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{{Brucellosis}}
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==Overview==
'''Editor-In-Chief:''' [[User:C Michael Gibson|C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com <nowiki>[1]</nowiki>]; '''Associate Editor(s)-in-Chief:''' [[User:Raviteja Reddy Guddeti|Raviteja Guddeti, M.B.B.S.]] [mailto:ravitheja.g@gmail.com <nowiki>[2]</nowiki>] [[User:Danitza Lukac|Danitza Lukac]] {{VD}}
'''Brucellosis''' is a [[zoonosis]] (infectious disease transmitted from animals to humans) caused by bacteria of the genus ''[[Brucella]]''. ''[[Brucella]]'' is usually transmitted via the digestive route to the human host. Following transmission, [[white blood cells]] [[phagocyte]] the pathogen and transports it via the [[hematologic]] or [[lymphatic]] route to different organs, specially to those of the [[reticuloendothelial system]].<ref name="pmid9204307">{{cite journal| author=Corbel MJ| title=Brucellosis: an overview. | journal=Emerg Infect Dis | year= 1997 | volume= 3 | issue= 2 | pages= 213-21 | pmid=9204307 | doi=10.3201/eid0302.970219 | pmc=PMC2627605 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9204307  }} </ref><ref name="aa">Brucelosis. Wikipedia. https://es.wikipedia.org/wiki/Brucelosis. Accessed on February 2, 2016</ref> Brucellosis must be differentiated from [[typhoid fever]], [[malaria]], [[tuberculosis]], [[lymphoma]], [[dengue]], [[leptospirosis]] and [[Rheumatic disease|rheumatic diseases]].<ref name="enf">Enfermedades infecciosas: Brucelosis -Diagnóstico de Brucelosis,Guia para el Equipo de Salud. Ministerio de Salud-Argentina. http://www.msal.gob.ar/images/stories/bes/graficos/0000000304cnt-guia-medica-brucelosis.pdf. Accessed on February 2, 2016</ref> Brucellosis is not very common in the United States, but brucellosis can be very common within countries that do not have good standardized and effective public health and domestic animal health programs. Areas currently listed as high risk are the Mediterranean Basin (Portugal, Spain, Southern France, Italy, Greece, Turkey, North Africa), South and Central America, Eastern Europe, Asia, Africa, the Caribbean, and the Middle East.<ref name="c">Brucellosis. CDC. http://www.cdc.gov/brucellosis/exposure/index.html.html. Accessed on February 3, 2016</ref> Common risk factors in the development of brucellosis are: consuming unpasteurized dairy products, unsafe hunting practices and occupational risks such as slaughther house workers, meat-packing employees, veterinarian and laboratory workers.<ref name="c">Brucellosis. CDC. http://www.cdc.gov/brucellosis/exposure/index.html. Accessed on February 1, 2016</ref> If left untreated, patients with brucellosis may progress to develop focal infections, relapses or chronic brucellosis.<ref name="f">Brucellosis. CDC. http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/brucellosis. Accessed on February 3, 2016</ref> Common complications of brucellosis include [[hepatitis|granulomatous hepatitis]], [[arthritis]], [[sacroiliitis]], [[meningitis]], [[orchitis]], [[epididymitis]]  [[uveitis]], and [[endocarditis]]. The prognosis of brucellosis is good with adequate treatment. Relapse may occur, and symptoms may continue for years.<ref name="f">Brucellosis. Medline Plus. https://www.nlm.nih.gov/medlineplus/ency/article/000597.htm. Accessed on February 3, 2016</ref><ref name="abc">FAO/WHO/OIE Brucellosis in humans and animals. WHO (2006). http://www.who.int/csr/resources/publications/Brucellosis.pdf Accessed on February 3, 2016  </ref><ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on February 1, 2016</ref> Symptoms of brucellosis include [[undulant fever]], [[night sweats]] (with characteristic smell, likened to wet hay), and [[joint pain]].<ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on February 4, 2016</ref> Patients with brucellosis are usually well-appearing.<ref name="aa">Madkour M. Madkour's Brucellosis. Springer Science & Business Media; 2012.</ref> Common physical examination findings include hepatomegaly, splenomegaly, and lymphadenopathy.<ref name="pmid15930423">{{cite journal| author=Pappas G, Akritidis N, Bosilkovski M, Tsianos E| title=Brucellosis. | journal=N Engl J Med | year= 2005 | volume= 352 | issue= 22 | pages= 2325-36 | pmid=15930423 | doi=10.1056/NEJMra050570 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15930423  }} </ref> The mainstay of therapy for brucellosis is [[Antimicrobial drug|antimicrobial therapy]].  The preferred regimen for uncomplicated brucellosis is a combination of [[Doxycycline]] and [[Streptomycin]]. [[Rifampin]] is the drug of choice for brucellosis in pregnancy. For children less than 8 years of age, the preferred regimen is either [[Gentamycin]] or a combination of [[ Trimethoprim-sulfamethoxazole]] and [[Streptomycin]].<ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on February 1, 2016</ref><ref name="h">Brucellosis. CDC. http://www.cdc.gov/brucellosis/treatment/index.html. Accessed on February 5, 2016</ref> The optimal way to prevent brucellosis is by not consuming unpasteurized dairy or undercooked meat, and having safe occupational practices. There are no available vaccines for humans against brucellosis.<ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on February 5, 2016</ref><ref name="j">Brucellosis. CDC. http://www.cdc.gov/brucellosis/prevention/index.html. Accessed on February 5, 2016</ref>


==Historial Perspective==
== Overview ==
In 1887, [[David Bruce (microbiologist)|David Bruce]], a Scottish pathologist and microbiologist, was the first to discover the association between [[Brucella|''Brucella'']] and the development of brucellosis.<ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on February 1, 2016</ref>
[[Brucellosis]] is an ancient [[zoonotic]] disease. It is caused by [[bacteria]] of the genus [[Brucella]]. It is usually acquired by consuming [[Unpasteurized milk|unpasteurized]] dairy or undercooked meat products. Patients with brucellosis usually present with [[undulant fever]], [[night sweats]] and [[joint pain]]. Brucellosis can be easily treated with [[antibiotics]]. If left untreated, patients with brucellosis may progress to develop focal organ involvement, [[Relapse|relapses]] or [[chronic]] brucellosis. [[Prognosis]] is good with treatment.


==Pathophysiology==
== Historial Perspective ==
''[[Brucella]]'' is usually transmitted via the digestive route to the human host. Following transmission, [[white blood cells]] [[phagocyte]] the pathogen and transport it via the [[hematologic]] or [[lymphatic]] route to different organs, specially those of the [[reticuloendothelial system]].<ref name="pmid9204307">{{cite journal| author=Corbel MJ| title=Brucellosis: an overview. | journal=Emerg Infect Dis | year= 1997 | volume= 3 | issue= 2 | pages= 213-21 | pmid=9204307 | doi=10.3201/eid0302.970219 | pmc=PMC2627605 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9204307 }} </ref><ref name="aa">Brucelosis. Wikipedia. https://es.wikipedia.org/wiki/Brucelosis. Accessed on February 2, 2016</ref>
According to some studies, there is evidence that [[Brucellosis]] occurred in animals 60 million years ago and 3 million years ago in human beings. In 450 BC, Hippocrates described a disease similar to [[Brucellosis]].<ref name="pmid27031903">{{cite journal| author=Akpinar O| title=Historical perspective of brucellosis: a microbiological and epidemiological overview. | journal=Infez Med | year= 2016 | volume= 24 | issue= 1 | pages= 77-86 | pmid=27031903 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27031903 }}</ref>


==Causes==
== Pathophysiology ==
[[Human]] brucellosis is caused by four [[Brucella|Brucellae]] species: [[Brucella abortus|''B. abortus'']], [[Brucella canis|''B. canis'']], [[Brucella melitensis|''B. melitensis'']], and ''B. suis''.<ref name="aba">Brucella. Wikipedia. https://en.wikipedia.org/wiki/Brucella#Characteristics. Accessed on February 2, 2016</ref>
''[[Brucella|Brucellosis]]'' is a [[zoonotic]] disease. [[Humans]] could be infected by eating undercook meat or raw [[Dairy product|dairy]] products, inhalation of the [[bacteria]] and direct contact of [[bacteria]] with [[skin]] [[wounds]] or [[Mucous membranes|mucous membranes.]] Following transmission, [[white blood cells]] [[phagocyte]] the [[pathogen]] and transports it via hematologic or [[Lymphatic system|lymphatic route]] to different organs, specially to those of the [[reticuloendothelial system]]. Endotoxic [[lipopolysaccharide]] LPS plays an important role in: survival of bacteria inside [[Monocytic|monocytic cel]]<nowiki/>l, supressing [[Lysosome|phagosome-lysosome fusion]] and internalizing bacteria into [[endoplasmic reticulum]].<ref name="pmid15930423">{{cite journal| author=Pappas G, Akritidis N, Bosilkovski M, Tsianos E| title=Brucellosis. | journal=N Engl J Med | year= 2005 | volume= 352 | issue= 22 | pages= 2325-36 | pmid=15930423 | doi=10.1056/NEJMra050570 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15930423  }}</ref><ref name=":0">{{Cite web|url=https://www.cdc.gov/brucellosis/transmission/index.html|title=CDC|date=|access-date=|website=|publisher=|last=|first=}}</ref><ref name="pmid8698508">{{cite journal| author=Zhan Y, Liu Z, Cheers C| title=Tumor necrosis factor alpha and interleukin-12 contribute to resistance to the intracellular bacterium Brucella abortus by different mechanisms. | journal=Infect Immun | year= 1996 | volume= 64 | issue= 7 | pages= 2782-6 | pmid=8698508 | doi= | pmc=174139 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8698508  }}</ref>


==Differentiating Brucellosis from other Diseases==
== Causes ==
Brucellosis must be differentiated from [[typhoid fever]], [[malaria]], [[tuberculosis]], [[lymphoma]], [[dengue]], [[leptospirosis]] and [[Rheumatic disease|rheumatic diseases]].<ref name="enf">Enfermedades infecciosas: Brucelosis -Diagnóstico de Brucelosis,Guia para el Equipo de Salud. Ministerio de Salud-Argentina. http://www.msal.gob.ar/images/stories/bes/graficos/0000000304cnt-guia-medica-brucelosis.pdf. Accessed on February 2, 2016</ref>
[[Human]] brucellosis is caused by four [[Brucella|Brucellae]] species: [[Brucella abortus|''B. abortus'']], [[Brucella canis|''B. canis'']], [[Brucella melitensis|''B. melitensis'']], and ''B. suis''.<ref>{{Cite web|url=http://www.who.int/csr/resources/publications/Brucellosis.pdf|title=WHO|last=|first=|date=|website=|publisher=|access-date=}}</ref>.


==Epidemiology and Demographics==
== Differentiating Brucellosis from other Diseases ==
Brucellosis is not very common in the United States, but brucellosis can be very common within countries that do not have good standardized and effective public health and domestic animal health programs. Areas currently listed as high risk are the Mediterranean Basin (Portugal, Spain, Southern France, Italy, Greece, Turkey, North Africa), South and Central America, Eastern Europe, Asia, Africa, the Caribbean, and the Middle East.<ref name="c">Brucellosis. CDC. http://www.cdc.gov/brucellosis/exposure/index.html.html. Accessed on February 3, 2016</ref>
[[Brucellosis]] must be differentiated from [[Typhoid fever]], [[Malaria]], [[Tuberculosis]], [[Lymphoma]], [[Dengue fever|Dengue]], [[Leptospirosis]], [[Rheumatology|Rheumatic disease]], [[Epstein-barr virus]], [[Toxoplasmosis]], [[Cytomegalovirus]], and [[Human Immunodeficiency Virus|HIV]].  


==Risk Factors==
== Epidemiology and Demographics ==
Common risk factors in the development of brucellosis are consuming unpasteurized dairy products, unsafe hunting practices and occupational risks such as slaughther house workers, meat-packing employees, veterinarian, and laboratory workers.<ref name="c">Brucellosis. CDC. http://www.cdc.gov/brucellosis/exposure/index.html. Accessed on February 1, 2016</ref>
Worldwide, the [[incidence]] of [[Brucellosis]] ranges from a low of 0.01 per 100,000 to high of 200 per 100,000 individuals. [[Case fatality rate]] is less than 2% when untreated. [[Brucellosis]] most commonly affects [[men]] in [[age]] group between 20 to 45 years old. Areas currently listed as high risk are the Mediterranean Basin (Portugal, Spain, Southern France, Italy, Greece, Turkey, North Africa), South and Central America, Eastern Europe, Asia, Africa, the Caribbean and the Middle East


==Screening==
== Risk Factors ==
There are no guidelines for brucellosis screening. Some [[Endemic (epidemiology)|endemic]] areas screen family members of patients with brucellosis. <ref name="pmid25934639">{{cite journal| author=Sanodze L, Bautista CT, Garuchava N, Chubinidze S, Tsertsvadze E, Broladze M et al.| title=Expansion of brucellosis detection in the country of Georgia by screening household members of cases and neighboring community members. | journal=BMC Public Health | year= 2015 | volume= 15 | issue=  | pages= 459 | pmid=25934639 | doi=10.1186/s12889-015-1761-y | pmc=PMC4432945 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25934639  }} </ref> <ref name="pmid19011744">{{cite journal| author=Tabak F, Hakko E, Mete B, Ozaras R, Mert A, Ozturk R| title=Is family screening necessary in brucellosis? | journal=Infection | year= 2008 | volume= 36 | issue= 6 | pages= 575-7 | pmid=19011744 | doi=10.1007/s15010-008-7022-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19011744  }} </ref>
Common [[Risk factor|risk factors]] in the development of brucellosis are: consuming [[Unpasteurized milk|unpasteurized]] dairy products or raw meat products, unsafe hunting practices and occupational risks.<ref>{{Cite web|url=https://www.cdc.gov/brucellosis/exposure/|title=CDC|last=|first=|date=|website=|publisher=|access-date=}}</ref>


==Natural history, Complications and Prognosis ==
== Screening ==
If left untreated, patients with brucellosis may progress to develop focal infections, relapses or chronic brucellosis.<ref name="f">Brucellosis. CDC. http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/brucellosis. Accessed on February 3, 2016</ref> Common [[Complication (medicine)|complications]] of brucellosis include [[hepatitis|granulomatous hepatitis]], [[arthritis]], [[sacroiliitis]], [[meningitis]], [[orchitis]], [[epididymitis]]  [[uveitis]], and [[endocarditis]]. The [[prognosis]] of brucellosis is good with adequate treatment. Relapse may occur, and symptoms may continue for years.<ref name="f">Brucellosis. Medline Plus. https://www.nlm.nih.gov/medlineplus/ency/article/000597.htm. Accessed on February 3, 2016</ref><ref name="abc">FAO/WHO/OIE Brucellosis in humans and animals. WHO (2006). http://www.who.int/csr/resources/publications/Brucellosis.pdf Accessed on February 3, 2016  </ref><ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on February 1, 2016</ref>
There are no guidelines for [[screening]] [[Brucellosis]].<ref name="pmid25934639">{{cite journal| author=Sanodze L, Bautista CT, Garuchava N, Chubinidze S, Tsertsvadze E, Broladze M et al.| title=Expansion of brucellosis detection in the country of Georgia by screening household members of cases and neighboring community members. | journal=BMC Public Health | year= 2015 | volume= 15 | issue=  | pages= 459 | pmid=25934639 | doi=10.1186/s12889-015-1761-y | pmc=PMC4432945 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25934639  }}</ref><ref name="pmid19011744">{{cite journal| author=Tabak F, Hakko E, Mete B, Ozaras R, Mert A, Ozturk R| title=Is family screening necessary in brucellosis? | journal=Infection | year= 2008 | volume= 36 | issue= 6 | pages= 575-7 | pmid=19011744 | doi=10.1007/s15010-008-7022-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19011744  }}</ref>


==Diagnosis ==
== Natural history, Complications and Prognosis ==
===Criteria===
If left untreated, patients with brucellosis may progress to develop focal organal involvement, [[Relapse|relapses]] or chronic brucellosis. Common complications of brucellosis include: [[Hepatitis|granulomatous hepatitis]], [[arthritis]], [[sacroiliitis]], [[meningitis]], [[orchitis]], [[epididymitis]] [[uveitis]], and [[endocarditis]]. The [[prognosis]] of brucellosis is good with adequate treatment.<ref name="pmid8699960">{{cite journal| author=Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M et al.| title=Complications associated with Brucella melitensis infection: a study of 530 cases. | journal=Medicine (Baltimore) | year= 1996 | volume= 75 | issue= 4 | pages= 195-211 | pmid=8699960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8699960  }}</ref><ref name="pmid17901634">{{cite journal| author=Mantur BG, Amarnath SK, Shinde RS| title=Review of clinical and laboratory features of human brucellosis. | journal=Indian J Med Microbiol | year= 2007 | volume= 25 | issue= 3 | pages= 188-202 | pmid=17901634 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901634  }}</ref><ref name="pmid159304">{{cite journal| author=Overturf ML, Druihet RE, Fitz A| title=The effects of kallikrein, plasmin, and thrombin on hog kidney renin. | journal=J Biol Chem | year= 1979 | volume= 254 | issue= 23 | pages= 12078-83 | pmid=159304 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=159304  }}</ref><ref>Doganay M, Aygen B. Human brucellosis: An overview. Int J Infect Dis 2003; 7:173.</ref>
The diagnosis of brucellosis is based on clinical and laboratory criteria.<ref name="e">Brucellosis 2010 Case Definition. CDC. http://wwwn.cdc.gov/nndss/conditions/brucellosis/case-definition/2010/. Accessed on February 2, 2016</ref>  


===History and Symptoms===
== Diagnosis ==
Symptoms of brucellosis include [[undulant fever]], [[night sweats]] (with characteristic smell, likened to wet hay), and [[joint pain]].<ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on February 4, 2016</ref>


===Physical Examination===
=== Principles of Diagnosis  ===
Patients with brucellosis are usually well-appearing.<ref name="aa">Madkour M. Madkour's Brucellosis. Springer Science & Business Media; 2012.</ref> Common physical examination findings include hepatomegaly, splenomegaly, and lymphadenopathy.<ref name="pmid15930423">{{cite journal| author=Pappas G, Akritidis N, Bosilkovski M, Tsianos E| title=Brucellosis. | journal=N Engl J Med | year= 2005 | volume= 352 | issue= 22 | pages= 2325-36 | pmid=15930423 | doi=10.1056/NEJMra050570 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15930423  }} </ref>
[[Diagnosis]] is based on history of potential exposure, presentation consistent with the disease, and supporting [[laboratory]] findings.<ref name=":02">Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016</ref><ref name="pmid86999602">{{cite journal| author=Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M et al.| title=Complications associated with Brucella melitensis infection: a study of 530 cases. | journal=Medicine (Baltimore) | year= 1996 | volume= 75 | issue= 4 | pages= 195-211 | pmid=8699960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8699960  }}</ref><ref name="pmid179016342">{{cite journal| author=Mantur BG, Amarnath SK, Shinde RS| title=Review of clinical and laboratory features of human brucellosis. | journal=Indian J Med Microbiol | year= 2007 | volume= 25 | issue= 3 | pages= 188-202 | pmid=17901634 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901634  }}</ref>
=== History and Symptoms ===
[[Brucellosis]] can present with diverse clinical presentation which include systemic [[flu]]-like symptoms and symptoms due to focal involvement of [[organs]].<ref name=":03">Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016</ref><ref name="pmid86999603">{{cite journal| author=Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M et al.| title=Complications associated with Brucella melitensis infection: a study of 530 cases. | journal=Medicine (Baltimore) | year= 1996 | volume= 75 | issue= 4 | pages= 195-211 | pmid=8699960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8699960  }}</ref><ref name="pmid179016343">{{cite journal| author=Mantur BG, Amarnath SK, Shinde RS| title=Review of clinical and laboratory features of human brucellosis. | journal=Indian J Med Microbiol | year= 2007 | volume= 25 | issue= 3 | pages= 188-202 | pmid=17901634 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901634  }}</ref><ref name="pmid159304233">{{cite journal| author=Pappas G, Akritidis N, Bosilkovski M, Tsianos E| title=Brucellosis. | journal=N Engl J Med | year= 2005 | volume= 352 | issue= 22 | pages= 2325-36 | pmid=15930423 | doi=10.1056/NEJMra050570 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15930423  }}</ref>
=== Physical Examination ===
Patients with brucellosis are usually well-appearing. Common physical examination observed include [[hepatomegaly]], [[splenomegaly]] and [[lymphadenopathy]].<ref name=":04">Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016</ref><ref name="pmid86999604">{{cite journal| author=Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M et al.| title=Complications associated with Brucella melitensis infection: a study of 530 cases. | journal=Medicine (Baltimore) | year= 1996 | volume= 75 | issue= 4 | pages= 195-211 | pmid=8699960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8699960  }}</ref><ref name="pmid179016344">{{cite journal| author=Mantur BG, Amarnath SK, Shinde RS| title=Review of clinical and laboratory features of human brucellosis. | journal=Indian J Med Microbiol | year= 2007 | volume= 25 | issue= 3 | pages= 188-202 | pmid=17901634 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901634  }}</ref><ref name="pmid159304234">{{cite journal| author=Pappas G, Akritidis N, Bosilkovski M, Tsianos E| title=Brucellosis. | journal=N Engl J Med | year= 2005 | volume= 352 | issue= 22 | pages= 2325-36 | pmid=15930423 | doi=10.1056/NEJMra050570 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15930423  }}</ref>
=== Laboratory Findings ===
The [[diagnosis]] of brucellosis can be confirmed by either a positive [[bacteria]]<nowiki/>l [[Culture medium|culture]] or a positive [[titre]] of anti-[[brucella]] [[antibodies]] on [[serological]] testings.<ref name=":05">Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016</ref><ref name="pmid86999605">{{cite journal| author=Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M et al.| title=Complications associated with Brucella melitensis infection: a study of 530 cases. | journal=Medicine (Baltimore) | year= 1996 | volume= 75 | issue= 4 | pages= 195-211 | pmid=8699960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8699960  }}</ref><ref name="pmid179016345">{{cite journal| author=Mantur BG, Amarnath SK, Shinde RS| title=Review of clinical and laboratory features of human brucellosis. | journal=Indian J Med Microbiol | year= 2007 | volume= 25 | issue= 3 | pages= 188-202 | pmid=17901634 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901634  }}</ref>
=== Other Diagnostic Studies ===
There is no specific [[X-rays|X-ray]], [[CT]] or [[MRI]] finding associated with [[Brucellosis]].<ref name=":06">Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016</ref><ref name="pmid86999606">{{cite journal| author=Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M et al.| title=Complications associated with Brucella melitensis infection: a study of 530 cases. | journal=Medicine (Baltimore) | year= 1996 | volume= 75 | issue= 4 | pages= 195-211 | pmid=8699960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8699960  }}</ref><ref name="pmid179016346">{{cite journal| author=Mantur BG, Amarnath SK, Shinde RS| title=Review of clinical and laboratory features of human brucellosis. | journal=Indian J Med Microbiol | year= 2007 | volume= 25 | issue= 3 | pages= 188-202 | pmid=17901634 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901634  }}</ref>
== Treatment ==


===Laboratory Findings===
=== Medical Therapy ===
A positive culture or presence of [[Brucella|''Brucella'']] antibody in [[Serological testing|serological tests]] are diagnostic of brucellosis.<ref name="e">Brucellosis 2010 Case Definition. CDC. http://wwwn.cdc.gov/nndss/conditions/brucellosis/case-definition/2010/. Accessed on February 2, 2016</ref>  
The mainstay of [[therapy]] for brucellosis is [[antimicrobial]] therapy. The preferred regimen for uncomplicated brucellosis is a combination of [[Doxycycline]] and [[Streptomycin]].  [[Rifampin|Rifampicin]] is the [[drug]] of choice for brucellosis in [[pregnancy]]. For children less than 8 years of age, the preferred regimen is either [[Gentamycin]] or a combination of [[ Trimethoprim-sulfamethoxazole]] and [[Streptomycin]].<ref name="h">Brucellosis. CDC. http://www.cdc.gov/brucellosis/treatment/index.html. Accessed on February 5, 2016</ref>  


===Other Diagnostic Studies===
=== Prevention ===
Spine x-ray, CT o MRI may be helpful in the diagnosis of focal brucellosis infection. Findings of Pedro Pons sign can be suggestive of brucellosis.<ref name="pmid16985128">{{cite journal| author=Pourbagher A, Pourbagher MA, Savas L, Turunc T, Demiroglu YZ, Erol I et al.| title=Epidemiologic, clinical, and imaging findings in brucellosis patients with osteoarticular involvement. | journal=AJR Am J Roentgenol | year= 2006 | volume= 187 | issue= 4 | pages= 873-80 | pmid=16985128 | doi=10.2214/AJR.05.1088 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16985128  }} </ref>


==Treatment==
[[Brucellosis]] can be prevented by not consuming [[Unpasteurized milk|unpasteurized]] dairy products or undercooked meat and having safe occupational practices.<ref name="h" />  
===Medical Therapy===
The mainstay of therapy for brucellosis is [[Antimicrobial drug|antimicrobial therapy]].  The preferred regimen for uncomplicated brucellosis is a combination of [[Doxycycline]] and [[Streptomycin]]. [[Rifampin]] is the drug of choice for brucellosis in pregnancy. For children less than 8 years of age, the preferred regimen is either [[Gentamycin]] or a combination of [[ Trimethoprim-sulfamethoxazole]] and [[Streptomycin]].<ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on February 1, 2016</ref><ref name="h">Brucellosis. CDC. http://www.cdc.gov/brucellosis/treatment/index.html. Accessed on February 5, 2016</ref>


===Prevention===
Effective measures for the [[primary prevention]] of brucellosis include not consuming unpasteurized dairy or undercooked meat, and having safe occupational practices. There are no available vaccines for humans against brucellosis.<ref name="j">Brucellosis. CDC. http://www.cdc.gov/brucellosis/prevention/index.html. Accessed on February 5, 2016</ref><ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on February 5, 2016</ref>


==References==
{{Reflist|2}}


[[Category:Bacterial diseases]]
== References ==
[[Category:Occupational diseases]]
# ↑ <sup>Jump up to:3.0</sup> <sup>3.1</sup> Enfermedades infecciosas: Brucelosis -Diagnóstico de Brucelosis,Guia para el Equipo de Salud. Ministerio de Salud-Argentina. http://www.msal.gob.ar/images/stories/bes/graficos/0000000304cnt-guia-medica-brucelosis.pdf. Accessed on February 2, 2016
[[Category:Zoonoses]]
# ↑ <sup>Jump up to:4.0</sup> <sup>4.1</sup> <sup>4.2</sup> <sup>4.3</sup> Brucellosis. CDC. http://www.cdc.gov/brucellosis/exposure/index.html.html. Accessed on February 3, 2016 Cite error: Invalid <code><nowiki><ref></nowiki></code> tag; name "c" defined multiple times with different content Cite error: Invalid <code><nowiki><ref></nowiki></code>tag; name "c" defined multiple times with different contentCite error: Invalid <code><nowiki><ref></nowiki></code> tag; name "c" defined multiple times with different content
# ↑ <sup>Jump up to:5.0</sup> <sup>5.1</sup> <sup>5.2</sup> <sup>5.3</sup> Brucellosis. CDC. http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/brucellosis. Accessed on February 3, 2016 Cite error: Invalid<code><nowiki><ref></nowiki></code> tag; name "f" defined multiple times with different content Cite error: Invalid <code><nowiki><ref></nowiki></code> tag; name "f" defined multiple times with different content Cite error: Invalid <code><nowiki><ref></nowiki></code>tag; name "f" defined multiple times with different content
# ↑ <sup>Jump up to:6.0</sup> <sup>6.1</sup> FAO/WHO/OIE Brucellosis in humans and animals. WHO (2006). http://www.who.int/csr/resources/publications/Brucellosis.pdf Accessed on February 3, 2016
# ↑ <sup>Jump up to:9.0</sup> <sup>9.1</sup> Brucellosis. CDC. http://www.cdc.gov/brucellosis/treatment/index.html. Accessed on February 5, 2016
# ↑ <sup>Jump up to:10.0</sup> <sup>10.1</sup> Brucellosis. CDC. http://www.cdc.gov/brucellosis/prevention/index.html. Accessed on February 5, 2016
# ↑ <sup>Jump up to:14.0</sup> <sup>14.1</sup> Brucellosis 2010 Case Definition. CDC. http://wwwn.cdc.gov/nndss/conditions/brucellosis/case-definition/2010/. Accessed on February 2, 2016
# Jump up↑ Pourbagher A, Pourbagher MA, Savas L, Turunc T, Demiroglu YZ, Erol I; et al. (2006). [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16985128 "Epidemiologic, clinical, and imaging findings in brucellosis patients with osteoarticular involvement."]. ''AJR Am J Roentgenol''. '''187''' (4): 873–80. PMID [http://www.ncbi.nlm.nih.gov/pubmed/16985128 16985128]. [[Digital object identifier|doi]]:[http://dx.doi.org/10.2214%2FAJR.05.1088 10.2214/AJR.05.1088].
 
[[Category:Disease]]
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[[Category:Pulmonology]]
[[Category:Hepatology]]
[[Category:Rheumatology]]
[[Category:Nephrology]]
[[Category:Emergency medicine]]
[[Category:Infectious disease]]
[[Category:Infectious disease]]
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Latest revision as of 20:44, 29 July 2020

Brucellosis Microchapters

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Overview

Historical Perspective

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Epidemiology and Demographics

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Danitza Lukac Vishal Devarkonda, M.B.B.S[1]

Overview

Brucellosis is an ancient zoonotic disease. It is caused by bacteria of the genus Brucella. It is usually acquired by consuming unpasteurized dairy or undercooked meat products. Patients with brucellosis usually present with undulant fever, night sweats and joint pain. Brucellosis can be easily treated with antibiotics. If left untreated, patients with brucellosis may progress to develop focal organ involvement, relapses or chronic brucellosis. Prognosis is good with treatment.

Historial Perspective

According to some studies, there is evidence that Brucellosis occurred in animals 60 million years ago and 3 million years ago in human beings. In 450 BC, Hippocrates described a disease similar to Brucellosis.[1]

Pathophysiology

Brucellosis is a zoonotic disease. Humans could be infected by eating undercook meat or raw dairy products, inhalation of the bacteria and direct contact of bacteria with skin wounds or mucous membranes. Following transmission, white blood cells phagocyte the pathogen and transports it via hematologic or lymphatic route to different organs, specially to those of the reticuloendothelial system. Endotoxic lipopolysaccharide LPS plays an important role in: survival of bacteria inside monocytic cell, supressing phagosome-lysosome fusion and internalizing bacteria into endoplasmic reticulum.[2][3][4]

Causes

Human brucellosis is caused by four Brucellae species: B. abortus, B. canis, B. melitensis, and B. suis.[5].

Differentiating Brucellosis from other Diseases

Brucellosis must be differentiated from Typhoid fever, Malaria, Tuberculosis, Lymphoma, Dengue, Leptospirosis, Rheumatic disease, Epstein-barr virus, Toxoplasmosis, Cytomegalovirus, and HIV.

Epidemiology and Demographics

Worldwide, the incidence of Brucellosis ranges from a low of 0.01 per 100,000 to high of 200 per 100,000 individuals. Case fatality rate is less than 2% when untreated. Brucellosis most commonly affects men in age group between 20 to 45 years old. Areas currently listed as high risk are the Mediterranean Basin (Portugal, Spain, Southern France, Italy, Greece, Turkey, North Africa), South and Central America, Eastern Europe, Asia, Africa, the Caribbean and the Middle East

Risk Factors

Common risk factors in the development of brucellosis are: consuming unpasteurized dairy products or raw meat products, unsafe hunting practices and occupational risks.[6]

Screening

There are no guidelines for screening Brucellosis.[7][8]

Natural history, Complications and Prognosis

If left untreated, patients with brucellosis may progress to develop focal organal involvement, relapses or chronic brucellosis. Common complications of brucellosis include: granulomatous hepatitis, arthritis, sacroiliitis, meningitis, orchitis, epididymitis uveitis, and endocarditis. The prognosis of brucellosis is good with adequate treatment.[9][10][11][12]

Diagnosis

Principles of Diagnosis

Diagnosis is based on history of potential exposure, presentation consistent with the disease, and supporting laboratory findings.[13][14][15]

History and Symptoms

Brucellosis can present with diverse clinical presentation which include systemic flu-like symptoms and symptoms due to focal involvement of organs.[16][17][18][19]

Physical Examination

Patients with brucellosis are usually well-appearing. Common physical examination observed include hepatomegaly, splenomegaly and lymphadenopathy.[20][21][22][23]

Laboratory Findings

The diagnosis of brucellosis can be confirmed by either a positive bacterial culture or a positive titre of anti-brucella antibodies on serological testings.[24][25][26]

Other Diagnostic Studies

There is no specific X-ray, CT or MRI finding associated with Brucellosis.[27][28][29]

Treatment

Medical Therapy

The mainstay of therapy for brucellosis is antimicrobial therapy. The preferred regimen for uncomplicated brucellosis is a combination of Doxycycline and Streptomycin. Rifampicin is the drug of choice for brucellosis in pregnancy. For children less than 8 years of age, the preferred regimen is either Gentamycin or a combination of Trimethoprim-sulfamethoxazole and Streptomycin.[30]

Prevention

Brucellosis can be prevented by not consuming unpasteurized dairy products or undercooked meat and having safe occupational practices.[30]


References

  1. ↑ Jump up to:3.0 3.1 Enfermedades infecciosas: Brucelosis -Diagnóstico de Brucelosis,Guia para el Equipo de Salud. Ministerio de Salud-Argentina. http://www.msal.gob.ar/images/stories/bes/graficos/0000000304cnt-guia-medica-brucelosis.pdf. Accessed on February 2, 2016
  2. ↑ Jump up to:4.0 4.1 4.2 4.3 Brucellosis. CDC. http://www.cdc.gov/brucellosis/exposure/index.html.html. Accessed on February 3, 2016 Cite error: Invalid <ref> tag; name "c" defined multiple times with different content Cite error: Invalid <ref>tag; name "c" defined multiple times with different contentCite error: Invalid <ref> tag; name "c" defined multiple times with different content
  3. ↑ Jump up to:5.0 5.1 5.2 5.3 Brucellosis. CDC. http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/brucellosis. Accessed on February 3, 2016 Cite error: Invalid<ref> tag; name "f" defined multiple times with different content Cite error: Invalid <ref> tag; name "f" defined multiple times with different content Cite error: Invalid <ref>tag; name "f" defined multiple times with different content
  4. ↑ Jump up to:6.0 6.1 FAO/WHO/OIE Brucellosis in humans and animals. WHO (2006). http://www.who.int/csr/resources/publications/Brucellosis.pdf Accessed on February 3, 2016
  5. ↑ Jump up to:9.0 9.1 Brucellosis. CDC. http://www.cdc.gov/brucellosis/treatment/index.html. Accessed on February 5, 2016
  6. ↑ Jump up to:10.0 10.1 Brucellosis. CDC. http://www.cdc.gov/brucellosis/prevention/index.html. Accessed on February 5, 2016
  7. ↑ Jump up to:14.0 14.1 Brucellosis 2010 Case Definition. CDC. http://wwwn.cdc.gov/nndss/conditions/brucellosis/case-definition/2010/. Accessed on February 2, 2016
  8. Jump up↑ Pourbagher A, Pourbagher MA, Savas L, Turunc T, Demiroglu YZ, Erol I; et al. (2006). "Epidemiologic, clinical, and imaging findings in brucellosis patients with osteoarticular involvement.". AJR Am J Roentgenol. 187 (4): 873–80. PMID 16985128. doi:10.2214/AJR.05.1088.
  1. ↑ Akpinar O (2016). "Historical perspective of brucellosis: a microbiological and epidemiological overview". Infez Med. 24 (1): 77–86. PMID 27031903.
  2. ↑ Pappas G, Akritidis N, Bosilkovski M, Tsianos E (2005). "Brucellosis". N Engl J Med. 352 (22): 2325–36. doi:10.1056/NEJMra050570. PMID 15930423.
  3. ↑ "CDC".
  4. ↑ Zhan Y, Liu Z, Cheers C (1996). "Tumor necrosis factor alpha and interleukin-12 contribute to resistance to the intracellular bacterium Brucella abortus by different mechanisms". Infect Immun. 64 (7): 2782–6. PMC 174139. PMID 8698508.
  5. ↑ "WHO" (PDF).
  6. ↑ "CDC".
  7. ↑ Sanodze L, Bautista CT, Garuchava N, Chubinidze S, Tsertsvadze E, Broladze M; et al. (2015). "Expansion of brucellosis detection in the country of Georgia by screening household members of cases and neighboring community members". BMC Public Health. 15: 459. doi:10.1186/s12889-015-1761-y. PMC 4432945. PMID 25934639.
  8. ↑ Tabak F, Hakko E, Mete B, Ozaras R, Mert A, Ozturk R (2008). "Is family screening necessary in brucellosis?". Infection. 36 (6): 575–7. doi:10.1007/s15010-008-7022-6. PMID 19011744.
  9. ↑ Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M; et al. (1996). "Complications associated with Brucella melitensis infection: a study of 530 cases". Medicine (Baltimore). 75 (4): 195–211. PMID 8699960.
  10. ↑ Mantur BG, Amarnath SK, Shinde RS (2007). "Review of clinical and laboratory features of human brucellosis". Indian J Med Microbiol. 25 (3): 188–202. PMID 17901634.
  11. ↑ Overturf ML, Druihet RE, Fitz A (1979). "The effects of kallikrein, plasmin, and thrombin on hog kidney renin". J Biol Chem. 254 (23): 12078–83. PMID 159304.
  12. ↑ Doganay M, Aygen B. Human brucellosis: An overview. Int J Infect Dis 2003; 7:173.
  13. ↑ Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016
  14. ↑ Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M; et al. (1996). "Complications associated with Brucella melitensis infection: a study of 530 cases". Medicine (Baltimore). 75 (4): 195–211. PMID 8699960.
  15. ↑ Mantur BG, Amarnath SK, Shinde RS (2007). "Review of clinical and laboratory features of human brucellosis". Indian J Med Microbiol. 25 (3): 188–202. PMID 17901634.
  16. ↑ Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016
  17. ↑ Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M; et al. (1996). "Complications associated with Brucella melitensis infection: a study of 530 cases". Medicine (Baltimore). 75 (4): 195–211. PMID 8699960.
  18. ↑ Mantur BG, Amarnath SK, Shinde RS (2007). "Review of clinical and laboratory features of human brucellosis". Indian J Med Microbiol. 25 (3): 188–202. PMID 17901634.
  19. ↑ Pappas G, Akritidis N, Bosilkovski M, Tsianos E (2005). "Brucellosis". N Engl J Med. 352 (22): 2325–36. doi:10.1056/NEJMra050570. PMID 15930423.
  20. ↑ Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016
  21. ↑ Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M; et al. (1996). "Complications associated with Brucella melitensis infection: a study of 530 cases". Medicine (Baltimore). 75 (4): 195–211. PMID 8699960.
  22. ↑ Mantur BG, Amarnath SK, Shinde RS (2007). "Review of clinical and laboratory features of human brucellosis". Indian J Med Microbiol. 25 (3): 188–202. PMID 17901634.
  23. ↑ Pappas G, Akritidis N, Bosilkovski M, Tsianos E (2005). "Brucellosis". N Engl J Med. 352 (22): 2325–36. doi:10.1056/NEJMra050570. PMID 15930423.
  24. ↑ Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016
  25. ↑ Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M; et al. (1996). "Complications associated with Brucella melitensis infection: a study of 530 cases". Medicine (Baltimore). 75 (4): 195–211. PMID 8699960.
  26. ↑ Mantur BG, Amarnath SK, Shinde RS (2007). "Review of clinical and laboratory features of human brucellosis". Indian J Med Microbiol. 25 (3): 188–202. PMID 17901634.
  27. ↑ Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9, 2016
  28. ↑ Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M; et al. (1996). "Complications associated with Brucella melitensis infection: a study of 530 cases". Medicine (Baltimore). 75 (4): 195–211. PMID 8699960.
  29. ↑ Mantur BG, Amarnath SK, Shinde RS (2007). "Review of clinical and laboratory features of human brucellosis". Indian J Med Microbiol. 25 (3): 188–202. PMID 17901634.
  30. ↑ 30.0 30.1 Brucellosis. CDC. http://www.cdc.gov/brucellosis/treatment/index.html. Accessed on February 5, 2016
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