The oral mucosa is colonized by over 200 microbial species. Thus, the potential for bacterial and fungal infections is high, with a need for innate defense mechanisms. The oral cavity is comprised of at least four microbial ecological niches with a certain degree of variability in the composition of their indigenous flora: the saliva, the tongue, and the tooth-associated supragingival and subgingival plaques (Slots, 1992). The most predominant indigenous bacterial flora in saliva, tongue and supragingival plaque are members of the Streptococcus species. These commensal bacteria may modulate yeast colonization by competing for nutrients and adhesion sites. Evidence for a protective role of the oral bacterial flora against fungal infection is derived from the fact that use of broad-spectrum antibiotics in humans and animals promotes oral Candida infection (Samaranayake et al., 1994; Deslauriers et al., 1995). In fact, many animal and in vitro studies have shown that oral Candida colonization can be inhibited by oral Streptococci (Liljemark and Gibbons, 1973; Samaranayake et al., 1994). Coaggregation of C. albicans or C. dubliniensis with the oral bacterium Fusobacterium nucleatum has been described in subgingival plaque, and may play a role in the pathogenesis of periodontal infections. The extent of coaggregation varied between the two Candida species, was inhibitable by mannose or a-methyl manno-side in both cases, and appeared to be due to the presence of a heat-stable Candida receptor (Jabra-Rizk et al., 1999).
Candida species are also part of the commensal flora in the oral cavity, with oral asymptomatic Candida carriage rates varying among different age groups. The highest asymptomatic Candida carriage rates (65-80%) were reported for healthy children
(Odds, 1988), the elderly (Wilkieson et al., 1991), and HIV+ patients (Campisi et al., 2002; Myers et al., 2003). C. albicans colonizes the oral mucosa at higher rates than many other mucosal sites in humans, but very few healthy carriers develop clinical signs of the oral infection (Odds, 1988). This is in contrast to other mucosal sites such as the vagina, where the carriage rate by healthy individuals is approximately 25% and clinical infection can be observed in otherwise healthy women (Sobel, 1988). C. albicans is frequently isolated from the saliva, tongue, and subgingival plaque (Redding et al., 1988, 2002; Phelan et al., 1997), and it is a change in the oral host environment that determines whether colonization will progress to infection.
3. Epidemiology, Clinical, and Histopathologic Characteristics of Oral Candidiasis
General risk factors for oropharyngeal candidiasis (OPC) are the two extremes of age (Odds, 1988), trauma (O'Grady and Reade, 1993), salivary gland hypofunction (Scully et al., 1994), dental prostheses (Odds, 1988), broad-spectrum antibiotic therapy, and topical use of corticosteroids (Deslauriers et al., 1995), as well as nutritional factors (Rennie et al., 1983; Samaranayake, 1986). Among the systemic conditions that predispose patients to OPC are diabetes mellitus, HIV infection, immunosuppressive therapy, Sjogren's syndrome, and radiation therapy for head and neck cancer (reviewed in Scully et al., 1994). In most types of high-risk patients, C. albi-cans is still the main etiologic agent of oral candidiasis (Scully et al., 1994). However, over the last 15 years new Candida species have emerged as the infectious agent respon sible for some of these infections in special patient categories, such as HIV+ patients and patients receiving radiation treatment of head and neck tumors (Redding et al., 1999; O'Daniels et al., 2000). The most commonly reported non-albicans Candida species involved are C. dubliniensis, C. glabrata, C. krusei, and C. tropicalis (O'Daniels et al., 2000; Redding, 2001).
Interestingly, up to 90% of HIV+ patients have had at least one episode of OPC, and their susceptibility to oral candidiasis is not paralleled by susceptibility to vaginal or disseminated infection (Scully et al., 1994). Although HIV-associated OPC is predominantly caused by C. albicans (Vargas and Joly, 2002; Myers et al., 2003), non-albicans Candida species have emerged as etiologic agents of oral candidiasis in certain HIV+ patients (O'Daniels et al., 2000; Redding,
2001). C. dubliniensis was isolated from as many as 32% of HIV+ patients with clinical signs of this infection (Coleman et al., 1997) and it can apparently be the sole causative agent detectable in some of these patients (O'Daniels et al., 2000; Vargas and Joly,
2002). More recent epidemiologic evidence suggests that the prevalence of C. dublinien-sis infection in this patient population is much lower than originally proposed and ranges between 5% and 10% (Giammanco et al., 2002; Vargas and Joly, 2002). Because typically C. dubliniensis shows the same pattern of antifungal susceptibility as C. albi-cans, in the vast majority of cases distinction between the two species is not required for successful treatment (Redding, 2001).
OPC is also a common infection in patients receiving radiation treatment of head and neck tumors (Redding et al., 1999). This infection is thought to be due to destruction of salivary gland tissue and hyposalivation (Fotos and Hellstein, 1992). Recently, an increase in oral candidiasis has been reported in head and neck cancer patients receiving radiation therapy, which is due to infection with one or more non-albicans Candida species (Redding, 2001).
In fact, fungi other than C. albicans were detected in 59% of the head and neck cancer patients with positive cultures, whereas 27% of the culture-positive patients harbored C. albicans in combination with other species (Redding et al., 1999, 2001). One of the most frequently isolated Candida species from these patients is C. glabrata (Redding et al., 1999). In recent years C. glabrata has emerged as an important pathogen in humans, being the second or third leading agent of candidiasis at all sites (reviewed in Fidel et al., 1999). Because C. glabrata is most often co-isolated with C. albicans, its role as a causative agent in OPC has been controversial. Also, its pathogenicity has been difficult to demonstrate experimentally due to its much lower virulence in animal models of infection (reviewed in Fidel et al., 1999). However, oral infection with mixed C. albicans and C. glabrata may be clinically more severe (Redding et al., 2002) and reports of C. glabrata as the only detectable species from oral lesions have been rising steadily (Redding et al., 1999, 2001, 2002). This is particularly important since unlike C. dubliniensis, C. glabrata isolated from oral lesions is much more resistant to standard antifungal treatment than C. albicans (Redding et al., 1999, 2001). As a result, C. glabrata oral infection is suspected in most cases when the patient does not respond to routine doses of fluconazole (Redding et al., 2002). Interestingly, C. glabrata is also associated with increased oral carriage rates among the elderly, especially the ones wearing oral prostheses (Lockhart et al., 1999). In the elderly, denture stomatitis and angular cheilitis are the most common denture-related infections (Espinoza et al., 2003), and the most frequently isolated species from these lesions is C. albicans (Leigh et al., 2002; Dar-Odeh and Shehabi, 2003).
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The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.