Brucellosis 425881 224208197 2008-07-07T20:27:58Z 128.173.100.42 /* External links */ Updated genomeID for PATRIC link to reflect new value (so useful data is shown! {{DiseaseDisorder infobox | Name = Brucellosis | ICD10 = {{ICD10|A|23||a|20}} | ICD9 = {{ICD9|023}} | ICDO = | Image = Brucella spp.JPG | Caption = | OMIM = | MedlinePlus = 000597 | eMedicineSubj = med | eMedicineTopic = 248 | DiseasesDB = 1716 | }} '''Brucellosis''', also called '''undulant fever''', or '''Malta fever''', in humans is a highly contagious [[zoonosis]] ([[infectious disease]] transmitted from animals to humans) caused by eating of raw minced meat is also a common cause of the infection ''[[Brucella]]''. ''Brucella'' spp. are small, [[gram-negative]], non-motile, non-spore-forming rods. ''Brucella'' spp. are facultative intracellular parasites causing chronic disease, which usually persists for life. Brucellosis is a bacterial disease of both humans and animals recognized since the 19th century. ==History and nomenclature== The disease now called brucellosis, under the name "Mediterranean fever", first came to the attention of [[United Kingdom|British]] medical officers in Malta during the [[Crimean War]] in the 1850s. The causal relationship between organism and disease was first established by Dr. [[David Bruce (microbiologist)|David Bruce]] in 1887. <ref>{{cite book | author = Wilkinson, Lise| title = "Brucellosis", In Kiple, Kenneth F. (ed.), ''The Cambridge World History of Human Disease'', [[Cambridge]]: [[Cambridge University Press]])| year = 1993|}}</ref> In [[1897]] [[Denmark|Danish]] [[veterinarian]] [[Bernhard Lauritz Frederik Bang|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 [[ranching|ranchers]] discuss the disease or [[vaccine]]. [[Maltese people|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 Arabia]]n neurologists discovered '''neurobrucellosis''', a neurological involvement in brucellosis.<ref name=Ravi>Ravi Malhotra (2004), "Saudi Arabia", ''Practical Neurology'' '''4''': 184-185.</ref> ==Transmission and incubation== [[Image:American Bison.jpg|thumb|[[American Bison]] involved in a brucellosis vaccine study]] The disease is transmitted primarily through contaminated or untreated [[milk]] (and its derivatives) or through direct contact with infected animals, which may include [[dog]]s, [[pig]]s, [[camel]]s and [[ruminants]], primarily [[sheep]], [[goat]]s, [[cattle]], [[American Bison|bison]]. This also includes contact with their [[carcass]]es. Leftovers from parturition are also extremely rich in highly virulent brucellae. Infection may also occur by ingesting contaminated grass, roughage, feed, or water <ref>Deyoe, B.L. 1980. Brucellosis. In Amstutz, H.E. (ed.). Bovine Medicine and Surgery. American Veterinary Publications, Santa Barbara, California, pp. 285-297.</ref> Once the susceptible animal ingests the organism, the bacterium progresses to the regional [[lymph node]]s 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 organism [[colonisation|colonize]] the [[uterus]], [[placenta]], [[udder]], and/or regional lymph nodes. Although the most common clinical [[Medical sign|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. == 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). ===Brucellosis in cattle=== The bacteria ''Brucella abortus'' is the principal cause of brucellosis in cattle. The bacteria are shed from an infected animal at or around the time of calfing or abortion. Once exposed, the likelihood of an animal becoming infected is variable, depending on age, pregnancy status, and other intrinsic factors of the animal as well as the amount of bacteria to which the animal was exposed.<ref>Radostits, O.M., C.C. Gay, D.C. Blood, and K.W. Hinchcliff. 2000. Veterinary Medicine, A textbook of the Diseases of Cattle, Sheep, Pigs, Goats and Horses. Harcourt Publishers Limited, London, pp. 867-882.</ref> The most common clinical signs of cattle infected with ''Brucella abortus'' are high incidences of abortions, arthritic joints and retention of after-birth, known as retained [[placenta]]. There are two main causes for spontaneous abortion in animals. The first is due to erythrotol, which can promote infections in the fetus and placenta. Second is due to the lack of anti-Brucella activity in the amniotic fluid. Males can also harbor the bacteria in their reproductive tracts, namely [[seminal vesicles]], [[ampullae]], [[testicles]], and [[epididymides]]. Dairy herds in the USA are tested at least once a year with the Brucella Milk Ring Test<ref>{{cite journal |last= Hamilton |first= Addieءؤئؤيسبييس V. |coauthors= Albert V. Hardy |date= 1950-03 |title= The Brucella Ring Test |journal= [[American Journal of Public Health]] |volume= 40 |issue= 3 |pages= 321–323 |url= http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1528431 |accessdate= 2007-03-18 |pmid= 15405523 }}</ref> (BRT). Cows that are confirmed to be infected are often killed. In the United States, [[veterinarians]] are required to [[Vaccination|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.<ref>{{cite web |url= http://www.inspection.gc.ca/english/anima/heasan/man/avmmva/avmmva_mod8e.shtml |title= Reportable Diseases |accessdate= 2007-03-18 |work= Accredited Veterinarian’s Manual |publisher= Canadian Food Inspection Agency }}</ref> The first state-federal cooperative efforts towards eradication of brucellosis caused by ''Brucella abortus'' in the U.S. began in 1934. ===Brucellosis in the Greater Yellowstone area=== Wild [[bison]] and [[elk]] in the Greater [[Yellowstone]] Area (GYA) are the last remaining reservoir of ''Brucella abortus'' in the U.S. The recent transmission of brucellosis from elk to cattle in Idaho and Wyoming illustrates how brucellosis in wildlife in the GYA may negatively affect cattle. Eliminating brucellosis from this area is a challenge because these animals are on [[public land]] and there are many viewpoints involved in the management of these animals. ===Brucellosis in dogs=== The causative agent of brucellosis in [[dog]]s 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 disc]] (causing [[discospondylitis]]). Symptoms of brucellosis in dogs include abortion in female dogs and [[scrotum|scrotal]] inflammation and [[orchitis]] (inflammation of the testicles) in males. Fever is uncommon. Infection of the eye can cause [[uveitis]], 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.<ref name=Ettinger_1995>{{cite book|author=Ettinger, Stephen J.;Feldman, Edward C.|title=Textbook of Veterinary Internal Medicine|edition=4th ed.|publisher=W.B. Saunders Company|year=1995|id=ISBN 0721646794 }}</ref> ==Brucellosis in humans== ===Symptoms=== [[Image:Brucella granuloma.jpg|thumb|[[Granuloma]] and [[necrosis]] in the liver of a guinea pig infected with ''Brucella suis'']] 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 [[fever]]s, sweating, weakness, [[anaemia]], [[headache]]s, [[clinical depression|depression]] and muscular and bodily pain. The symptoms are like those associated with many other [[fever|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: # 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 [[wiktionary:sequela|sequelae]] are highly variable and may include [[hepatitis|granulomatous hepatitis]], [[arthritis]], [[spondylitis]], [[anaemia]], [[leukopenia]], [[thrombocytopenia]], [[meningitis]], [[uveitis]], [[optic neuritis]] and [[endocarditis]]. ===Treatment and prevention=== [[Antibiotics]] like [[tetracyclins]], [[rifampicin]] and the [[aminoglycosides]] [[streptomycin]] and [[gentamicin]] are effective against Brucella bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubates within [[cell (biology)|cell]]s. 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.<ref>{{cite journal | title=Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in the treatment of brucellosis in humans | year=2006 | author=Roushan MRH, Mohraz M, Hajiahmadi M, Ramzani A, Valayati AA | journal=Clin Infect Dis | volume=42 | issue=8 | pages=1075&ndash;80 | doi=10.1086/501359}}</ref> 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 succefully to treat neurobrucellosis. <ref>{{cite journal | title= Neurobrucellosis: Clinical and therapeutic features | year=1992 | author=McLean DR, Russell N, Khan MY | journal=Clin Infect Dis | volume=15 | pages=582&ndash;90 }}</ref> 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. ===Biological warfare=== In 1954, ''B. suis'' became the first agent [[biological warfare|weaponized]] by the U.S. at its [[Pine Bluff Arsenal]] in Arkansas. ''Brucella'' species survive well in aerosols and resist drying. ''Brucella'' and all other remaining biological weapons in the US arsenal were destroyed in 1971-72 when the U.S. offensive biological weapons (BW) program was discontinued. <ref >{{cite book|author=Woods, Lt Col Jon B. (ed.)|title=[http://www.usamriid.army.mil/education/bluebookpdf/USAMRIID%20BlueBook%206th%20Edition%20-%20Sep%202006.pdf ''USAMRIID’s Medical Management of Biological Casualties Handbook'']|edition=6th ed.|publisher=[[USAMRIID|U.S. Army Medical Institute of Infectious Diseases]], Fort Detrick, Maryland|year=April 2005|pages = 53}}</ref> The United States BW program focused on three agents of the ''Brucella'' group: * Porcine Brucellosis (Agent US) * Bovine Brucellosis (Agent AB) * Caprine Brucellosis (Agent AM) Agent US was in advanced development by the end of the [[Second World War]]. When the 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 the Second World War. 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. ==Historical names== ''In addition to "Malta Fever" and "undulant fever", the following obsolete names have previously been applied to brucellosis:'' *Mediterranean fever *continued fever *Cyprus fever *goat fever *Gibraltar fever *Crimean fever *mountain fever *Neapolitan fever *rock fever *slow fever *''febris melitensis'' *''febris undulans'' *Bruce's septicemia *''melitensis septicemia'' *melitococcosis *''Brucelliasis'' *''Milk Sickness'' ==Popular culture references== {{Trivia|date=September 2007}} *The disease was referred to in the song "Play It All Night Long" by [[American singer/songwriter]] [[Warren Zevon]]. The song is about a presumably Southern farming family going through hard times: "The cattle all have brucellosis, we'll get through somehow." * In [[Flannery O'Connor]]'s short story "The Enduring Chill," the protagonist Asbury is diagnosed with undulant fever. In an act of defiance against what he considers his mother's overbearing ways, he violates a strict rule on her dairy farm by drinking raw milk. The brucellosis he contracts reduces him to a invalid dependent on his mother's care. *It was also mentioned in ''[[All Creatures Great and Small|All Things Bright and Beautiful]]'', one volume in the memoirs of [[James Herriot]], a Scottish veterinarian who began practice in the 1930s. James Herriot is the pen name of veterinarian James Alfred Wight *It was prominently featured in one of the episodes of TV show ''[[House (TV series)|House]]'' entitled "[[Euphoria]]". *A Brucellosis-like disease called "calpine feaver" was mentioned in ''Silence of the Goats'', an episode of the animated show [[Weird Years]]. *The character Renzi in the [[Kydd]] series of novels contracts undulant fever in the book Command<ref>{{cite book | title=Command | last=Stockwin | first=Julian | authorlink=Julian Stockwin | publisher=McBooks Press | location=London | edition=1st ed. | date=2007 | id=ISBN 1-590-13120-7 }}</ref> *Hillary Clinton was offered a fermented milk drink while traveling on a state trip through Mongolia when she was First Lady. When her personal physician found out she had accepted the drink, he ordered her to take a strong course of antibiotics to protect against the risk of brucellosis. ==References== {{Reflist}} ==See also== * [[Swine brucellosis]] * [[Florence Nightingale]] (She may have suffered from brucellosis in the Crimea.) * [[Wildlife disease]] ==External links== * [http://patric.vbi.vt.edu/genome/overview.php?genomeId=8788 ''Brucella abortus'' biovar 1 str. 9-941] (from [http://patric.vbi.vt.edu/ PATRIC], the PathoSystems Resource Integration Center, a [http://www3.niaid.nih.gov/ NIAID] Bioinformatics Resource Center) * [http://patric.vbi.vt.edu/genome/overview.php?genomeId=25 ''Brucella melitensis'' biovar Abortus 2308] (from [http://patric.vbi.vt.edu/ PATRIC], the PathoSystems Resource Integration Center, a [http://www3.niaid.nih.gov/ NIAID] Bioinformatics Resource Center) * [http://www.cdc.gov/ncidod/dbmd/diseaseinfo/brucellosis_g.htm Prevention about Brucellosis] from [[Center for Disease Control]] * [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12217720&ordinalpos=23&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum High rate of brucellosis in humans in ancient Pompeii] * {{WhoNamedIt|synd|819}} * {{GPnotebook|53805059}} * {{FPnotebook|ID14}} *[http://www.veterinarypartner.com/Content.plx?P=A&S=0&C=0&A=2428 ''Brucellosis in Dogs'' from The Pet Health Library] *[http://patric.vbi.vt.edu/organism/overview.php?organismId=1 Brucella from PATRIC] *[http://bbp.hegroup.org/ Brucella Bioinformatics Portal] *[http://wildlifedisease.nbii.gov/diseasehome.jsp?disease=Brucellosis&pagemode=submit Brucellosis Fact Sheet] {{Bacterial diseases}} [[Category:Bacterial diseases]] [[Category:Animal diseases]] [[Category:Occupational diseases]] [[Category:Zoonoses]] [[Category:Dog diseases]] [[Category:Biological weapons]] [[Category:Microbiology]] [[ar:داء البروسيلات]] [[bs:Bruceloza]] [[bg:Бруцелоза]] [[cs:Brucelóza]] [[de:Brucellose]] [[et:Brutselloos]] [[es:Brucelosis]] [[eu:Bruzelosi]] [[fa:تب مالت]] [[fr:Brucellose]] [[hr:Bruceloza]] [[it:Brucellosi]] [[he:ברוצלוזיס]] [[nl:Brucellose]] [[ja:ブルセラ症]] [[no:Brucellose]] [[pl:Bruceloza]] [[pt:Brucelose]] [[ro:Bruceloză]] [[ru:Бруцеллёз]] [[sr:Бруцелоза]] [[fi:Bruselloosi]] [[sv:Bangs sjukdom]] [[tr:Bruselloz]]