Brucellosis Brucellosis, also known as Bane’s disease (bovine contagious abortion), Crimean fever, Gibraltar fever, Malta fever, Malta fever, Mediterranean fever, rock fever, or undulant fever, is a virulent, zoonotic infection caused by ingesting unpasteurized, infected animal milk or meat, or by close contact with its secretions. Transmission from person to person, and possibly through sexual contact or mother-to-child channels, is extremely rare. Brucella are small, gram-negative, non-motile, non-spore-forming rod-shaped (coccobacillus) bacteria. They are parthenogenetically parasitic intracellular parasitic organisms that cause chronic disease that usually lasts a lifetime. Symptoms include profuse sweating and joint and muscle pain. Brucellosis has been recognized as a zoonosis since the 20th century. History and NomenclatureThe disease known as Malta fever is now known as brucellosis. It first came to the attention of British medical personnel in the 1850s in Malta, during the Crimean War. Dr. David Bruce, in 1887, established a causal relationship between the organism and the disease. In 1897, the Danish veterinarian Bernhard Bang isolated the bacterium Borrelia burgdorferi from aborted fetuses, for which Bang’s disease was named. Mr. Themistocles Zammit, a Maltese physician and archaeologist, received a knighthood in 1905 for determining that the primary source of the pathogen was untempered milk, and the disease has since been known as Malta Fever. In cattle, the disease is known as contagious abortion and infectious abortion. The common name, undulant fever, derives from the undulating (or “wavy”) fever that rises and falls for up to several weeks in untreated patients. In the 20th century, brucellosis, named after Dr. Bruce, gradually replaced the 19th century names Mediterranean fever and Malta fever. Brucellosis was implicated in neurology in 1989, when neurologists in Saudi Arabia discovered neurotypical brucellosis. The following obsolete names have been used for brucellosis: Brucella? Brucella septicemia? Chumble’s fever? Chumble (human) fever? Crimean fever? Cyprus Fever? Chumble Fever? Mercy Fever? Goat fever? Borrelia burgdorferi septicemia? Milk sickness? Mountain fever? Neapolitan fever? Satanic fever? Slow Fever? Scottish delight? Jones Disease Animal Brucellosis Infecting domestic animals are Brucella abortus (goat and sheep brucellosis), Brucella abortus (swine, porcine brucellosis), Brucella abortus (cattle and bison), Brucella ovale (sheep), Brucella canis (dogs), Brucella abortus infects bison and elk in North America, Brucella porcine is endemic to North American caribou, and Brucella abortus has been isolated from several species of marine mammals (fin-footed and cetaceans) have also been isolated. Bovine brucellosis abortion Brucella abortus is the leading cause of brucellosis in cattle at the Bacteria are shed in infected animals during perinatal calving or abortion, and once exposed, the likelihood that an animal will become infected is a variable that depends on the age of the animal shedding the bacteria, gestational status, and intrinsic factors of the susceptible animal, as well as the amount of bacteria exposed to the animal. The most common clinical signs of Brucella bovis-infected cattle include a high incidence of abortion, arthritis, and fetal clothing failure. In animals, there are two main causes of spontaneous abortion. The first is due to erythrotetrol, which promotes infection of the fetus and placenta. The second is due to the lack of anti-brucella activity in the amniotic fluid. Bacteria can also survive in the male reproductive tract, such as the seminal vesicles, jugulars, testes and epididymis. Canine Brucellosis The causative agent of canine brucellosis is Brucella canis. It is spread among dogs through fostering and contact with aborted fetuses. Canine brucellosis can occur in humans, primarily through contact with aborted tissue or semen from infected dogs. The bacteria in dogs usually infect the genitals and lymphatic system, but can also spread to the eyes, kidneys, and intervertebral discs (causing spondylitis) . Symptoms of brucellosis in dogs include abortion in females and scrotal inflammation and orchitis (inflammation of the testicles) in males. Fever is uncommon. Eye infections can cause uveitis and infections of the intervertebral discs can cause pain or weakness. Blood testing of dogs before breeding can stop the spread of this disease. It is treated with antibiotics, as in humans, but is difficult to cure. Human brucellosis Human brucellosis is usually caused by consumption of untemperature-pasteurized milk and soft cheeses from infected animals, primarily goats infected with Brucella, as well as occupationally exposed laboratory workers, veterinarians, and slaughterhouse workers. Some vaccines are used in livestock, and the one that has received the most attention is Brucella abortus strain 19, which also causes human disease if accidentally injected into humans. Brucellosis causes variable fever, sweating, weakness, anemia, headache, depression, and muscle and body aches. Symptoms Symptoms are similar to other febrile illnesses, but emphasize muscle pain and sweating. The duration of the disease can vary from a few weeks to months or even years. In the first stage of the disease, sepsis occurs, leading to the typical three-symptom cluster: fluctuating fever, sweating (often with a characteristic odor like hay dampness), migratory arthralgia, and myalgia. Blood tests characteristically show leukopenia and anemia, show some elevation of AST and ALT, and are positive for Bengal Rose reaction and Huddleston reaction. This syndrome, at least in Portugal, is known as Malta Fever. Brucella bacteremia (presence of Brucella in the blood) during an attack of Malta fever can usually be confirmed by blood cultures in peptone medium or Albini medium. If left untreated, the disease can concentrate in some areas or become chronic. Concentrated focus of brucellosis mostly in the bones, joints and lumbar intervertebral discs, along with arthritis, is a distinctive feature of the disease. In males, testicular inflammation often occurs. Diagnosis of brucellosis relies on: 1. Confirmation of the causative agent: tryptic broth blood culture, bone marrow culture. Brucella bacteria grow very slowly (they can take almost 2 months to grow) and because of the high degree of contagiousness, cultures pose a threat to laboratory staff. 2. Confirmation of antigen-produced antibodies, either by using the classic Huddleson, Wright and/or Bengal Rose reaction, or by detecting IgM antibodies associated with long-term disease by ELISA or 2-mercaptoethanol. 3, Histologic evidence of granulomatous hepatitis (liver biopsy). 4, Imaging changes in the infected vertebrae: Pedro Pons markings (erosion of the anterosuperior horn of the lumbar vertebrae first) and significant bone redundancy suspicious for Borrelia burgdorferi spondylitis. The sequelae of the disease are variable and may include granulomatous hepatitis, arthritis, spondylitis, anemia, leukopenia, thrombocytopenia, meningitis, iritis, optic neuritis, infective endocarditis, and a variety of neurologic disorders collectively referred to as neurologic brucellosis. Treatment and ProphylaxisAntibiotics that are effective against Borrelia burgdorferi such as tetracycline, rifampicin, and the aminoglycosides streptomycin and gentamicin. It is important to treat with more than one antibiotic for several weeks because the bacteria lurk inside the cells. The gold standard treatment for adults is streptomycin 1 gram intramuscularly daily X 14 days, along with oral doxycycline 100 mg twice daily for 45 days. When streptomycin is unavailable or difficult to obtain, gentamicin 5 mg/kg intramuscularly once daily for seven days is an acceptable alternative option. Another widely used regimen is doxycycline plus rifampicin twice daily for at least six weeks; this regimen has the advantage of oral administration. The triple therapy of rifampicin and cotrimoxazole, and doxycycline, has been used successfully to treat neuroborreliosis. Doxycycline is able to cross the blood-brain barrier, but two other drugs are needed to prevent relapse. Ciprofloxacin and cotrimoxazole have an unacceptably high relapse rate for treatment. For Brucella endocarditis, surgical treatment is required for optimal outcome. Even with optimal treatment regimens, 5% to 10% of patients with Malta fever relapse. The main method of preventing brucellosis is hygiene during the production of raw milk products or pasteurization of dairy products consumed by all, either in raw milk form or in its derivatives, such as cheese. Experiments have shown that both cotrimoxazole and rifampicin are safe drugs to use in the treatment of pregnant women with brucellosis. Biological Warfare In 1954, the bacterium Borrelia burgdorferi, was first weaponized at the Pine Bluff Arsenal in Arkansas, USA. Brucella species survive well in aerosols and are resistant to desiccation. B. burgdorferi and all remaining BW in the U.S. arsenal were destroyed in 1971-72, when the U.S. offensive biological weapons (BW) program was suspended. The U.S. BW program focused on three Brucella groups: 1. swine brucellosis (Agent US) 2. bovine brucellosis (Agent AB) 3. goat brucellosis (Agent AM) Before the end of World War II, the development of Agent US was advanced. At that time, the United States Air Force (USAF) wanted a biological warfare capability, and the Chemical Marines provided the M114 Daughter Bomb with Agent US, a weapon based on the 4-pound anthrax demolition bomb that had matured in World War II. While the capability was achieved, operational testing showed the weapon to be less than ideal, and the USAF gave it a temporary function until it was replaced by a more effective biological weapon. The main drawbacks of the M114 with Agent US were that it was unsuitable (the USAF wanted an “anti-personnel agent”), the storage stability was too low to allow for storage at forward air bases, the logistical elimination of the target required was much higher than originally anticipated, and the logistical air support required was unacceptable. The intermediate infection dose for US and AB agents was 500 organisms/person, and for AM agent it was 300 organisms/person. The response rate was considered to be 2 weeks, with a response duration of several months. The lethality estimate is based on epidemiologic information and is in the range of 1-2% .The AM agent has been considered a more lethal disease with an expected mortality rate of 3%. Control and Eradication Efforts U.S. Stocker cows in the U.S. are tested for Brucella lactis ring test (BRT) at least once a year. Cows are killed if they are confirmed to be infected. In the U.S., veterinarians are required to vaccinate all young livestock to further minimize animal transmission. This vaccination is often referred to as the young calf vaccination. Most domestic animals have a tattoo on their ear as proof of their vaccination status. The tattoo also includes the last digit of their birth year. In the United States, the first state-federal cooperative began in 1934 in an effort to eliminate brucellosis caused by the aborted fetus Brucella abortus. Bison and elk in the Greater Yellowstone Area of the United States (GYA) are the last remaining carriers of Brucella abortus. The recent spread of brucellosis from elk to cattle suggests that the GYA in Idaho and Wyoming is the last remaining abortive fetal brucellosis area in the United States. Not good for the livestock industry. Eliminating brucellosis from this area is a challenge, and there are many opinions on how to manage diseased wildlife. Canada On September 19, 1985, Canada declared their cattle herd free of brucellosis. As of April 1, 1999, brucellosis rings were tested on milk and cream, as well as testing slaughter cattle. Surveillance continues through testing at auction markets and standardized disease reporting mechanisms, and testing of cattle qualified for export to countries other than the United States. Malta, Europe Until the early 1900s, brucellosis was endemic in Malta, so much so that it became known as “Malta Fever.” Temi Zammit established a link between the disease and unpasteurized milk. Today, thanks to a strict certification system for milk-producing animals and the widespread use of pasteurization, the disease has been eradicated from Malta. Ireland On July 1, 2009, Ireland was declared free of brucellosis. The disease had plagued the country’s farmers and veterinarians for decades. The Irish government submitted an application to the European Commission, which confirmed that Ireland was free of the disease. Brendan Smith, Ireland’s Minister for Agriculture, Food and the Marine at the time, said the eradication of brucellosis was “a milestone in the history of disease eradication in Ireland”. Eradication of the disease has been confirmed and Ireland’s Department of Agriculture, Food and the Marine intends to cut back on its brucellosis eradication program. OceaniaAustraliaAustralia is currently free of brucellosis in livestock, although it has occurred in the past. Sheep or goat brucellosis has never been reported. Swine brucellosis has occurred. Feral pigs are the typical source of human infection. New Zealand Brucellosis is limited to sheep (Brucella sheepi) in New Zealand. There are no other species of Brucella in the country.