Brucellosis laboratory findings: Difference between revisions

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{{Brucellosis}}
{{Brucellosis}}
{{CMG}}; {{AE}} {{RT}}
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==Overview==
==Overview==
Brucellosis is diagnosed in a laboratory by finding [[Brucella]] organisms in samples of blood or [[bone marrow]]. Also, blood tests can be done to detect antibodies against the bacteria. If this method is used, two blood samples should be collected 2 weeks apart <ref>http://www.cdc.gov/ncidod/dbmd/diseaseinfo/brucellosis_g.htm# </ref>.
The diagnosis of brucellosis can be confirmed by either a positive [[Bacterial cultures|bacterial culture]] or a positive titer of anti-[[Brucella|b''rucella'']] [[antibodies]] on serological testing.


==Laboratory Findings==
==Laboratory Findings==
* [[Complete blood count]] and differential count - [[leukopenia]], [[anemia]]
Laboratory findings of brucellosis include the following:<ref name="g" /><ref name=":0">Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9th, 2017</ref><ref>Colmenero JD, Reguera JM, Martos F, Sánchez-De-Mora D, Delgado M, Causse M; et al. (1996). [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8699960 "Complications associated with Brucella melitensis infection: a study of 530 cases."]. ''Medicine (Baltimore)''. '''75''' (4): 195–211. PMID [http://www.ncbi.nlm.nih.gov/pubmed/8699960 8699960]</ref><ref name=":1">Mantur BG, Amarnath SK, Shinde RS (2007). [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17901634 "Review of clinical and laboratory features of human brucellosis."]. ''Indian J Med Microbiol''. '''25''' (3): 188–202. PMID [http://www.ncbi.nlm.nih.gov/pubmed/17901634 17901634]</ref><ref>Pappas G, Akritidis N, Bosilkovski M, Tsianos E (2005). [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15930423 "Brucellosis."]. ''N Engl J Med''. '''352''' (22): 2325–36. PMID [http://www.ncbi.nlm.nih.gov/pubmed/15930423 15930423].</ref><ref name="pmid23236528">{{cite journal| author=Dean AS, Crump L, Greter H, Hattendorf J, Schelling E, Zinsstag J| title=Clinical manifestations of human brucellosis: a systematic review and meta-analysis. | journal=PLoS Negl Trop Dis | year= 2012 | volume= 6 | issue= 12 | pages= e1929 | pmid=23236528 | doi=10.1371/journal.pntd.0001929 | pmc=3516581 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23236528  }}</ref><ref>Young EJ (1995). [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7546364 "Brucellosis: current epidemiology, diagnosis, and management."]. ''Curr Clin Top Infect Dis''. '''15''': 115–28. PMID [http://www.ncbi.nlm.nih.gov/pubmed/7546364 7546364]</ref><ref>Aygen B, Doganay M, Sumerkan B, et al. Clinical manifestations, complications and treatment of brucellosis: a retrospective evaluation of 480 patients. Med Malad Infect 2002; 32:485.</ref><ref name="pmid21623056">{{cite journal| author=Zamani A, Kooraki S, Mohazab RA, Zamani N, Matloob R, Hayatbakhsh MR et al.| title=Epidemiological and clinical features of Brucella arthritis in 24 children. | journal=Ann Saudi Med | year= 2011 | volume= 31 | issue= 3 | pages= 270-3 | pmid=21623056 | doi=10.4103/0256-4947.81543 | pmc=3119967 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21623056  }}</ref><ref>Mousa AM, Bahar RH, Araj GF, Koshy TS, Muhtaseb SA, al-Mudallal DS; et al. (1990). [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2330811 "Neurological complications of brucella spondylitis."]. ''Acta Neurol Scand''. '''81''' (1): 16–23. PMID [http://www.ncbi.nlm.nih.gov/pubmed/2330811 2330811]</ref><ref>Pappas G, Bosilkovski M, Akritidis N, Mastora M, Krteva L, Tsianos E (2003). [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13130417 "Brucellosis and the respiratory system."]. ''Clin Infect Dis''. '''37''' (7): e95–9. PMID [http://www.ncbi.nlm.nih.gov/pubmed/13130417 13130417]. [[Digital object identifier|doi]]:[http://dx.doi.org/10.1086%2F378125 10.1086/378125]</ref><ref>Herrick JA, Lederman RJ, Sullivan B, et al. Brucella arteritis: clinical manifestations, treatment, and prognosis. Lancet Infect Dis 2014; 14:520.</ref><ref name="pmid18162038">{{cite journal| author=Ariza J, Bosilkovski M, Cascio A, Colmenero JD, Corbel MJ, Falagas ME et al.| title=Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations. | journal=PLoS Med | year= 2007 | volume= 4 | issue= 12 | pages= e317 | pmid=18162038 | doi=10.1371/journal.pmed.0040317 | pmc=2222927 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18162038  }}</ref>
* [[Liver function tests]] - elevation of [[AST]] and [[ALT]]
{| class="wikitable"
* Demonstration of the agent: blood cultures in tryptose broth, bone marrow cultures. The growth of brucellae is extremely slow (they can take until 2 months to grow) and the culture poses a risk to laboratory personnel due to high infectivity of brucellae.
! colspan="3" |Laboratory findings in Brucellosis
* 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]] ([[liver biopsy|hepatic biopsy]])
| rowspan="7" |Blood
|[[Complete blood count]]  
|Complete [[Blood]] Count may reveal:
*Mild [[leukopenia]]
*Mild [[anemia]]  
*[[Lymphocytosis|Relative lymphocytosis]]
*[[Thrombocytopenia]]
|-
|[[Erythrocyte sedimentation rate|ESR]]
|Normal or raised
|-
|[[CRP]]
|Normal or raised
|-
|[[Liver function tests|Liver function test]]
|Liver function test may reveal:
*Mild increase in [[hepatic]] [[enzymes]] 
*Mild increase in [[bilirubin]]
|-
|Culture
|
*The isolation and identification of [[Brucella|''Brucella'']] can confirm a diagnosis of brucellosis.
*[[Brucella|''Brucella'']] is most commonly isolated from blood cultures (blood cultures are positive between the 7th and 21st day)
*It can also, however, be isolated from:
**[[Bone marrow]] ([[gold standard (test)|Gold standard test]])
**[[Cerebrospinal fluid]]
**[[Wounds]]
**[[Purulent]] [[discharge]]
**[[Synovial fluid|Joint fluid]]<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><ref name="g">Brucellosis. CDC. http://www.cdc.gov/brucellosis/clinicians/bacterial-isolation.html. Accessed on February 4, 2016</ref>
|-
|Serological tests
|Serological Tests
*'''There are two types of serological tests, based on:'''
**Antibody production against [[lipopolysaccharide]]
**Antibody production against other [[bacterial]] [[antigens]]
*'''For a diagnosis to be made using serology, two serum samples are required:'''
**The first [[serum]] sample should be taken when a person is acutely ill (≤7 days after symptom onset)
**The second serum sample should be drawn 2-4 weeks later to check for a rise in [[antibodies]] (a fourfold or greater rise in antibodies would bean an individual is positive for brucellosis).
**If submission of paired sera is not possible, a probable diagnosis can be made with a single serum sample.
*'''Brucella microagglutination test (BMAT)'''
**A modified version of the serum (tube) agglutination test (SAT), that can detect antibodies to [[Brucella|''Brucella'']] species: [[Brucella abortus|abortus]], [[Brucella melitensis|melitensis]] or suis.
**There is no [[Serological testing|serological test]] available to detect [[antibodies]] to [[Brucella canis|''B. canis'']].
**An '''''agglutination''''' '''''titre greater than 1:160''''' is considered '''significant in nonendemic areas'''.
**An '''''agglutination''''' '''''titre greater than 1:320''''' is considered '''significant in endemic areas'''.
**Due to the similarity of the O [[polysaccharide]] of [[Brucella|''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 [[Immunoglobulin M|M immunoglobulins]] may occur.
**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.
**[[Serology]] is not currently available to monitor persons for RB51 vaccine exposure or for [[Brucella canis|''Brucella canis'']] exposure.
*'''Rose Bengal'''
**Rose bengal has a positive predictive value is approximately 99% for patients with acute and chronic brucellosis.
**Rose bengal measures [[IgM]] and [[IgG]] antibodies.
*'''2-mercaptoethanol (2-ME)'''
**2-ME measures [[IgG]] [[antibodies]]
*'''Antihuman globulin (Coombs)'''
**Used in chronic brucellosis patients with negative seroagglutination because they have [[IgG]] non-agglutinating antibodies.
*'''Indirect enzyme linked immunosorbent assay (ELISA)'''
**[[ELISA test|ELISA]] typically uses cytoplasmic [[proteins]] as [[antigens]].
**[[ELISA test|ELISA]] measures [[IgM]], [[IgG]], and [[IgA]] with better [[Sensitivity (tests)|sensitivity]] and [[Specificity (tests)|specificity]] than the SAT in most recent comparative studies.
*'''Dipstick assays'''
**New and promising, based on the binding of [[Brucella|''Brucella'']] [[IgM]] [[antibodies]], and found to be simple, accurate and rapid.
*'''Brucellacapt test'''
**A single-step immunocapture assay for the detection of total anti-[[Brucella|''Brucella'']] antibodies, is an increasingly used adjunctive test when resources permit.
|-
|Molecular tests
|'''PCR'''
*[[PCR]] is a fast and specific diagnostic tool to confirm the diagnosis of brucellosis
*Many varieties of [[PCR]] have been developed (e.g. nested [[PCR]], realtime [[PCR]] and [[PCR]]-[[ELISA test|ELISA]]) and found to have superior [[Specificity (tests)|specificity]] and [[Sensitivity (tests)|sensitivity]] in detecting both primary infection and relapse after treatment.
*Unfortunately, these have yet to be 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 (medicine)|chronic]] brucellosis.<ref name="pmid15930423" /><ref name="b">Brucellosis. CDC. http://www.cdc.gov/brucellosis/transmission/index.html. Accessed on February 1, 2016</ref><ref name="a">Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on January 29, 2016</ref><ref name="aa">Brucelosis. Wikipedia. https://es.wikipedia.org/wiki/Brucelosis. Accessed on February 2, 2016</ref>
|}


[[Image:Brucella granuloma.jpg|thumb|center|400px|[[Granuloma]] and [[necrosis]] in the liver of a guinea pig infected with ''Brucella suis'']]
==== Tissue Biopsy ====
<br clear=left/>
[[Liver]] and [[lymph node]] biopsy may reveal non-[[Caseous necrosis|caseating]] [[granuloma]].<ref name=":0" /><ref name=":1" />
 
==== CSF analysis ====
[[CSF analysis]] may reveal [[lymphocytosis]] and low glucose level.<ref name=":0" /><ref name=":1" />
 
==== Synovial fluid analysis ====
[[Synovial fluid]] analysis may reveal [[lymphocytic]] predominate with [[granulocyte]] count which  does not generally exceed 15,000 cells/microL and low [[glucose]] levels.<ref name=":0" /><ref name=":1" />
 
==Gallery==
 
<gallery>
 
Image: Brucellosis12.jpeg| Brucella abortus bacteria grown on a medium of sheep’s blood agar (SBA) 72hrs. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis11.jpeg| Brucella abortus bacteria grown on a medium of sheep’s blood agar (SBA) 72hrs. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis10.jpeg| Brucella abortus bacteria grown on a medium of sheep’s blood agar (SBA) 72hrs. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Brucellosis09.jpeg|Brucella suis bacteria grown on chocolate medium 72hrs. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis08.jpeg|Brucella sis bacteria grown on chocolate medium 72hrs. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis07.jpeg|Brucella bacteria grown on MacConkey agar (MAC) medium 24hrs (10x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis06.jpeg|Brucella suis bacteria cultured on chocolate agar medium 48hrs (10x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis05.jpeg|Brucella suis bacteria cultured on SBA 24hrs (10x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis04.jpeg|Brucella suis bacteria cultured on SBA 72hrs (10x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis03.jpeg|Brucella suis bacteria cultured on SBA 48hrs (10x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis02.jpeg|Brucella suis bacteria cultured on Thayer-Martin (TM) agar medium 48hrs (10x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Brucellosis02.jpeg|Brucella suis bacteria cultured on chocolate agar medium 24hrs (10x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
</gallery>


==References==
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Latest revision as of 20:44, 29 July 2020

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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 LukacVishal Devarkonda, M.B.B.S[3]

Overview

The diagnosis of brucellosis can be confirmed by either a positive bacterial culture or a positive titer of anti-brucella antibodies on serological testing.

Laboratory Findings

Laboratory findings of brucellosis include the following:[1][2][3][4][5][6][7][8][9][10][11][12][13]

Laboratory findings in Brucellosis
Blood Complete blood count Complete Blood Count may reveal:
ESR Normal or raised
CRP Normal or raised
Liver function test Liver function test may reveal:
Culture
Serological tests Serological Tests
  • There are two types of serological tests, based on:
  • For a diagnosis to be made using serology, two serum samples are required:
    • The first serum sample should be taken when a person is acutely ill (≤7 days after symptom onset)
    • The second serum sample should be drawn 2-4 weeks later to check for a rise in antibodies (a fourfold or greater rise in antibodies would bean an individual is positive for brucellosis).
    • If submission of paired sera is not possible, a probable diagnosis can be made with a single serum sample.
  • Brucella microagglutination test (BMAT)
  • Rose Bengal
    • Rose bengal has a positive predictive value is approximately 99% for patients with acute and chronic brucellosis.
    • Rose bengal measures IgM and IgG antibodies.
  • 2-mercaptoethanol (2-ME)
  • Antihuman globulin (Coombs)
    • Used in chronic brucellosis patients with negative seroagglutination because they have IgG non-agglutinating antibodies.
  • Indirect enzyme linked immunosorbent assay (ELISA)
  • Dipstick assays
    • New and promising, based on the binding of Brucella IgM antibodies, and found to be simple, accurate and rapid.
  • Brucellacapt test
    • A single-step immunocapture assay for the detection of total anti-Brucella antibodies, is an increasingly used adjunctive test when resources permit.
Molecular tests PCR
  • PCR is a fast and specific diagnostic tool to confirm the diagnosis of brucellosis
  • Many varieties of PCR have been developed (e.g. nested PCR, realtime PCR and PCR-ELISA) and found to have superior specificity and sensitivity in detecting both primary infection and relapse after treatment.
  • Unfortunately, these have yet to be 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.[14][15][16][17]

Tissue Biopsy

Liver and lymph node biopsy may reveal non-caseating granuloma.[2][4]

CSF analysis

CSF analysis may reveal lymphocytosis and low glucose level.[2][4]

Synovial fluid analysis

Synovial fluid analysis may reveal lymphocytic predominate with granulocyte count which does not generally exceed 15,000 cells/microL and low glucose levels.[2][4]

Gallery

References

  1. ↑ 1.0 1.1 Brucellosis. CDC. http://www.cdc.gov/brucellosis/clinicians/bacterial-isolation.html. Accessed on February 4, 2016
  2. ↑ 2.0 2.1 2.2 2.3 Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on December 9th, 2017
  3. ↑ 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
  4. ↑ 4.0 4.1 4.2 4.3 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
  5. ↑ Pappas G, Akritidis N, Bosilkovski M, Tsianos E (2005). "Brucellosis.". N Engl J Med. 352 (22): 2325–36. PMID 15930423.
  6. ↑ Dean AS, Crump L, Greter H, Hattendorf J, Schelling E, Zinsstag J (2012). "Clinical manifestations of human brucellosis: a systematic review and meta-analysis". PLoS Negl Trop Dis. 6 (12): e1929. doi:10.1371/journal.pntd.0001929. PMC 3516581. PMID 23236528.
  7. ↑ Young EJ (1995). "Brucellosis: current epidemiology, diagnosis, and management.". Curr Clin Top Infect Dis. 15: 115–28. PMID 7546364
  8. ↑ Aygen B, Doganay M, Sumerkan B, et al. Clinical manifestations, complications and treatment of brucellosis: a retrospective evaluation of 480 patients. Med Malad Infect 2002; 32:485.
  9. ↑ Zamani A, Kooraki S, Mohazab RA, Zamani N, Matloob R, Hayatbakhsh MR; et al. (2011). "Epidemiological and clinical features of Brucella arthritis in 24 children". Ann Saudi Med. 31 (3): 270–3. doi:10.4103/0256-4947.81543. PMC 3119967. PMID 21623056.
  10. ↑ Mousa AM, Bahar RH, Araj GF, Koshy TS, Muhtaseb SA, al-Mudallal DS; et al. (1990). "Neurological complications of brucella spondylitis.". Acta Neurol Scand. 81 (1): 16–23. PMID 2330811
  11. ↑ Pappas G, Bosilkovski M, Akritidis N, Mastora M, Krteva L, Tsianos E (2003). "Brucellosis and the respiratory system.". Clin Infect Dis. 37 (7): e95–9. PMID 13130417. doi:10.1086/378125
  12. ↑ Herrick JA, Lederman RJ, Sullivan B, et al. Brucella arteritis: clinical manifestations, treatment, and prognosis. Lancet Infect Dis 2014; 14:520.
  13. ↑ Ariza J, Bosilkovski M, Cascio A, Colmenero JD, Corbel MJ, Falagas ME; et al. (2007). "Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations". PLoS Med. 4 (12): e317. doi:10.1371/journal.pmed.0040317. PMC 2222927. PMID 18162038.
  14. ↑ 14.0 14.1 Pappas G, Akritidis N, Bosilkovski M, Tsianos E (2005). "Brucellosis". N Engl J Med. 352 (22): 2325–36. doi:10.1056/NEJMra050570. PMID 15930423.
  15. ↑ Brucellosis. CDC. http://www.cdc.gov/brucellosis/transmission/index.html. Accessed on February 1, 2016
  16. ↑ Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on January 29, 2016
  17. ↑ Brucelosis. Wikipedia. https://es.wikipedia.org/wiki/Brucelosis. Accessed on February 2, 2016
  18. ↑ 18.00 18.01 18.02 18.03 18.04 18.05 18.06 18.07 18.08 18.09 18.10 18.11 "Public Health Image Library (PHIL)".

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