eMedicine Specialties > Emergency Medicine > Warfare - Chemical, Biological, Radiological, Nuclear and Explosives

CBRNE - Brucellosis

Gerald E Maloney Jr, DO, FAAEM, Senior Instructor, Department of Emergency Medicine, Case Western Reserve University School of Medicine; Director of Medical Toxicology, Department of Emergency Medicine; Associate Medical Director, MetroLifeFlight, MetroHealth Medical Center, Cleveland, OH

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.

Differential Diagnoses

Other Problems to Be Considered

Typhus
Sacroiliitis
Erythema nodosum
Vasculitis

Workup

Laboratory Studies

• Blood cultures
  • Blood cultures are positive in 10-90% of patients but are not particularly helpful in initial diagnosis of the disease.
  • Keep them for 2 months and reculture them onto solid media every week.
  • Because of the ease of aerosol transmission, handle any potential Brucella specimens under a biohazard hood.
• Antibody testing
  • Antibody testing is the most reliable method for diagnosing brucellosis.
  • The best test is the tube agglutination method, which tests for anti-O-polysaccharide antibody. Titers of 1:160 or higher are diagnostic.
  • Enzyme-linked immunosorbent assay (ELISA) methods lack standardization.
• Cerebrospinal fluid cultures
  • Obtain cerebrospinal fluid (CSF) cultures for suggested meningitis.
  • CSF demonstrates lymphocytic pleocytosis, elevated protein, and normal-to-low glucose.
  • CSF cultures are positive for brucellosis less than 50% of the time, but antibody testing of the fluid yields a diagnosis.
• Complete blood count
  • CBC likely is ordered routinely as part of an evaluation for a patient with potential infectious disease.
  • Leukocytosis is rare, and a significant number of patients are neutropenic.
  • Anemia can be observed with chronic infection.
  • Thrombocytopenia may be observed secondary to hepatosplenomegaly or from immune thrombocytopenia.
• Urinalysis and/or urine cultures
  • Urinalysis and/or culture and sensitivity may be sent in the presence of symptoms of urinary tract infection. It most likely demonstrates a sterile pyuria, similar to tuberculosis.
  • Send urine cultures, since the organism grows from the urine if the genitourinary tract is infected.
• Arthrocentesis: Although significant joint effusion is uncommon, occasionally arthrocentesis may be needed to exclude septic arthritis. The joint aspirate demonstrates an exudative fluid with low cell counts and mononuclear predominance.

Imaging Studies

• Chest radiography: Obtain a chest radiograph if respiratory symptoms are present or if a source of infection is not apparent. Chest radiographic findings in brucellosis are usually normal.
• Cranial CT: Obtain a cranial CT scan for altered mental status or focal neurologic deficits. Although often normal, the CT scan may reveal evidence of acute or chronic brucella leptomeningitis, subarachnoid hemorrhage, or cerebral abscess.
• Echocardiography
  • Echocardiography is used to evaluate for possible endocarditis. The primary site of vegetation is the aortic valve, with the sinus of Valsalva most commonly affected, followed by the mitral valve.
  • Mycotic aneurysms of the aorta or carotids may be observed on duplex arteriography.
• Ultrasonography: Use of ultrasonography to diagnose testicular abscess from brucellosis has been reported; low-resistance flow appears to be characteristic for these tumors.²

Procedures

• Arthrocentesis: Perform arthrocentesis for suggested septic arthritis. The joint aspirate demonstrates an exudative fluid with low cell counts and mononuclear predominance. Patients with brucellosis rarely present with acute monoarticular arthritis.
• Bone marrow biopsy: Although not an emergency department (ED) procedure, bone marrow biopsy may be required to establish a diagnosis in certain patients.
• Liver biopsy: While not an ED procedure, percutaneous biopsy may be needed in the patient with liver granulomas to obtain a specimen for diagnosis.

Treatment

Prehospital Care

Prehospital care for brucellosis is supportive.

• As the symptoms generally are vague and presentation rarely life threatening, emergency medical service (EMS) care should focus on stabilization, as needed, and transport.
• If a proximate bioterrorist attack is known or strongly suggested at the time of patient contact, appropriately decontaminate the patient. In the event of a covert undiscovered attack, patients may become symptomatic well after the time that decontamination is necessary.
• As in the care of any patient with a potentially transmissible disease, use appropriate precautions (eg, gloves, mask, gown).
• If the patient presents as part of a known, immediately proximate bioterrorism incident, EMS providers should notify the hospital to undertake appropriate decontamination and isolation measures.

Emergency Department Care

Given the nonspecific patient complaints, a diagnosis of brucellosis is unlikely in the ED. With an appropriate history, an astute clinician may suspect it.

• Respiratory isolation usually is not necessary, as long as close contact with the respiratory tract is not made. Wear masks for intubation, suctioning, or other maneuvers that may expose the caregiver to a large concentration of aerosolized particles.
• The appropriate antibiotic therapy for brucellosis is combination therapy with doxycycline and rifampin or streptomycin. If brucellosis is strongly suggested, consult a specialist to determine the proper antibiotic regimen. There is some evidence of growing resistance to rifampin in some areas, though ciprofloxacin and aminoglycosides maintain good coverage.
• Provide supportive care for any specific symptoms and obtain appropriate tests targeted to affected organ systems as determined by history and physical.

Consultations

• The primary specialist to consult is an infectious disease specialist. Determine proper serologic tests, cultures, further diagnostic evaluations, and the correct antibiotic therapy in conjunction with the infectious disease specialist.
• Depending on the degree of damage to individual organ systems, contact the appropriate specialist (eg, cardiology for endocarditis).

Medication

The appropriate antibiotic therapy for brucellosis has been studied to some degree. Doxycycline (100 mg PO bid for 6 wk) is the most appropriate monotherapy in simple infection; however, relapse rates approach 40% for monotherapy treatment. Rifampin (600-900 mg/d) usually is added to doxycycline for a full 6-week course. In patients with spondylitis or sacroiliitis, doxycycline plus streptomycin (1 g/d IM for 3 wk) was found to be more effective than the doxycycline/rifampin combination. Streptomycin currently is favored over rifampin for combination therapy of any significant infection. In pediatric patients older than 8 years, doxycycline (5 mg/kg/d for 3 wk) plus gentamicin (5 mg/kg/d IM for the first 5 d) was the recommended therapy. For children younger than 8 years, trimethoprim/sulfamethoxazole (TMP-SMZ) for 3 weeks and a 5-day course of gentamicin were most effective. TMP-SMZ also was effective in treating pregnant women, either as a single agent or in combination with rifampin or gentamicin.

Fluoroquinolones have a high relapse rate when used as monotherapy. Fluoroquinolones added to doxycycline have no advantage over the other regimens described, but may be preferred in an area where resistance to rifampin is high. No uniform recommendation exists for treatment of meningitis or endocarditis; however, TMP-SMZ plus rifampin remains the preferred combination. In endocarditis, early replacement of the infected valve is recommended, along with medical therapy. Corticosteroids are recommended in CNS infection, but data supporting their utility are lacking. Also prescribe symptomatic treatment for pain and fever.

A meta-analysis comparing rates of resistance among several potential biological weapons found that doxycycline was the most effective antibiotic, with lower rates of resistance than seen with fluoroquinolones. In brucellosis, doxycycline for 45 days with either streptomycin or gentamicin seems to be the best regimen based on recent data.

Antibiotics

Indicated to abolish infection. Therapy must cover all likely pathogens in the context of the clinical setting.

Doxycycline (Doryx, Vibramycin, Bio-Tab)

Several different controlled and retrospective trials have established efficacy as treatment for brucellosis. Because of concerns regarding treatment failures, combination therapy with rifampin or an aminoglycoside now is recommended, although it remains approved for use as monotherapy.

Dosing

Adult

200 mg/d PO, usually divided into 100 mg PO bid; may be administered IV if needed; duration is 3-6 wk

Pediatric

5 mg/kg/d PO for 3 wk

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause photosensitivity; can cause nausea and erosive esophagitis, especially if taken hs; may deposit in teeth, although less than with tetracycline; safe to use in renal failure

Rifampin (Rifadin, Rimactane)

Used in combination therapy with doxycycline, TMP-SMZ, or gentamicin for treatment of brucellosis.

Dosing

Adult

600-900 mg PO/IV qd

Pediatric

10-20 mg/kg PO/IV qd; not to exceed 600 mg

Interactions

Multiple drug-drug interactions; notably, decreases serum levels of most antiretrovirals; decreases effectiveness of beta-blockers; decreases effectiveness of oral contraceptives; decreases phenytoin levels; decreases effectiveness of anticoagulants and sulfonylureas; increases conversion of INH into its hepatotoxic metabolites; levels increase with concurrent use of antiretrovirals and TMP-SMZ; also decreases levels of methadone, precipitating withdrawal

Contraindications

Documented hypersensitivity; preexisting liver disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor liver enzymes before starting therapy and repeat if symptoms of potential hepatotoxicity develop; causes brownish discoloration of body fluids; stains contact lenses; may cause drug-induced lupus; if taken irregularly or restarted after an interval of no medication, may cause "flu syndrome" with fever, chills, myalgias, and dyspnea

Sulfamethoxazole and trimethoprim (Bactrim, Septra)

Used as adjunctive therapy with gentamicin in treating infection in children <8 y; used as monotherapy or combined with rifampin or gentamicin to treat infection in pregnant females. Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Dosing

Adult

1 double strength tab PO bid (160/800)
8-10 mg/kg IV divided q6, 8, or 12h

Pediatric

5 mL/10 kg (40/200) PO bid

Interactions

Competes with creatinine for tubular reabsorption and thus may increase serum creatinine; hyperkalemia observed in 20% of patients; may cause thrombocytopenia and aseptic meningitis; frequently causes GI disturbances; occasionally may cause severe reactions in form of Stevens-Johnson syndrome or TEN; increases levels of phenytoin, rifampin, and loperamide; increases activity of warfarin; enhances bone marrow suppression when administered with methotrexate; decreases effectiveness of oral contraceptives

Contraindications

Documented hypersensitivity; relatively contraindicated in asthmatics, as sensitivity to the sulfa molecule may cause bronchospasm; relatively contraindicated in thrombocytopenic patients, as thrombocytopenia may worsen

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid in sulfa-allergic patients or in concurrent use with rifampin

Gentamicin (Garamycin, Gentacidin)

Aminoglycosides have been used for several years to treat brucellosis; studies to date have shown gentamicin to be the preferred aminoglycoside to treat infection as combined therapy with either TMP-SMZ or doxycycline in children. Adult dose is either once-daily dosing or a multiple-daily dose.

Dosing

Adult

Once-daily dose: 5.1 mg/kg IV/IM qd
Multiple-daily dose: 2 mg/kg loading dose, IV followed by 1.7 mg/kg IV/IM q8h; continue for 5 d

Pediatric

5 mg/kg IM for 5 d, in combination with either doxycycline or TMP-SMZ

Interactions

Increases nephrotoxicity of contrast agents, cyclosporin, cis -platinum, NSAIDs, amphotericin B, and vancomycin; increases ototoxicity of loop diuretics and noise; potentiates neuromuscular blocking agents

Contraindications

Documented hypersensitivity; avoid if possible in patients with impaired renal function or sensorineural deafness because of known nephrotoxicity and ototoxicity; once daily dosing is associated with decreased risk of nephrotoxicity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with renal failure or if IV contrast is planned; check levels at minimum q3d and adjust dose based on level and calculated creatinine clearance

Streptomycin

Has been used for several years to treat brucellosis; used in combination with doxycycline, especially for spondylitis or sacroiliitis; augments bacteriocidal action of other agents used to treat brucellosis.

Dosing

Adult

15 mg/kg IM; not to exceed 1 g/d IM qd for 3 wk

Pediatric

20-40 mg/kg IM qd; not to exceed 1 g qd

Interactions

Increases nephrotoxicity of contrast agents, cyclosporin, cis -platinum, NSAIDs, amphotericin B, and vancomycin; increases ototoxicity of loop diuretics and noise; potentiates neuromuscular blocking agents

Contraindications

Documented hypersensitivity; if possible avoid in patients with preexisting renal disease or vestibular disease because of ototoxicity and nephrotoxicity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal failure and preexisting vestibulocochlear disease; adjust dose based on creatinine clearance ratio; determine BUN and creatinine prior to starting therapy; perform weekly audiograms for treatment duration

Corticosteroids

Indicated to reduce inflammation and improve neurologic outcome in patients with neurobrucellosis.

Dexamethasone (Decadron, AK-Dex)

Use of corticosteroids is reserved for symptomatic brucella meningitis. Although generally recommended, scientific evidence supporting their use is lacking. No consensus exists on optimal dosing, frequency, or duration of therapy.

Dosing

Adult

0.15 mg/kg IV q8h

Pediatric

0.6 mg/kg/d IV divided into q6h doses for 2 d prior to starting antibiotics

Interactions

Barbiturates, carbamazepine, phenytoin, rifampin, and isoniazid may reduce effectiveness; estrogens enhance effect

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use may cause mood changes, seizures, hyperglycemia, GI bleeding, and HPA axis suppression; long-term use is rare

Follow-up

Further Inpatient Care

• Starting the appropriate antibiotic therapy is the mainstay of care.
• Depending on what other systems are involved, more specialized care may be needed.
• Use appropriate precautions (eg, mask, gloves, eye protection) for respiratory procedures or handling body fluids.
• Handle specimens from the patient in the lab under biosafety level III conditions.
• Tests and other procedures are discussed in Lab Studies.

Further Outpatient Care

• Outpatient care consists of completing the course of antibiotics, treating any exposed patients, and avoiding contact with the initial source of infection.
• Arrange outpatient follow-up care with the infectious disease specialist and any other necessary specialist.
• Strongly emphasize the need to complete the full 6-week course of antibiotics, as failure to do so increases the risk of relapse.

Inpatient & Outpatient Medications

• Administer antibiotic and corticosteroid therapy as outlined in the Medication section. Also administer any additional drugs needed for symptomatic treatment (eg, antipyretics, analgesics). Additional medication is based on the patient's presenting symptoms.

Transfer

• Transfer to another facility depends on the needs of the patient. As most patients do not require highly specialized interventions, the need to transfer should not be frequent.
• Personnel involved in the transfer should maintain respiratory and contact precautions, and the vehicle should be decontaminated after transport as needed.

Deterrence/Prevention

• Avoiding the source of infection prevents reinfection. Better handling of infected animals or animal products is paramount.
• As no human vaccine is available, immunization is not an option for humans, but immunization of animals reduces the pool of vectors and thereby reduces human infection.
• As the brucellosis vaccine is attenuated for animals but not humans, accidental percutaneous exposure to the vaccine may cause disease. Labs should handle all specimens under biosafety level III conditions.
• Military personnel should take appropriate precautions if use of biological weapons by an unfriendly source is anticipated.

Complications

• Complications are rare in the patient who is treated appropriately.
• The primary complication is the need for valve replacement in the patient with endocarditis.
• Residual musculoskeletal complaints may be present in the patient with long-term infection and sacroiliitis.
• Relapse of infection may occur in 10% of patients.

Prognosis

• Most patients with brucellosis recover completely without lasting sequelae, provided they receive appropriate antibiotic treatment. The relapse rate is approximately 10%, even with treatment. Prognosis generally is excellent.

Patient Education

• Center patient education on the need for strict compliance with the antibiotic regimen and the need to avoid potential sources of infection. This primarily involves avoidance of infected animals or stricter precautions (eg, gloves, mask) when dealing with a potentially infected animal.
• Advise farmers and ranchers to immunize their cattle against the disease as needed.
• Laboratory workers should maintain the appropriate level of containment.
• Travelers to regions where the disease is endemic need to take precautions against infection (eg, avoid potentially contaminated dairy products).
• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Biological Warfare and Personal Protective Equipment.

Miscellaneous

Medicolegal Pitfalls

• As brucellosis manifests in such a nonspecific manner, the diagnosis can be difficult. The primary pitfall is failure to consider possible Brucella infection in a patient with history that suggests a possible source of infection (eg, farmer, traveler to an endemic region, veterinarian).
• In a patient with endocarditis or meningitis and history suggestive of possible exposure, failure to treat for brucellosis is a potential downfall.
• Brucella species have not yet been implicated in any major bioterrorism incident; however, were they used in such a way, patients may not present until several weeks later. Detailed history and knowledge of such potential exposures in the recent past is essential. Given the rare occurrences of brucellosis in the United States, especially in more urban areas, any clustering of brucellosis cases should be thoroughly investigated and reported to public health officials because a biological warfare attack could be the cause.

Special Concerns

• Pregnancy: B abortus is associated strongly with miscarriage in cattle. Whether this increases the risk of spontaneous abortion in humans more than other severe bacterial infection is unknown. Therefore, consider any pregnant female with brucellosis to carry an increased risk of spontaneous abortion. Brucella species may be transmitted across the placenta.
• Pediatric: Pediatric brucellosis is more common than originally suspected; however, given the relative infrequency of infection in the US, it is still rare. The presentation is similar in neonates, children, and adults.
• Zoonosis: As brucellosis is a zoonotic infection, immunization of at-risk animals reduces the number of infected animals and therefore the reservoir of infection. Results of an assessment and simulation study on the planned brucellosis control program in Egypt showed that removal of infected animals under the actual implementation of the program would likely permit brucellosis to remain endemic in the goat and sheep population.³

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Keywords

Malta fever, Crimean fever, undulant fever, Brucella, zoonotic infection, brucellosis infection, brucellae, Brucella suis, Brucella melitensis, Brucella abortus, Brucella canis, Brucella species

Contributor Information and Disclosures

Author

Gerald E Maloney Jr, DO, FAAEM, Senior Instructor, Department of Emergency Medicine, Case Western Reserve University School of Medicine; Director of Medical Toxicology, Department of Emergency Medicine; Associate Medical Director, MetroLifeFlight, MetroHealth Medical Center, Cleveland, OH
Gerald E Maloney Jr, DO, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, American College of Osteopathic Emergency Physicians, American Osteopathic Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Jerry L Mothershead, MD, Medical Readiness Consultant, Medical Readiness and Response Group, Battelle Memorial Institute; Advisor, Technical Advisory Committee, Emergency Management Strategic Healthcare Group, Veteran's Health Administration; Adjunct Associate Professor, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences
Jerry L Mothershead, MD is a member of the following medical societies: American College of Emergency Physicians and National Association of EMS Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Robert G Darling, MD, FACEP, Clinical Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Director, Center for Disaster and Humanitarian Assistance Medicine
Robert G Darling, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, and Association of Military Surgeons of the US
Disclosure: Nothing to disclose.

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