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Key Diagnostic Tests.

• Serum tube agglutination
• Blood and bone marrow cultures (can take up to 6 weeks to confirm presence)

A gram-stain of Brucella showing the coccobacillary shape and Gram-negative staining. (magnification unknown)	Colony appearance: Brucella grows slowly, even on rich media to give pinpoint, translucent colonies with a smooth surface.
Source: Centers for Disease Control, Public Health Image Library #1937	Source: CDC/ Courtesy of Larry Stauffer, Oregon State Public Health Laboratory, Public Health Image Library #1902,

The incubation period is typically 5-60 days but can be even longer. Brucellosis is incapacitating rather than killing (fatality in about 2% (range 2-13%) of cases). Symptoms include intermittent fever, headaches, sweating, chills, malaise, body aches (muscles, joints, lower back), and anorexia. Typically, it takes eight days from the onset of symptoms to diagnose the disease.

The disease may also affect the urogenital tract and liver. Fatalities are rare (<5% of patients) and usually occur when the heart is infected leading to endocarditis or the nervous system becomes involved. Chronic infection can lead to damage to major weight-bearing joints and the spinal column. The disease can last for weeks or months.

Medical and Physical Countermeasures.

Vaccination (Immunoprophylaxis)

A vaccine is not available. Attenuated live vaccines for livestock are not attenuated in man and occassional infection of large animal veterinarians comes from the vaccine.

Antibiotics

Patients can recover without the use of antibiotics although recovery is slow and can take up to a year with frequent relapses. Treatment with combinations of antibiotics is preferred. Preferred combinations are doxycycline and rifampin or trimethoprim/sulfamethoxazole (Bactrim) or fluoroquinones such as ciprofloxacin. Streptomycin or other aminoglycosides may need to be used if endocarditis develops.

Antibiotic Resistance

Species-specific subtypes of B. melitensis can be differentiated by antibiotic resistance. The older names for B. melitensis identify a set of subtypes that are specific for different species (B. suis is specific for swine, B. abortus is specific for cattle.)

There does not appear to be any coherent body of information about plasmid-borne antibiotic resistance in Brucella.

Supportive care

• Patients need to be encouraged to eat to avoid weight loss.
• Drain and dry abscesses.
• Frequently monitor temperature during the acute phase. This is when complications are likely to arise.
• In the case of endocarditis, heart valve replacement may be necessary.
• Severe cases may also need intravenous and oral corticosteroids to treat inflammation.

Decontamination

Brucella is relatively hardy, but not a robust agent. It can survive freezing and thawing and can survive for several weeks in milk, water, urine, or damp soil. It will die relatively quickly in dry conditions and is killed by sunlight. Contaminated objects are easily sterilized or disinfected by common methods and agents such as phenol- or formalin-based disinfectants. Pasteurization is effective for treatment of contaminated dairy products.

Agent Properties and Potential Uses

Brucellosis was considered as a weapon by the United States from the earliest days of its biological weapons program in World War II and it was weaponized by the US until the destruction of the stockpile in the 1970's. Others have also been interested in it. It is primarily a disease of livestock, especially cattle and can cause severe economic damage to farmers. It can be used against humans, especially by aerosol dispersion or by contamination of food or milk, and has the advantage of being debilitating without being fatal. Even under the best storage conditions it has a half-life of a few weeks.

Until recently it was thought that there were several species of Brucella but the more recent view is that they are all subtypes of one species (B. melitensis, also described as a genospecies) with different preferences for animal hosts.

Terrorist Acquisition and Attempted Use.

• In early 1999, a New Hampshire woman was admitted to hospital and eventually diagnosed with brucellosis but without any traditional risk factors. Her family came forward with microbiological equipment, solution and cultures belonging to her live-in boyfriend. They were found to contain Brucella. The man was a foreign national and claimed to be a marine biologist. However, it is unclear why he should be interested in brucellosis. The woman eventually died of complications from the disease and the incident is being treated as a possible bioterrorism event.

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History and Natural History

Brucella is distributed worldwide, affecting reindeer in Alaska and Siberia, camels in the Middle East, and cattle, pigs, goats, and sheep throughout the world. It causes abortion in females and inflammation of the testes (orchitis) in males. Normally, humans catch it from aborted fetuses, slaughtering infected animals, or from contaminated meat or milk. The disease is uncommon in the US and Europe, due largely to its elimination from cattle herds. It does not appear to be transmitted effectively by insect vectors, reducing the risk of the disease spreading beyond the target area.

The military effectiveness of the disease may first have been demonstrated in Malta in the 19th Century. An unknown disease, called Malta fever, was debilitating large numbers of British soldiers garrisoned there. The disease was shown to be caused by a bacterium being passed through milk from infected goats. This discovery was made by a young British doctor, David Bruce, who went on to become one of the legends of microbiology and the genus Brucella bears his name. Bruce recovered the bacterium from the liver of a British soldier who had died of the disease. He was able to culture it and when injected into chimpanzees, they developed symptoms of the disease. The outbreak was brought under control by removing goats' milk from the soldiers diet. Despite the importance of his work to the British Army, Bruce's work was first published in French.

While Britain was focused on anthrax, brucellosis was the first microorganism that the United States chose to develop as a weapon, it even has the military code name US. The reasons for this included its low lethality, relative ease of manufacture, and its susceptibility to sunlight. The agent could be dispersed at night to affect those out in the open, that is, an army in the field without affecting civilians in houses. The bacterium would be killed shortly after sunrise, leaving civilians at low risk of infection, as it is not transmitted person-to-person. Field tests with live agents were conducted in the 1950's and it was shown that it could be effectively disseminated in four pound bombs.

Although US stocks were destroyed by order of the Nixon administration, some munitions were lost track of and some were discovered by accident in the mid-1990's at Wright-Patterson AFB in Dayton, Ohio. There was no risk of infection, but the incident could have been embarrassing.