Brucellosis, also called undulant fever, or Malta fever, is a highly contagious zoonosis caused by ingestion of unsterilized milk or meat from infected animals, or close contact with their secretions. Brucella spp. are small, gram-negative, non-motile, non-spore-forming rods, which function as facultative intracellular parasites that cause chronic disease, which usually persists for life. Brucellosis has been recognized in both animals and humans since the 19th century.
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.
The disease is transmitted primarily through contaminated or untreated milk (and its derivatives) or through direct contact with infected animals, which may include dogs, pigs, camels and ruminants, primarily sheep, goats, cattle, bison. This also includes contact with their carcasses. Leftovers from parturition are also extremely rich in highly virulent brucellae. Infection may also occur by ingesting contaminated grass, roughage, feed, or water. Once the susceptible animal ingests the organism, the bacterium progresses to the regional lymph nodes where it resides during the incubation period. The incubation period is the time between inoculation (entry into the host) and the appearance of signs and symptoms of the disease, and may range from two weeks to two months and longer in case of brucellosis. After a subsequent brief phase when the bacteria are in the bloodstream, the organisms colonize the uterus, placenta, udder, and/or regional lymph nodes. Although the most common clinical sign of brucellosis in cattle is abortion, no overt clinical signs may be seen with it. The animal is likely to be seronegative shortly after exposure due to the lag time between exposure and seroconversion or clinical disease. Brucellae, along with leptospira, have the unique property of being able to penetrate through intact human skin so infection by mere hand contact with infectious material is likely to occur.
Dairy herds in the USA are tested at least once a year with the Brucella Milk Ring Test (BRT). Cows that are confirmed to be infected are often killed. In the United States, veterinarians are required to vaccinate all young stock, thereby further reducing the chance of zoonotic transmission.
Canada declared their cattle herd brucellosis-free on September 19, 1985. Brucellosis ring testing of milk and cream, as well as testing of slaughter cattle, ended April 1, 1999. Monitoring continues through auction market testing, standard disease reporting mechanisms, and testing of cattle being qualified for export to countries other than the USA.
The first state-federal cooperative efforts towards eradication of brucellosis caused by Brucella abortus in the U.S. began in 1934.
Brucellosis in humans is usually associated with the consumption of unpasteurized milk and soft cheeses made from the milk of infected animals, primarily goats, infected with Brucella melitensis and with occupational exposure of laboratory workers, veterinarians and slaughterhouse workers. Some vaccines used in livestock, most notably B. abortus strain 19, also cause disease in humans if accidentally injected. Brucellosis induces inconstant fevers, sweating, weakness, anaemia, headaches, depression and muscular and bodily pain.
The symptoms are like those associated with many other febrile diseases, but with emphasis on muscular pain and sweating. The duration of the disease can vary from a few weeks to many months or even years. In first stage of the disease, septicaemia occurs and leads to the classic triad of undulant fevers, sweating (often with characteristic smell, likened to wet hay) and migratory arthralgia and myalgia. In blood tests, is characteristic the leukopenia and anaemia, some elevation of AST and ALT and positivity of classic Bengal Rose and Huddleson reactions. This complex is, at least in Portugal, known as the Malta fever. During episodes of Malta fever, melitococcemia (presence of brucellae in blood) can usually be demonstrated by means of blood culture in tryptose medium or Albini medium. If untreated, the disease can give origin to focalizations or become chronic. The focalizations of brucellosis occur usually in bones and joints and spondylodisciitis of lumbar spine accompanied by sacroiliitis is very characteristic of this disease. Orchitis is also frequent in men.
Diagnosis of brucellosis relies on:
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 cheese. Experiments have shown that cotrimoxyzol and rifampin are both safe drugs to use in treatment of pregnant women who have Brucellosis.
The United States BW program focused on three agents of the Brucella group:
Agent US was in advanced development by the end of World War II. When the U.S. Air Force (USAF) wanted a biological warfare capability, the Chemical Corps offered Agent US in the M114 bomblet, based after the 4-pound bursting bomblet developed for anthrax in World War II. Though the capability was developed, operational testing indicated that the weapon was less than desirable, and the USAF termed it an interim capability until replaced by a more effective biological weapon. The main drawbacks of the M114 with Agent US was that it was incapacitating (the USAF wanted "killer" agents), the storage stability was too low to allow for storing at forward air bases, and the logistical requirements to neutralize a target were far higher than originally anticipated, requiring unreasonable logistical air support.
Agents US and AB had a median infective dose of 500 org/person, and AM was 300 org/person. The rate-of-action was believed to be 2 weeks, with a duration of action of several months. The lethality estimate was based on epidemiological information at 1 - 2%. AM was always believed to be a more virulent disease, and a 3% fatality rate was expected.