Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in recurrent vulvovaginal candidiasis.

AIM: Recurrent vulvovaginal candidiasis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. Most RVVC studies use animal models, and there is still a lack of observation on human tissue samples and effective therapy to reduce recurrence. MATERIALS AND METHODS: We observed CD163+ macrophages and NLRP3 expression by immunohistochemistry, also investigated bacteria and fungi co-invasion by fluorescence in situ hybridization from 144 human vaginal biopsy tissues (48 RVVC, 48 VVC, 48 healthy volunteers), and we also explored the effect of combining metronidazole in the treatment of RVVC. RESULTS: A large number of neutrophils, lymphocytes and plasma cells infiltrated the mucosa, basement membrane and submucosa, accompanied by significantly overexpressed NLRP3 inflammasome. While CD163+ macrophages often infiltrated under the basement membrane in patients with RVVC, 29.2% of cases were found Gardnerella and fungi jointly invaded the vaginal mucosas. RVVC vaginal mucosal histopathology revealed mucosal inflammatory responses dominated by neutrophils, which may involve activation of NLRP3 and immune tolerance of M2 macrophages (CD163+ ). Fluconazole combined with metronidazole can achieve higher efficiency (95.8% vs. 70.8%) and reduce the recurrence rate more (8.3% vs. 37.5%) at 6-month follow-up. CONCLUSION: Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in RVVC. The combined medication will need to further evaluate in future.

Vulvovaginal candidiasis in a murine model of diabetes emphasizing the invasive ability of etiological agents.

Aim: To compare the pathogenesis of vulvovaginal candidiasis by three Candida species in diabetic mice. Materials & methods: Estrogenized and diabetic mice were challenged with C. albicans, C. tropicalis and C. glabrata. Results: Diabetic animals infected with C. albicans and C. tropicalis maintained the highest fungal burden, despite of high levels of proinflammatory cytokines (IL-6 and TNF-α), respectively. For C. glabrata, the results were similar in diabetic and nondiabetic groups. Conclusion:C. tropicalis was as invasive as C. albicans, and both were more effective than C. glabrata. This ability was attributed to filamentation, which may be stimulated by glucose levels from vaginal fluid. In addition, the high burden may be attributed to the apparent immunological inefficiency of the diabetic host.

Effect of intrauterine device insertion on Candida species in cervicovaginal specimen identified by polymerase chain reaction technic: A longitudinal study on Iranian women.

AIM: To assess the effects of copper T-380-A intrauterine device (IUD) insertion on Candida species in cervicovaginal specimen by a molecular method, polymerase chain reaction. METHODS: This is a longitudinal prospective study performed on 95 women attending Health Centers of Tehran, Iran in 2012, who selected copper T-380-A IUD for contraception and had no history of local or systemic antibiotics or antifungals use during the previous 2 weeks. Cervicovaginal specimens were twice collected and cultured on Sabouraud dextrose agar and CHROMagar Candida, before and 3 months after IUD insertion. Finally, a molecular method, PCR-RFLP was performed for identification of Candida species. P-values <0.05 were considered significant. RESULTS: The mean age of participants was 28 ± 7.44 years. Positive Candida cultures were significantly increased 3 months after IUD insertion (25.3% vs 11.6%, P = 0.007). The most common identified species before and after IUD insertion, were Albicans, Glabrata and then both 'Albicans & Glabrata', respectively. The prevalence of Albicans and Glabrata decreased, while both 'Albicans & Glabrata' increased insignificantly. CONCLUSION: There was more than about fourfold increase in positive Candida cultures after IUD insertion. As the prevalence of simultaneous infection with both 'Albicans & Glabrata' species which are resistant to usual treatment, increased, it seems necessary to provide more intensive follow-up care for IUD users.

High glucose-mediated overexpression of ICAM-1 in human vaginal epithelial cells increases adhesion of Candida albicans.

To investigate the involvement of ICAM-1 in the adhesion of Candida to the genitourinary epithelial cells in high glucose, we examined the adhesion of Candida albicans or Candida glabrata to human vaginal epithelial cells (VK2/E6E7) or human vulvovaginal epidermal cells (A431). These cells were cultured in 100, 500 or 3000 mg/dL glucose for three days and inoculated with Candida for 60 minutes. Followed by, adhering of Candida to the cells, which were counted. While the adhesion of Candida albicans to VK2/E6E7 significantly increased in the high glucose, A431 did not. We next examined the expression of ICAM-1 as a ligand on the epithelial cells. ICAM-1 expression was increased in VK2/E6E7 cultured in the high glucose; however, the expression level in A431 was not high compared with VK2/E6E7. This data suggested that ICAM-1 functions as one of ligands in the adhesion of Candida albicans to the vaginal epithelial cells in a high glucose environment. Impact statement What is already known on the subject: Candida's complement receptor is involved in the adhesion to epithelial cells. The expression of this receptor has been reported to increase as glucose concentration increases. This is considered as a contributing factor to the high risk for vulvovaginal candidiasis (VVC) in diabetes. On the host side, diabetic patients have a factor that facilitates adhesion of Candida to epithelial cells. This factor has been unknown until recently. What the results of this study add: In this study, we used a vaginal epithelial cell line and showed that the adhesion of C. albicans to cells increased at higher glucose concentrations. At the same time, ICAM-1 expression of cells also increased. Thereby, it is suggested that the expression of ICAM-1 in vaginal epithelial cells is increased by glucose such as urinary sugar in diabetic patients and is a condition for facilitating adhesion of Candida. What the implications are of these findings for clinical practice and/or further research: We expect not only host immune dysfunction but also alteration in epithelial cells will be focussed on as a cause of VVC in diabetic patients.

Vulvovaginal candidiasis: Etiology, symptomatology and risk factors.

OBJECTIVE: To determine epidemiological, clinical and mycological characteristics of vulvovaginal candidiasis (VVC) in Tunisian population and to evaluate predisposing factors. PATIENTS AND METHODS: In this retrospective study, 2160 vaginal swabs were performed over 2 years (January 2014-December 2015). It was carried out at the laboratory of Parasitology and Mycology, Rabta Hospital in Tunisia. After swab collecting, direct examination and culture on Sabouraud Chloramphenicol and Sabouraud Chloramphenicol Actidione media were implemented to research yeasts. Then identifying of yeast species was through chlamydosporulation test and auxanogram. For each patient, a questionnaire was filled noting age, medical and surgical history, symptoms and risk factors. Statistical analysis of data was performed on SPSS 16 using Khi2 test, P<0.05 was considered significant. RESULTS: Direct examination was positive showed spore and/or pseudohypha in 24.72%. Candida albicans was isolated most frequently (76.61%) followed by Candida glabrata (17.18%). The maximum frequency of Candida-positive cultures was in 25-34 years old age group. Leucorrhea was the most common symptom (72.25%) followed by vulvar prurits (63.23%), dyspareunia (32.25%) and urinary burning (24.92%). Only pregnancy was correlated positively with VVC. CONCLUSION: It appears from our study that VVC is relatively common in Tunisia. His diagnosis results from confrontation of anamnestic, clinical and mycological data. The knowledge of risk factors and their correction would be necessary to prevent the occurrence of VVC, especially in its recurrent form.

Etiología de la candidiasis vulvovaginal recidivante en la Atención Primaria de Salud en Santa Catarina, Brasil / Etiology of recurrent vulvovaginal candidiasis in the National Health System in Santa Catarina, Brazil / Etiologia da candidíase vulvovaginal recorrente na Atenção Primária à Saúde em Santa Catarina, Brasil

El objetivo del presente trabajo fue destacar las características epidemiológicas que puedan subsidiar la Atención Primaria de Salud (APS) en mujeres portadoras de candidiasis vulvovaginal (CVV) y candidiasis vulvovaginal recidivante (CVVR), a partir de estudios realizados en tres municipios del sur de Brasil. A través del examen micológico de la secreción vaginal de 300 mujeres con sospecha clínica de CVV o CVVR se identificaron las especies prevalentes de Candida, correlacionándose los hallazgos con los principales factores de riesgo mencionados en la literatura. Fueron confirmadas levaduras en 90 (30%) casos, resultando las especies más frecuentes C. albicans (61,1%), C. krusei (16,7%), C. tropicalis (6,7%), C. glabrata (4,4%) y Candida spp. (11,1%). En los casos de CVVR, C. albicans fue la especie más encontrada, con una prevalencia superior a la observada en la CVV. C. krusei apareció como la segunda especie más prevalente en todas las muestras, resaltando la importancia del diagnóstico a nivel de especie, dada la resistencia intrínseca al fluconazol. Las informaciones epidemiológicas del estudio son útiles para que los gestores de la Atención Primaria de Salud (APS) y los profesionales de la Salud puedan tener subsidios adicionales para actuar preventivamente en el caso de candidiasis vulvovaginales.

The main purpose of this work was to highlight epidemiological characteristics serving as subsidies to health promotion activities for vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) by the national health system, in three cities in southern Brazil. Through the mycological examination of vaginal secretions of 300 women with clinical suspicion of VVC or RVVC, Candida-prevalent species were identified and they were correlated with the main risk factors mentioned in the literature. Yeasts were confirmed in 90 (30%) cases, resulting in C. albicans 61.1%, C. krusei 16.7%, C. tropicalis 6.7%, C. glabrata 4.4% and others 11.1%. C. albicans was the species most commonly found in cases of RVVC, with levels higher than the prevalence of the species in the VVC. C. krusei prevailed as the second most prevalent species in both samples, emphasizing the importance of diagnosing the species level, due to its intrinsic resistance to fluconazole. The epidemiological information of the study is useful for managers of the National Health Care System, as well as direct health professionals, who can have new subsidies to act preventively against vulvovaginal candidiasis.

O objetivo do presente trabalho foi destacar as características epidemiológicas que possam subsidiar a Atenção Primária à Saúde (APS) em mulheres portadoras de candidíase vulvovaginal (CVV) e candidíase vulvovaginal recorrente (CVVR), a partir de estudos realizados em três municípios do sul do Brasil. Através do exame micológico da secreção vaginal de 300 mulheres com suspeita clínica de CVV ou CVVR foram identificadas as espécies prevalentes de Candida, correlacionando os achados com os principais fatores de risco mencionados na literatura. Foram detectadas leveduras em 90 (30%) dos casos, resultando as espécies mais frequentes C. albicans (61,1%), C. krusei (16,7%), C. tropicalis (6,7%), C. glabrata (4,4%) e Candida spp. (11,1%). Nos casos de CVVR, C. albicans foi a espécie mais encontrada, com uma prevalência superior à observada nos casos de CVV. C. krusei apareceu como a segunda espécie mais prevalente em todas as amostras, ressaltando a importância do diagnóstico em nível de espécie, devido à resistência intrínseca ao fluconazol. As informações epidemiológicas deste estudo são úteis para que os gestores da Atenção Primária à Saúde (APS) e os profissionais da Saúde Pública possam ter subsídios adicionais para atuar preventivamente nos casos de candidíases vulvovaginais.

Chronic granulomatous disease presenting with hypogammaglobulinemia.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder caused by inherited defects in the nicotinamide adenine dinucleotide phosphate oxidase complex. The neutrophils of patient with CGD can ingest bacteria normally, but the oxidative processes that lead to superoxide anion formation, hydrogen peroxide production, nonoxidative pathway activation, and bacterial killing are impaired. Serious infections result from microorganisms that produce catalase. Immunoglobulin levels of patients with CGD are usually normal or elevated. We describe a patient with CGD associated with hypogammaglobulinemia, an unusual co-occurrence.

Topical therapy for mucosal yeast infections.

Mucosal yeast infection is best understood as a consequence of compromised mucosal cell-mediated and innate immunity. Defense against oral candidiasis is dominantly cell mediated. The innate immune system may play the main role in regulating vulvovaginal yeast infection. Conditions that compromise cell-mediated immunity such as leukemia, severe illness and HIV infection must be considered as predisposing factors for recurrent oral candidiasis. Compromise of vaginal innate immunity due to mucosal allergy or due to a genetic defect such as mannose-binding lectin deficiency contributes to chronic vulvovaginal yeast infection. Treatment of cofactors must be considered in order to achieve control in recurrent mucosal yeast infection.

Recurrent infections in children with nickel allergic contact dermatitis.

Some patients with nickel (Ni) allergic contact dermatitis (ACD) suffer from systemic symptoms after ingestion of Ni-rich foods, a condition termed Systemic Nickel Allergy Syndrome (SNAS). The aim of this study is to investigate in children the relationship between Ni ACD and lymphocyte subsets or susceptibility to infections. Nineteen children with Ni ACD and 18 controls matched for sex and age were enrolled. All participants underwent patch test, skin prick test and clinical assessment. Serum immunoglobulins and flow cytometry for lymphocyte subset study were also evaluated. In children with Ni ACD a higher incidence of recurrent upper respiratory tract infections and recurrent otitis media were detected. Serum levels of immunoglobulins and lymphocyte subsets did not show significant changes (p>0.05) between the two groups studied. We can hypothesize that in children with Ni ACD the risk of recurrent infections is increased. Although the clinical manifestations of SNAS are still controversial, we can suppose that recurrent infections may be considered a clinical symptom of this syndrome.

Are glucocorticoids a consistent risk factor for infections in rheumatoid arthritis patients under treatment with methotrexate and etanercept?

OBJECTIVE: To evaluate the incidence of infections in subjects with rheumatoid arthritis (RA), treated with an anti-TNFalpha blocker during one year follow-up. The aim of the study was focused to evaluate the number of infectious episodes in two groups of patients treated with etanercept (ETN) plus methotrexate (MTX) or ETN plus MTX and glucocorticoid drugs (GCs/prednisone) for a 12 months period. MATERIALS AND METHODS: Sixty-nine out of 122 RA patients treated with an anti-TNFalpha drug (ETN) were included in an outpatient control system within the Immunology Department Sapienza-University of Rome-II; School of Medicine. RA patients were studied during the first year after ETN introduction. Particularly 20 RA patients have been included in a subgroup. For these 20 patients infections have been monitored for 2 years: 12 months before and 12 months after ETN treatment starting. RESULTS: According to drugs administration protocols, after a careful screening aiming to exclude latent tuberculosis infection, 20 patients have been treated with ETN (10 of them received treatment in association to MTX, while 10 were given a GCs therapy plus MTX). During the one-year ETN treatment period, 7 infections have been described in the group treated with ETN, MTX and GCs and no infection in the group treated with ETN and MTX. After analysing the infection number in the two groups of patients, in the year preceding biological treatment no significant change arose. CONCLUSIONS: The risk of infections in subjects treated with the biological drug ETN is well known. Our data show that after one year therapy the [ETN+MTX+GCs] group is marked by a greater frequency of infectious episodes compared to the subjects treated with ETN plus MTX. Therefore, the additional infectious risk appears to be related to steroid therapy itself, though infections were not serious.

Effect of experimental diabetes on the development and maintenance of vulvovaginal candidiasis in female rats.

OBJECTIVE: The purpose of this study was to develop an experimental model of diabetes in female rats and verify its influence on vulvovaginal candidiasis. STUDY DESIGN: The animals were divided into control and diabetic groups. Diabetes was induced with the use of an intravenous solution of alloxan (42 mg/kg bodyweight). One week after confirmation of hyperglycemia, the inoculation of Candida albicans yeast, previously standardized from a vaginal isolate, in concentrations of about 5 x 10(8), was performed. Infection control was made through vaginal culture, Papanicolaou cytology, and scanning electron microscopy (SCEM). RESULTS: The results pointed to different glycemias between the control (74.8 +/- 2.6) and experimental groups (543.1 +/- 12.1) and a significant bodyweight decrease (227.6 +/- 4.77 and 204 +/- 6.39, respectively). The positive infection was shown by culture, Papanicolaou test, and SCEM in the experimental group. CONCLUSION: Diabetes mellitus causes hyperglycemia, which was favorable to the vaginal colonization and infection by C albicans.

Vaginal colonization with Candida spp. in human immunodeficiency virus-infected women: a cohort study.

We have conducted a longitudinal study on factors associated with candidal vaginal colonization, a precursor of vaginitis, in a cohort of HIV-infected women in Italy. All consecutive women attending a single, tertiary care clinical site were offered free screening for sexually transmitted infections and genital disorders every 6-12 months. Candidal vaginal colonization was defined as a positive culture for Candida spp. in an asymptomatic woman. From January 1998 to July 2002 we analysed 214 women. The baseline prevalence of candidal vaginal colonization was 16.8%. In the logistic regression analysis, the time since HIV infection > or =36 months (odds ratio [OR] = 0.18, 95% confidence interval [CI] 0.016-0.53, P = 0.002) and a plasma viral load > or =10,000 copies/mL (OR = 3.9, 95% CI 1.03-14.9, P = 0.045) were independently associated with candidal colonization. Among 130 women who were followed for a mean period of 24 months, the incidence of vaginal colonization was 10.7/100 women-years. In the Cox regression analysis, a CD4(+) T-lymphocytes count <100 cells/microL during the follow-up was associated with an increased risk of candidal vaginal colonization (OR = 4.45, C.I. = 1.20-16.81, P = 0.03). Risk of candidal vaginal colonization episodes in HIV-infected women significantly increase when CD4(+) T-lymphocytes are less than 100.

Candidíase vulvovaginal: uma revisão de literatura / Vulvovaginal candidiasis: a review

A candidíase vulvovaginal é a infecção da mucosa vaginal causada por fungos do gênero Candida, colonizantes habituais do trato gastrintestinal, que podem, em condições especiais, tornar-se patogênicos. É uma das causas mais comuns de vaginite, com incidência aproximada de 25 porcento, que acomete cerca de 75 porcento das mulheres, pelo menos uma vez na vida e se caracteriza por leucorréia, prurido intenso, hiperemia vulvar, disúria e dispareunia. Vários fatores predisponentes estão relacionados com a ocorrência da candidíase vulvovaginal: gravidez, diabetes mellitus, uso de anticoncepcionais hormonais, terapia de reposição hormonal, antibióticos e corticóides, doenças imunossupressoras e outros. Para haver infeção é necessário um estímulo estrogênico alto, razão pela qual sua ocorrência é mais comum durante o menacme e na mulher climatérica sob terapia de reposição hormonal, sendo o processo de adesão do fungo primordial para que ela se estabeleça. Entre as mulheres que apresentam candidíase vulvovaginal, cerca de 5 porcento desenvolve a forma recorrente, definida por pelo menos quatro episódios de vaginite por cândida sp no intervalo de um ano. O diagnóstico é essencialmente clínico, podendo ser corroborado por exame microscópico e excepcionalmente por cultura. O tratamento pode ser tópico e/ou sistêmico, sendo os imidazóis as drogas mais indicadas

Susceptibility to vaginal candidiasis under different conditions in mice.

In order to study the susceptibility of murine vaginal mucosa to Candida albicans under different conditions, vaginal lavage fluid and vaginal tissue of mice were observed and compared between murine models with normal immune system (estrogen-treated mice) and immunosuppressed murine model, and between primary infection model of vaginal candidiasis and secondary infection one. The average level of colony forming unit (CFU) from the immuosuppressed group was higher than that from estrogen-treated group at each time point and the peak time was delayed. The differences between the two groups were statistically significant (P < 0.05) from the fourth day after inoculation. A significant difference existed in the average level of CFU between the control group and the estrogen-treated group (P < 0.05), and between the control group and the immuosuppressed group (P < 0.01). It was concluded that the vaginal mucosa from the immunosuppressed mice is more susceptible to Candida albicans and no difference is found in susceptibility between mice with primary infection and secondary infection.

[Vaginal candidiasis--treatment protocols using miconazole and fluconazole]. / Vaginalna kandidoza--protokoli na lechenie s myconazol i fluconazol.

The incidence of fungal infections is growing in the last 20 years. The epidemiological studies show that 45% of all vaginal infections are caused by Candida albicans or other Candida species. 7 out of 10 women suffer from yeast infection at least once in a lifetime and 4 out of 10 have multiple recurrences. 20-55% of women have asyptomatic vaginal colonization with Candida species. It is strongly believed that fungal infection is not sexually transmitted disease. The route of transmission is oral and it is estrogene dependant. The diagnosis is based on macroscopic, microscopic examination (KOH preparation), culture and rarely Pap test. Treatment of vaginal candidiosis is based on two principles: elimination of predisposing factors antifungal treatment Local treatment is the first line of choice in cases of acute vaginal yeast infection with 84-90% success rate. There are a variety of local preparations on our market including Nizoral, Clotrimazole, Canesten, Gyno-Daktarine, Gyno-Pevaryl, Miconazole. Different groups of broad spectrum oral antimycotics are also used including Nystatine, Ketoconazole (Nizoral), Fluconazole (Diflucan, Fungolon, Mycosyst), itraconazole (Orungal). The treatment of chronic, recurrent and resistant forms of vaginal candidosis is carried out with prolonged local and/or systemic therapy for a period of at least 6 months. Different regimes of therapy are proposed. Fluconazole is an oral drug of choice for continuous treatment of vaginal yeast infection with the least toxicity.

Follow-up of users of intrauterine device with and without bacterial vaginosis and other cervicovaginal infections.

This study aimed to assess the prevalence of bacterial vaginosis (BV) and other cervicovaginal infections, as well as the incidence of complications among new users of IUD, 1 and 6 months after its insertion, in the City of Campinas, Brazil. A total of 223 women who had a TCu-380A IUD inserted from May through November 2001, were included in the study. After the IUD insertion all women were scheduled to two additional visits: after 1 month and after 6 months, when they were interviewed and a pelvic examination was performed, along with a collection of specimens from the vagina and the endocervix for laboratory testing. The Nugent's criterion was used for the BV diagnosis. They were also evaluated with regard to presence of complications possibly related to IUD insertion and use, i.e., abnormal bleeding, dysmenorrhea, expulsion and pelvic inflammatory disease. The prevalence of cervicovaginal infections was 29.1%, BV being the most frequent (19.7%). Dysmenorrhea was more frequent among women with BV than among women without BV (p = 0.03). A trend of abnormal bleeding being more frequent among women with BV was also found. In conclusion, BV after 1 month of IUD insertion was not associated with IUD complications, with the exception of dysmenorrhea.

Vulvovaginal candidiasis.

VVC represents a spectrum of disease. Although there is a clear need for better use of diagnostic modalities and development of better treatment alternatives, most patients with VVC, even the complicated cases, at least have the perspective of achieving adequate control of their symptoms. Future advances, particularly in the area of home diagnostics, may help to optimize use of currently available medicines.

Spectrum and proteinase production of yeasts causing vaginitis in Saudi Arabian women.

BACKGROUND: Yeast vaginitis is a common infection. Data on the identity and prevalence of the etiological species would serve both epidemiological and therapeutic ends. Proteinase secretion by the invading yeast has been implicated in facilitating infection. Hence a prospective study was conducted to determine the species causing vaginitis in women from Saudi Arabia and the yeast's ability to produce proteinase. MATERIAL/METHODS: The subjects were patients with clinical signs of vaginitis. A high vaginal swab specimen from each patient was cultured, and only women yielding heavy yeast growth were enrolled. The isolated yeasts were identified by routine procedures, then evaluated for proteinase production in a medium containing bovine serum albumin. RESULTS: A total of 500 patients were studied. Candida albicans was the major species to cause vaginitis (59%), followed by C. glabrata (31%), C. tropicalis (4%), C. krusei (3.2%), Saccharomyces cerevisiae (1.6%), C. parapsilosis (0.6%), and C. kefyr (0.6%). All isolates of C. albicans and C. parapsilosis and 95% of C. tropicalis produced proteinase, while isolates from the remaining species did not. CONCLUSIONS: These results indicate that 59.6% of yeast vaginitis in women from Saudi Arabia is caused by C. albicans, and 31.6% by C. glabrata. Of relatively low prevalence were C. tropicalis and C. krusei. The study also revealed that both proteinase producers and non-producers were involved in causing vaginitis, indicating that proteinase secretion is not an essential factor in the pathogenesis of yeast vaginitis.

Persistent colonization and transient suppression of DTH responses in an estrogen-dependent vaginal candidosis murine model.

Recurrence of vaginal candidosis in women of childbearing age has been attributed to several predisposing factors including the presence of significant amounts of estrogen in the reproductive tract. In this study, the effect of estrogen on the level of C. albicans colonization, persistence of infection and suppression of DTH responses was investigated in an estrogen-dependent vaginal candidosis murine model. Mice were first injected subcutaneously with 0.5 mg of estradiol valerate 72 hours prior to C. albicans intravaginal inoculation and at weekly intervals thereafter for a period of up to 4 weeks; the inoculum consisted of 2 x 10(7) stationary-phase C. albicans blastoconidia in a volume of 20 microl. C. albicans colonization was evaluated in the spleen, liver, kidney, small intestine and reproductive tract of estrogen-treated and control mice 72 hours following inoculation, DTH responses were evaluated 2 and 5 weeks following primary inoculation and persistence of infection was evaluated at days 2, 3, 4, 8, 12, 19 and 26 post inoculation. Estrogen-treated mice exhibited higher levels of C. albicans colonization compared with control mice; this was most evident in the small intestine and reproductive tract. Estrogen treatment resulted in pronounced suppression of C. albicans-specific DTH responses; in that average footpad swelling was 4.7 mm in untreated mice compared with 2.3 mm in estrogen-treated mice. Long-term estrogen treatment resulted in the persistence of infection; in contrast, C. albicans infection resolved by day 8 post inoculation in untreated mice. DTH responses assayed 5 weeks post primary inoculation in treated mice were on average 4.1 mm, this was similar to that observed in untreated mice tested for DTH response 2 and 5 weeks post primary inoculation. These results suggest that, on the one hand, estrogen has an enhancing effect on C. albicans colonization and persistence of infection. On the other, estrogen seems to suppress DTH responses within the first 2 weeks post infection; persistence of infection under the influence of estrogen, however, seems to coexist with detectable systemic cell-mediated immunity.

Growth inhibition of Candida albicans by human vaginal epithelial cells.

Vulvovaginal candidiasis (VVC) is a common mucosal infection caused by Candida species in women of childbearing age. Although acute VVC affects a large number of women and is often precipitated by hormonal fluctuations involving high estrogen levels, recurrent VVC (RVVC) affects another 5%-10% of women without any known predisposing factors. We have recently reported that vaginal epithelial cells from nonhuman primates and mice inhibit the growth of Candida albicans in vitro, which may represent an innate host defense mechanism against C. albicans at the vaginal mucosa. In the present study, we show that vaginal epithelial cells collected from healthy women with no history of VVC also exhibit anti-Candida activity, with no differences in activity at various stages of the menstrual cycle. Women diagnosed with RVVC, on the other hand, have reduced epithelial cell anti-Candida activity. These results are further evidence that vaginal epithelial cells provide an innate host resistance mechanism against Candida and that reduced activity may contribute to RVVC.