Title: Brucellosis

{{short description|Human and animal disease}}
{{cs1 config|name-list-style=vanc}}
{{MCN|date=March 2025}}
{{Infobox medical condition (new)
| name = Brucellosis
| synonyms = undulant fever, undulating fever, Mediterranean fever, Malta fever, Cyprus fever, rock fever (''Micrococcus melitensis'')&lt;ref&gt;{{cite journal|journal=Journal of Maltese History |volume=4 |issue=1 |page=41 |publisher=Department of History, [[University of Malta]] |location=[[Malta]] |url=http://www.um.edu.mt/__data/assets/pdf_file/0005/238838/JMH_-_2014_Wyatt.pdf |title=How did Sir David Bruce forget Zammit and his goats ? |last=Wyatt |first=H. Vivian |date=2014 |archive-date=2016-07-21 |archive-url=https://web.archive.org/web/20160721183732/http://www.um.edu.mt/__data/assets/pdf_file/0005/238838/JMH_-_2014_Wyatt.pdf |issn=2077-4338 }} [https://web.archive.org/web/20160721183442/http://www.um.edu.mt/arts/history/journal/volume_4%2C_number_1_2014 Journal archive]&lt;/ref&gt;
| field = [[Infectious disease (medical specialty)|Infectious disease]]|
| caption = 
| pronounce = 
| symptoms = fever, chills, loss of appetite, sweats, weakness, fatigue, joint pain, muscle pain, back pain, headache.&lt;ref name=Brucellosis&gt;{{cite web |title=Brucellosis |url=https://www.mayoclinic.org/diseases-conditions/brucellosis/symptoms-causes/syc-20351738 |website=mayoclinic.org |publisher=Mayo Clinic |access-date=June 5, 2022}}&lt;/ref&gt;
| complications = central nervous system infections (meningitis, encephalitis), inflammation and infection of the spleen and liver, infection and inflammation of the epididymus and testicles (epididymo-orchitis), arthritis, inflammation of the inner lining of the heart chambers (endocarditis).&lt;ref name=Brucellosis /&gt;
| onset = 
| duration = 
| types = 
| causes = Ingestion of bacteria within the genus ''[[Brucella]]''
| risks = 
| diagnosis = x-rays, computerized tomography (CT) scan or magnetic resonance imaging (MRI), cerebrospinal fluid culture, echocardiography.&lt;ref&gt;{{cite web |title=Brucellosis |url=https://www.mayoclinic.org/diseases-conditions/brucellosis/diagnosis-treatment/drc-20351744 |website=mayoclinic.org |publisher=Mayo Clinic |access-date=June 5, 2022}}&lt;/ref&gt;
| differential = 
| prevention = avoid unpasteurized dairy foods, cook meat thoroughly, wear gloves, take safety precautions in high-risk workplaces, vaccinate domestic animals.&lt;ref name=Brucellosis /&gt;
| treatment = [[antibiotics]]
| medication = [[doxycycline]], [[rifampicin]], [[aminoglycosides]] {{specify|date=March 2025}}
| prognosis = 
| frequency = 
| deaths = 
}}
'''Brucellosis'''&lt;ref&gt;{{cite news |url=http://education.yahoo.com/reference/dictionary/entry/brucellosis |title=Brucellosis |work=American Heritage Dictionary |archive-url=https://web.archive.org/web/20110606062045/http://education.yahoo.com/reference/dictionary/entry/brucellosis |archive-date=2011-06-06 }}&lt;/ref&gt; is a [[zoonosis]] spread primarily via ingestion of [[raw milk|unpasteurized milk]] from infected animals.&lt;ref&gt;{{cite web|url=http://www.dhsspsni.gov.uk/brucellosis-pathway.pdf |archive-url=https://web.archive.org/web/20071013043717/http://www.dhsspsni.gov.uk/brucellosis-pathway.pdf |archive-date=2007-10-13 |title=Diagnosis and Management of Acute Brucellosis in Primary Care |date=August 2004 |publisher=Brucella Subgroup of the Northern Ireland Regional Zoonoses Group}}&lt;/ref&gt; It is also known as '''undulant fever''', '''Malta fever''', and '''Mediterranean fever'''.&lt;ref&gt;{{cite journal | vauthors = Di Pierdomenico A, Borgia SM, Richardson D, Baqi M | title = Brucellosis in a returned traveller | journal = CMAJ | volume = 183 | issue = 10 | pages = E690-2 | date = July 2011 | pmid = 21398234 | pmc = 3134761 | doi = 10.1503/cmaj.091752 }}&lt;/ref&gt;

The bacteria causing this disease, ''[[Brucella]]'', are small, [[Gram-negative]], nonmotile, nonspore-forming, rod-shaped ([[Coccobacillus|coccobacilli]]) bacteria. They function as [[Facultative parasite|facultative]] [[intracellular parasite]]s, causing [[Chronic (medicine)|chronic disease]], which usually persists for life. Four species infect humans: ''B. abortus'', ''B. canis'', ''B. melitensis'', and ''B. suis''. ''B. abortus'' is less virulent than ''B. melitensis'' and is primarily a disease of cattle. ''B. canis'' affects dogs. ''B. melitensis'' is the most virulent and invasive species; it usually infects goats and occasionally sheep. ''B. suis'' is of intermediate virulence and chiefly infects pigs. Symptoms include [[Diaphoresis|profuse sweating]] and [[Arthralgia|joint]] and [[Myalgia|muscle pain]]. Brucellosis has been recognized in animals and humans since the early 20th century.&lt;ref&gt;Park. K., Park's textbook of preventive and social medicine, 23rd edition. Page 290-91&lt;/ref&gt;&lt;ref&gt;{{Citation |last=Roy |first=Rabindra |title=Chapter-23 Biostatistics |date=2013 |work=Mahajan and Gupta Textbook of Preventive and Social Medicine |pages=434–449 |publisher=Jaypee Brothers Medical Publishers (P) Ltd |doi=10.5005/jp/books/12262_23 |doi-broken-date=1 July 2025 |isbn=978-93-5090-187-8 }}&lt;/ref&gt;
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==Signs and symptoms==
[[File:BrucellosisGraph.png|right|thumb|200px|A graph of the cases of brucellosis in humans in the United States from the years 1993–2010 surveyed by the Centers for Disease Control and Prevention through the National Notifiable Diseases Surveillance System&lt;ref&gt;{{cite web |publisher=CDC |url=https://www.cdc.gov/brucellosis/resources/surveillance.html|title=Brucellosis: Resources: Surveillance|date=2018-10-09}}&lt;/ref&gt;]]

The symptoms are like those associated with many other [[fever|febrile]] diseases, but with emphasis on muscular pain and night sweats. The duration of the disease can vary from a few weeks to many months or even years.

In the first stage of the disease, [[bacteremia]] occurs and leads to the classic triad of undulant fevers, sweating (often with a characteristic foul, moldy smell sometimes likened to wet hay), and migratory [[arthralgia]] and [[myalgia]] (joint and muscle pain).&lt;ref&gt;{{Citation |last1=Hayoun |first1=Michael A. |title=Brucellosis |date=2023 |url=https://www.ncbi.nlm.nih.gov/books/NBK441831/ |work=StatPearls |access-date=2023-11-08 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28722861 |last2=Muco |first2=Erind |last3=Shorman |first3=Mahmoud}}&lt;/ref&gt; Blood tests characteristically reveal a [[leukopenia|low number of white blood cells]] and [[anemia|red blood cells]], show some elevation of [[liver enzyme]]s such as [[aspartate aminotransferase]]&lt;!-- (AST) --&gt; and [[alanine aminotransferase]]&lt;!-- (ALT) --&gt;, and demonstrate positive Bengal rose and Huddleston reactions. Gastrointestinal symptoms occur in 70% of cases and include [[nausea]], [[vomiting]], [[decreased appetite]], unintentional weight loss, abdominal pain, [[constipation]], [[diarrhea]], [[hepatomegaly|an enlarged liver]], [[hepatitis|liver inflammation]], [[liver abscess]], and [[splenomegaly|an enlarged spleen]].&lt;ref&gt;{{Cite web |title=Access Anytime Anywhere |url=https://my.clevelandclinic.org/ |access-date=2025-06-07 |website=Cleveland Clinic |language=en}}&lt;/ref&gt;

This complex is, at least in Portugal, Israel, Palestine, Syria, Iran, and Jordan, known as Malta fever. During episodes of Malta fever, melitococcemia (presence of brucellae in the blood) can usually be demonstrated using blood culture in tryptose medium or Albini medium. If untreated, the disease can give rise to focalizations{{clarify|date=June 2020}} or become chronic. The focalizations of brucellosis usually occur in bones and joints, and [[osteomyelitis]] or [[spondylodiscitis]] of the lumbar spine, accompanied by [[sacroiliitis]], is very characteristic of this disease. [[Orchitis]] is also common in men.

The consequences of ''Brucella'' infection are highly variable and may include [[arthritis]], [[spondylitis]], [[thrombocytopenia]], [[meningitis]], [[uveitis]], [[optic neuritis]], [[endocarditis]], and various neurological disorders collectively known as neurobrucellosis.

==Cause==
[[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 consumption of unpasteurized milk and soft cheeses made from the milk of infected animals—often goats—infected with ''B. melitensis'', and with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers. These infected animals may be healthy and asymptomatic.&lt;ref&gt;{{cite journal | vauthors = Wyatt HV | title = How Themistocles Zammit found Malta Fever (brucellosis) to be transmitted by the milk of goats | journal = Journal of the Royal Society of Medicine | volume = 98 | issue = 10 | pages = 451–4 | date = October 2005 | pmid = 16199812 | pmc = 1240100 | doi = 10.1177/014107680509801009 | publisher = The Royal Society of Medicine Press | oclc = 680110952 }}&lt;/ref&gt; Some vaccines used in livestock, most notably ''B. abortus'' strain 19, also cause disease in humans if accidentally injected. Brucellosis induces inconstant [[fever]]s, miscarriage, sweating, weakness, [[anemia]], [[headache]]s, [[clinical depression|depression]], and muscular and bodily pain. The other strains,  ''B. suis'' and ''B. canis'', cause infection in pigs and dogs, respectively.&lt;ref&gt;{{Cite web |title=Top-ranked Hospital in the Nation |url=https://www.mayoclinic.org/ |access-date=2025-06-07 |website=Mayo Clinic |language=en}}&lt;/ref&gt;

Overall findings support that brucellosis poses an [[occupational safety and health|occupational risk]] to [[goat farmer]]s with specific areas of concern including weak awareness of disease [[transmission (medicine)|transmission]] to humans and lack of knowledge on specific safe farm practices such as [[quarantine]] practices.&lt;ref&gt;{{cite journal |display-authors=6 |vauthors=Peck ME, Jenpanich C, Amonsin A, Bunpapong N, Chanachai K, Somrongthong R, Alexander BH, Bender JB |date=January 2019 |title=Knowledge, Attitudes and Practices Associated with Brucellosis among Small-Scale Goat Farmers in Thailand |journal=Journal of Agromedicine |volume=24 |issue=1 |pages= 56–63 |doi=10.1080/1059924X.2018.1538916 |pmid=30350754 |s2cid=53034163}}&lt;/ref&gt;

=== Wildlife reservoirs and zoonotic transmission ===
Brucellosis affects both domestic and wildlife species, with the latter serving as significant reservoirs that contribute to disease persistence and transmission. Notably, bison, elk, wild boars, and deer have been identified as carriers, particularly in North America and Europe&lt;ref&gt;{{Cite journal |last1=Godfroid |first1=Jacques |last2=Al Dahouk |first2=Sascha |last3=Pappas |first3=Georgios |last4=Roth |first4=Felix |last5=Matope |first5=Gift |last6=Muma |first6=John |last7=Marcotty |first7=Tanguy |last8=Pfeiffer |first8=Dirk |last9=Skjerve |first9=Eystein |date=2013-05-01 |title=A &quot;One Health&quot; surveillance and control of brucellosis in developing countries: Moving away from improvisation |url=https://linkinghub.elsevier.com/retrieve/pii/S0147957112001014 |journal=Comparative Immunology, Microbiology and Infectious Diseases |series=Special issue: One Health |volume=36 |issue=3 |pages=241–248 |doi=10.1016/j.cimid.2012.09.001 |pmid=23044181 |hdl=2263/21766 |issn=0147-9571|hdl-access=free |url-access=subscription }}&lt;/ref&gt; Humans can contract the disease through direct handling of infected animals, aerosol exposure, or consumption of undercooked game meat.&lt;ref&gt;{{Cite web |last=CDC |date=2024-06-04 |title=About Brucellosis |url=https://www.cdc.gov/brucellosis/about/index.html#:~:text=People%20can%20get%20brucellosis%20by,products%20made%20from%20contaminated%20milk. |access-date=2025-03-19 |website=Brucellosis |language=en-us}}&lt;/ref&gt; Additionally, the wildlife trade has been implicated in the geographical spread of brucellosis, as the movement and sale of infected animals, particularly in unregulated markets, introduce the bacteria into new ecosystems, increasing disease risks for both humans and animals.&lt;ref&gt;{{Cite journal |last1=Karesh |first1=William B. |last2=Cook |first2=Robert A. |last3=Bennett |first3=Elizabeth L. |last4=Newcomb |first4=James |date=July 2005 |title=Wildlife Trade and Global Disease Emergence |url=http://wwwnc.cdc.gov/eid/article/11/7/05-0194_article.htm |journal=Emerging Infectious Diseases |volume=11 |issue=7 |pages=1000–1002 |doi=10.3201/eid1107.050194 |issn=1080-6040 |pmc=3371803 |pmid=16022772}}&lt;/ref&gt; Reports from Central Asia and sub-Saharan Africa highlight cases where wildlife trafficking has facilitated brucellosis outbreaks in non-endemic regions.&lt;ref&gt;{{Cite journal |last1=Qureshi |first1=Kamal A. |last2=Parvez |first2=Adil |last3=Fahmy |first3=Nada A. |last4=Abdel Hady |first4=Bassant H. |last5=Kumar |first5=Shweta |last6=Ganguly |first6=Anusmita |last7=Atiya |first7=Akhtar |last8=Elhassan |first8=Gamal O. |last9=Alfadly |first9=Saeed O. |last10=Parkkila |first10=Seppo |last11=Aspatwar |first11=Ashok |date=2023-12-12 |title=Brucellosis: epidemiology, pathogenesis, diagnosis and treatment–a comprehensive review |journal=Annals of Medicine |language=en |volume=55 |issue=2 |article-number=2295398 |doi=10.1080/07853890.2023.2295398 |issn=0785-3890 |pmc=10769134 |pmid=38165919}}&lt;/ref&gt;

=== Transmission through hunting and game meat consumption ===
Hunters and individuals who consume wild game face an elevated risk of brucellosis exposure due to direct contact with infected animals and inadequate meat preparation. Transmission can occur during field-dressing or handling of infected carcasses, as ''Brucella'' bacteria can enter the body through skin abrasions, mucous membranes, or inhalation of aerosolized pathogens.&lt;ref&gt;{{Cite web |title=Brucellosis |url=https://www.pa.gov/agencies/pgc/wildlife/wildlife-health/wildlife-diseases/brucellosis.html |access-date=2025-03-19 |website=www.pa.gov |language=en}}&lt;/ref&gt; Additionally, the consumption of undercooked or improperly handled wild game meat remains a significant risk factor, particularly in regions where game animals constitute a primary food source. Implementing protective measures, such as the use of [[personal protective equipment]] (PPE) during handling and ensuring thorough cooking of game meat, is essential to mitigating the risk of brucellosis transmission within hunting communities.

==Diagnosis==
[[File:Coombs Gel Test.jpg|thumb|250px|Brucella Coombs Gel Test. Seropositivity detected to GN177]]
[[File:Rose Bengal Deneyi.jpg|thumb|250px|Rose Bengal Plate Test.]]
The diagnosis of brucellosis relies on:&lt;ref&gt;{{Cite web |title=Top-ranked Hospital in the Nation |url=https://www.mayoclinic.org/ |access-date=2025-06-07 |website=Mayo Clinic |language=en}}&lt;/ref&gt;
# Demonstration of the agent: blood cultures in tryptose broth, bone marrow cultures. The growth of brucellae is extremely slow (they can take up to two months to grow), and the culture poses a risk to laboratory personnel due to the 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 on hepatic biopsy
# Radiologic alterations in infected vertebrae: the Pedro Pons sign (preferential erosion of the anterosuperior corner of lumbar vertebrae) and marked osteophytosis are suspicious of brucellic spondylitis.
Definite diagnosis of brucellosis requires the isolation of the organism from the blood, body fluids, or tissues, but serological methods may be the only tests available in many settings. Positive blood culture yield ranges between 40 and 70% and is less commonly positive for ''B. abortus'' than ''[[Brucella melitensis|B. melitensis]]'' or  ''B. suis''. Identification of specific [[antibodies]] against bacterial [[lipopolysaccharide]] and other [[antigens]] can be detected by the standard agglutination test ([[Agglutination (biology)|SAT]]), rose Bengal, 2-mercaptoethanol (2-ME), antihuman [[globulin]] (Coombs') and indirect enzyme-linked immunosorbent assay ([[ELISA]]). SAT is the most commonly used [[serology]] in endemic areas.&lt;ref&gt;{{cite journal | vauthors = Franco MP, Mulder M, Gilman RH, Smits HL | title = Human brucellosis | journal = The Lancet. Infectious Diseases | volume = 7 | issue = 12 | pages = 775–86 | date = December 2007 | pmid = 18045560 | doi = 10.1016/S1473-3099(07)70286-4 | bibcode = 2007LanID...7..775F }}&lt;/ref&gt;&lt;ref&gt;{{cite journal | vauthors = Al Dahouk S, Nöckler K | title = Implications of laboratory diagnosis on brucellosis therapy | journal = Expert Review of Anti-Infective Therapy | volume = 9 | issue = 7 | pages = 833–45 | date = July 2011 | pmid = 21810055 | doi = 10.1586/eri.11.55 | s2cid = 5068325 | doi-access = free }}&lt;/ref&gt; An agglutination titre greater than 1:160 is considered significant in nonendemic areas and greater than 1:320 in endemic areas.{{citation needed|date=May 2021}}

Due to the similarity of the O [[polysaccharide]] of ''Brucella'' to that of various other [[Gram-negative bacteria]] (e.g. ''[[Francisella tularensis]]'', ''[[Escherichia coli]]'', ''[[Salmonella urbana]]'', ''[[Yersinia enterocolitica]]'', ''[[Vibrio cholerae]]'', and ''[[Stenotrophomonas maltophilia]]''), the appearance of cross-reactions of class M [[immunoglobulin]]s may occur. The inability to diagnose ''B. canis'' by SAT due to lack of cross-reaction is another drawback. False-negative SAT may be caused by the presence of blocking antibodies (the [[prozone phenomenon]]) in the α2-globulin (IgA) and in the α-globulin (IgG) fractions.{{citation needed|date=June 2021}}

Dipstick assays are new and promising, based on the binding of ''Brucella'' IgM antibodies, and are simple, accurate, and rapid. ELISA typically uses cytoplasmic proteins as antigens. It measures IgM, IgG, and IgA with better sensitivity and specificity than the SAT in most recent comparative studies.&lt;ref&gt;{{cite journal | vauthors = Mantur B, Parande A, Amarnath S, Patil G, Walvekar R, Desai A, Parande M, Shinde R, Chandrashekar M, Patil S | display-authors = 6 | title = ELISA versus conventional methods of diagnosing endemic brucellosis | journal = The American Journal of Tropical Medicine and Hygiene | volume = 83 | issue = 2 | pages = 314–8 | date = August 2010 | pmid = 20682874 | pmc = 2911177 | doi = 10.4269/ajtmh.2010.09-0790 }}&lt;/ref&gt; The commercial Brucellacapt test, a single-step immunocapture assay for the detection of total anti-''Brucella'' antibodies, is an increasingly used adjunctive test when resources permit. [[Polymerase chain reaction|PCR]] is fast and should be specific. Many varieties of PCR have been developed (e.g., nested PCR, real-time PCR, and PCR-ELISA) and found to have superior specificity and sensitivity in detecting both primary infection and relapse after treatment.&lt;ref&gt;{{cite journal | vauthors = Yu WL, Nielsen K | title = Review of detection of Brucella spp. by polymerase chain reaction | journal = Croatian Medical Journal | volume = 51 | issue = 4 | pages = 306–13 | date = August 2010 | pmid = 20718083 | pmc = 2931435 | doi = 10.3325/cmj.2010.51.306 }}&lt;/ref&gt; Unfortunately, these are not standardized for routine use, and some centres have reported persistent PCR positivity after clinically successful treatment, fuelling the controversy about the existence of prolonged chronic brucellosis.{{citation needed|date=May 2021}}

Other laboratory findings include normal peripheral white cell count, and occasional [[leucopenia]] with relative [[lymphocytosis]]. The serum biochemical profiles are commonly normal.&lt;ref&gt;{{cite journal | vauthors = Vrioni G, Pappas G, Priavali E, Gartzonika C, Levidiotou S | title = An eternal microbe: Brucella DNA load persists for years after clinical cure | journal = Clinical Infectious Diseases | volume = 46 | issue = 12 | pages = e131-6 | date = June 2008 | pmid = 18462106 | doi = 10.1086/588482 | doi-access = free }}&lt;/ref&gt;

==Prevention==

=== Livestock vaccination and disease surveillance ===
Vaccination is the most effective method for controlling brucellosis in livestock. In cattle, the most common vaccines are  Brucella abortus strain 19 and RB51,&lt;ref&gt;{{Cite web |title=Disease Alert: Bovine Brucellosis |url=https://www.aphis.usda.gov/livestock-poultry-disease/cattle/bovine-brucellosis |access-date=2025-03-19 |website=www.aphis.usda.gov |language=en}}&lt;/ref&gt; while for goats and sheep, B. melitensis Rev-1 is used. Other methods include regular serological screening, and the culling of infected animals helps prevent the spread of disease. In many countries, mandatory vaccination programs&lt;ref&gt;{{Cite journal |last1=Singh |first1=Balbir B. |last2=Kostoulas |first2=Polychronis |last3=Gill |first3=Jatinder P. S. |last4=Dhand |first4=Navneet K. |date=2018-05-10 |editor-last=Wunder |editor-first=Elsio |title=Cost-benefit analysis of intervention policies for prevention and control of brucellosis in India |journal=PLOS Neglected Tropical Diseases |language=en |volume=12 |issue=5 |article-number=e0006488 |doi=10.1371/journal.pntd.0006488 |doi-access=free |issn=1935-2735 |pmc=5963803 |pmid=29746469}}&lt;/ref&gt; and test-and-slaughter policies have been shown to significantly reduce brucellosis incidence in livestock populations.&lt;ref&gt;{{Cite journal |last1=Zamri-Saad |first1=M. |last2=Kamarudin |first2=M. I. |date=2016-12-01 |title=Control of animal brucellosis: The Malaysian experience |journal=Asian Pacific Journal of Tropical Medicine |volume=9 |issue=12 |pages=1136–1140 |doi=10.1016/j.apjtm.2016.11.007 |pmid=27955740 |issn=1995-7645|doi-access=free }}&lt;/ref&gt;&lt;ref&gt;{{Cite journal |last1=Bahmani |first1=Nasrin |last2=Bahmani |first2=Afshin |date=January 2022 |title=A review of brucellosis in the Middle East and control of animal brucellosis in an Iranian experience |url=https://journals.lww.com/10.1097/MRM.0000000000000266 |journal=Reviews in Medical Microbiology |language=en |volume=33 |issue=1 |pages=e63–e69 |doi=10.1097/MRM.0000000000000266 |issn=2770-3150|url-access=subscription }}&lt;/ref&gt;

=== Food safety and pasteurization ===
Brucellosis is commonly transmitted to humans through the consumption of unpasteurized dairy products, particularly raw milk and cheese. Pasteurization is one of the most effective methods to eliminate ''Brucella'' with many countries implementing it while hosting public educational campaigns to discourage the consumption of raw dairy.&lt;ref&gt;{{Cite journal |last1=Dadar |first1=Maryam |last2=Tiwari |first2=Ruchi |last3=Sharun |first3=Khan |last4=Dhama |first4=Kuldeep |date=2021-01-01 |title=Importance of brucellosis control programs of livestock on the improvement of one health |journal=Veterinary Quarterly |language=en |volume=41 |issue=1 |pages=137–151 |doi=10.1080/01652176.2021.1894501 |issn=0165-2176 |pmc=7946044 |pmid=33618618}}&lt;/ref&gt;

=== Wildlife reservoirs and disease control ===
Wild animals, including bison, elk, wild boars, and deer, serve as natural reservoirs for ''Brucella''. Spillover infections from wildlife to livestock pose ongoing challenges, particularly in regions with dairy farms.&lt;ref&gt;{{Cite journal |last1=Bardenstein |first1=Svetlana |last2=Grupel |first2=Daniel |last3=Blum |first3=Shlomo E. |last4=Motro |first4=Yair |last5=Moran-Gilad |first5=Jacob |date=2023 |title=Public and animal health risks associated with spillover of Brucella melitensis into dairy farms |journal=Microbial Genomics |volume=9 |issue=4 |page=001014 |doi=10.1099/mgen.0.001014 |doi-access=free |issn=2057-5858 |pmc=10210956 |pmid=37115199}}&lt;/ref&gt; Control measures include restricted feeding areas, selective culling, and experimental wildlife vaccination programs. Hunters and individuals handling game meat are advised to wear protective gloves and cook meat thoroughly to prevent infection.&lt;ref&gt;{{Cite web |last=CDC |date=2024-06-04 |title=About Brucellosis |url=https://www.cdc.gov/brucellosis/about/index.html |access-date=2025-03-19 |website=Brucellosis |language=en-us}}&lt;/ref&gt;

=== Occupational safety and laboratory precautions ===
Brucellosis poses an occupational hazard for veterinarians, farmers, slaughterhouse workers, and laboratory personnel who handle infected animals or biological specimens. Common preventive measures include the use of personal protective equipment (PPE), proper ventilation in slaughterhouses, and adherence to laboratory biosafety protocols.&lt;ref&gt;{{Cite journal |last1=Pereira |first1=Carine Rodrigues |last2=Cotrim de Almeida |first2=João Vitor Fernandes |last3=Cardoso de Oliveira |first3=Izabela Regina |last4=Faria de Oliveira |first4=Luciana |last5=Pereira |first5=Luciano José |last6=Zangerônimo |first6=Márcio Gilberto |last7=Lage |first7=Andrey Pereira |last8=Dorneles |first8=Elaine Maria Seles |date=2020-05-11 |editor-last=Lin |editor-first=Tao |title=Occupational exposure to Brucella spp.: A systematic review and meta-analysis |journal=PLOS Neglected Tropical Diseases |language=en |volume=14 |issue=5 |article-number=e0008164 |doi=10.1371/journal.pntd.0008164 |doi-access=free |issn=1935-2735 |pmc=7252629 |pmid=32392223}}&lt;/ref&gt; Accidental exposure in laboratory settings can occur through aerosolized bacteria or direct contact with infected samples, necessitating post-exposure antibiotic prophylaxis.&lt;ref&gt;{{Cite web |last=CDC |date=2024-06-24 |title=Laboratory Risks for Brucellosis |url=https://www.cdc.gov/brucellosis/hcp/laboratory-risks/index.html |access-date=2025-03-19 |website=Brucellosis |language=en-us}}&lt;/ref&gt;

=== Public health education and community awareness ===
Educational initiatives are essential to reducing brucellosis transmission, particularly in rural communities where unpasteurized dairy products remain widely consumed. Public health campaigns emphasize the importance of basic knowledge of brucellosis disease and transmission, safe food handling, and vaccination compliance.&lt;ref&gt;{{Cite journal |last1=Ghugey |first1=Satish L. |last2=Setia |first2=Maninder S. |last3=Deshmukh |first3=Jyotsna S. |date=August 2022 |title=The effects of health education intervention on promoting knowledge, beliefs and preventive behaviors on brucellosis among rural population in Nagpur district of Maharashtra state, India |journal=Journal of Family Medicine and Primary Care |language=en |volume=11 |issue=8 |pages=4635–4643 |doi=10.4103/jfmpc.jfmpc_1562_21 |doi-access=free |issn=2249-4863 |pmc=9638594 |pmid=36352929}}&lt;/ref&gt;

=== International disease control efforts and One Health integration ===
Brucellosis control relies on a One Health approach integrating human, animal, and environmental health. Global organizations, including the World Health Organization (WHO), Food and Agriculture Organization (FAO), World Organisation for Animal Health (WOAH), and United Nations Environment Programme (UNEP),&lt;ref&gt;{{Cite web |title=Quadripartite Secretariat for One Health |url=https://www.who.int/teams/one-health-initiative/quadripartite-secretariat-for-one-health#:~:text=The%20One%20Health%20Joint%20Plan,and%20prevent%20potential%20future%20pandemics |access-date=2025-03-19 |website=www.who.int |language=en}}&lt;/ref&gt; advocate for integrated strategies to manage health threats across humans, animals, plants, and the environment, to prevent prevent future pandemics. Collaborative efforts to identify risk factors enhances outbreak surveillance, livestock vaccination programs, and food safety regulations such as mandatory pasteurization, ensuring a sustainable and comprehensive approach disease management.&lt;ref&gt;{{Cite book |last1=FAO |url=https://openknowledge.fao.org/items/fddae6a2-e7ef-4a2a-ad54-2463dbbb0b32 |title=One Health Joint Plan of Action, 2022–2026 |last2=UNEP |last3=WHO |last4=WOAH |date=2022 |publisher=FAO ; UNEP ; WHO ; World Organisation for Animal Health (WOAH) |isbn=978-92-5-136957-9 |language=English}}&lt;/ref&gt;  

==Treatment==
[[Antibiotic]]s such as [[tetracycline]]s, [[rifampicin]], and the [[aminoglycoside]]s [[streptomycin]] and [[gentamicin]] are effective against ''Brucella'' bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubate within [[cell (biology)|cells]].{{citation needed|date=June 2021}}

The gold standard treatment for adults is daily [[intramuscular injection]]s of streptomycin 1&amp;nbsp;g for 14 days and oral [[doxycycline]] 100&amp;nbsp;mg twice daily for 45 days (concurrently). Gentamicin 5&amp;nbsp;mg/kg by intramuscular injection once daily for 7 days is an acceptable substitute when streptomycin is not available or contraindicated.&lt;ref name=&quot;pmid16575723&quot;&gt;{{cite journal | vauthors = Hasanjani Roushan MR, Mohraz M, Hajiahmadi M, Ramzani A, Valayati AA | title = Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in the treatment of brucellosis in humans | journal = Clinical Infectious Diseases | volume = 42 | issue = 8 | pages = 1075–80 | date = April 2006 | pmid = 16575723 | doi = 10.1086/501359 | doi-access = free }}&lt;/ref&gt; Another widely used regimen is doxycycline plus rifampicin twice daily for at least 6 weeks. This regimen has the advantage of oral administration. A triple therapy of doxycycline, with rifampicin and [[co-trimoxazole]], has been used successfully to treat neurobrucellosis.&lt;ref name=&quot;pmid1420670&quot;&gt;{{cite journal | vauthors = McLean DR, Russell N, Khan MY | title = Neurobrucellosis: clinical and therapeutic features | journal = Clinical Infectious Diseases | volume = 15 | issue = 4 | pages = 582–90 | date = October 1992 | pmid = 1420670 | doi = 10.1093/clind/15.4.582 }}&lt;/ref&gt; Doxycycline plus streptomycin regimen (for 2 to 3 weeks) is more effective than doxycycline plus rifampicin regimen (for 6 weeks).&lt;ref&gt;{{cite journal | vauthors = Yousefi-Nooraie R, Mortaz-Hejri S, Mehrani M, Sadeghipour P | title = Antibiotics for treating human brucellosis | journal = The Cochrane Database of Systematic Reviews | volume = 10 | article-number = CD007179 | date = October 2012 | issue = 10 | pmid = 23076931 | pmc = 6532606 | doi = 10.1002/14651858.cd007179.pub2 }}&lt;/ref&gt;

Doxycycline can cross the [[blood–brain barrier]], but requires the addition of two other drugs to prevent relapse. [[Ciprofloxacin]] and co-trimoxazole therapy are 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 to 10% of patients with Malta fever.{{citation needed|date=June 2021}}

==Prognosis==
The mortality of the disease in 1909, as recorded in the British Army and Navy stationed in Malta, was 2%. The most frequent cause of death was [[endocarditis]]. Recent advances in [[antibiotics]] and surgery have been successful in preventing death due to endocarditis. Prevention of human brucellosis can be achieved by eradication of the disease in animals by vaccination and other veterinary control methods, such as testing herds/flocks and slaughtering animals when infection is present. Currently, no effective vaccine is available for humans. Boiling milk before consumption, or before using it to produce other dairy products, is protective against transmission via ingestion. Changing the traditional food habits of eating raw meat, liver, or bone marrow is necessary, but difficult to implement.{{citation needed|date=September 2017}} Patients who have had brucellosis should probably be excluded indefinitely from donating blood or organs. {{citation needed|date=June 2024}} Exposure of diagnostic laboratory personnel to ''Brucella'' organisms remains a problem in both endemic settings and when brucellosis is unknowingly imported by a patient.&lt;ref&gt;{{cite journal | vauthors = Yagupsky P, Baron EJ | title = Laboratory exposures to brucellae and implications for bioterrorism | journal = Emerging Infectious Diseases | volume = 11 | issue = 8 | pages = 1180–5 | date = August 2005 | pmid = 16102304 | pmc = 3320509 | doi = 10.3201/eid1108.041197 }}&lt;/ref&gt; After appropriate risk assessment, staff with significant exposure should be offered postexposure prophylaxis and followed up serologically for 6 months.&lt;ref&gt;{{cite journal | title = Laboratory-acquired brucellosis--Indiana and Minnesota, 2006 | url = https://archive.org/details/sim_mmwr-morbidity-mortality-weekly-report_2008-01-18_57_2/page/38 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 57 | issue = 2 | pages = 39–42 | date = January 2008 | pmid = 18199967 | author1 = Centers for Disease Control Prevention (CDC) }}&lt;/ref&gt;

==Epidemiology==

=== Argentina ===
According to a study published in 2002, an estimated 10–13% of farm animals were infected with ''Brucella'' species.&lt;ref&gt;{{cite journal | vauthors = Samartino LE | title = Brucellosis in Argentina | journal = Veterinary Microbiology | volume = 90 | issue = 1–4 | pages = 71–80 | date = December 2002 | pmid = 12414136 | doi = 10.1016/s0378-1135(02)00247-x }}&lt;/ref&gt; Annual losses from the disease were calculated at around [[US$]]60&amp;nbsp;million. Since 1932, [[SENASA|government agencies]] have undertaken efforts to contain the disease. {{As of|2022}}, all cattle aged 3–8 months must receive the ''Brucella abortus'' strain 19 vaccine.&lt;ref&gt;{{cite web|title =Brucelosis Bovina|url = https://www.argentina.gob.ar/senasa/programas-sanitarios/cadenaanimal/bovinos-y-bubalinos/bovinos-y-bubalinos-produccion-primaria/brucelosis-bovina|website = SENASA - Argentine Government|date = 2022|archive-url = https://web.archive.org/web/20160216183342/https://viejaweb.senasa.gov.ar/contenido.php?to=n&amp;in=857&amp;io=20833|archive-date = 2016-02-16|url-status = live}}&lt;/ref&gt;

===Australia===
[[Australia]] is free of cattle brucellosis, although it occurred in the past. Brucellosis of sheep or goats has never been reported. Brucellosis of pigs does occur. Feral pigs are the typical source of human infections.&lt;ref&gt;{{cite web|url=http://access.health.qld.gov.au/hid/InfectionsandParasites/BacterialInfections/brucellosis_fs.asp |title=Queensland Health: Brucellosis |date=2010-11-24 |access-date=2011-06-06 |publisher=State of Queensland (Queensland Health) |archive-url=https://web.archive.org/web/20110422145254/http://access.health.qld.gov.au/hid/InfectionsandParasites/BacterialInfections/brucellosis_fs.asp |archive-date=2011-04-22 }}&lt;/ref&gt;&lt;ref&gt;
Lehane, Robert (1996) ''Beating the Odds in a Big Country: The eradication of bovine brucellosis and tuberculosis in Australia'', CSIRO Publishing, {{ISBN|0-643-05814-1}}
&lt;/ref&gt;

===Canada===
On 19 September 1985, the [[Canadian government]] declared its cattle population brucellosis-free. Brucellosis ring testing of milk and cream, and testing of cattle to be slaughtered, ended on 1 April 1999. Monitoring continues through testing at auction markets, through standard disease-reporting procedures, and testing of cattle being qualified for export to countries other than the United States.&lt;ref&gt;{{cite web |url= http://www.inspection.gc.ca/english/anima/heasan/man/avmmva/avmmva_mod8e.shtml |title= Reportable Diseases |access-date= 2007-03-18 |work= Accredited Veterinarian's Manual |publisher= Canadian Food Inspection Agency |archive-date= 2007-02-08 |archive-url= https://web.archive.org/web/20070208153207/http://www.inspection.gc.ca/english/anima/heasan/man/avmmva/avmmva_mod8e.shtml }}&lt;/ref&gt;

===China===
An outbreak infecting humans took place in [[Lanzhou]] in 2019 after the Lanzhou Biopharmaceutical Plant, which was involved in vaccine production, accidentally pumped out the bacteria into the atmosphere in exhaust air due to use of expired disinfectant.&lt;ref&gt;[https://www.news.com.au/lifestyle/health/health-problems/china-reports-outbreak-of-brucellosis-disease-way-larger-than-originally-thought/news-story/b5c191369b19dc2aa8cc6b84e025b79a China reports outbreak of brucellosis disease 'way larger' than originally thought] 18 September 2020 ''www.news.com.au'', accessed 18 September 2020&lt;/ref&gt;&lt;ref&gt;{{cite web |title=兰州药厂泄漏事件布病患者：肿痛无药可吃，有人已转成慢性病_绿政公署_澎湃新闻-The Paper |url=https://www.thepaper.cn/newsDetail_forward_9215336 |website=www.thepaper.cn |access-date=2 June 2021}}&lt;/ref&gt;

According to Georgios Pappas, an infectious-disease specialist and author of a report published in the journal ''[[Clinical Infectious Diseases]]'',&lt;ref name=Pappas&gt;{{cite journal|last=Pappas|first=Georgios|date=15 November 2022|title=The Lanzhou Brucella Leak: The Largest Laboratory Accident in the History of Infectious Diseases?|url=https://academic.oup.com/cid/article-abstract/75/10/1845/6604450 |journal=Clinical Infectious Diseases|volume=75|issue=10|pages=1845–1847|doi=10.1093/cid/ciac463 |pmid=35675697 |url-access=subscription}}&lt;/ref&gt; the result was &quot;possibly the largest laboratory accident in the history of infectious diseases.&quot; According to Pappas, out of nearly 70,000 people tested, more than 10,000 were seropositive, citing figures compiled by the provincial health authorities in Lanzhou's Gansu province. Pappas also states that Chinese documents show that more than 3,000 people living near the plant applied for compensation, an indication of at least a mild illness.&lt;ref name=Warwick&amp;Willman&gt;{{cite news|last1=Warwick|first1=Joby|last2=Willman|first2=David|date=April 12, 2023|title=China's struggles with lab safety carry danger of another pandemic|url=https://www.washingtonpost.com/investigations/interactive/2023/china-lab-safety-risk-pandemic/? |newspaper=[[The Washington Post]]|location=Washington D.C.}}&lt;/ref&gt;

===Europe===
[[File:B.melitensis in Europe.svg|300px|thumb|Disease incidence map of ''B. melitensis'' infections in animals in Europe during the first half of 2006
{{legend|#AADE00|never reported}}
{{legend|#EFED00|not reported in this period}}
{{legend|#FF8800|confirmed clinical disease}}
{{legend|#FF1100|confirmed infection}}
{{legend|#C0C0C0|no information}}]]

====Malta====
Until the early 20th century, the disease was [[Endemic (epidemiology)|endemic]] in Malta to the point of it being referred to as &quot;Maltese fever&quot;. Since 2005, due to a strict regimen of certification of milk animals and widespread use of pasteurization, the illness has been eradicated from Malta.&lt;ref&gt;{{cite book|title=Brucellosis, The Malta Experience|last= Naudi|first= John Rizzo |year= 2005| publisher= Publishers Enterprises group (PEG) Ltd.|location=Malta|isbn=978-99909-0-425-3}}&lt;/ref&gt;

====Republic of Ireland====
[[Republic of Ireland|Ireland]] was declared free of brucellosis on 1 July 2009. It had troubled the country's farmers and veterinarians for several decades.&lt;ref name=&quot;Ireland free of brucellosis&quot;&gt;{{cite web |url=http://www.rte.ie/news/2009/0701/farming.html |title=Ireland free of brucellosis |date=2009-07-01 |access-date=2009-07-01 |publisher=[[RTÉ]]}}&lt;/ref&gt;&lt;ref name=&quot;Ireland declared free of brucellosis&quot;&gt;{{cite news |url=http://www.irishtimes.com/newspaper/breaking/2009/0701/breaking61.htm |title=Ireland declared free of brucellosis |date=2009-07-01 |access-date=2009-07-01 |newspaper=[[The Irish Times]] |quote=Michael F Sexton, president of Veterinary Ireland, which represents vets in practice, said: &quot;Many vets and farmers in particular suffered significantly with brucellosis in past decades and it is greatly welcomed by the veterinary profession that this debilitating disease is no longer the hazard that it once was.&quot; |archive-date=2021-04-03 |archive-url=https://web.archive.org/web/20210403195950/https://www.irishtimes.com/news/ireland-declared-free-of-brucellosis-1.842628 }}&lt;/ref&gt; The [[Government of Ireland|Irish government]] submitted an application to the [[European Commission]], which verified that Ireland had been liberated.&lt;ref name=&quot;Ireland declared free of brucellosis&quot;/&gt; [[Brendan Smith (politician)|Brendan Smith]], Ireland's then [[Minister for Agriculture, Food and the Marine]], said the elimination of brucellosis was &quot;a landmark in the history of disease eradication in Ireland&quot;.&lt;ref name=&quot;Ireland free of brucellosis&quot;/&gt;&lt;ref name=&quot;Ireland declared free of brucellosis&quot;/&gt; Ireland's [[Department of Agriculture, Food and the Marine]] intends to reduce its brucellosis eradication programme now that eradication has been confirmed.&lt;ref name=&quot;Ireland free of brucellosis&quot;/&gt;&lt;ref name=&quot;Ireland declared free of brucellosis&quot;/&gt;

====UK====
Mainland Britain has been free of brucellosis since 1979, although there have been episodic reintroductions since.&lt;ref name=vpc&gt;[https://veterinary-practice.com/article/monitoring-brucellosis-in-great-britain Monitoring brucellosis in Great Britain] 3 September 2020 ''veterinary-practice.com'', accessed 18 September 2020&lt;/ref&gt; The last outbreak of brucellosis in Great Britain was in cattle in Cornwall in 2004.&lt;ref name=vpc/&gt;&lt;ref&gt;[https://www.gov.uk/guidance/brucellosis Guidance Brucellosis: how to spot and report the disease] 18 October 2018 ''www.gov.uk'', accessed 18 September 2020&lt;/ref&gt; Northern Ireland was declared officially brucellosis-free in 2015.&lt;ref name=vpc/&gt;

===New Zealand===
Brucellosis in [[New Zealand]] is limited to sheep (''B. ovis''). The country is free of all other species of ''Brucella''.&lt;ref&gt;{{cite web |url=http://www.biosecurity.govt.nz/pests/brucellosis |title=MAF Biosecurity New Zealand: Brucellosis |access-date=2011-06-06 |publisher=Ministry of Agriculture and Forestry of New Zealand |archive-url=https://web.archive.org/web/20120320111250/http://www.biosecurity.govt.nz/pests/brucellosis |archive-date=2012-03-20 }}&lt;/ref&gt;

===United States===
Dairy herds in the U.S. are tested at least once a year to be certified brucellosis-free&lt;ref&gt;{{cite book|title=Brucellosis Eradication APHIS 91–45–013|date=October 2003|publisher=United States Department of Agriculture|page=14}}&lt;/ref&gt; with the ''Brucella'' milk ring test.&lt;ref name=&quot;pmid15405523&quot;&gt;{{cite journal | vauthors = Hamilton AV, Hardy AV | title = The brucella ring test; its potential value in the control of brucellosis | journal = American Journal of Public Health and the Nation's Health | volume = 40 | issue = 3 | pages = 321–3 | date = March 1950 | pmid = 15405523 | pmc = 1528431 | doi = 10.2105/AJPH.40.3.321 | url = }}&lt;/ref&gt; Cows confirmed to be infected are often killed. In the United States, [[veterinarian]]s are required {{Citation needed|reason=Required or encouraged?|date=July 2013}} to [[Vaccination|vaccinate]] all young stock, to further reduce the chance of [[Zoonosis|zoonotic]] transmission. This vaccination is usually referred to as a &quot;calfhood&quot; vaccination. Most cattle receive a tattoo in one of their ears, serving as proof of their vaccination status. This tattoo also includes the last digit of the year they were born.&lt;ref name=&quot;vermont&quot;&gt;{{cite web|author=Vermont Beef Producers |title=How important is calfhood vaccination? |url=http://www.vermontbeefproducers.org/NewFiles/AsktheVet/Fall%2002.pdf |archive-url=https://web.archive.org/web/20080509134048/http://www.vermontbeefproducers.org/NewFiles/AsktheVet/Fall%2002.pdf |archive-date=2008-05-09 }}&lt;/ref&gt;

The first state–federal cooperative efforts towards eradication of brucellosis caused by ''B. abortus'' in the U.S. began in 1934.{{citation needed|date=June 2021}}

Brucellosis was originally imported to North America with non-native domestic cattle (''Bos taurus''), which transmitted the disease to wild [[bison]] (''Bison bison'') and [[elk]] (''Cervus canadensis''). No records exist of brucellosis in ungulates native to America until the early 19th century.&lt;ref&gt;{{cite journal |title=On the Origin of Brucellosis in Bison of Yellowstone National Park: A Review | first1 = Mary | last1 = Meagher | first2 = Margaret E. | last2 = Meyer |journal=Conservation Biology |volume=8 |issue=3 |pages=645–653 |date=September 1994 |jstor=2386505 |url= http://www.buffalofieldcampaign.org/habitat/documents2/Meagher_and_Meyer_Origin_of_Brucellosis.pdf |doi=10.1046/j.1523-1739.1994.08030645.x | bibcode = 1994ConBi...8..645M |access-date=2017-01-07 |archive-url=https://web.archive.org/web/20170108002515/http://www.buffalofieldcampaign.org/habitat/documents2/Meagher_and_Meyer_Origin_of_Brucellosis.pdf |archive-date=2017-01-08 }}&lt;/ref&gt;

==History==
[[File:The members of the Mediterranean Fever Commission. Wellcome L0022610.jpg|thumb|300px|[[David Bruce (microbiologist)|David Bruce]] (centre), with members of the Mediterranean Fever Commission (Brucellosis)]]
[[File:Sir Temi Zammit laboratory.jpeg|thumb|300px|The lab in which Sir [[Themistocles Zammit]] and the Mediterranean Fever Commission carried out research about brucellosis from 1904 to 1906 is located within the [[Castellania (Valletta)|Castellania]] in [[Valletta]], [[Malta]].]]

Brucellosis first came to the attention of [[United Kingdom|British]] medical officers in the 1850s in Malta during the [[Crimean War]], and was referred to as Malta Fever. [[Jeffery Allen Marston]] (1831–1911) described his case of the disease in 1861. The causal relationship between organism and disease was first established in 1887 by [[David Bruce (microbiologist)|David Bruce]].&lt;ref&gt;{{cite book | last = Wilkinson | first = Lise | chapter= Brucellosis |editor-last = Kiple | editor-first = Kenneth F. |title=The Cambridge World History of Human Disease |publisher=[[Cambridge University Press]]| year = 1993}}&lt;/ref&gt;&lt;ref&gt;{{WhoNamedIt2|synd|819|Brucellosis}} named after {{WhoNamedIt|doctor|871|Major-General Sir David Bruce}}&lt;/ref&gt; Bruce considered the agent spherical and classified it as a [[coccus]].{{citation needed|date=December 2022}}

In 1897, [[Denmark|Danish]] [[veterinarian]] [[Bernhard Lauritz Frederik Bang|Bernhard Bang]] isolated a [[bacillus (shape)|bacillus]] as the agent of heightened spontaneous abortion in cows, and the name &quot;Bang's disease&quot; was assigned to this condition. Bang considered the organism rod-shaped and classified it as a [[bacillus]]. At the time, no one knew that this bacillus had anything to do with the causative agent of Malta fever.&lt;ref&gt;{{cite book |last=Evans |first=Alice |url=https://history.nih.gov/display/history/Evans%2C+Alice+C.+1963 |archive-url=https://web.archive.org/web/20200510013402/https://history.nih.gov/display/history/Evans%2C+Alice+C.+1963 |archive-date=May 10, 2020 |title=Dr. Alice C. Evans Memoir |year=1963 |language=en}}&lt;/ref&gt;

Maltese scientist and archaeologist [[Themistocles Zammit]] identified unpasteurized goat milk as the major etiologic factor of undulant fever in June 1905.&lt;ref&gt;{{cite journal|journal=Journal of Maltese History |volume=4 |issue=2 |pages=54–56 |publisher=Department of History, [[University of Malta]] |location=[[Malta]] |url=https://www.um.edu.mt/__data/assets/pdf_file/0007/269908/JMH-2015Wyatt.pdf |title=The Strange Case of Temi Zammit's missing experiments |last=Wyatt |first=H. Vivian |date=2015 |archive-date=2016-07-21 |archive-url=https://web.archive.org/web/20160721183634/http://www.um.edu.mt/__data/assets/pdf_file/0007/269908/JMH-2015Wyatt.pdf |issn=2077-4338 }} [https://web.archive.org/web/20160721183426/http://www.um.edu.mt/arts/history/journal/volume4%2Cnumber2%2C2015 Journal archive]&lt;/ref&gt;

In the late 1910s, American bacteriologist [[Alice Catherine Evans|Alice C. Evans]] was studying the Bang bacillus and gradually realized that it was virtually indistinguishable from the Bruce coccus.&lt;ref name=&quot;de_Kruif_1932&quot;&gt;{{cite book | last = de Kruif | first = Paul |author-link=Paul de Kruif |chapter=Ch. 5 Evans: death in milk |title=Men Against Death |publisher=Harcourt, Brace  |location=New York |year=1932 |oclc=11210642 |chapter-url=https://books.google.com/books?id=IokwAAAAIAAJ&amp;q=editions:IokwAAAAIAAJ}}&lt;/ref&gt; The short-rod versus oblong-round morphologic borderline explained the leveling of the erstwhile bacillus/coccus distinction (that is, these &quot;two&quot; pathogens were not a coccus versus a bacillus but rather were one [[coccobacillus]]).&lt;ref name=&quot;de_Kruif_1932&quot;/&gt; The Bang bacillus was already known to be [[enzootic]] in American dairy cattle, which showed itself in the regularity with which herds experienced contagious abortion.&lt;ref name=&quot;de_Kruif_1932&quot;/&gt; Having made the discovery that the bacteria were certainly nearly identical and perhaps totally so, Evans then wondered why Malta fever was not widely diagnosed or reported in the United States.&lt;ref name=&quot;de_Kruif_1932&quot;/&gt; She began to wonder whether many cases of vaguely defined febrile illnesses were in fact caused by the drinking of raw (unpasteurized) milk.&lt;ref name=&quot;de_Kruif_1932&quot;/&gt; During the 1920s, this hypothesis was vindicated. Such illnesses ranged from undiagnosed and untreated gastrointestinal upset to misdiagnosed&lt;ref name=&quot;de_Kruif_1932&quot;/&gt; febrile and painful versions, some even fatal. This advance in bacteriological science sparked extensive changes in the American dairy industry to improve [[food safety]]. The changes included making [[pasteurization]] standard and greatly tightening the standards of cleanliness in milkhouses on [[dairy farming|dairy farms]]. The expense prompted delay and skepticism in the industry,&lt;ref name=&quot;de_Kruif_1932&quot;/&gt; but the new hygiene rules eventually became the norm. Although these measures have sometimes struck people as overdone in the decades since, being unhygienic at milking time or in the milkhouse, or drinking raw milk, is not a safe alternative.{{citation needed|date=June 2021}}

In the decades after Evans's work, this genus, which received the name ''[[Brucella]]'' in honor of Bruce, was found to contain several species with varying virulence. The name &quot;brucellosis&quot; gradually replaced the 19th-century names Mediterranean fever and Malta fever.&lt;ref name = &quot;Wyatt_2004&quot;&gt;{{cite journal|journal=British Medical Journal|last=Wyatt|first=Harold Vivian |date=31 July 2004|title= Give A Disease A Bad Name|jstor=25468794|issn=0959-535X|oclc=198096808|volume=329|issue=7460|pages=272–278|publisher=BMJ Publishing Group Ltd.|doi=10.1136/bmj.329.7460.272|pmc=498028}}&lt;/ref&gt;

Neurobrucellosis, a neurological involvement in brucellosis, was first described in 1879. In the late 19th century, its symptoms were described in more detail by M. Louis Hughes, a Surgeon-Captain of the [[Royal Army Medical Corps]] stationed in Malta who isolated ''brucella'' organisms from a patient with meningo-encephalitis.&lt;ref&gt;{{cite book|title=Brucellosis|last=Madkour|first=M. Monir|year=2014|publisher=Elsevier Science|isbn=978-1-4831-9359-5|page=160}}&lt;/ref&gt; In 1989, [[neurologists]] in Saudi Arabia made significant contributions to the medical literature involving neurobrucellosis.&lt;ref name=Ravi&gt;{{cite journal | last = Malhotra | first = Ravi |year=2004 |title=Saudi Arabia| journal=Practical Neurology |volume=4 |pages=184–185|doi=10.1111/j.1474-7766.2004.03-225.x |issue=3 | doi-broken-date = 8 December 2025 }}&lt;/ref&gt;&lt;ref name=&quot;pmid15037461&quot;&gt;{{cite journal | vauthors = Al-Sous MW, Bohlega S, Al-Kawi MZ, Alwatban J, McLean DR | title = Neurobrucellosis: clinical and neuroimaging correlation | journal = AJNR. American Journal of Neuroradiology | volume = 25 | issue = 3 | pages = 395–401 | date = March 2004 | pmid = 15037461 | pmc = 8158553 | url = http://www.ajnr.org/cgi/pmidlookup?view=long&amp;pmid=15037461 }}&lt;/ref&gt;

These obsolete names have previously been applied to brucellosis:&lt;ref name = &quot;Wyatt_2004&quot; /&gt;&lt;ref&gt;{{cite magazine |url= http://content.time.com/time/magazine/article/0,9171,928363,00.html |title=Medicine: Goat Fever|date=1928-12-10|magazine=Time|access-date=2017-05-01|issn=0040-781X}}&lt;/ref&gt;
{{Columns-list|colwidth=22em|
* Crimean fever
* Cyprus fever
* Gibraltar fever
* Goat fever
* Italian fever
* Neapolitan fever
}}

===Biological warfare===
''Brucella'' species had been weaponized by several advanced countries by the mid-20th century. In 1954, ''B. suis'' became the first agent [[biological warfare|weaponized]] by the United States at its [[Pine Bluff Arsenal]] near [[Pine Bluff, 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 American offensive biological warfare  program was discontinued by order of President [[Richard Nixon]].&lt;ref&gt;{{cite book| last = Woods | first = Jon B. |title=USAMRIID's Medical Management of Biological Casualties Handbook |url=http://www.usamriid.army.mil/education/bluebookpdf/USAMRIID%20BlueBook%206th%20Edition%20-%20Sep%202006.pdf |edition=6th |publisher=[[USAMRIID|U.S. Army Medical Institute of Infectious Diseases]] |location=Fort Detrick, Maryland |date=April 2005 |page=53 |archive-url=https://web.archive.org/web/20070609104204/http://www.usamriid.army.mil/education/bluebookpdf/USAMRIID%20BlueBook%206th%20Edition%20-%20Sep%202006.pdf |archive-date=2007-06-09 }}&lt;/ref&gt;

The experimental American bacteriological warfare program focused on three agents of the ''Brucella'' group:{{citation needed|date=June 2021}}
* [[Swine brucellosis|Porcine brucellosis]] (agent US)
* Bovine brucellosis (agent AA)
* Caprine brucellosis (agent AM)

Agent US was in advanced development by the end of [[World War II]]. When the [[United States Air Force]] (USAF) wanted a biological warfare capability, the [[Chemical Corps]] offered Agent US in the [[M114 bomblet]], based on the four-pound bursting bomblet developed for spreading [[anthrax]] during World War II. Though the capability was developed, operational testing indicated the weapon was less than desirable, and the USAF designed it as an interim capability until it could eventually be replaced by a more effective biological weapon.{{citation needed|date=May 2021}}

The main drawback of using the M114 with Agent US was that it acted mainly as an incapacitating agent, whereas the USAF administration wanted deadly weapons. The stability of M114 in storage was too low to allow for storing it at forward air bases, and the logistical requirements to neutralize a target were far higher than originally planned. Ultimately, this would have required too much logistical support to be practical in the field.{{citation needed|date=May 2021}}

Agents US and AA had a median infective dose of 500 organisms/person, and for Agent AM, it was 300 organisms/person. The incubation time was believed to be about 2 weeks, with a duration of infection of several months. The lethality estimate was, based on epidemiological information, 1 to 2
per cent. Agent AM was believed to be a somewhat more virulent disease, with a fatality rate of 3 per cent being expected.{{citation needed|date=June 2021}}

==Other animals==
Species infecting domestic livestock are ''[[Brucella abortus|B. abortus]]'' (cattle, bison, and elk), ''[[Brucella canis|B. canis]]'' (dogs), ''[[Brucella melitensis|B. melitensis]]'' (goats and sheep), ''[[Brucella ovis|B. ovis]]'' (sheep), and ''[[Swine brucellosis|B. suis]]'' (caribou and pigs). ''Brucella'' species have also been isolated from several marine mammal species (cetaceans and pinnipeds).{{citation needed|date=May 2021}}

===Cattle===
''[[Brucella abortus|B. abortus]]'' is the principal cause of brucellosis in cattle. The bacteria are shed from an infected animal at or around the time of calving or [[Spontaneous abortion|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 number of bacteria to which the animal was exposed.&lt;ref&gt;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. {{ISBN|0702027774}}.&lt;/ref&gt; The most common clinical signs of cattle infected with ''B. abortus'' are high incidences of abortions, arthritic joints, and retained [[placenta]].{{citation needed|date=June 2021}}

The two main causes for spontaneous abortion in animals are [[erythritol]], which can promote infections in the fetus and placenta,{{clarify|date=July 2022}}, and the lack of anti-''Brucella'' activity in the amniotic fluid. Males can also harbor the bacteria in their reproductive tracts, namely [[seminal vesicle]]s, [[ampulla of ductus deferens|ampullae]], [[testicle]]s, and [[epididymis]]es.{{citation needed|date=June 2021}}

===Dogs===
The causative agent of brucellosis in [[dog]]s, ''[[Brucella canis|B. canis]]'', is transmitted to other dogs through breeding and contact with aborted fetuses. Brucellosis can occur in humans who 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 eyes, [[kidney]]s, and [[intervertebral disc]]s. Brucellosis in the intervertebral disc is one possible cause of [[discospondylitis]]. Symptoms of brucellosis in dogs include abortion in female dogs and  [[scrotum|scrotal]] inflammation and [[orchitis]] 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.&lt;ref name=&quot;Ettinger_1995&quot;&gt;{{cite book| last1 = Ettinger | first1 = Stephen J | last2 = Feldman | first2 = Edward C. |title=Textbook of Veterinary Internal Medicine|edition=4th|publisher=W.B. Saunders Company|year=1995|isbn=978-0-7216-4679-4 }}&lt;/ref&gt;

===Aquatic wildlife===
Brucellosis in cetaceans is caused by the bacterium ''[[Brucella ceti|B. ceti]]''. First discovered in the aborted fetus of a [[bottlenose dolphin]], the structure of ''B. ceti'' is similar to ''Brucella'' in land animals. ''B. ceti'' is commonly detected in two suborders of cetaceans, the [[Mysticeti]] and [[Odontoceti]]. The Mysticeti include four families of [[baleen whales]], filter-feeders, and the Odontoceti include two families of toothed cetaceans ranging from dolphins to sperm whales. ''B. ceti'' is believed to transfer from animal to animal through sexual intercourse, maternal feeding, aborted fetuses, placental issues, from mother to fetus, or through fish reservoirs. Brucellosis is a reproductive disease, so it has an extreme negative impact on the population dynamics of a species. This becomes a greater issue when the already low population numbers of cetaceans are taken into consideration. ''B. ceti'' has been identified in four of the 14 cetacean families, but the antibodies have been detected in seven of the families. This indicates that ''B. ceti'' is common amongst cetacean families and populations. Only a small percentage of exposed individuals become ill or die. However, particular species apparently are more likely to become infected by ''B. ceti''. The harbor porpoise, striped dolphin, white-sided dolphin, bottlenose dolphin, and common dolphin have the highest frequency of infection amongst odontocetes. In the mysticetes families, the northern minke whale is by far the most infected species. Dolphins and porpoises are more likely to be infected than cetaceans such as whales. Concerning sex and age biases, the infections do not seem influenced by an individual's age or sex. Although fatal to cetaceans, ''B. ceti'' has a low infection rate for humans.&lt;ref&gt;{{cite journal | vauthors = Guzmán-Verri C, González-Barrientos R, Hernández-Mora G, Morales JA, Baquero-Calvo E, Chaves-Olarte E, Moreno E | title = Brucella ceti and brucellosis in cetaceans | journal = Frontiers in Cellular and Infection Microbiology | volume = 2 | page = 3 | year = 2012 | pmid = 22919595 | pmc = 3417395 | doi = 10.3389/fcimb.2012.00003 | doi-access = free }}&lt;/ref&gt;

=== Terrestrial wildlife ===
The disease in its various strains can infect multiple wildlife species, including elk (''Cervus canadensis''), bison (''Bison bison''), African buffalo (''Syncerus caffer''), European wild boar (''Sus scrofa''), caribou (''Rangifer tarandus''), moose (''Alces alces''), and marine mammals (see section on aquatic wildlife above).&lt;ref name=&quot;Brucellosis at Threecolumn&quot;/&gt;&lt;ref&gt;{{cite journal | vauthors = Godfroid J | title = Brucellosis in wildlife | journal = Revue Scientifique et Technique | volume = 21 | issue = 2 | pages = 277–86 | date = August 2002 | pmid = 11974615 | doi = 10.20506/rst.21.2.1333 | url = http://www.oie.int/doc/ged/D514.PDF | access-date = 2016-10-07 | archive-date = 2015-06-06 | archive-url = https://web.archive.org/web/20150606124753/http://www.oie.int/doc/ged/D514.PDF }}&lt;/ref&gt; While some regions use vaccines to prevent the spread of brucellosis between infected and uninfected wildlife populations, no suitable brucellosis vaccine for terrestrial wildlife has been developed.&lt;ref name=&quot;Godfroid Garin-Bastjui Blasco&quot;&gt;{{cite journal | vauthors = Godfroid J, Garin-Bastuji B, Saegerman C, Blasco JM | title = Brucellosis in terrestrial wildlife | journal = Revue Scientifique et Technique | volume = 32 | issue = 1 | pages = 27–42 | date = April 2013 | pmid = 23837363 | doi = 10.20506/rst.32.1.2180 | url = http://www.oie.int/doc/ged/D12397.PDF | citeseerx = 10.1.1.1020.9652 | access-date = 2016-10-07 | archive-date = 2015-06-06 | archive-url = https://web.archive.org/web/20150606122947/http://www.oie.int/doc/ged/D12397.PDF }}&lt;/ref&gt; This gap in medicinal knowledge creates more pressure for management practices that reduce spread of the disease.&lt;ref name=&quot;Godfroid Garin-Bastjui Blasco&quot; /&gt;

Wild bison and elk in the greater [[Yellowstone]] area are the last remaining reservoir of ''B. abortus'' in the US. The recent transmission of brucellosis from elk back to cattle in Idaho and Wyoming illustrates how the area, as the last remaining reservoir in the United States, may adversely affect the livestock industry. Eliminating brucellosis from this area is a challenge, as many viewpoints exist on how to manage diseased wildlife. However, the [[Wyoming Game and Fish Department]] has recently begun to protect scavengers (particularly [[coyote]]s and [[red fox]]) on elk feedgrounds, because they act as sustainable, no-cost, biological control agents by removing infected elk fetuses quickly.&lt;ref&gt;{{cite journal | vauthors = Cross PC, Maichak EJ, Brennan A, Scurlock BM, Henningsen J, Luikart G | title = An ecological perspective on Brucella abortus in the western United States | journal = Revue Scientifique et Technique | volume = 32 | issue = 1 | pages = 79–87 | date = April 2013 | pmid = 23837367 | doi = 10.20506/rst.32.1.2184 | url = https://www.nps.gov/yell/learn/nature/upload/09cross7987.pdf | archive-url = https://web.archive.org/web/20160416021217/https://www.nps.gov/yell/learn/nature/upload/09cross7987.pdf | archive-date = April 16, 2016 }}&lt;/ref&gt;

The National Elk Refuge in Jackson, Wyoming, asserts that the intensity of the winter feeding program affects the spread of brucellosis more than the population size of elk and bison.&lt;ref name=&quot;Brucellosis at Threecolumn&quot;&gt;{{cite web|url=https://www.fws.gov/nwrs/threecolumn.aspx?id=2147512596|title=Brucellosis|year=2016|website=www.fws.gov|publisher=U.S. Fish &amp;Wildlife Service|access-date=2016-10-03|archive-date=2016-10-09|archive-url=https://web.archive.org/web/20161009180947/https://www.fws.gov/nwrs/threecolumn.aspx?id=2147512596}}&lt;/ref&gt; Since concentrating animals around food plots accelerates spread of the disease, management strategies to reduce herd density and increase dispersion could limit its spread.&lt;ref name=&quot;Brucellosis at Threecolumn&quot; /&gt;

== See also ==
* [[Brucella suis]]

== References ==
{{Reflist}}

== Further reading ==
* [https://www.who.int/news-room/fact-sheets/detail/brucellosis WHO fact sheet on brucellosis]
* [https://web.archive.org/web/20100714202209/http://patricbrc.org/portal/portal/patric/Taxon?cType=taxon&amp;cId=234    Brucella] genomes and related information at [http://patricbrc.org/    PATRIC], a Bioinformatics Resource Center funded by [https://www.niaid.nih.gov/    NIAID]
* [https://web.archive.org/web/20040212170120/http://www.cdc.gov/ncidod/dbmd/diseaseinfo/brucellosis_g.htm Prevention about Brucellosis] from [[Centers for Disease Control]]
* {{cite journal | vauthors = Capasso L | title = Bacteria in two-millennia-old cheese, and related epizoonoses in Roman populations | journal = The Journal of Infection | volume = 45 | issue = 2 | pages = 122–7 | date = August 2002 | pmid = 12217720 | doi = 10.1053/jinf.2002.0996 }} – re high rate of brucellosis in humans in ancient Pompeii
* [http://ecdc.europa.eu/en/healthtopics/brucellosis/Pages/index.aspx Brucellosis], factsheet from [[European Centre for Disease Prevention and Control]]

{{Medical resources
| ICD11           = {{ICD11|1B95}}
| ICD10           = {{ICD10|A|23||a|20}}
| ICD9            = {{ICD9|023}}
| ICDO            =
| OMIM            =
| MedlinePlus     = 000597
| eMedicineSubj   = med
| eMedicineTopic  = 248
| DiseasesDB      = 1716
| MeshID          = D002006
| Orphanet        = 1304
}}
{{U.S. biological weapons}}
{{Bacterial diseases}}
{{Bacterial cutaneous infections}}
{{Authority control}}

[[Category:Animal bacterial diseases]]
[[Category:Bacterium-related cutaneous conditions]]
[[Category:Biological agents]]
[[Category:Bovine diseases]]
[[Category:Dog diseases]]
[[Category:Occupational diseases]]
[[Category:Sheep and goat diseases]]
[[Category:Zoonoses]]
[[Category:Zoonotic bacterial diseases]]