Can be an acute, subacute or chronic granulomatous process.

Highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions.

Brucella species are small, gram-negative, nonmotile, nonspore-forming, rod-shaped coccobacilli bacteria.

Facultative intracellular parasites: Four species infect humans: B. abortus, B. canis, B. melitensis, and B. suis.

A chronic disease, which usually persists for life.

Common host animals are goats, sheep, cattle, pigs, and dogs.

Brucellosis is the most common zoonosis globally, but it is rare in United States with approximately 100 cases annually, owing to eradication programs that rely on identification and slaughter of infected herds, strict, milk pasteurization regulations, and vaccination of livestock.

Areas in which a brucellosis is highly endemic include Latin America, the Mediterranean region, South, and East Asia.

B. abortus is less virulent than B. melitensis and is primarily a disease of cattle.

B. canis affects dogs.

B. melitensis is the most virulent and invasive species; it usually infects goats and occasionally sheep.

B. suis is of intermediate virulence and chiefly infects pigs.

Exposure most commonly occurs by ingestion of unpasteurized dairy products.

Exposure can also occur after inhalation of infectious aerosols or direct inoculation with infected animal tissue through mucous membranes or abrasions of the skin.

Individuals at high risk include: veterinarians, farmers, slaughterhouse workers, and persons, working in animal laboratories.

Infection can occur with inocula as low as 10 to 100 organisms.

After the invasion organisms are transported to lymph nodes, and the Brucella species are phagocytized by macrophages that disseminate them throughout the host reticuloendothelial system to the bone marrow, liver, and spleen.

The pathogen survives in macrophages vacuoles.

Clinical presentation is highly variable, with illness ranging from self-limiting to severe.

Symptoms occur within three months after exposure and indicate acute brucellosis, with chronic presentations, lasting greater than 12 months, reflecting inadequate treatment.

Subclinical symptoms are common and non-specific symptoms such as diaphoresis, fatigue, headache, malaise, and sweating are reported in more than 80% of acute cases

Symptoms include profuse sweating and joint and muscle pain and fever.

Fever is almost universally present, and is classically intermittent with gradual waxing and waning.

The duration of the disease can vary from a few weeks to many months or even years.

Bacteremia occurs in the first stage of brucellosis and leads to the triad of undulant fevers, sweating and migratory arthralgia and myalgia.

Physical examination may reveal hepatosplenomegaly and lymphadenopathy.

Laboratory tests usually reveal a low number of white blood cells and red blood cells, show some elevation of liver enzymes and demonstrate positive Bengal Rose and Huddleston reactions.

Induces inconstant fevers, miscarriage, sweating, weakness, anemia, headaches, depression, and muscular and bodily pain.

It may involve every organ system.

Gastrointestinal symptoms occur in 70% of cases.

GI symptoms include nausea, vomiting, decreased appetite, unintentional weight loss, abdominal pain, constipation, diarrhea, hepatomegaly, liver inflammation, liver abscess, and an enlarged spleen.

Hepato-splenic involvement is apparent in 30-60% of cases and is generally characterized by mild hepatitis.

Hepatic brucellomas are infrequent and occur in less than 2% of cases, and generally represent the chronic form of the disease.

If untreated, the disease can result in focalization or become chronic.

It can localize in bones and joints and spondylodiscitis of the lumbar spine accompanied by sacroiliitis is very characteristic of this disease.

Osteoarticular complications, including sacroiliitis, and peripheral arthritis, are the most frequently encountered complications and a present  in 20-30% of cases.

Orchitis is also common in men.

Cardiac complications and neurologic complications are uncommon, but account for the predominance of severe illness and death attributable to brucellosis.

Diagnosis of brucellosis relies on: positive blood cultures, or bone marrow cultures, demonstration of antibodies against the agent, histologic evidence of granulomatous hepatitis on hepatic biopsy, radiologic alterations in infected vertebrae,

The agglutination test is the most commonly used serology in endemic areas.

Laboratory findings include normal peripheral white cell count, and occasional leukopenia with relative lymphocytosis.

Serum agglutination test is the most widely used  serodiagnostic texts and detects antibodies to smooth lipopolysaccharide in the outer membrane.

ELISA testing is preferred to distinguish acute from chronic illness.

PCR and 16sRNA gene sequencing can facilitate diagnosis and monitoring of treatment.

Blood cultures have a sensitivity of 46 to 90% depending upon the stage of infection and pathogen burden.

Bone marrow cultures have high sensitivity up to 80 to 95%.

Pan agglutination titer greater than 1:160 is considered significant in nonendemic areas and greater than 1:320 in endemic areas.

It can take up to two months for the bacterium to grow.

The culture poses a risk to laboratory personnel due to high infectivity of brucellae.

Up to 40% of clinical laboratory staff exposed to Brucella cultures or infected materials, become infected.

Complications include: arthritis, spondylitis, thrombocytopenia, meningitis, uveitis, optic neuritis, endocarditis, and neurological disorders collectively known as neurobrucellosis.

Usually associated with consumption of unpasteurized milk and soft cheeses made from the milk of animals infected with Brucella melitensis (primarily goats) and with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers.

B. abortus strain 19 livestock vaccine may cause human disease in those accidental injected.

Dairy herds in the USA are tested at least once a year to be certified brucellosis-free.

Cows confirmed to be infected are often killed.

Vaccinations to further reduce the chance of zoonotic transmission are required.

Antibiotics such as tetracyclines, rifampin, and the aminoglycosides streptomycin and gentamicin are effective drugs.

The use of more than one antibiotic is needed for several weeks, because the bacteria incubate within cells.

Surveillance using serological tests, play an important role in campaigns to eliminate the disease.

Animal testing for disease-control purposes is practiced.

Amimal vaccination is often used to reduce the incidence of infection.

Treatment requires long-term therapy with antibiotics that can maintain an efficacy after penetration into acidic intracellular Brucella containing vacuoles.

Doxycycline administered for six weeks combined with an intravenous aminoglycoside for the first week results in lower risks of treatment, failure, and relapse, than doxycycline and rifampin.

Fluoroquinolones may be used instead of doxycycline in the event of unacceptable side effects.

Complicated infection should be treated with three agents often including ceftriaxone for 4 to 6 weeks and longer treatment durations for up to six months.

Doxycycline plus rifampin twice daily for at least six weeks.

A triple therapy of doxycycline, with rifampin and co-trimoxazole, has been used successfully to treat neurobrucellosis.

Ciprofloxacin and co-trimoxazole therapy is associated with an unacceptably high rate of relapse.

Surgery is required for endocarditis due to Brucellosis.

Despite optimal therapy 5-10% of patients relapse.

Pasteurizing all raw milk products is the main way to prevent brucellosis.

The most frequent cause of death before antibiotics was endocarditis.

Death is uncommon at this time.

No effective vaccine is available.

Boiling milk is protective against transmission via ingestion.

Eating raw meat, liver, or bone marrow is prohibited.

Patients with a history of brucellosis should probably be excluded indefinitely from donating blood or organs.

Exposure of diagnostic laboratory personnel to Brucella organisms occurs when brucellosis is unknowingly imported by a patient.

With significant exposure one should be offered postexposure prophylaxis with doxycycline and followed up serologically for six months.

Species infecting domestic livestock are B. abortus (cattle, bison, and elk), B. canis (dogs), B. melitensis (goats and sheep), B. ovis (sheep), and B. suis (caribou and pigs). Brucella species have also been isolated from several marine mammal species (cetaceans and pinnipeds).

Hunters are at additional risk for exposure to brucellosis due to increased contact with susceptible wildlife.

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