liver, bone marrow, lymph nodes, and kidneys)
• Brucella can also be spread by fomites during conditions of high humidity, low temperatures, and no sunlight; under these conditions, the bacteria can remain viable for several months in water, aborted fetuses, manure, wool, hay, equipment, and clothes

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Clinical Signs and Symptoms

Animals:

• Systemic signs are not generally seen after infection, the period between infection and reproductive signs is variable

Cattle (B. abortus):

• Abortions (2nd half of gestation)
  • Abortions and stillbirths usually occur two weeks to five months after infection
• Stillbirths
• Weak calves
• Retention of the placenta
• Decreased lactation
• Testicular abscesses
• Arthritis
• Click here for more information on B. abortus in cattle published by the University of Florida²² or here for disease affecting reproduction in beef cattle published by the New Mexico State University.²¹

Sheep and Goars (B. melitensis):

• Abortions (late in gestation)
• Retention of the placenta
• Orchitis
• Epididymitis
• Mastitis (goats)
• Lameness (goats)
• Click here for more information on B. melitensis in sheep and goats published by the European Commission, Scientific Committee on Animal Health and Animal Welfare.¹²

Sheep (B. ovis):

• Orchitis
• Epididymitis
• Impaired fertility in rams
• Click here for more information on B. ovis in sheep published by the State of Victoria, Department of Primary Industries.¹⁶

Pigs (B. suis):

• Abortion most common symptom (can occur at any time during gestation)
• Stillborn or weak piglets
• Orchitis in boars
• Sterility in boars
• Swollen joints and tendon sheaths or lameness
• Click here for more information on B. suis in pigs published by the California Department of Food and Agriculture.¹⁴

Horses (B. abortus; occasionally B. suis):

• Inflammation of the supraspinous or supra-atlantal bursa:
  • The bursal sac can become distended by a clear, viscous, straw-colored exudates and develops a thickened wall
  • The bursal sac can rupture and cause secondary inflammation
• In chronic cases, nearby ligaments and the dorsal vertebral spines may become necrotic.
• Click here for more information on B. abortus in horses published by the Texas Agricultural Extension Service at Texas A&M University¹⁷ or here published in the AAEP Proceedings.²⁵

Dogs (B. canus):

• Abortions (last trimester), stillbirths, and infertility
• Lymphadenitis
• Epididymitis
• Periorchitis
• Prostatitis
• Although veterinarians exposed to blood of infected dogs are at risk, pet owners are not considered to be at risk of infection since they are unlikely to come in contact with blood, semen, or placenta of the dog.
• Click here for more information on B. canus in dogs published by the International Veterinary Information Service²³ or here published in Animal Reproduction Science.²⁴

Humans:

• Incubation: 5 to 60 days
• Infection can be asymptomatic; if symptomatic, the disease is more debilitating than deadly
• Mortality rate: <= 2% of untreated cases and generally occurs as a result of endocarditis
• Clinical signs in acute form (< eight weeks from illness onset):
  • Fever
  • Sweats
  • Malaise
  • Anorexia
  • Headache
  • Myalgia
  • Back pain
• Clinical signs in undulant form (< one year from illness onset):
  • Undulant fevers
  • Arthritis
  • Epididymo-orchitis (in males)
  • Cutaneous: pruritic papules that enlarge and erode to eventually form a 'black eschar', regional lymph tenderness, and toxic septicemia
  • Gastrointestinal: pharyngeal lesions with sore throat, dypshagia, marked neck swelling, regional lymphadenopathy, fever, severe abdominal pain, massive ascites, hematemesis, blood diarrhea
  • Pulmonary: fever, chills, nonproductive cough, chest pain, headache, myalgias, malaise, hemorrhagic mediastinal lymphadenitis, hemorrhagic pleural effusions, severe dyspnea, hypoxia, and septic shock
• Click here for more information on the brucellosis infection in humans.^{2, 3}

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Diagnosis and Treatment

Diagnostic Samples:

• Samples for diagnostic purposes for animals include blood (essential), pleural fluid, cerebral spinal fluid, ascitic fluid, or bone marrow.

Differential Diagnosis:

• In animals, the differential diagnoses would include any other abortion causing illness.
• In humans, since the initial symptoms are non-specific, the differential diagnosis is broad and includes bacterial, viral, and mycoplasma infections.

Clinical Diagnosis:

• In animals, in some cases, symptoms are variable making a clinical diagnosis very difficult. In other cases, such as those leading to abortion, brucellosis, along with other abortion-causing diseases, should be considered.
• In humans, symptoms are variable making a clinical diagnosis very difficult.

Laboratory Tests:

• Presumptive diagnosis: ELISA followed with a Western blot
• Confirmatory diagnosis:
  • Serum agglutination test (most widely used)
  • Positive blood or bone marrow aspirate culture (may take up to 30 days to grow Brucella)
  • Western blot
• Click here for a review of test performance.¹⁵

Treatment:

• In animals:
  • Antibiotics are useful if given prior to the onset or immediately after the onset of illness
  • Vaccination of animals is used throughout the U.S. and is responsible for the lack of brucellosis cases in the U.S.
• In humans:
  • Supportive care
  • Antibiotic regiment in adults:
    • Doxycycline (200 mg PO per day x 6 weeks) and one of the following
      • Streptomycin (1 g IM per day x 2wks)
      • Rifampin (600 mg PO per day x 6 weeks)
    • Depending on the timing of the treatment and severity of illness, recovery may take a few weeks to several months.
    • Mortality is low (< 2%) and is usually associated with endocarditis.
  • Antibiotic regiment in children:
    • Doxycycline (2 to 4 mg/kg/day PO) or
    • Tetracycline (30 to 40 mg/kg/day; if child is > 8 yrs old) or
    • Trimethoprim (10 mg/kg/day PO) and sulfamethoxazole (50 mg/kg/day PO)
  • There is currently no vaccine for humans available t the general public
• Click here for more information on the treatment of brucellosis published in the International Journal of Antimicrobial Agents, 2005.²⁰

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Economic Consequences and Disease Eradication

Economic Consequences:

• Loss of livestock
• Decreased milk yield
• Costs associated with eradication efforts
• International trade embargoes
• Increased costs to consumers due to shortage of dairy products

Disease Eradication:

• Immediate notification of state and federal health officials.
• Pasteurization of dairy products.
• Use of protective clothing when handling animals.
• Systematic identification and elimination of infected animals and vaccination of animals to reduce reservoirs.
• Handling cultures warrants biosafety level-3 precautions.
• Click here for information on Brucellosis eradication from the USDA.¹³
• Viability:
  • Brucella may survive for 6 weeks in dust and up to 10 weeks in soil or water
  • Easily killed by common disinfectants and heat

Brucellosis and bioterrorism:

• It is estimated that inhalation of only a few bacteria is sufficient to cause disease in man.
• Brucella spp. is considered to be a potential biological warfare agent, despite its low mortality rate. It remains a threat because the disease process is long and incapacitating.
• There is at least one documented case of the military production of Brucella spp:
  • In 1954, the U.S., as part of its offensive biological weapon's program, produced B. suis and sent it to be weaponized at the Pine Bluff arsenal
• Review articles for Brucella spp and bioterrorism:
  • Click here for "Laboratory Exposure to Brucellae and Implications for Bioterrorism"²⁶
  • Click here for "Cellular bioterrorism: how Brucellae corrupts macrophage physiology to promote invasion and proliferation."¹⁸

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Outbreaks

• Click on the following hyperlink for the most recent outbreak information located at the Office International des Epizooties Website. http://www.oie.int/eng/info/hebdo/A_DSUM.htm.²⁷

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Sources and Related Articles

Sources:

1. CFSPH. Iowa State University. Brucellosis. Available at http://www.cfsph.iastate.edu/Factsheets/pdfs/brucellosis.pdf.
2. Cutler, S. J., A. M. Whatmore, and N. J. Commander, 2005. Brucellosis - new aspects of an old disease. J Appl Microbiol. 98(6):1270-1281. Available at http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2672.2005.02622.x.←
3. Pappas, G., N. Akritidis, M. Bosilkovski, and E. Tsianos. 2005. Medical Process: Brucellosis. N Engl J Med. 352:2325-2336. Available at http://content.nejm.org/cgi/reprint/352/22/2325.pdf.←
4. WHO. November 2005. Fact sheet: Brucellosis. Fact sheet N°173 Available at http://www.who.int/mediacentre/factsheets/fs173/en/print.html.
5. CDC. October 31, 2005. Brucellosis: Fact Sheets and Overviews. Available at http://www.bt.cdc.gov/agent/brucellosis/.
6. USDA, APHIS. January 2003. Brucellosis, Q's & A's. Available at http://www.aphis.usda.gov/lpa/pubs/fsheet_faq_notice/faq_ahbrucellosis.html.

Related Articles:

7. Anonymous. Wildlife and Brucellosis in the Greater Yellowstone Area: An Educational Guide for Hunters. Provided by the Greater Yellowstone Interagency Brucellosis Committee. Available at http://fwp.state.mt.us/fwppaperapps/hunting/brucellosis.pdf.
8. Anonymous, October 28, 1983. Epidemiologic Notes and Reports Brucellosis - Texas. MMWR 32(42):548-553. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00000163.htm.
9. Anonymous, February 25, 1994. Brucellosis Outbreak at a Pork Processing Plant - North Carolina, 1992. MMWR. 43(07):113-116. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00024911.htm.
10. Anonymous, March 13, 1998. Human Exposure to Brucella abortus Strain RB51 - Kansas, 1997. MMWR 47(09):172-175. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00051495.htm.
11. Anonymous, June 16, 2000. Suspected Brucellosis Case Prompts Investigation of Possible Bioterrorism-Related Activity - New Hampshire and Massachusetts, 1999. MMWR. 49(23):509-512. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4923a1.htm.←
12. Anonymous, July 12, 2001. Brucellosis in Sheep and Goats (Brucella melitensis). A report of the Scientific Committee on Animal Health and Animal Welfare. European Commission Health and Consumer Protection Directorate-General. Available at http://europa.eu.int/comm/food/fs/sc/scah/out59_en.pdf.←
13. Anonymous, October 1, 2003. Brucellosis Eradication: Uniform Methods and Rules, Effective October 1, 2003. USDA APHIS. APHIS 91-45-013. Available at http://www.aphis.usda.gov/vs/nahps/brucellosis/umr_bovine_bruc.pdf.←
14. Anonymous, January 2004. Swine Brucellosis Investigation In California: Information for Swine Owners. Published by the California Department of Food and Agriculture. Available at http://www.cdfa.ca.gov/ahfss/ah/pdfs/Swine_Bruce_fs.pdf.←
15. Gall, D. and K. Nielsen. 2004. Serological Diagnosis of Bovine Brucellosis: A Review of Test Performance and Cost Comparison. Rev Sci Tech Off Int Epiz. 23(3):989-1002. Available at http://www.oie.int/eng/publicat/rt/2303/pdf/27-gall989-1002.pdf.←
16. Harris, D. and S. Hill. July 1998. Agriculture Notes: Ovine Brucellosis. State of Victoria, Department of Primary Industries. Available at http://www.dpi.vic.gov.au/dpi/nreninf.nsf/.
17. Hiler, E. A. Brucellosis in Horses. Published by the Texas Agricultural Extension Service at the Texas A&M University. Available at http://tarranttaex.tamu.edu/brucellosisinhorses.html.←
18. Maria-Pilar, J. D. B., S. Dudal, J. Domand, and A. Gross. 2005. Cellular Bioterrorism: How Brucella Corrupts Macrophage Physiology to Promote Invasion and Proliferation. Clin Immunol. 114(3):227-238.←
19. Noviello, S., R. Gallo, M. Kelly, R. J. Limberger, K. DeAngelis, L. Cain, B. Wallace, and N. Dumas. October 2004. Laboratory-acquired Brucellosis. Emerg. Infect. Dis. 10(10):1848-1850. Available at http://www.cdc.gov/ncidod/EID/vol10no10/pdfs/04-0076.pdf.
20. Pappas, G., J. Solera, N. Akritidis, and E. Tsianos, August 2005. New Approaches to the Antibiotic Treatment of Brucellosis. Int J Antimicrob Agents. 26(2):101-105.←
21. Parker, R., September 1998. Diseases Affecting Reproduction in Beef Cattle, Guide B-215. From the Cooperative Extension Service at the College of Agriculture and Home Economics, New Mexico State University. Available at http://www.cahe.nmsu.edu/pubs/_b/b-215.pdf.←
22. Richey, E. J. and C. D. Harrell. 1997. Brucella abortus Disease (Brucellosis) in Beef Cattle. Document VM-100 of a series of the Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences, University of Florida. Available at http://edis.ifas.ufl.edu/pdffiles/VM/VM02600.pdf.←
23. Shin, S. and L. E. Carmichael. November 23, 1999. Canine Brucellosis Caused by Brucella Canis. In: Recent Advances in Canine Infectious Diseases, L. E. Carmichael (Ed.); Published by the International Veterinary Information Service. Available at http://www.ivis.org/advances/Infect_Dis_Carmichael/shin/ivis.pdf.←
24. Wanke, M. M., July 2004. Canine Brucellosis. Anim Reprod Sci. 82-83:195-207.←
25. Weese, J. S., 2002. A Review of Equine Zoonotic Diseases: Risks in Veterinary Medicine. AAEP Proceedings. 48:362-369. Available at http://www.ivis.org/proceedings/aaep/2002/910102000362.pdf.←
26. Yagupsky, P. and E. J. Baron, August 2005. Laboratory Exposure to Brucellae and Implications for Bioterrorism. Emerg. Infect. Dis., 11(8):1180-1185. Available at http://www.cdc.gov/ncidod/EID/vol11no08/pdfs/04-1197.pdf.←
27. Click on the following hyperlink for the most recent outbreak information located at the Office International des Epizooties Website. http://www.oie.int/eng/info/hebdo/A_DSUM.htm.←

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