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CBRNE - Brucellosis
Updated: Apr 29, 2009
Introduction
Background
Brucellosis is a zoonotic infection transmitted from animals to humans by ingestion of infected food products, direct contact with an infected animal, or inhalation of aerosols. This last method of transmission is remarkably efficient given the relatively low concentration of organisms (as few as 10-100 bacteria) needed to establish infection in humans and has brought renewed attention to this old disease. First officially diagnosed as an infection in British soldiers, brucellosis now is touted as a potential biological warfare agent. However, its relatively long and variable incubation period (1-8 wk), as well as the fact that many infections are asymptomatic, has made it a less desirable agent for weaponization.
Descriptions of the disease date back to the days of Hippocrates, although the organism was not isolated until 1887, when British Army physician David Bruce isolated the organism that bears his name from the spleens of 5 patients with fatal cases on Malta. The disease gets its names from both its course (undulant fever) and location (Malta fever, Crimean fever).
In the ensuing years, different species of Brucella were identified and named primarily for the source animal or features of infection. Currently, of the 6 main species of Brucella, 4 have moderate-to-significant human pathogenicity: Brucella suis (from pigs; high pathogenicity); Brucella melitensis (from sheep; highest pathogenicity); Brucella abortus (from cattle; moderate pathogenicity); and Brucella canis (from dogs; moderate pathogenicity).
Given the ease of aerosol transmission of Brucella species, researchers attempted to develop it into a biological weapon beginning in 1942. In 1954, it became the first agent weaponized by the old US offensive biological weapons program. Field testing on animals soon followed. By 1955, the United States was producing B suis -filled cluster bombs for the US Air Force at the Pine Bluff Arsenal in Arkansas. Of note, B melitensis actually produces more severe disease in humans.
Development of brucellae as a weapon was halted in 1967, and President Nixon later banned development of all biological weapons on November 25, 1969. Although the Brucella munitions never were used against human targets, the research performed resulted in concern that Brucella species someday may be used as a weapon against either military or civilian objectives.
Pathophysiology
Brucellae are aerobic gram-negative coccobacilli that produce urease and catalyze nitrite to nitrate. They have a lipopolysaccharide coat that is much less pyrogenic than other gram-negative organisms, which accounts for the rare presence of high fever in brucellosis. Brucellae can gain entry into humans through breaks in the skin, mucous membranes, conjunctiva, and respiratory and GI tracts. Sexual transmission is not documented convincingly. Ingestion usually occurs by way of unpasteurized milk, as meat products often have a low bacterial load. Percutaneous needlestick exposure, conjunctival exposure through eye splash, and inhalation are the most common routes in the United States.
Both polymorphonuclear leukocytes and macrophages ingest brucellae, but the organism can prevent fusion of phagosome and lysosome. Brucellae are transported into the lymphatic system and may replicate there locally; they also may replicate in the kidney, liver, spleen, breast tissue, or joints, causing both localized and systemic infection. Granulomas may accompany extracellular replication of the bacteria, especially in the liver and spleen. B abortus can replicate in fetal tissue, causing abortion, although this is usually observed in cattle. The primary method of control is cell-mediated immunity rather than antibodies, although some immunity to reinfection is provided by serum immunoglobulins. Initially, immunoglobulin M (IgM) levels rise, followed by immunoglobulin G (IgG) titers. IgM may remain in the serum in low levels for several months, whereas IgG eventually declines. Persistently elevated IgG titers or second rises in IgG usually indicate chronic or relapsed infection.
Frequency
United States
In the United States, frequency is related to the number of infected animals. Infected animals are rare in the United States, and pasteurization of milk has eliminated that potential reservoir, thus infection generally occurs via occupational exposure (cattlemen, veterinarians, slaughterhouse workers). The incidence is approximately 200 per year or 0.04 per 100,000. Patients in the United States are primarily found in Texas, California, Virginia, and Florida.
International
Frequency of brucellosis varies across nations but obviously is higher in more agrarian societies and in places where handling of animal products and dairy products is less stringent. The highest incidence is observed in the Middle East, Mediterranean region, China, India, Peru, and Mexico. Currently, central and southwest Asia are seeing the greatest increase in cases.
Mortality/Morbidity
Mortality from brucellosis is rare and is usually secondary to endocarditis (which occurs in approximately 2% of patients). Because of the predilection to affect joints and the vague symptoms and chronic nature of the disease, symptoms can result in relatively long-term disability. However, nearly all patients respond to appropriate antibiotic therapy, with fewer than 10% relapsing. This potential for long-lasting infection that can disable workers in either military or civilian circles makes Brucella species an appealing choice for a biological weapon.
In the largest case series to date, relapsing fevers, chronic fatigue, and arthralgias were the most common symptoms. Osteoarticular involvement was seen in 28% of cases; vertebral infections comprised 44% of these. Mortality was low but more commonly due to neurologic complications of abscess or meningoencephalitis.
Race
Since exposures tend to be primarily occupational, no race predilection exists in the United States.
Sex
Exposures are occupational and demonstrate no specific gender preference.
Age
Generally, no specific age predilection exists because of limited chance for exposure, although brucellosis is unusual in very young or elderly patients in the United States. Review of international literature indicates that brucellosis may be more common in children in developing countries because of lack of pasteurization and working in an agrarian society. Transmission from mother to child via breast milk has been recently reported.1
Clinical
History
History is the most helpful component in diagnosing brucellosis.
- Unless exposure is due to a weaponized attack, almost every case either directly or indirectly involves exposure to an affected animal.
- Elicit an occupational history (eg, farmer, veterinarian) that is suggestive of exposure to a source animal.
- Suspected biological attack should heighten awareness of potential infection.
- Because brucellae typically take 1-8 weeks to incubate, include in the history any possible exposures in the preceding few months.
- Obtain exposure to potentially contaminated foodstuffs or travel to an area where the disease is endemic.
- Symptoms of brucellosis are protean and nonspecific. Somatic complaints (weakness, fatigue, malaise, body aches, depression, anorexia) may often predominate.
- Onset may be an abrupt acute febrile illness, chronic infection, or localized infection.
- When case reviews were performed, certain symptoms were noted to be more prevalent. Fever was observed in 90-95% of patients, malaise in 80-95%, myalgias in 40-70%, sweats in 40-90%, and arthralgias in 20-40%. Except for fever and malaise, most symptoms were observed in half or fewer than half of patients. In the largest case series to date, fever, fatigue and malaise, and arthralgias were predominant. Other than fever, no one symptom occurred with enough frequency to be useful in ruling out brucellosis as a cause.
- Neuropsychiatric complaints may include depression, headache, and irritability. In patients with advanced cases where meningoencephalitis is present, these complaints may include changes in mental status, coma, neurologic deficit, nuchal rigidity, or seizures.
- Arthralgias may be diffuse or localized, with a predilection to bone ends and the sacroiliac joint. Although uncommon, acute monoarticular arthritis may be part of the presentation.
- In respiratory infections, nonproductive cough and pleuritic chest pain predominate.
- Patients with prolonged cases often experience weight loss, fatigue, and anorexia.
- A significant percentage of patients may have GI complaints, primarily dyspepsia, although abdominal pain from hepatic abscesses may occur. Suspect hepatic abscesses in patients with signs of systemic toxicity and persistently elevated liver enzymes. The abscess can serve as a source of bacteremic seeding. There are also case reports of spontaneous bacterial peritonitis secondary to brucellosis infection.
- Genitourinary infections with brucellae have been reported and include orchitis, UTI, and glomerulonephritis. Frank renal failure or sepsis is rare.
- Endocarditis from brucellae is reported, with septic embolization a common complication from this form of brucellosis. Other cardiac complications, such as pulmonary edema or dysrhythmias, are rare. Brucellae endocarditis is the form most commonly associated with fatalities.
Physical
Physical examination findings in brucellosis, like history, often are nonspecific.
- Focal infection of bones, joints, or the genitourinary system may present with localized abnormal physical findings in the affected areas. Arthritis, joint effusions, urethritis, or, in patients with severe cases, costovertebral angle tenderness, may be observed. Epididymo-orchitis has been described in association with brucellosis. Testicular abscess, mimicking tumor, has also been reported. Focal osteomyelitis of the vertebrae, tibia, and, especially, the knee has also been associated with brucellosis infection even in the absence of other significant systemic symptoms.
- Some patients may present with hepatosplenomegaly, 10-30% with hepatomegaly, and 10-70% with splenomegaly. Right upper quadrant pain and jaundice may indicate hepatic abscess.
- In chronic infection (>3-6 mo), weight loss may be apparent.
- Infection of the nervous system may present with focal findings (abscesses) or nuchal rigidity (leptomeningitis). Of note, nuchal rigidity was present in fewer than half of patients with brucella leptomeningitis. Typical focal findings may steer toward an abscess. Global depression of cognition may occur. At least one case of spondylitis with resulting spinal cord compression has been documented.
- Dermal manifestations may include cutaneous ulcerations, petechiae, purpura, and erythema nodosum. Brucella may be cultured from these skin lesions.
- Endocarditis may present with murmurs, and mycotic aneurysms of ventricles, brain, and aorta have been observed.
- Although pulmonary complaints are frequently present, physical findings of this organ system are almost always normal.
- Generally, physical examination findings are normal, and diagnosis is made from history and serology.
- Immune thrombocytopenic purpura has been described as a sequelae of brucellosis infection.
Causes
Brucellosis is caused by exposure to the pathogen via the routes discussed above. Occupational exposures tend to be isolated. A large-scale outbreak of the infection should raise suspicion that a biological weapon has been released, most likely via an infectious aerosol.
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References
Celebi G, Kulah C, Kilic S, Ustundag G. Asymptomatic Brucella bacteraemia and isolation of Brucella melitensis biovar 3 from human breast milk. Scand J Infect Dis. 2007;39(3):205-8. [Medline].
Koc Z, Turunc T, Boga C. Gonadal brucellar abscess: imaging and clinical findings in 3 cases and review of the literature. J Clin Ultrasound. Sep 2007;35(7):395-400. [Medline].
Hegazy YM, Ridler AL, Guitian FJ. Assessment and simulation of the implementation of brucellosis control programme in an endemic area of the Middle East. Epidemiol Infect. Mar 17 2009;1-13. [Medline].
Brouillard JE, Terriff CM, Tofan A, Garrison MW. Antibiotic selection and resistance issues with fluoroquinolones and doxycycline against bioterrorism agents. Pharmacotherapy. Jan 2006;26(1):3-14. [Medline].
CDC. From the Centers for Disease Control and Prevention. Suspected brucellosis case prompts investigation of possible bioterrorism-related activity--New Hampshire and Massachusetts, 1999. JAMA. Jul 19 2000;284(3):300-2. [Medline].
Dimitrov Ts, Panigrahi D, Emara M, et al. Seroepidemiological and microbiological study of brucellosis in Kuwait. Med Princ Pract. Jul-Aug 2004;13(4):215-9. [Medline].
Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. Aug 6 1997;278(5):399-411. [Medline].
Hasanjani Roushan MR, Mohraz M, Hajiahmadi M, et al. Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in the treatment of brucellosis in humans. Clin Infect Dis. Apr 15 2006;42(8):1075-80. [Medline].
Henry NK, Wilson WR, Hendley JO. Infections caused by Brucella, Francisella Tularensis, Pasteurella, Yersinia species, and Bordetella pertussis. In: Stein, ed. Internal Medicine. 5th ed. 1998:1604-1607.
Hoover DL, Friedlander AM. Brucellosis. In: Textbook of Military Medicine: Medical Aspects of Chemical and Biological Warfare. 1997:513-521.
Kocak I, Dundar M, Culhaci N, Unsal A. Relapse of brucellosis simulating testis tumor. Int J Urol. Aug 2004;11(8):683-5. [Medline].
Mantur BG, Akki AS, Mangalgi SS, et al. Childhood brucellosis--a microbiological, epidemiological and clinical study. J Trop Pediatr. Jun 2004;50(3):153-7. [Medline].
Med Lett Drugs Ther. Drugs and vaccines against biological weapons. Med Lett Drugs Ther. Feb 12 1999;41(1046):15-6. [Medline].
Pappas G, Papadimitriou P, Akritidis N, et al. The new global map of human brucellosis. Lancet Infect Dis. Feb 2006;6(2):91-9. [Medline].
Taliani G, Bartoloni A, Tozzi A, et al. Lumbar pain in a married couple who likes cheese: brucella strikes again!. Clin Exp Rheumatol. Jul-Aug 2004;22(4):477-80. [Medline].
Tohme A, Zein E, El Rassi B, et al. [Human brucellosis in Lebanon. Clinical features and therapeutic responses in 88 patients]. J Med Liban. Jul-Sep 2004;52(3):149-55. [Medline].
Tur BS, Suldur N, Ataman S, et al. Brucellar spondylitis: a rare cause of spinal cord compression. Spinal Cord. May 2004;42(5):321-4. [Medline].
Ustun I, Ozcakar L, Arda N, et al. Brucella glomerulonephritis: case report and review of the literature. South Med J. Dec 2005;98(12):1216-7. [Medline].
White SR, Eitzen EM. Hazardous materials exposure. In: Emergency Medicine: A Comprehensive Study Guide. 5th ed. 2000:1201-14.
Young EJ. Brucella species. In: Principles and Practices of Infectious Diseases. 3rd ed. 1995:2053-2057.
Further Reading
Keywords
Malta fever, Crimean fever, undulant fever, Brucella, zoonotic infection, brucellosis infection, brucellae, Brucella suis, Brucella melitensis, Brucella abortus, Brucella canis, Brucella species
