History and nomenclature
The disease now called brucellosis, under the name "Mediterranean fever", first came to the attention of British medical officers in Malta during the CrimeanWar in the 1850s. The causal relationship between organism and disease was first established by Dr. David Bruce in 1887.
In 1897 Danish Veterinarian Bernhard Bang isolated Brucella abortus as the agent and the additional name Bang's disease was assigned. In modern usage "Bang's disease" is often shortened to just "bangs" when ranchers discuss the disease or vaccine.
Maltese doctor and archaeologist Sir Temi Zammit identified unpasteurized milk as the major source of the pathogen in 1905, and it has since become known as Malta Fever, or deni rqiq locally. In cattle this disease is also known as contagious abortion and infectious abortion.
The popular name "undulant fever" originates from the characteristic undulance (or "wave-like" nature) of the fever which rises and falls over weeks in untreated patients. In the 20th Century, this name, along with "brucellosis" (after Brucella, named for Dr Bruce), gradually replaced the 19th Century names "Mediterranean fever" and "Malta fever".
In 1989, Saudi Arabian neurologists discovered neurobrucellosis, a neurological involvement in brucellosis.
Brucellosis in animals
Species infecting domestic livestock are B. melitensis (goats and sheep), B. suis (pigs, see Swine brucellosis), B. abortus (cattle and bison), B. ovis (sheep), and B. canis (dogs). B. abortus also infects bison and elk in North America and B. suis is endemic in caribou. Brucella species have also been isolated from several marine mammal species (pinnipeds and cetaceans.)
The causative agent of brucellosis in dogs is Brucella canis. It is transmitted to other dogs through breeding and contact with aborted fetuses. Brucellosis can occur in humans that come in contact with infected aborted tissue or semen. The bacteria in dogs normally infect the genitals and lymphatic system, but can also spread to the eye, kidney, and intervertebral causing discospondylitis). Symptoms of brucellosis in dogs include abortion in female dogs and scrotal inflammation and orchitis (inflammation of the testicles) in males. Fever is uncommon. Infection of the eye can cause uvitis, and infection of the intervertebral disc can cause pain or weakness. Blood testing of the dogs prior to breeding can prevent the spread of this disease. It is treated with antibiotics as with humans, but it is difficult to cure.
Diagnosis of brucellosis relies on:
- Demonstration of the agent: blood cultures in tryptose broth, bone marrow cultures. The growth of brucellae is extremely slow (they can take until 2 months to grow) and the culture poses a risk to laboratory personnel due to high infectivity of brucellae.
- Demonstration of antibodies against the agent either with the classic Huddleson, Wright and/or Bengal Rose reactions, either with ELISA or the 2-mercaptoethanol assay for IgM antibodies associated with chronic disease
- Histologic evidence of granulomatous hepatitis (hepatic biopsy)
- Radiologic alterations in infected vertebrae : the Pedro Pons sign (preferential erosion of antero-superior corner of lumbar vertebrae) and marked osteophytosis are suspicious of brucellic spondylitis.
The disease's sequelae are highly variable and may include granulomatous hepatitis, arthritis, spondylitis, anemia, leukopenia,thrombocytopenia, meningitis, uvitis, neuritis and endocarditis.
Treatment and prevention
Antibiotic like tetracyclins, rifampicin and the aminoglykosides streptomycin and gentamycin are effective against Brucella bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubates within cells.
The gold standard treatment for adults is daily intramuscular injections of streptomycin 1 g for 14 days and oral doxycycline 100 mg twice daily for 45 days (concurrently). Gentamicin 5 mg/kg by intramuscular injection once daily for 7 days is an acceptable substitute when streptomycin is not available or difficult to obtain. Another widely used regimen is doxycycline plus rifampin twice daily for at least 6 weeks. This regimen has the advantage of oral administration. A triple therapy of doxycycline, together with rifampin and cotrimoxazole has been used successfully to treat neurobrucellosis. Doxycycline is able to cross the blood-brain barrier, but requires the addition of two other drugs to prevent relapse. Ciprofloxacin and co-trimoxazole therapy is associated with an unacceptably high rate of relapse. In brucellic endocarditis surgery is required for an optimal outcome. Even with optimal antibrucellic therapy relapses still occur in 5-10 percent of patients with Malta fever. The main way of preventing brucellosis is by using fastidious hygiene in producing raw milk products, or by pasteurization of all milk that is to be ingested by human beings, either in its pure form or as a derivate, such as cheeese. Experiments have shown that cotrimoxyzol and rifampin are both safe drugs to use in treatment of pregnant women who have Brucellosis.
Biological warfare
In 1954, B. suis became the first agent weaponized by the United States at its Pine Bluff Arsenall in Arkansas. Brucella species survive well in aerosols and resist drying. Brucella and all other remaining biological weapons in the U.S. arsenal were destroyed in 1971-72 when the U.S. offensive biological weapons (BW) program was discontinued.