|
|
| Line 1: |
Line 1: |
| __NOTOC__
| | {{reflist|2}}__NOTOC__ |
| {{CMG}}; {{AE}}{{DL}}{{VD}}
| |
| {{Brucellosis}}
| |
| == Overview ==
| |
| ''[[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]].
| |
| | |
| == Pathophysiology ==
| |
| ''[[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]]. The pathophysiology of Brucellosis can be described in the following steps:<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><ref name="pmid1574477">{{cite journal| author=Larralde de Luna M, Raspa ML, Ibargoyen J| title=Oral-facial-digital type 1 syndrome of Papillon-Léage and Psaume. | journal=Pediatr Dermatol | year= 1992 | volume= 9 | issue= 1 | pages= 52-6 | pmid=1574477 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1574477 }} </ref><ref name="pmid2915152">{{cite journal| author=Gazapo E, Gonzalez Lahoz J, Subiza JL, Baquero M, Gil J, de la Concha EG| title=Changes in IgM and IgG antibody concentrations in brucellosis over time: importance for diagnosis and follow-up. | journal=J Infect Dis | year= 1989 | volume= 159 | issue= 2 | pages= 219-25 | pmid=2915152 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2915152 }} </ref><ref name="pmid10858243">{{cite journal| author=Arenas GN, Staskevich AS, Aballay A, Mayorga LS| title=Intracellular trafficking of Brucella abortus in J774 macrophages. | journal=Infect Immun | year= 2000 | volume= 68 | issue= 7 | pages= 4255-63 | pmid=10858243 | doi= | pmc=101738 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10858243 }} </ref><ref name="pmid12414154">{{cite journal| author=Boschiroli ML, Ouahrani-Bettache S, Foulongne V, Michaux-Charachon S, Bourg G, Allardet-Servent A et al.| title=Type IV secretion and Brucella virulence. | journal=Vet Microbiol | year= 2002 | volume= 90 | issue= 1-4 | pages= 341-8 | pmid=12414154 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12414154 }} </ref><ref name="pmid15694858">{{cite journal| author=Lapaque N, Moriyon I, Moreno E, Gorvel JP| title=Brucella lipopolysaccharide acts as a virulence factor. | journal=Curr Opin Microbiol | year= 2005 | volume= 8 | issue= 1 | pages= 60-6 | pmid=15694858 | doi=10.1016/j.mib.2004.12.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15694858 }} </ref><ref name="pmid12414174">{{cite journal| author=DelVecchio VG, Kapatral V, Elzer P, Patra G, Mujer CV| title=The genome of Brucella melitensis. | journal=Vet Microbiol | year= 2002 | volume= 90 | issue= 1-4 | pages= 587-92 | pmid=12414174 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12414174 }} </ref><ref name="pmid11782541">{{cite journal| author=Moreno E, Moriyon I| title=Brucella melitensis: a nasty bug with hidden credentials for virulence. | journal=Proc Natl Acad Sci U S A | year= 2002 | volume= 99 | issue= 1 | pages= 1-3 | pmid=11782541 | doi=10.1073/pnas.022622699 | pmc=117501 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11782541 }} </ref><ref name="pmid12414149">{{cite journal| author=Gorvel JP, Moreno E| title=Brucella intracellular life: from invasion to intracellular replication. | journal=Vet Microbiol | year= 2002 | volume= 90 | issue= 1-4 | pages= 281-97 | pmid=12414149 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12414149 }} </ref><ref name="pmid12525425">{{cite journal| author=Ko J, Splitter GA| title=Molecular host-pathogen interaction in brucellosis: current understanding and future approaches to vaccine development for mice and humans. | journal=Clin Microbiol Rev | year= 2003 | volume= 16 | issue= 1 | pages= 65-78 | pmid=12525425 | doi= | pmc=145300 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12525425 }} </ref><ref name="pmid12414158">{{cite journal| author=Dornand J, Gross A, Lafont V, Liautard J, Oliaro J, Liautard JP| title=The innate immune response against Brucella in humans. | journal=Vet Microbiol | year= 2002 | volume= 90 | issue= 1-4 | pages= 383-94 | pmid=12414158 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12414158 }} </ref>
| |
| | |
| === Transmission===
| |
| According to CDC, humans are generally infected with Brucellosis in one of the following three ways:<ref name="pmid15930423" /><ref>{{Cite web|url=CDC|title=https://www.cdc.gov/brucellosis/transmission/index.html|last=|first=|date=|website=|publisher=|access-date=}}</ref>
| |
| {| class="wikitable"
| |
| ! colspan="2" |ROUTE OF TRANSMISSION
| |
| |-
| |
| |[[Gastrointestinal]]
| |
| |
| |
| Eating undercooked meat or consuming [[Unpasteurized milk|unpasteurized]]/raw dairy products
| |
| |-
| |
| |[[Inhalation]]
| |
| |
| |
| [[Breathing]] in the [[bacteria]] that cause brucellosis (inhalation)
| |
| |-
| |
| |[[Cutaneous]]
| |
| |
| |
| [[Bacteria]] entering the body through skin [[wounds]] or [[mucous membranes]]
| |
| |-
| |
| |Other modes of transmission
| |
| |
| |
| *Person-to-person spread of [[brucellosis]] is extremely rare.
| |
| *Infected mothers who are breast-feeding may transmit the infection to their infants.
| |
| *Sexual transmission has been rarely reported.
| |
| *While uncommon, [[transmission]] may also occur via [[Transplantation|tissue transplantation]] or [[blood transfusions]].
| |
| |}
| |
| | |
| === '''Incubation''' ===
| |
| [[Incubation period]] of Brucellosis varies from one to four weeks. But occasionally, it may be as long as several months.
| |
| | |
| === '''Dissemination''' ===
| |
| Following transmission, Brucellae is ingested by [[macrophages]] and [[Polymorphonuclear cells|polymorphonuclea]]<nowiki/>r cells. On ingestion, they replicate [[intracellularly]] inside the lysed cells and disseminate systemically.
| |
| ===Seeding===
| |
| * On [[transmission]], bacteria is actively [[phagocytosed]] by neurophilic [[granulocytes]] and [[monocytes]].
| |
| | |
| *On entry into the body, [[Brucella|Brucellae]] multiply in the [[Neutrophil|neutrophilic]] [[granulocytes]] and [[monocytes]], initially in [[lymph nodes]], which is followed by systemic hematogenous spread resulting in multiple localizing [[infection]]
| |
| | |
| ===Immune response===
| |
| Brucellosis elicits both [[Humoral immunity|humoral]] and [[Cell-mediated immunity|cell-mediated]] [[immune]] responses:<ref name="pmid15930423" /><ref name=":0" /><ref name="pmid8698508" /><ref name="pmid1574477" /><ref name="pmid2915152" /><ref name="pmid10858243" /><ref name="pmid12414154" /><ref name="pmid15694858" /><ref name="pmid12414174" /><ref name="pmid27672085">{{cite journal| author=Khan M, Harms JS, Marim FM, Armon L, Hall CL, Liu YP et al.| title=The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response. | journal=Infect Immun | year= 2016 | volume= 84 | issue= 12 | pages= 3458-3470 | pmid=27672085 | doi=10.1128/IAI.00531-16 | pmc=5116723 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27672085 }}</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>
| |
| ====Humoral immune response====
| |
| * [[Humoral immune system|Humoral]] response has a limited role in protecting host from [[Brucellosis|Brucellae]].
| |
| * On activation, [[Chronic lymphocytic leukemia|B-cell]] produce [[IgM]] class antibody, which is followed by [[IgG]] antibodies .
| |
| * Antibodies promote clearance of extracellular bacteria and facilitate [[phagocytosis]] of the Brucellae.
| |
| | |
| ====Cell mediates immune response====
| |
| *Tumor necrosis factor α ([[TNF-α]]) produce on activation of [[cell mediated immunity]], stimulates [[T lymphocytes]] and [[macrophages]], which help in eliminating intracellular [[brucellae]]. Virulent brucellae tend to suppress the activity of tumor necrosis factor α (TNF-α) and [[IFN|IFN-gamma]].
| |
| *Cytokines such as [[interleukin (IL)]] 12 promote production of Interferon γ ([[Interferon|IFN-γ]]) responses. IFN-γ, which drives [[TH1]]-type responses and stimulates [[macrophage]] activation. [[Cytokines]], which include , [[IL-6]], [[IL-4]]<nowiki/>and [[IL-10]], down-regulate the protective response.
| |
| | |
| ==Pathogenesis==
| |
| The pathogenesis of brucellosis is complex and not fully understood:<ref name="pmid15930423" /><ref name=":0" /><ref name="pmid8698508" /><ref name="pmid1574477" /><ref name="pmid2915152" /><ref name="pmid10858243" /><ref name="pmid12414154" /><ref name="pmid15694858" /><ref name="pmid12414174" /><ref>Barquero-Calvo E, Chaves-Olarte E, Weiss DS, et al. Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection. PLoS One 2007; 2:e631.</ref><ref>Gorvel JP, Moreno E. Brucella intracellular life: from invasion to intracellular replication. Vet Microbiol 2002; 90:281.</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>
| |
| | |
| By avoiding [[innate immunity]], [[Brucella infection|brucella]] survive with in [[Monocytic|monocytic cells]].
| |
| *Endotoxic [[lipopolysaccharide]] (LPS), plays a key role in survival of bacteria inside [[monocytic]] cell.
| |
| *[[LPS]] helps in survival of the bacteria inside the [[monocytic]] cell, by suppressing [[phagosome]]–[[lysosome]] fusion, internalizing bacteria into [[endoplasmic reticulum]] and inhibiting [[apoptosis]] of infected cell.
| |
| *Type IV secretion system (VirB) and type III secretion system, that regulates [[intracellular]] survival and trafficking has been identified, although type 3 not yet confirmed. Secretion system plays an important role in [[intracellular]] transport of the bacteria Acid-stable [[proteins]] produced by brucella, facilitates the survival in [[phagosomes]]
| |
| *Cu-Zn superoxide dismutase, produced by brucellae, gives them resistance from [[reactive oxygen]] intermediates.
| |
| *Two component BvrS/BvrR system, codes for [[External|histidine]] [[kinase]] [[sensor]]. Histidine kinase sensor plays an important role in controlling the expression of [[molecular]] determinants which are necessary for cell invasion.<ref name="pmid159304232">{{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>
| |
| *[[Hemolysin|Hemolysins]] help the bacteria to be realeased from a [[cell]] and induce cell [[necrosis]].
| |
| ==Genetics==
| |
| There is no known genetic association to Brucellosis.
| |
| | |
| == Microscopic Pathology ==
| |
| <gallery>
| |
| Image:Brucella-histo.jpg|thumb|200px|Brucella spp. are poorly staining, small gram-negative coccobacilli (0.5-0.7 x 0.6-1.5 µm), and are seen mostly as single cells and appearing like “fine sand”.
| |
| Image:Bruce-granulomanecrosis.jpg|thumb|200px|Histopathology of guinea pig liver in experimental Brucella suis infection. Granuloma with necrosis.
| |
| </gallery>
| |
| | |
| ==Reference==
| |
| {{reflist|2}} | |