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| ==Pathophysiology==
| | Classification: |
| ===Vaginal Defensive mechanisms aganist Candida===
| | (1) |
| ====Innate Mechanisms====
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| {| class="wikitable"
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| !Defense
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| !Mechanism of protection
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| !Evidence of protection
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| |-
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| |[[Epithelial cells]]
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| *[[In vitro]] inhibition of [[Candida]] growth<ref name="pmid16239581">{{cite journal| author=Barousse MM, Espinosa T, Dunlap K, Fidel PL| title=Vaginal epithelial cell anti-Candida albicans activity is associated with protection against symptomatic vaginal candidiasis. | journal=Infect Immun | year= 2005 | volume= 73 | issue= 11 | pages= 7765-7 | pmid=16239581 | doi=10.1128/IAI.73.11.7765-7767.2005 | pmc=1273905 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16239581 }}</ref>
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| *Protective role [[in vivo]] unknown
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| *Patients with recurrent [[candida]] infections have decreased anti-Candida activity
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| |-
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| |[[Mannose]]-binding [[lectin]]
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| *[[Epithelial cell]] associated [[protein]] which binds to [[Candida]] surface mannan.<ref name="pmid18715406" />
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| *Inhibits [[Candida]] growth by activating [[complement]]<ref name="pmid15243942">{{cite journal| author=Ip WK, Lau YL| title=Role of mannose-binding lectin in the innate defense against Candida albicans: enhancement of complement activation, but lack of opsonic function, in [[phagocytosis]] by human dendritic cells. | journal=J Infect Dis | year= 2004 | volume= 190 | issue= 3 | pages= 632-40 | pmid=15243942 | doi=10.1086/422397 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15243942 }}</ref>
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| *Activity is genetically determined
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| *Decreased expression can increase the susceptibility for [[vaginal colonization]] of [[candida]] and leading to [[vaginitis]]
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| |Vaginal [[bacterial flora]]
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| *[[Lactobacillus]] species compete for nutrients.
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| *[[Bacteriocins]] and [[hydrogen peroxide]] inhibit yeast growth/[[germination]]
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| *Role in protection aganist vaginitis still unclear
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| |-
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| |Phagocytic systems/polymononuclear [[leukocytes]], [[mononuclear cells]], [[complement]]
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| *Mainly found in [[lamina propria]] in experimental vaginitis, help in reducing the [[yeast]] load and its invasion by [[phagocytosis]] and intracellular killing<ref name="pmid340470">{{cite journal| author=Diamond RD, Krzesicki R, Jao W| title=Damage to pseudohyphal forms of Candida albicans by neutrophils in the absence of serum in vitro. | journal=J Clin Invest | year= 1978 | volume= 61 | issue= 2 | pages= 349-59 | pmid=340470 | doi=10.1172/JCI108945 | pmc=372545 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=340470 }}</ref>
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| *[[Nitric oxide]] has anti-Candida activity
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| *Role in protection still unclear
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| |}
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| ====Adaptive Mechanisms====
| | Candidiasis can be classified according to the site of infection into: |
| {| class="wikitable"
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| !Defense
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| !Mechanism
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| !Role in Protection
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| |-
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| |[[Immunoglobulin]] mediated [[immunity]]
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| |Systemic [[IgM]], [[IgG]], and local [[IgA]] antibodies are produced in response to the infection<ref name="pmid4556009">{{cite journal| author=Waldman RH, Cruz JM, Rowe DS| title=Immunoglobulin levels and antibody to Candida albicans in human cervicovaginal secretions. | journal=Clin Exp Immunol | year= 1972 | volume= 10 | issue= 3 | pages= 427-34 | pmid=4556009 | doi= | pmc=1713147 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4556009 }}</ref>
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| | Localoized mucocutaneous: |
| *Protective role not proven.
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| *Elevated [[titres]] of vaginal anti-Candida [[IgG]], [[IgA]] are detected in women with recurrent vaginitis
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| *Persistent symptoms could be attributed to anti-Candida [[IgE]]<ref name="pmid8809464">{{cite journal| author=Fidel PL, Sobel JD| title=Immunopathogenesis of recurrent vulvovaginal candidiasis. | journal=Clin Microbiol Rev | year= 1996 | volume= 9 | issue= 3 | pages= 335-48 | pmid=8809464 | doi= | pmc=172897 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8809464 }}</ref>
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| |-
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| |[[Cell Mediated Immunity]]
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| [[Interleukin 4]] (Th2) inhibits anti-Candida activity of [[nitric oxide]] and protective pro-inflammatory Th1 [[cytokines]].<ref name="pmid15735412">{{cite journal| author=Fidel PL| title=Immunity in vaginal candidiasis. | journal=Curr Opin Infect Dis | year= 2005 | volume= 18 | issue= 2 | pages= 107-11 | pmid=15735412 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15735412 }}</ref>
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| *Role in protection from [[vulvovaginitis]] is still not clear
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| *It is still a hypothesis<ref name="pmid15102806">{{cite journal| author=Fidel PL, Barousse M, Espinosa T, Ficarra M, Sturtevant J, Martin DH et al.| title=An intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of vulvovaginal candidiasis. | journal=Infect Immun | year= 2004 | volume= 72 | issue= 5 | pages= 2939-46 | pmid=15102806 | doi= | pmc=387876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15102806 }}</ref>
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| *Patients with recurrent infection have undetectable Th2 [[cytokines]].
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| |}
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| ===Candida Virulence Factors===
| | Oropharyngeal candidiasis |
| *[[C. albicans]] exists as [[blastospores]], [[germ tubes]], [[pseudomycelia]], [[true mycelia]] and [[chlamydospores]] on special [[culture]] media. [[C. glabrata]] exists exclusively in [[blastospores]].
| | Esophageal candidiasis |
| *All strains of [[Candida]] species possess a [[yeast]] surface [[mannoprotein]] which helps in adhering to [[epithelial cells]] of the [[vagina]].<ref name="pmid17560449">{{cite journal |vauthors=Sobel JD |title=Vulvovaginal candidosis |journal=Lancet |volume=369 |issue=9577 |pages=1961–71 |year=2007 |pmid=17560449 |doi=10.1016/S0140-6736(07)60917-9 |url=}}</ref><ref name="pmid3895958">{{cite journal |vauthors=Sobel JD |title=Epidemiology and pathogenesis of recurrent vulvovaginal candidiasis |journal=Am. J. Obstet. Gynecol. |volume=152 |issue=7 Pt 2 |pages=924–35 |year=1985 |pmid=3895958 |doi= |url=}}</ref>
| | Candida vulvovaginitis |
| *[[Germination]] of the spores helps in colonizing the vagina.<ref name="pmid6327527">{{cite journal| author=Sobel JD, Muller G, Buckley HR| title=Critical role of germ tube formation in the pathogenesis of candidal vaginitis. | journal=Infect Immun | year= 1984 | volume= 44 | issue= 3 | pages= 576-80 | pmid=6327527 | doi= | pmc=263631 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6327527 }} </ref>
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| *Proteolytic enzymes, toxins and [[phospholipase]] destroy the [[proteins]] that normally impair [[fungal]] invasion, enhancing the ability of [[Candida]] to colonize the [[vagina]].<ref name="pmid17560449">{{cite journal |vauthors=Sobel JD |title=Vulvovaginal candidosis |journal=Lancet |volume=369 |issue=9577 |pages=1961–71 |year=2007 |pmid=17560449 |doi=10.1016/S0140-6736(07)60917-9 |url=}}</ref><ref name="pmid3895958">{{cite journal |vauthors=Sobel JD |title=Epidemiology and pathogenesis of recurrent vulvovaginal candidiasis |journal=Am. J. Obstet. Gynecol. |volume=152 |issue=7 Pt 2 |pages=924–35 |year=1985 |pmid=3895958 |doi= |url=}}</ref><ref name="pmid2688924">{{cite journal |vauthors=Sobel JD |title=Pathogenesis of Candida vulvovaginitis |journal=Curr Top Med Mycol |volume=3 |issue= |pages=86–108 |year=1989 |pmid=2688924 |doi= |url=}}</ref><ref name="pmid12761103">{{cite journal| author=Schaller M, Bein M, Korting HC, Baur S, Hamm G, Monod M et al.| title=The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium. | journal=Infect Immun | year= 2003 | volume= 71 | issue= 6 | pages= 3227-34 | pmid=12761103 | doi= | pmc=155757 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12761103 }}</ref>
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| *[[Phenotypic switching]] of [[Candida]] is described in patients with recurrent vaginitis.<ref name="pmid3284370">{{cite journal| author=Soll DR| title=High-frequency switching in Candida albicans and its relations to vaginal candidiasis. | journal=Am J Obstet Gynecol | year= 1988 | volume= 158 | issue= 4 | pages= 997-1001 | pmid=3284370 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3284370 }}</ref>
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| *[[C. albicans]] can form [[biofilm]]s on the [[intrauterine devices]] or sponges, causing disease recurrence.<ref name="pmid25935553">{{cite journal| author=Muzny CA, Schwebke JR| title=Biofilms: An Underappreciated Mechanism of Treatment Failure and Recurrence in Vaginal Infections. | journal=Clin Infect Dis | year= 2015 | volume= 61 | issue= 4 | pages= 601-6 | pmid=25935553 | doi=10.1093/cid/civ353 | pmc=4607736 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25935553 }}</ref>
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| ===Pathogenesis===
| | Invasive Candidiasis: |
| *[[Candida (genus)|Candida]] vulvovaginitis is a microbial disease and not all patients with detectable pathogen are symptomatic. Multiple [[risk factors]] and the imbalance in the protective vaginal defenses predispose patients to develop active disease.
| | More serious and usually presenting in an immunocompromised host. |
| *[[Candida]] vaginal infections are more common in the reproductive age group because of the high concentration of [[estrogen]] as it increases the amount of [[glycogen]] in the [[vagina]] providing a carbon source for [[Candida]] organisms to [[colonize]]. It also increases the adherence of [[Candida]] to the [[vaginal epithelial cells]].<ref name="pmid11592551">{{cite journal| author=Dennerstein GJ, Ellis DH| title=Oestrogen, glycogen and vaginal candidiasis. | journal=Aust N Z J Obstet Gynaecol | year= 2001 | volume= 41 | issue= 3 | pages= 326-8 | pmid=11592551 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11592551 }}</ref>
| | |
| *The most common source of the infection is from the [[perianal]] area. Other less common source is [[sexual transmission]] and persistence of organisms in the [[vagina]] after treatment which is responsible for recurrence.<ref name="pmid333134">{{cite journal| author=Miles MR, Olsen L, Rogers A| title=Recurrent vaginal candidiasis. Importance of an intestinal reservoir. | journal=JAMA | year= 1977 | volume= 238 | issue= 17 | pages= 1836-7 | pmid=333134 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=333134 }}</ref>
| | Candidaemia |
| *The initial step of infection is [[colonization]] and symptoms appear with the invasion of the [[blastospores]] or [[pseudohyphae]] of the [[vaginal wall]].<ref name="pmid9880475">{{cite journal| author=Fidel PL, Vazquez JA, Sobel JD| title=Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. | journal=Clin Microbiol Rev | year= 1999 | volume= 12 | issue= 1 | pages= 80-96 | pmid=9880475 | doi= | pmc=88907 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9880475 }}</ref>
| | Candida endophthalmitis |
| *The understanding of the transition from asymptomatic vaginal colonization with [[Candida]] to symptomatic [[vulvovaginitis]] is not clear.<ref name="pmid3895958">{{cite journal |vauthors=Sobel JD |title=Epidemiology and pathogenesis of recurrent vulvovaginal candidiasis |journal=Am. J. Obstet. Gynecol. |volume=152 |issue=7 Pt 2 |pages=924–35 |year=1985 |pmid=3895958 |doi= |url=}}</ref><ref name="pmid2688924">{{cite journal |vauthors=Sobel JD |title=Pathogenesis of Candida vulvovaginitis |journal=Curr Top Med Mycol |volume=3 |issue= |pages=86–108 |year=1989 |pmid=2688924 |doi= |url=}}</ref>
| | Candida endocarditis |
| | Candida osteoarticular disease |
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| | ------------------------------------------------------------------------------------------------- |
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| | Pathophysiology: |
| | |
| | Candida is a normal commensal of skin and mucous membranes. A competent immune system and an intact regenerating healthy skin prevent the virulence of Candida. |
| | |
| | The main virulence factors that mediate the infection: (2) |
| | Secreting molecules that mediate adherence into host cells |
| | Production of hydrolases which has a lytic effect on tissues and facilitate the invasion by the bacteria. |
| | Polymorphism: Candida has the ability to grow either as pseudohyphae (elongated elipsoid form) or in a yeast form (rounded to oval budding form. While the role of polymorphism is not clearly understood in the virulence of Candida, it’s noted that species capable of producing the most severe form of the disease has this ability. |
| | Biofilm production: which means the ability to form a thick layer of the organism on the mucosal surfaces or even on catheters and dentures. |
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| ==References== | | ==References== |
Classification:
(1)
Candidiasis can be classified according to the site of infection into:
Localoized mucocutaneous:
Oropharyngeal candidiasis
Esophageal candidiasis
Candida vulvovaginitis
Invasive Candidiasis:
More serious and usually presenting in an immunocompromised host.
Candidaemia
Candida endophthalmitis
Candida endocarditis
Candida osteoarticular disease
Pathophysiology:
Candida is a normal commensal of skin and mucous membranes. A competent immune system and an intact regenerating healthy skin prevent the virulence of Candida.
The main virulence factors that mediate the infection: (2)
Secreting molecules that mediate adherence into host cells
Production of hydrolases which has a lytic effect on tissues and facilitate the invasion by the bacteria.
Polymorphism: Candida has the ability to grow either as pseudohyphae (elongated elipsoid form) or in a yeast form (rounded to oval budding form. While the role of polymorphism is not clearly understood in the virulence of Candida, it’s noted that species capable of producing the most severe form of the disease has this ability.
Biofilm production: which means the ability to form a thick layer of the organism on the mucosal surfaces or even on catheters and dentures.
References