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Pathophysiology

Vaginal Defensive mechanisms aganist Candida

Innate Mechanisms

Defense	Mechanism of protection	Evidence of protection
Vaginal epithelial cells	In vitro inhibition of Candida growth	Protective role in vivo unknown Patients with recurrent candida infections have decreased anti-Candida activity
Mannose-binding lectin	Epithelial cell associated protein which binds to Candida surface mannan. Inhibits Candida growth by activating complement Activity is genetically determined	Decreased expression can increase the susceptibility for vaginal colonization of candida and leading to vaginitis
Activated lactoferrin	Fungistatic and fungicidal activity	Role in protection aganist infection is not clear
Vaginal bacterial flora	Lactobacillus species compete for nutrients. Bacteriocins and hydrogen peroxide inhibit yeast growth/germination	Role in protection aganist vaginitis still unclear
Phagocytic systems/polymononuclear leukocytes, mononuclear cells, complement	Mainly found in lamina propria in experimental vaginitis, help in reducing the yeast load and its invasion by phagocytosis and intracellular killing Nitric oxide has anti-Candida activity	Role in protection still unclear

Adaptive Mechanisms

Defense	Mechanism	Role in Protection
Immunoglobulin mediated immunity	Systemic IgM, IgG, and local IgA antibodies are produced in response to the infection	Protective role not proven. Elevated titres of vaginal anti-Candida IgG, IgA are detected in women with recurrent vaginitis Persistent symptoms could be attributed to anti-Candida IgE
Cell Mediated Immunity	Interleukin 4 (Th2) inhibits anti-Candida activity of nitric oxide and protective pro-inflammatory Th1 cytokines.	Role in protection from vulvovaginitis is still not clear It is still a hypothesis Patients with recurrent infection have undetectable Th2 cytokines.

Candida Virulence Factors

• C. albicans exists as blastospores, germ tubes, pseudomycelia, true mycelia and chlamydospores on special culture media. C. glabrata exists exclusively in blastospores.
• All strains of Candida species possess a yeast surface mannoprotein which helps in adhering to epithelial cells of the vagina.
• Germination of the spores helps in colonizing the vagina.
• Proteolytic enzymes, toxins and phospholipase destroy the proteins that normally impair fungal invasion, enhancing the ability of Candida to colonize the vagina.
• Phenotypic switching of Candida is described in patients with recurrent vaginitis.
• C. albicans can form biofilms on the intrauterine devices or sponges, causing disease recurrence.

Pathogenesis

• 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.
• 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.
• 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.
• The initial step of infection is colonization and symptoms appear with the invasion of the blastospores or pseudohyphae of the vaginal wall.
• The understanding of the transition from asymptomatic vaginal colonization with Candida to symptomatic vulvovaginitis is not clear.