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==Overview==
==Overview==
A positive [[Culture media|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>  
A positive culture or presence of [[Brucella|''Brucella'']] antibody in 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>  


==Laboratory Findings==
==Laboratory Findings==
* [[Complete blood count]]:
====Complete blood count:====
**Mild [[leukopenia]]
*Mild [[leukopenia]]
**Mild [[anemia]]  
*Mild [[anemia]]  
**[[Lymphocytosis|Relative lymphocytosis]]
*[[Lymphocytosis|Relative lymphocytosis]]
**[[Thrombocytopenia]]
*[[Thrombocytopenia]]
* [[Liver function tests]]:
**Mild transaminasemia<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="b">Brucellosis. CDC. http://www.cdc.gov/brucellosis/transmission/index.html. Accessed on February 1, 2016</ref>


'''Bacterial Isolation:'''
==== Liver function tests: ====
*The isolation and identification of [[Brucella|''Brucella'']] can confirm a [[diagnosis]] of brucellosis. [[Brucella|''Brucella'']] is most commonly isolated from [[blood cultures]].
*Mild transaminasemia<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="b">Brucellosis. CDC. http://www.cdc.gov/brucellosis/transmission/index.html. Accessed on February 1, 2016</ref>
 
=== '''Bacterial Isolation:''' ===
*The isolation and identification of [[Brucella|''Brucella'']] can confirm a diagnosis of brucellosis.  
*[[Brucella|''Brucella'']] is most commonly isolated from blood cultures.
*It can also, however, be isolated from:
*It can also, however, be isolated from:
**[[Bone marrow]]
**[[Bone marrow]]
Line 25: Line 27:
**[[Synovial fluid|Joint fluid]]<ref name="g">Brucellosis. CDC. http://www.cdc.gov/brucellosis/clinicians/bacterial-isolation.html. Accessed on February 4, 2016</ref><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>  
**[[Synovial fluid|Joint fluid]]<ref name="g">Brucellosis. CDC. http://www.cdc.gov/brucellosis/clinicians/bacterial-isolation.html. Accessed on February 4, 2016</ref><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>  


'''Serological tests:'''
=== '''Serological tests:''' ===
*There are two types of [[Serological testing|serological tests]], based on:
*'''There are two types of serological tests, based on:'''
**"Antibody production against lipopolysaccharide"  
**"Antibody production against lipopolysaccharide"  
**"Antibody production against other bacterial antigens"
**"Antibody production against other bacterial antigens"
*For a [[diagnosis]] to be made using [[serology]], two [[serum]] samples are required.
*'''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 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).
**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.
**If submission of paired sera is not possible, a probable diagnosis can be made with a single serum sample.
*''Brucella microagglutination test (BMAT):''  
*'''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.  
**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'']].
**There is no serological test available to detect antibodies to [[Brucella canis|''B. canis'']].
**An [[Agglutination (biology)|''agglutination'']] ''titre greater than 1:160'' is considered significant in nonendemic areas.
**An '''''agglutination''''' '''''titre greater than 1:160''''' is considered '''significant in nonendemic areas'''.
**An [[Agglutination (biology)|''agglutination'']] ''titre greater than 1:320'' is considered significant in [[Endemic (epidemiology)|endemic]] areas.
**An '''''agglutination''''' '''''titre greater than 1:320''''' is considered '''significant in endemic areas'''.
**Due to the similarity of the O polysaccharide of [[Brucella]] to that of various other [[Gram-negative bacteria]] (e.g. [[Francisella tularensis]], [[Escherichia coli]], Salmonella urbana, [[Yersinia enterocolitica]], [[Vibrio cholerae]], and [[Stenotrophomonas maltophilia]]) the appearance of cross-reactions of class [[Immunoglobulin M|M immunoglobulins]] may occur.
**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 test result|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.
**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]] exposure.
**Serology is not currently available to monitor persons for RB51 vaccine exposure or for [[Brucella canis|''Brucella canis'']] exposure.
*''Rose Bengal'':
*'''Rose Bengal:'''
**Rose bengal has a [[positive predictive value]] is approximately 99% for [[patients]] with [[Acute (medical)|acute]] and [[Chronic (medical)|chronic]] brucellosis.
**Rose bengal has a positive predictive value is approximately 99% for patients with acute and chronic brucellosis.
**Rose bengal measures [[IgM]] and [[IgG]] [[antibodies]].
**Rose bengal measures [[IgM]] and [[IgG]] antibodies.
*''2-mercaptoethanol (2-ME)'':
*'''2-mercaptoethanol (2-ME):'''
**2-ME measures [[IgG]] [[antibodies]].
**2-ME measures [[IgG]] antibodies.
*''Antihuman globulin ([[Coombs' Test|Coombs]]):''
*'''Antihuman globulin (Coombs):'''
**Used in [[Chronic (medical)|chronic]] brucellosis patients with negative seroagglutination because they have [[IgG]] non-agglutinating [[Antibodies|antibodies.]]
**Used in chronic brucellosis patients with negative seroagglutination because they have [[IgG]] non-agglutinating antibodies.
*''[[Enzyme linked immunosorbent assay (ELISA)|Indirect enzyme linked immunosorbent assay (ELISA)]]:''
*'''Indirect enzyme linked immunosorbent assay (ELISA)''''':''
**[[ELISA test|ELISA]] typically uses [[cytoplasmic]] [[proteins]] as [[antigens]].  
**[[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.
**[[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:''  
*'''Dipstick assays:'''  
**New and promising, based on the binding of [[Brucella]] [[IgM]] [[antibodies]], and found to be simple, accurate, and rapid.
**New and promising, based on the binding of [[Brucella|''Brucella'']] [[IgM]] antibodies, and found to be simple, accurate, and rapid.
*''Brucellacapt test:''  
*'''Brucellacapt test:'''  
**A single-step immunocapture assay for the detection of total anti-[[Brucella]] [[antibodies]], is an increasingly used adjunctive test when resources permit.
**A single-step immunocapture assay for the detection of total anti-[[Brucella|''Brucella'']] antibodies, is an increasingly used adjunctive test when resources permit.
*''[[PCR]]:''
*'''PCR''''':''
**Is fast and specific.  
**Is fast and specific.  
**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.  
**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">{{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="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>
**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">{{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="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>


Revision as of 14:24, 9 February 2016

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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

Overview

A positive culture or presence of Brucella antibody in serological tests are diagnostic of brucellosis.[1]

Laboratory Findings

Complete blood count:

Liver function tests:

Bacterial Isolation:

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 species: abortus, melitensis or suis.
    • There is no serological test available to detect antibodies to 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 to that of various other Gram-negative bacteria (e.g. Francisella tularensis, Escherichia coli, Salmonella urbana, Yersinia enterocolitica, Vibrio cholerae, and Stenotrophomonas maltophilia) the appearance of cross-reactions of class M 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 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):
  • 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.
  • PCR:
    • Is fast and specific.
    • 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.[2][3][5][6]

Gallery

References

  1. ↑ Brucellosis 2010 Case Definition. CDC. http://wwwn.cdc.gov/nndss/conditions/brucellosis/case-definition/2010/. Accessed on February 2, 2016
  2. ↑ 2.0 2.1 2.2 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. ↑ 3.0 3.1 Brucellosis. CDC. http://www.cdc.gov/brucellosis/transmission/index.html. Accessed on February 1, 2016
  4. ↑ Brucellosis. CDC. http://www.cdc.gov/brucellosis/clinicians/bacterial-isolation.html. Accessed on February 4, 2016
  5. ↑ Brucellosis. Wikipedia. https://en.wikipedia.org/wiki/Brucellosis. Accessed on January 29, 2016
  6. ↑ Brucelosis. Wikipedia. https://es.wikipedia.org/wiki/Brucelosis. Accessed on February 2, 2016
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 "Public Health Image Library (PHIL)".

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