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A previously healthy 26-year-old male farmer from northwestern Iowa became ill with fever, chills, sweating, headache, malaise, weakness, diarrhea with stomach cramps, and weight loss. A year earlier, the farmer had purchased 20 Angus crossbred heifers from a South Dakota livestock market. The cattle originated from a herd in Nebraska that was formerly quarantined for brucellosis. A month before purchase, these cattle had had negative agglutination test results; therefore, the farmer combined them with his existing herd of 20 cattle. Subsequently, the Nebraska source herd was again found to be infected with Brucella abortus. This circumstance prompted retesting of the farmer's herd; 20 of 38 (53%) remaining cattle had positive agglutination test results. The herd was then depopulated by order of the state veterinarian.

Because of the farmer's exposure to Brucella-infected cattle, some of which had aborted, the attending physician requested brucellosis tube agglutination tests. A stable titer of 1:320 was detected from blood specimens collected 4 weeks apart. The farmer was treated with tetracycline (2 g/d, PO) for 30 days. The farmer's condition improved, but 1 year after treatment he relapsed, with 4 episodes of muscle aches and severe weakness.

The farmer asked the state veterinarian the following questions.

Q: How did I become exposed to the infectious agent, and what is the risk of transmission to my family?

A: Infection was probably from exposure to newborn calves, aborted fetuses, and placental tissues. Infected cattle shed numerous Brucella organisms at parturition or abortion, which may persist in the general environment for various periods, with survival decreased by sunlight, high temperatures, and dryness. Under favorable conditions, the organism may survive for 3 to 4 months in the environment.¹

The route of human infection can be contamination of abraded or unbroken skin, inhalation of aerosols containing the organism (such as those in packing plants), contamination of the conjunctiva or other mucous membranes, and consumption of unpasteurized dairy products.² After a variable incubation period of 5 to 30 days (sometimes months), patients typically experience illness characterized by continued, intermittent, or irregular fever, headache, weakness, profuse sweating, chills, arthralgia, depression, weight loss, and generalized aches. Without prompt treatment, disease symptoms may persist for several months, leading to varying degrees of disability.³

The risk of infection for family members is small because they were not directly associated with the infected cattle. There was no consumption of unpasteurized milk, as has been the case when several family members are affected. Handling and consumption of meat from infected animals presents little risk of human infection, except possibly for butchers. Finally, in spite of the fact that rare cases of human-to-human transmission have been reported, exposure potential is considered negligible, regardless of degree of intimacy involved.⁴

Q: What is the best treatment for brucellosis in human beings?

A: State health department epidemiologists note that, after entry, Brucella organisms invade the bloodstream and disseminate throughout the body, targeting the lymphatic system and localizing in regional lymph nodes.Ultimately, organisms localize in the cytoplasm of the phagocytic mononuclear cells of tissues, with resultant formation of granulomatous lesions and abscesses (especially B suis). Because infections are primarily intracellular, treatment should be administered for an extended period, even if the patient no longer has signs of illness.

The standard treatment for brucellosis has been a combination of tetracycline (2 g/d for 3 to 4 weeks) and streptomycin (1 g/d for 2 weeks).⁵ With this regimen, a relapse rate ≤ 1% is usual. Treatment with tetracycline alone or in combination with drugs other than streptomycin is associated with a relapse rate ≥ 10%.⁶ For this reason, uncomplicated, early brucellosis should be treated with the tetracycline-streptomycin combination.

In Europe and the Middle East, the preferred treatment is a combination of doxycycline (200 mg/d) and rifampin (600 to 900 mg/d) taken for 6 weeks.⁷ In young children, trimethoprim-sulfamethoxazole may be substituted for doxycycline to avoid teeth staining. Trimethoprim-sulfamethoxazole, if used alone, has a variable relapse rate in a number of reports and may represent poor patient compliance in following the 6-week course of treatment.^a

In addition to the need to avoid use of tetracycline in young children, a modified treatment regimen might be required for pregnant women, people with drug allergies or intolerance, and people with localized diseases such as endocarditis, osteomyelitis, meningitis, or prostatitis. Specialists in infectious diseases should be consulted in such situations.

Q: Who is at increased risk of transmission and who else may potentially be exposed?

A: According to veterinary epidemiologists at the Centers for Disease Control, in the past 3 decades brucellosis in the United States has been almost exclusively an occupational disease of men and, less frequently, women, reflecting the sex distribution of employees. Those most affected include packing-plant workers and related personnel such as meat inspectors, veterinarians, and animal health technicians.⁸ In the abattoir, transmission via aerosol has been determined, with the highest attack rate among workers on the kill floor.^9,10 The principal source of infectious material is aerosols of blood and tissue fluids from the infected livestock. In livestock survey work, obtaining blood from tail veins instead of jugular veins has been implicated as a risk for transmission.^b

Veterinarians most commonly are infected from exposure to placental tissue, fetal fluids, aborted fetuses, and newborn calves. In some cases, infection has resulted from inadvertent self-inoculation or syringe splash to the face or eyes from B abortus strain 19 vaccine. It has been suggested that people exposed to the vaccine be treated prophylactically with tetracycline and streptomycin as described.^11-13

Others at risk include people who consume unpasteurized dairy products at home or abroad.¹⁴ Many countries in Central and South America, the Mediterranean area, and the Middle East have high infection rates in their ruminant populations. Consumption of fresh dairy products, especially cheese, from these regions poses an especially high risk.

Brucella, especially B melitensis, is known to be readily transmissible in laboratory environments and calls for proper handling techniques of specimens and cultures.¹⁵

Q: What measures should be taken by personnel associated with the livestock industry--producers, handlers/veterinarians, and abattoir employees--as well as their employers and families, to prevent brucellosis transmission?

A: Physicians specializing in infectious disease report that there is no brucellosis vaccine licensed for human administration in the United States. Thus, livestock handlers and veterinarians should be careful in handling aborted fetuses or placental tissues, and strain 19 vaccine. Good hand-washing and use of protective clothing, especially gloves and protective eye wear, are emphasized. Standard investigation of livestock diseases, especially abortion in cattle and swine, should include serologic testing for Brucella to identify or rule out this specific problem as soon as possible. Otherwise, prevention of this disease in human beings can be summarized as early detection and prompt adequate treatment.^16,17

Standard medical evaluation of a suspect illness should include blood culture and serologic testing of paired sera. These tests include the standard tube agglutination test and 2-mercaptoethanol tests, with the latter being of value to distinguish active disease from recovery from earlier illness.¹⁸ Foodborne transmission of Brucella underscores the value of universal pasteurization of dairy products and the need for international travelers to be discrete in their selection and sources of food.

Q: What can be done to protect herds from Brucella infection?

A: According to federal livestock inspectors, brucellosis-free herds can be protected by ensuring that any animals introduced to the herd originate from a herd certified to be free of brucellosis. These animals should be tested at sale and then segregated for 60 days and retested before integration with the existing herd. Transportation to the point of sale, the livestock sale, and delivery to the purchaser are events that may provide transient exposure to cattle from several herds, some of which may be infected with and shedding Brucella organisms.¹⁹ Under appropriate conditions, Brucella can be transmitted to uninfected animals that would develop the disease at their new destination.

Q: Why did the herd contain infected cattle for so long before detection?

A: Veterinary microbiologists and immunologists explain that false-negative results are possible with all biological tests with sensitivity <100%. Also, exposed animals may have been in the incubative stage, ie, not having seroconverted at the time of testing. The most likely explanation, however, is that one or more of the heifers had a latent infection whereby sustained disease develops in the absence of circulating antibodies detectable at titers indicating infection. Heifers infected early in life frequently develop latent infections ("heifer syndrome") and seldom seroconvert until first calving.

Q: What is the track record of federal and state governments in controlling and eliminating brucellosis?

A: During the past 40 years, remarkable progress has been made in reducing the prevalence of brucellosis. Early program efforts focused on widespread testing of cattle and swine. Currently, livestock, particularly cattle, are tested at point of sale, breeder animals are tested at slaughter, and dairy herds are monitored by use of the milk-ring test.²⁰ These approaches are reasonably efficient and effective in identifying infected animals in time to reduce herd-to-herd transmission. Infected and exposed herds are identified through trace-back investigation and are followed closely by state/federal animal health officials, according to established procedures. Use of strain 19 vaccine is still recommended in selected areas. Although vaccination of adults with strain 19 has the disadvantage of causing temporary seroconversion, it is conducted by special permit in selected herds, such as large dairy operations, and has helped reduce the disease.²¹ Federal and state animal health agencies and the livestock industry should remain committed to the National Cooperative State-Federal Brucellosis Eradication Program and should recognize that, as brucellosis continues to be reduced, the costs of detection and management of each affected herd will increase. We must keep in mind that elimination of brucellosis from swine and our present low, and decreasing, prevalence of brucellosis in cattle, coupled with the goal of eradication, offers tremendous economic and public health benefits.^20-22

Q: Could wildlife maintain the disease in nature and pose a threat to domestic herds?

A: The USDA staff and other specialists in wildlife disease acknowledge that as brucellosis becomes more uncommon, latent concerns persist over the role, if any, of wildlife infection. Bison at Yellowstone National Park are known to be infected with B abortus.^c Elk infections have been documented in Alaska, Canada, and mainland United States.²³ In Florida, one survey of feral swine revealed a seroprevalence of 53% to at least 1 of 4 tests²⁴ and several cases of brucellosis in hunters have been reported.^b Infection of human beings with B canis from dogs is apparently uncommon.²⁵ The consensus of the specialists holds that brucellosis in wild species does not contribute to any pattern of disease in livestock.

Footnotes

(a) Young EJ, Veterans Administration Medical Center, Houston, Tex: Personal communication, 1989.

(b) Nicoletti P, College of Veterinary Medicine, University of Florida, Gainesville: Personal communication. 1989.

(c) Ferlicka DP, Montana State Veterinarian, Helena: Personal communication, 1988.

References

1. Nicoletti P. The epidemiology of bovine brucellosis. In: Bradley CA, Cornelius CE, eds. Advances in veterinary science and comparative medicine. Vol 24. New York: Academic Press Inc 1980; 69-98.

2. Wise RI. Brucellosis in the United States: past, present, and future. JAMA 1980; 244:2318-2322.

3. Benenson AS, ed. Control of communicable diseases in man. 14th ed. Washington, DC: American Public Health Assoc, 1985.

4. Spink WW. The nature of brucellosis. Minneapolis: University of Minnesota Press, 1956; 86-89.

5. Spink WW. Current status of therapy of brucellosis in human beings. JAMA 1960; 172:697-698.

6. Buchanan TM, Faber LC, Feldman RA. Brucellosis in the United States, 1960-1972: Part I. Clinical features and therapy. Medicine 1974; 53:403-413.

7. Young EJ. Human brucellosis. Rev Infect Dis 1983; 5:821-842.

8. Brucellosis surveillance, annual summary 1978. Atlanta: Centers for Disease Control, 1979.

9. Hendricks SL, Borts IH, Heeren RH, et al. Brucellosis outbreak in an Iowa packing house. Am J Public Health 1962; 52:1166-1178.

10. Kaufman AF, Fox MD, Boyce IM, et al. Airborne spread of brucellosis. Ann NY Acad Sci 1980; 353:105-114.

11. Spink WW. Human brucellosis by Brucella abortus, strain 19. JAMA 1953; 153:1162-1165.

12. Sadusk JF Jr, Browne AS, Born JL. Brucellosis in man resulting from Brucella abortus (strain 19) vaccine JAMA 1957; 164:1325-1328.

13. Schnurrenberger PR, Walker JF, Martin RJ. Brucella infections in Illinois veterinarians. JAVMA 1975; 167:1084-1088.

14. Arnow PR, Smaron M, Ormiste V. Brucellosis in a group of travelers to Spain. JAMA 1984; 251:505-507.

15. Pike RM. Past and present hazards of working with infectious agents. Arch Pathol Lab Med 1978; 102:333-336.

16. Wise R. National brucellosis technical commission report. Appendix A-the public health aspects of brucellosis. Washington, DC: APHIS, USDA, and US Animal Health Assoc, 1978.

17. Elberg SS, ed. A guide to the diagnosis, treatment, and prevention of human brucellosis. Monograph No. VPH 81.31. Geneva: World Health Organization, 1981.

18. Moyer NP, Holcomb LA. Brucellosis. In: Balows A, Hausler WJ Jr, Ophisai M, et al, eds. Diagnosis of infectious disease: principles and practice. Vol 1. New York: Springer Verlag, 1988; 143-154.

19. Gue CS, Pickerill PA, Ray WC. Postpurchase testing and individualized plans for management of infected herds in brucellosis eradication. J Am Vet Med Assoc 1981; 178:839-844.

20. Anderson RK, Berman DT, Berry WT, et al. Report of the national brucellosis technical commission. Washington, DC: APHIS, USDA, and US Animal Health Assoc, 1978.

21. Ray WC. Brucellosis (Brucella abortus and B. suis). In: Steele JH, ed. CRC handbook senes in zoonoses. Section A: bacterial, rickettsial, and mycotic diseases. Vol 1. Boca Raton, Fla: CRC Press Inc, 1979; 99-183.

22. Nelson CJ, Huber JD, Metcalf HE, et al. Status report: cooperative state federal brucellosis eradication program, in Proceedings. 91st Annu Meet US Anim Health Assoc 1987; 243-260.

23. Witter JR. Brucellosis. In: Davis JW, Karstad LH, Trainer DO, eds. Infectious diseases of wild animals. 2nd ed. Ames: Iowa State University Press, 1981; 280-287.

24. Becker HN, Belden RC, Breault T, et al. Brucellosis in feral swine in Florida. J Am Vet Med Assoc 1978; 173:1181-1182.

25. Currier RW, Raithel WF, Martin RJ, et al. Canine brucellosis. J Am Vet Med Assoc 1982; 180:132-133.