Brucella

{{Short description|Genus of bacteria}} {{Automatic taxobox | image = Brucella melitensis.jpg | taxon = Brucella | authority = Meyer and Shaw 1920 (Approved Lists 1980) | subdivision_ranks = Species | subdivision_ref = <ref name=Brucella>{{cite web|vauthors=Euzéby JP, Parte AC |url=https://lpsn.dsmz.de/genus/brucella |title=''Brucella'' |access-date=May 15, 2021 |website=List of Prokaryotic names with Standing in Nomenclature (LPSN)}}</ref> | subdivision = * ''Brucella anthropi'' (Holmes ''et al''. 1988) Hördt ''et al''. 2020 * "''Brucella cetaceae''" Cloeckaert ''et al''. 2001 * ''Brucella ceti'' Foster ''et al''. 2007 * ''Brucella ciceri'' (Imran ''et al''. 2010) Hördt ''et al''. 2020 * ''Brucella cytisi'' (Zurdo-Piñeiro ''et al''. 2007) Hördt ''et al''. 2020 * ''Brucella daejeonensis'' (Woo ''et al''. 2011) Hördt ''et al''. 2020 * ''Brucella endophytica'' (Li ''et al''. 2016) Hördt ''et al''. 2020 * ''Brucella gallinifaecis'' (Kämpfer ''et al''. 2003) Hördt ''et al''. 2020 * ''Brucella grignonensis'' (Lebuhn ''et al''. 2000) Hördt ''et al''. 2020 * ''Brucella haematophila'' (Kämpfer ''et al''. 2007) Hördt ''et al''. 2020 * ''Brucella inopinata'' Scholz ''et al''. 2010 * ''Brucella intermedia'' (Velasco ''et al''. 1998) Hördt ''et al''. 2020 * ''Brucella lupini'' (Trujillo ''et al''. 2006) Hördt ''et al''. 2020 * "''Brucella maris''" Jahans ''et al''. 1997 * ''Brucella melitensis'' (Hughes 1893) Meyer and Shaw 1920 (Approved Lists 1980){{#tag:ref | ''Brucella abortus'', ''Brucella canis'', ''Brucella neotomae'', ''Brucella ovis'', and ''Brucella suis'' are all synonyms of ''Brucella melitensis''. | group = Note | name = melitensis}} ** ''Brucella abortus'' (Schmidt 1901) Meyer and Shaw 1920 (Approved Lists 1980) ** ''Brucella canis'' Carmichael and Bruner 1968 (Approved Lists 1980) ** ''Brucella neotomae'' Stoenner and Lackman 1957 (Approved Lists 1980) ** ''Brucella ovis'' Buddle 1956 (Approved Lists 1980) ** ''Brucella suis'' Huddleson 1929 (Approved Lists 1980) * ''Brucella microti'' Scholz ''et al''. 2008 * ''Brucella oryzae'' (Tripathi ''et al''. 2006) Hördt ''et al''. 2020 * ''Brucella papionis'' Whatmore ''et al''. 2014 * ''Brucella pecoris'' (Kämpfer ''et al''. 2011) Hördt ''et al''. 2020  * ''Brucella pinnipedialis'' Foster ''et al''. 2007 * ''Brucella pituitosa'' (Huber ''et al'' 2010) Hördt ''et al''. 2020 * ''Brucella pseudintermedia'' (Teyssier ''et al''. 2007) Hördt ''et al''. 2020 * ''Brucella pseudogrignonensis'' (Kämpfer ''et al''. 2007) Hördt ''et al''. 2020 * ''Brucella rhizosphaerae'' (Kämpfer ''et al''. 2008) Hördt ''et al''. 2020 * ''Brucella thiophenivorans'' (Kämpfer ''et al''. 2008) Hördt ''et al''. 2020 * ''Brucella tritici'' (Lebuhn ''et al''. 2000) Hördt ''et al''. 2020 * ''Brucella vulpis'' Scholz ''et al''. 2016 | synonyms = * ''Ochrobactrum'' Holmes ''et al''. 1988 }}

'''''Brucella''''' is a genus of Gram-negative bacteria,<ref name=Sherris>{{cite book | veditors = Ryan KJ, Ray CG | title = Sherris Medical Microbiology | edition = 4th | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0 }}</ref><ref name= Lopez-GoniICallaghanDO>{{cite book | vauthors = Lopez-Goni I | veditors = O'Callaghan D | year=2012 | title=''Brucella'': Molecular Microbiology and Genomics | publisher=Caister Academic Press | isbn= 978-1-904455-93-6}}</ref> named after David Bruce (1855–1931). They are small (0.5 to 0.7 by 0.6 to 1.5 μm), non-encapsulated, non-motile,<ref name=Ferooz_2010>{{cite journal | vauthors = Ferooz J, Letesson JJ | title = Morphological analysis of the sheathed flagellum of Brucella melitensis | journal = BMC Research Notes | volume = 3 | page = 333 | date = December 2010 | pmid = 21143933 | pmc = 3017070 | doi = 10.1186/1756-0500-3-333 | doi-access = free }}</ref> facultatively intracellular coccobacilli.

''Brucella'' spp. are the cause of brucellosis, which is a zoonosis transmitted by ingesting contaminated food (such as unpasteurized milk products), direct contact with an infected animal, or inhalation of aerosols. Transmission from human to human, for example, through sexual intercourse, or from mother to child, is exceedingly rare, but possible.<ref>{{cite web |url=http://www.dhsspsni.gov.uk/brucellosis-pathway.pdf |title=Diagnosis Management of Acute Brucellosis in Primary Care |date=August 2004 |website=Department of Health for Northern Ireland |publisher=Brucella Subgroup of the Northern Ireland Regional Zoonoses Group |archive-url=https://web.archive.org/web/20071013043717/http://www.dhsspsni.gov.uk/brucellosis-pathway.pdf |archive-date=2007-10-13 }}</ref> Minimum infectious exposure is between 10 and 100 organisms.

The different species of ''Brucella'' are genetically very similar, although each has a slightly different host specificity. Hence, the National Center for Biotechnology Information taxonomy includes most ''Brucella'' species under ''B. melitensis''.

The many names of brucellosis include (human disease/animal disease): * Malta fever/Bang's disease * Undulant fever/enzootic abortion * Mediterranean fever/epizootic abortion * Rock fever of Gibraltar/slinking of calves * Gastric fever/ram epididymitis * Contagious abortion/spontaneous abortion<ref>{{cite journal | vauthors = Mariana NX, Tatiane AP, Andréas BH, Renée MT, Renato LS | title=Pathogenesis of ''Brucella'' spp. | year=2010 | journal=The Open Veterinary Science Journal | volume=4 | pages=109–118 |doi=10.2174/1874318801004010109 | doi-access=free }}</ref>

== Human brucellosis == Sir David Bruce isolated ''B. melitensis'' from British soldiers who died from Malta fever in Malta. After exposure to ''Brucella'', humans generally have a two- to four-week latency period before exhibiting symptoms, which include acute undulating fever (>90% of all cases), headache, arthralgia (>50%), night sweats, fatigue, and anorexia.<ref name="Atluri">{{cite journal | vauthors = Atluri VL, Xavier MN, de Jong MF, den Hartigh AB, Tsolis RM | title = Interactions of the human pathogenic Brucella species with their hosts | journal = Annual Review of Microbiology | volume = 65 | pages = 523–541 | year = 2011 | pmid = 21939378 | doi = 10.1146/annurev-micro-090110-102905 }}</ref> Later complications may include arthritis or epididymo-orchitis, spondylitis, neurobrucellosis, liver abscess formation, and endocarditis, the latter potentially fatal.<ref name="Gorvel">{{cite journal | vauthors = Gorvel JP | title = Brucella: a Mr "Hide" converted into Dr Jekyll | journal = Microbes and Infection | volume = 10 | issue = 9 | pages = 1010–1013 | date = July 2008 | pmid = 18664389 | doi = 10.1016/j.micinf.2008.07.007 | doi-access = free }}</ref>

Human brucellosis is usually not transmitted from human to human; people become infected by contact with fluids from infected animals (sheep, cattle, or pigs) or derived food products, such as unpasteurized milk and cheese. Brucellosis is also considered an occupational disease because of a higher incidence in people working with animals (slaughterhouse cases). People may also be infected by inhalation of contaminated dust or aerosols, and as such, the CDC has labeled ''Brucella'' species as highly weaponizable. Human and animal brucellosis share the persistence of the bacteria in tissues of the mononuclear phagocyte system, including the spleen, liver, lymph nodes, and bone marrow. ''Brucella'' can also target the male reproductive tract.<ref name="Atluri"/>

Globally, an estimated 500,000 cases of brucellosis occur each year.<ref name="Atluri"/>

Malta fever was a major health problem to British troops in Malta in the 19th and early 20th centuries, resulting in over 6000 cases and 574 deaths.<ref name="Ariza.J 2007">{{cite journal | vauthors = Ariza J, Bosilkovski M, Cascio A, Colmenero JD, Corbel MJ, Falagas ME, Memish ZA, Roushan MR, Rubinstein E, Sipsas NV, Solera J, Young EJ, Pappas G | display-authors = 6 | title = Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations | journal = PLOS Medicine | volume = 4 | issue = 12 | article-number = e317 | date = December 2007 | pmid = 18162038 | pmc = 2222927 | doi = 10.1371/journal.pmed.0040317 | doi-access = free }}</ref> In 1860, J.A. Maraston, assistant surgeon in the British Army in Malta, gave the first accurate description of the disease he called "Mediterranean gastric remittent fever". In 1897, A.E. Wright, a pathologist in British army, developed the agglutination test, diagnostic of the disease.

In 1905, Zammit, a Maltese physician, identified goats as the source of infection. E. Bang, a Danish veterinarian, described the intracellular pathogen causing abortion in cattle in 1897, and named it ''Bacillus abortus''. In 1918, A. Evans, an American microbiologist, made the connection between'' B. abortus'' and'' Micrococcus melitensis'', and placed them in the Bacteriaceae.

In 1914, Mohler isolated an organism from the liver and spleen of pigs, ''B. suis''; ''B. neotome'', ''B. ovis'', and ''B. canis'' were described in 1957, 1963, and 1966, respectively.<ref name="Ariza.J 2007"/>

== Transmission == Zoonosis affecting domestic animals is caused by contact with milk, urine, and genital organs, which concentrate the causative organisms. Some reservoirs include buffalo and other animals, but mostly cattle.<ref>{{Cite web|url=https://www.cdc.gov/brucellosis/clinicians/brucella-species.html|title = Humans and Brucella Species {{pipe}} Clinicians {{pipe}} Brucellosis {{pipe}} CDC|date = 13 June 2019}}</ref> In humans, the disease is acquired from unpasteurised milk and products or undercooked meat (consumers), laboratory inhalation (lab workers), accidental skin penetration or abrasion (farmers, slaughterhouse workers, and veterinarians), and (rarely) conjunctival contact, blood transfusion, transplacental, and person-to-person.<ref>Ertem M, Kurekci AE," Brucella Species",2009, APPENDIX 2,Volume 49</ref><ref>{{cite journal | vauthors = Pradeepkiran JA, Sainath SB, Kumar KK, Bhaskar M | title = Complete genome-wide screening and subtractive genomic approach revealed new virulence factors, potential drug targets against bio-war pathogen Brucella melitensis 16M | journal = Drug Design, Development and Therapy | volume = 9 | pages = 1691–1706 | date = March 2015 | pmid = 25834405 | pmc = 4371898 | doi = 10.2147/DDDT.S76948 | doi-access = free }}</ref>

== Human disease == Brucellosis can affect any organ or organ system, and 90% of patients have a cyclical (undulant) fever. Though variable, symptoms can also include these clinical signs: headache, weakness, arthralgia, depression, weight loss, fatigue, and liver dysfunction. Foul-smelling perspiration is considered a classical sign. Between 20 and 60% of cases have osteoarticular complications: arthritis, spondylitis, or osteomyelitis. Hepatomegaly may occur, as can gastrointestinal complications.

Up to 20% of cases can have genitourinary involvement; orchitis and epididymitis are most common. Neurological symptoms include depression and mental fatigue. Cardiovascular involvement can include endocarditis resulting in death.

Chronic brucellosis is hard to define; length, type, and response to treatment are variable. Localized infection can occur. Blood donations of infected persons should not be accepted.<ref name="Poester.F 2010" />

The general agreement is that brucellosis in pregnant women is not linked to congenital malformations. The newborn can be either uninfected, which is more common, or infected with congenital or neonatal brucellosis. The majority of uninfected neonates delivered at term have a favorable outcome, whereas preterm births and cases with congenital brucellosis have an increased risk of neonatal death. Congenital brucellosis can be transmitted transplacentally, whereas neonatal brucellosis can be acquired through contact with body fluids secreted during birth or through postpartum breastfeeding. Congenital brucellosis, on the other hand, is a rare condition; most cases are associated with premature birth, and it affects about 2% of infants exposed to brucellosis in utero.<ref>{{cite journal | vauthors = Bosilkovski M, Arapović J, Keramat F | title = Human brucellosis in pregnancy - an overview | journal = Bosnian Journal of Basic Medical Sciences | volume = 20 | issue = 4 | pages = 415–422 | date = November 2020 | pmid = 31782698 | pmc = 7664790 | doi = 10.17305/bjbms.2019.4499 }}</ref> Congenitally infected infants can exhibit low birth weight, failure to thrive, jaundice, hepatomegaly, splenomegaly, respiratory difficulty, and general signs of sepsis (fever, vomiting). Some cases are asymptomatic.<ref name="Poester.F 2010">{{cite journal | vauthors = Padilla Poester F, Nielsen K, Ernesto Samartino L, Ling Yu W |title=Diagnosis of Brucellosis |journal=The Open Veterinary Science Journal |volume=4 |pages=46–60 |year=2010 |doi=10.2174/1874318801004010046 |doi-access=free }}</ref>

== Characteristics == ''Brucella'' species are small, Gram-negative, facultative coccobacilli, most lacking a capsule, endospores, or native plasmids. They are intracellular within the host organism, and show environmental persistence outside the host. The intracellular trafficking includes two or three main steps, starting with endosomal vacuoles, then endoplasmic reticulum-derived compartments and finally vacuoles having several markers of atypical autophagy.<ref name="ReferenceB">{{cite journal | vauthors = Celli J | title = The changing nature of the Brucella-containing vacuole | journal = Cellular Microbiology | volume = 17 | issue = 7 | pages = 951–958 | date = July 2015 | pmid = 25916795 | pmc = 4478208 | doi = 10.1111/cmi.12452 }}</ref> They survive extremes in temperature, pH, and humidity, and in frozen and aborted materials. They infect many species, but with some specificity.<ref name="ReferenceA">{{cite journal | vauthors = Sakran W, Chazan B, Koren A | title = [Brucellosis: clinical presentation, diagnosis, complications and therapeutic options] | language = Hebrew | journal = Harefuah | volume = 145 | issue = 11 | pages = 836–40, 860 | date = November 2006 | pmid = 17183958 | doi = | url = }}</ref>

The ''Brucella'' species belongs to the Rhizobiales group, in the Alphaproteobacteria class. They are growing by unipolar growth, like ''Agrobacterium tumefaciens'', ''Sinorhizobium meliloti'', and ''Ochrobactrum anthropi''.<ref>{{cite journal | vauthors = Brown PJ, de Pedro MA, Kysela DT, Van der Henst C, Kim J, De Bolle X, Fuqua C, Brun YV | display-authors = 6 | title = Polar growth in the Alphaproteobacterial order Rhizobiales | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 5 | pages = 1697–1701 | date = January 2012 | pmid = 22307633 | pmc = 3277149 | doi = 10.1073/pnas.1114476109 | doi-access = free | bibcode = 2012PNAS..109.1697B | jstor = 41477161 }}</ref> They usually have two chromosomes<ref name="ReferenceB"/> and their replication and segregation are temporally organized.<ref>{{cite journal | vauthors = Deghelt M, Mullier C, Sternon JF, Francis N, Laloux G, Dotreppe D, Van der Henst C, Jacobs-Wagner C, Letesson JJ, De Bolle X | display-authors = 6 | title = G1-arrested newborn cells are the predominant infectious form of the pathogen Brucella abortus | journal = Nature Communications | volume = 5 | page = 4366 | date = July 2014 | pmid = 25006695 | pmc = 4104442 | doi = 10.1038/ncomms5366 | bibcode = 2014NatCo...5.4366D }}</ref>

== Clinical manifestations == The gastrointestinal tract is affected in about 70% of cases, including anorexia, abdominal pain, vomiting, diarrhea, constipation, hepatomegaly, and splenomegaly. The liver is involved in most cases, but function tests are normal or mildly abnormal. Granulomas (''B. abortus''), hepatitis (''B. melitensis''), and abscesses (''B. suis'') are seen.

The skeletal system is affected in 20–60% of cases, including arthritis (hip, knee, and ankle), spondylitis, osteomyelitis, and sacroiliitis (most common). Lumbar vertebrae can be affected showing the classical radiological sign of vertebral erosion.  Neurological symptoms include meningitis, encephalitis, radiculopathy, peripheral neuropathy, intracerebral abscesses, and acute or chronic neck rigidity (<50%), and the cerebrospinal fluid can show lymphocytic pleocytosis, low sugar, increased protein, positive bacterial culture (<50%), and agglutination (positive in >95%).

Cardiovascular involvement is low (endocarditis at 2%), but is the major cause of mortality. Often, valve replacement and antibiotics are needed. Pericarditis and myocarditis are seen, too.

Pulmonary infection can be from inhalation or hematogenous sources, and can cause any chest syndrome. Rarely is'' Brucella'' isolated from sputum. Genitourinary infection can include epidydemoorchitis or pyonephrosis (rare). Cutaneous involvement is not specific. Hematological signs include anemia, leukopenia, and thrombocytopenia.<ref name="Hofer.E 2009">{{cite web | vauthors = Hofer E |title=Microbiological diagnosis of Brucella spp. and Austrian epidemiology of brucellosis (B. suis biovar 2) |year=2009 |url=http://www.rki.de/EN/Content/infections/Diagnostics/IntDiagnosticProjects/ENHPB/Meetings/Downloads/Brucella.pdf }}</ref>

==Diagnosis== ''Brucella'' is isolated from a blood culture on Castaneda medium or from bone marrow. Prolonged incubation (up to six weeks) may be required, as they are slow-growing, but on modern automated machines, the cultures often show positive results within 7 days. On Gram stain, they appear as dense clumps of Gram-negative coccobacilli and are exceedingly difficult to see. In recent years, molecular diagnostic techniques based on the genetic component of the pathogen have become more popular.<ref name="Lopez-GoniICallaghanDO" />

Differentiating ''Brucella'' from ''Salmonella'' is crucial, as the latter could also be isolated from blood cultures and is Gram-negative. Testing for urease would successfully accomplish the task; it is positive for ''Brucella'' and negative for ''Salmonella''. ''Brucella'' can also be seen in bone marrow biopsies.

Laboratory-acquired brucellosis is common.<ref name=Robichaud_2004>{{cite journal | vauthors = Robichaud S, Libman M, Behr M, Rubin E | title = Prevention of laboratory-acquired brucellosis | journal = Clinical Infectious Diseases | volume = 38 | issue = 12 | pages = e119–e122 | date = June 2004 | pmid = 15227634 | doi = 10.1086/421024 | doi-access = free }}</ref> This most often happens when the disease is not thought of until cultures become positive, by which time the specimens have already been handled by a number of laboratory staff. The idea of preventive treatment is to stop people who have been exposed to ''Brucella'' from becoming ill with the disease.  Polymerase chain reaction (PCR) shows promise for rapid diagnosis of ''Brucella'' species in human blood specimens. Positive PCR at the completion of treatment is not predictive of subsequent relapse. PCR testing for fluid and tissue samples other than blood has also been described. A history of animal contact is pivotal; in endemic area, it should be in the diagnosis of any nonspecific febrile illness.

In the laboratory, biochemical tests can be diagnostic.<ref name="Hofer.E 2009"/> Oxidase and catalase tests are positive for most members of the genus ''Brucella''.

{| class="wikitable" |- ! Test !! ''B. melitensis'' !! ''B. abortus'' !!'' B. suis'' !! ''B. neotomae'' !! ''B. ovis'' !! ''B. canis'' |- | Need to CO2 || - || + || - || - || + || - |- | production of H2S || - || + || + || + || - || - |- | Growth on basic fushin 0.002% || + || + || - || - || + || - |- | Growth on thionin 0.004% || - || - || + || - || + || + |- | Growth on thionin 0.002% || + || - || + || + || + || + |- | Destroy with Tb phage || - || + || - || - || - || - |}

<!-- repeat Total counts-normal/reduced.

Thrombocytopenia.

ESR/CRP-Normal/Increased.

CSF/Body fluid analysis-Lymphocytosis,low glucose levels, elevated ADA.

Biopsied samples of lymph node, liver-non casketing granuloma without acid fast bacilli.

Polymerase chain reaction (PCR) shows promise for rapid diagnosis of Brucella spp in human blood specimens. --> <!-- Positive PCR at the completion of treatment is not predictive of subsequent relapse.

PCR testing for fluid and tissue samples other than blood has also been described. --> Serum agglutination with a titer > 1:160 in the presence of a compatible illness supports the diagnosis of brucellosis. Demonstration of a four-fold or greater increase or decrease in agglutinating antibodies over four to 12 weeks provides even stronger evidence for the diagnosis.

ELISA is probably the second-most common serologic method.<ref name="Corbel.M.J 2006">Corbel.M.J," Brucellosis in humans and animals",2006, WHO/CDS/EPR, {{ISBN|92-4-154713-8}}{{page needed|date=December 2017}}</ref> The sensitivity of the ELISA was 100% when compared with blood culture, but only 44% compared with serologic tests other than ELISA. The specificity was >99%. In a study including 75 patients with brucellosis, five patients with positive ELISA had a negative tube agglutination test. In several ''Brucella''-endemic regions, the Febrile Antigen ''Brucella'' Agglutination Test (FBAT) is primarily used for diagnostics. Recent investigations on the use of FBAT have however illustrated its high inaccuracy in proper diagnosis, highlighting the difficulty of brucellosis control in low-income settings.<ref name=":0">{{Cite journal| vauthors = Karlsson PA, Persson C, Akoko J, Bett B, Lundkvist Å, Lindahl JF |date=2021-09-21|title=Using a One Health Case-Based Investigation for Improved Control of Brucellosis in Isiolo, Kenya|journal=Frontiers in Tropical Diseases|volume=2|article-number=711425|doi=10.3389/fitd.2021.711425|issn=2673-7515|doi-access=free|hdl=10568/115084|hdl-access=free}}</ref>

In the setting of ''Brucella'' arthritis, the synovial-fluid white blood cell count does not generally exceed 15,000 cells/μl.<ref name="Corbel.M.J 2006"/> In brucellosis, lymphocytes frequently predominate (in contrast to septic arthritis due to other bacteria, in which polymorphonuclear leukocytes frequently predominate.

The prognosis<ref>{{cite journal | vauthors = Blasco JM | title = Control and eradication strategies for brucella melitensis infection in sheep and goats | journal = Prilozi | volume = 31 | issue = 1 | pages = 145–165 | year = 2010 | pmid = 20703189 }}</ref> for brucellosis before the use of antibiotics had a mortality of 2%, mainly due to endocarditis, and morbidity was high, especially with ''B. melitensis''. Permanent nerve deafness and spinal cord damage often occurred.

Prevention<ref name="Corbel.M.J 2006"/> now includes: * Control of disease in domestic animals by immunization using ''B. abortus'' strain 19 and ''B. melitensis'' strain Rev 1: Vaccination in young cattle helps in protection, but does not offer full effectiveness. * Routine pasteurization of milk * In labs, strict biosafety precautions As regions endemic with ''Brucella'' primarily are low-income environments, approaching proper control of brucellosis remains a challenge. A recent case-based investigation in north-eastern Kenya illustrated how community engagement with veterinarians and medical professionals might contribute in preventive strategies, but that additional political engagement is called for to ensure proper diagnostic and treatment standards.<ref name=":0" />

==Treatment== No clinical trials exist to be relied on as a guide for optimal treatment, but an at least six-week course of rifampicin or gentamicin and doxycycline twice daily is the combination most often used, and appears to be efficacious;<ref name=Robichaud_2004 /><ref>E Torok. et al. Oxford Handbook Infect Dis and Microbiology, 2009{{page needed|date=December 2017}}</ref><ref>Gilbert DN et al. The Sanford guide to antimicrobial therapy 2013{{page needed|date=December 2017}}</ref><ref name="Maley2006">{{cite journal | vauthors = Maley MW, Kociuba K, Chan RC | title = Prevention of laboratory-acquired brucellosis: significant side effects of prophylaxis | journal = Clinical Infectious Diseases | volume = 42 | issue = 3 | pages = 433–434 | date = February 2006 | pmid = 16392095 | doi = 10.1086/499112 | doi-access = free }}</ref> the advantage of this regimen is that it is oral medication with no injections; however, a high rate of side effects (nausea, vomiting, loss of appetite) has also been reported.<ref name="Maley2006"/> The relatedness in treatment and endemic overlap of tuberculosis remains an issue however, as treatment of one might cause resistance in the second. Local dispensaries dealing first-hand with brucellosis are occasionally also not aware on how to treat properly, highlighting the need for reevaluation on implementation of international treatment regimes.<ref name=":0" />

As of August 2013, Allison Rice-Ficht, Ph.D. at Texas A&M University and her team claim to be close to creating a human vaccine. It would primarily be used to immunize members of the military in case of exposure to weaponized ''Brucella'' on the battlefield.<ref>{{cite web | url=https://vitalrecord.tamhsc.edu/17494/ | vauthors = Williamson B | title=Victory in the Battle against Brucella: From bench to battlefield |date=22 August 2013 | publisher=Vital Record: News from Texas A&M HSC}}</ref>

==Host specificity and animal brucellosis== ''Brucella'' species have been found primarily in mammals:<ref name="Atluri"/>

{| class="wikitable" !Species!! Host |- | ''B. melitensis''|| goats and sheep |- | ''B. abortus'' || cattle |- | ''B. canis'' || dogs |- | ''B. suis'' || pigs |- | ''B. ovis'' || sheep |- | ''B. neotomae'' || desert woodrat (''Neotoma lepida'') |- | ''B. pinnipedialis'' || seal |- | ''B. ceti'' || dolphin, porpoise, whale |- | ''B. microti'' || common vole (''Microtus arvalis'') |- | ''B. inopinata'' || unknown |- | ''B.'' papionis|| baboon |- |''B. vulpis'' |red fox (''Vulpes vulpes'') |}

Pathogenic ''Brucella'' species can cause abortion in female animals by colonization of placental trophoblasts, and sterility in male animals.<ref>{{cite journal | vauthors = Corbel MJ | title = Brucellosis: an overview | journal = Emerging Infectious Diseases | volume = 3 | issue = 2 | pages = 213–221 | year = 1997 | pmid = 9204307 | pmc = 2627605 | doi = 10.3201/eid0302.970219 }}</ref> Drugs with effects against ''Brucella'' include tetracyclines, aminoglycosides (streptomycin, [since 1947], gentamicin, netilmicin), rifampicin, quinolones (ciprofloxacin), and third-generation cephalosporins. Treatment for uncomplicated brucellosis includes: * Streptomycin + doxycycline for 6 weeks * TMP/SMX + doxycycline for 6 weeks * Rifampicin + doxycycline for 6 weeks

Treatment of complicated brucellosis (endocarditis, meningitis) has no uniform agreement, but usually uses three anti-''Brucella'' drugs for three months.

==The plague of Thebes== Brucellosis caused by ''B. abortus'' best fits the characteristics of the plague described in ''Oedipus Rex''. Although the disease progression of brucellosis in modern times may make it seem unlikely,  it was at least one agent in what may have been a multicomponent plague, along with ''Salmonella enterica'' serovar Typhi or another pathogen, or possibly the ancestral versions of ''Brucella'' were more lethal.<ref>{{cite journal | vauthors = Kousoulis AA, Economopoulos KP, Poulakou-Rebelakou E, Androutsos G, Tsiodras S | title = The plague of Thebes, a historical epidemic in Sophocles' Oedipus Rex | journal = Emerging Infectious Diseases | volume = 18 | issue = 1 | pages = 153–157 | date = January 2012 | pmid = 22261081 | pmc = 3310127 | doi = 10.3201/eid1801.AD1801 }}</ref>

==Genomics==

The ''Brucella'' genome includes two chromosomes; the first chromosome codes mostly for genes related to metabolism, while the second (smaller one) includes several genes related to pathogenicity. The genomes of most ''Brucella'' species have been sequenced,<ref name="GOLD Database">{{cite web|url=http://www.genomesonline.org/|title=GOLD Database|access-date=1 October 2012}}</ref> and typically encode 3,200 to 3,500 open reading frames (ORFs). Examples include: # [http://www.genomesonline.org/cgi-bin/GOLD/GOLDCards.cgi?goldstamp=Gc02057 Brucella abortus A13334], 3,401 ORFs # [http://www.genomesonline.org/cgi-bin/GOLD/GOLDCards.cgi?goldstamp=Gc00686 Brucella canis ATCC 23365], 3,408 ORFs # [http://www.genomesonline.org/cgi-bin/GOLD/GOLDCards.cgi?goldstamp=Gc00074 Brucella melitensis 16M], 3,279 ORFs # [http://www.genomesonline.org/cgi-bin/GOLD/GOLDCards.cgi?goldstamp=Gc01071 Brucella microti CCM 4915], 3,346 ORFs # [http://www.genomesonline.org/cgi-bin/GOLD/GOLDCards.cgi?goldstamp=Gc00570 Brucella ovis ATCC 25840], 3,193 ORFs # [http://www.genomesonline.org/cgi-bin/GOLD/GOLDCards.cgi?goldstamp=Gc01901 Brucella pinnipedialis B2/94], 3,505 ORFs # [http://www.genomesonline.org/cgi-bin/GOLD/GOLDCards.cgi?goldstamp=Gc00101 Brucella suis 1330], 3,408 ORFs

Genome data for these and other ''Brucella'' strains are available in the GOLD<ref name="GOLD Database"/> and PATRIC<ref name=Brucella_Patric>{{cite web|title=Brucella genomes in PATRIC|url=http://www.patricbrc.org/portal/portal/patric/Taxon?cType=taxon&cId=234|publisher=PATRIC|access-date=22 October 2012|archive-url=https://web.archive.org/web/20130510031858/http://patricbrc.org/portal/portal/patric/Taxon?cType=taxon&cId=234|archive-date=2013-05-10}}</ref> databases. Also, a public and [https://docs.google.com/spreadsheets/d/1QBPQEGx-mMyCTdYUn_th-vJZAaVg9xOldDJezOGISgA/edit?usp=sharing editable spreadsheet of ''B. abortus'' 2308W] genome annotation has been created, to be updated based on new discoveries. Also, the genome annotation is available in a user friendly table at the web page http://hdl.handle.net/11056/23125.

Bacterial small RNAs (sRNA) are an important class of regulatory molecules. Many ''Brucella'' sRNAs have been identified.{{citation needed|date=May 2021}}

==Phylogeny== The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN).<ref name=Brucella/> The phylogeny is based on whole-genome analysis.<ref name="Hördt">{{cite journal | vauthors = Hördt A, López MG, Meier-Kolthoff JP, Schleuning M, Weinhold LM, Tindall BJ, Gronow S, Kyrpides NC, Woyke T, Göker M | display-authors = 6 | title = Analysis of 1,000+ Type-Strain Genomes Substantially Improves Taxonomic Classification of ''''Alphaproteobacteria'''' | journal = Frontiers in Microbiology | volume = 11 | page = 468 | year = 2020 | pmid = 32373076 | pmc = 7179689 | doi = 10.3389/fmicb.2020.00468 | doi-access = free }}</ref>

{{Clade | style=font-size:75%;line-height:75% |1={{clade |label1='''''Brucella''''' |1={{clade |1={{clade |1=''Brucella thiophenivorans'' |2={{clade |1=''Brucella pituitosa'' |2={{clade |1=''Brucella grignonensis'' |2={{clade |1=''Brucella rhizosphaerae'' |2=''Brucella pseudogrignonensis'' }} }} }} }} |2={{clade |1={{clade |1=''Brucella intermedia'' |2={{clade |1=''Brucella lupini'' |2=''Brucella anthropi'' }} }} |2={{clade |1=''Brucella vulpis'' |2={{clade |1=''Brucella inopinata'' |2={{clade |1=''Brucella ovis'' |2={{clade |1=''Brucella neotomae'' |2={{clade |1={{clade |1=''Brucella abortus'' |2=''Brucella melitensis'' }} |2={{clade |1={{clade |1=''Brucella microti'' |2=''Brucella ceti'' }} |2={{clade |1=''Brucella suis'' |2=''Brucella canis'' }} }} }} }} }} }} }} }} }} |label2=outgroup |2=''Paenochrobactrum'' }} }}

==Effect of blue light== Infection of macrophages by ''B. abortus'' is stimulated by blue light in the wild type, but is limited in photochemically inactive and null mutants, indicating a flavin-containing histidine kinase functions as a photoreceptor regulating ''B. abortus'' virulence. Conversely, depriving ''Brucella'' of the blue wavelengths dropped its reproductive rate by 90%.<ref name="SciNEWS">{{cite web | vauthors = Berardelli P |date=August 23, 2007 |url=https://www.science.org/content/article/deadly-daylight |title=Deadly in the Daylight"] August 23, 2007 |work=Science }}</ref><ref name="SCIENCE">{{cite journal | vauthors = Swartz TE, Tseng TS, Frederickson MA, Paris G, Comerci DJ, Rajashekara G, Kim JG, Mudgett MB, Splitter GA, Ugalde RA, Goldbaum FA, Briggs WR, Bogomolni RA | display-authors = 6 | title = Blue-light-activated histidine kinases: two-component sensors in bacteria | journal = Science | volume = 317 | issue = 5841 | pages = 1090–1093 | date = August 2007 | pmid = 17717187 | doi = 10.1126/science.1144306 | s2cid = 20023182 | bibcode = 2007Sci...317.1090S }}</ref>

==Notes== {{Reflist|group=Note}}

== References == {{Reflist}}

== External links == * [https://patricbrc.org/view/Taxonomy/234#view_tab=overview Brucella] genomes and related information at [http://patricbrc.org/ PATRIC], a Bioinformatics Resource Center funded by [https://www.niaid.nih.gov/ NIAID] * [http://www.genomesonline.org/search.cgi?colcol=all&goldstamp=ALL&gen_type=ALL&org_name1=genus&gensp=Brucella&org_domain=ALL&org_status=ALL&size2=ALL&org_size=Kb&gen_gc=ALL&phylogeny2=ALL&gen_institution=ALL&gen_funding=ALL&gen_data=ALL&cont=ALL&gen_country=ALL&gen_pheno=ALL&gen_eco=ALL&gen_disease=ALL&gen_relevance=ALL&gen_avail=ALL&selection=submit+search Brucella Genome Projects] (from [http://www.genomesonline.org Genomes OnLine Database]) * [https://archive.today/20121211230153/http://img.jgi.doe.gov/cgi-bin/w/main.cgi?section=TaxonList&page=lineageMicrobes&genus=Brucella Comparative Analysis of Brucella Genomes] (at DOE's IMG system) * [https://web.archive.org/web/20071202112440/http://bbp.hegroup.org/ Brucella Bioinformatics Portal] * [http://apps-bibl.si.unav.es/sp/subjects/guide.php?subject=Brucel Brucellosis subject guide] {{Webarchive|url=https://web.archive.org/web/20160204042325/http://apps-bibl.si.unav.es/sp/subjects/guide.php?subject=Brucel |date=2016-02-04 }} of the [http://www.unav.edu University of Navarra]

Category:Hyphomicrobiales Category:Bacteria genera