Hyaluronan in vaginal secretions: association with recurrent vulvovaginal candidiasis

OBJECTIVE: We evaluated whether vaginal concentrations of hyaluronan were altered in women with recurrent vulvovaginal candidiasis (RVVC). STUDY DESIGN: Lavage samples from 17 women with acute RVVC, 27 women who were receiving a maintenance antifungal regimen, and 24 control women were tested for hyaluronan and interleukin (IL)-6, IL-12, and IL-23 by enzyme-linked immunosorbent assay. RESULTS: Median vaginal hyaluronan concentrations were 33.8 ng/mL (range, 21.6-66.3 ng/mL) in women with acute RVVC, 15.0 ng/mL (range, 11.2-50.6 ng/mL) in women who were receiving maintenance therapy, and 4.2 ng/mL (range, 3.6-12.0 ng/mL) in control subjects (P <= .02). The vaginal hyaluronan concentration was 27.4 ng/mL (range, 15.4-37.7 ng/mL) when Candida was detected by microscopy and 9.5 ng/mL (range, 7.7-14.6 ng/mL) in microscopy-negative cases (P = .0354). Elevated hyaluronan levels were associated with itching plus burning (40.7 ng/mL) or itching plus discharge (42.1 ng/mL), as opposed to itching only (6.2 ng/mL; P = .0152). Hyaluronan and IL-6 levels were correlated (P = .0009). CONCLUSION: Hyaluronan release is a component of the host response to a candidal infection and may contribute to symptoms.

Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis

Precis Women with recurrent vulvovaginal candidiasis (RVC) due to a polymorphism in codon 54 of the MBL2 gene respond better to fluconazole maintenance therapy than do women with other underlying causes. Objective To explain differences in response rates to maintenance therapy with fluconazole in women suffering from RVC by evaluating associations with a polymorphism in the gene coding for mannose-binding lectin (MBL). Design Follow-up study, neted case-control group. Setting Women attending vulvoginitis clinic for RVC. Population Women participating in a multicentric study in Belgium with a degressive dose of fluconazole for RVC (the ReCiDiF trial) were divided into good responders, intermediate responders and nonresponders according to the number of relapses they experienced during therapy. From 109 of these women with adequate follow-up data, vaginal lavage with 2 ml of saline were performed at the moment of a proven acute attack at inclusion in the study, before maintenance treatment was started. A buccal swab was obtained from 55 age-matched women without a history of Candida infections, serving as a control group. Methods Extracted DNA from buccal or vaginal cells was tested for codon 54 MBL2 gene polymorphism by polymerase chain reaction and endonuclease digestion. Main outcome measures Frequency of MBL2 condon 54 allele B in women with optimal or poor response to maintenance therapy in composition with controls. Results Women (n = 109) suffering from RVC were more likely to carry the variant MBL2 codon 54 allele B than control women (20 versus 6.6%, OR 3.4 [95% CI 1.3-8.2], P = 0.01). B alleles were present in 25% of the 36 women not suffering from any recurrence during the maintenance therapy with decreasing doses of fluconazole (OR 4.9 [95% CI 1.9-12.5], P = 0.0007 versus controls), in 20% of the 43 women with sporadic recurrences (OR 3.6 [95% CI 1.4-9.2], P = 0.007 versus controls) and in 15% of the 30 women who had to interrupt the treatment regimen due to frequent relapses (P = 0.097 versus controls). Conclusions The MBL2 codon 54 gene polymorphism is more frequent in Belgian women suffering from RVC than in controls. The presence of the B allele is associated with a superior response to fluconazole maintenance therapy as compared with RVC patients without this polymorphism. We conclude that RVC due to deficient MBL production is more easily helped with antifungal medication than is RVC due to some other mechanism.

Biofilm formation on intrauterine devices in patients with recurrent vulvovaginal candidiasis

A biofilm is a complex community of surface-associated cells enclosed in a polymer matrix. They attach to solid surfaces and their formation can be affected by growth conditions and co-infection with other pathogens. The presence of biofilm may protect the microorganisms from host defenses, as well as significantly reduce their susceptibility to antifungal agents. Pathogenic microbes can form biofilms on the inert surfaces of implanted devices such as catheters, prosthetic cardiac valves and intrauterine devices (IUDs). The present study was carried out to analyze the presence of biofilm on the surface of intrauterine devices in patients with recurrent vulvovaginal candidiasis, and to determine the susceptibility profile of the isolated yeasts to amphotericin B and fluconazole. Candida albicans was recovered from the IUDs and it was found to be susceptible to the antifungal agents when tested under planktonic growing conditions. These findings indicate the presence of the biofilm on the surface of the IUD as an important risk factor for recurrent vulvovaginal candidiasis.

Association between mannose-binding lectin and interleukin-1 receptor antagonist gene polymorphisms and recurrent vulvovaginal candidiasis

Objective The influence of functional polymorphisms in the genes coding for mannose-binding lectin (MBL) and interleukin-1 receptor antagonist (IL-1ra) on recurrent vulvovaginal candidiasis (RVVC) were examined in an urban Brazilian population. Methods DNA was isolated from buccal swabs of 100 women with RVVC and 100 control women and tested by gene amplification for a single nucleotide polymorphism in codon 54 of the MBL2 gene and for a length polymorphism in intron 2 of the IL1RN gene. Genotype and allele frequencies were compared between groups. Results The frequency of the variant MBL2 B allele, associated with reduced circulating and vaginal MBL concentrations, was 27.0% in RVVC and 8.5% in control women (p < .0001). The MBL2 B, B genotype was present in 12% of RVVC patients and 1% of controls (p = .0025). The IL1RN 2 allele frequency, associated with the highest level of unopposed IL-1 beta activity, was 24.0% in RVVC and 23.4% in controls. The IL1RN genotype distribution was also similar in both groups. Conclusion Carriage of the MBL2 codon 54 polymorphism, but not the IL1RN length polymorphism, predisposes to RVVC in Brazilian women.

Candida duobushaemulonii: an emerging rare pathogenic yeast isolated from recurrent vulvovaginal candidiasis in Brazil

The aim of this study was to identify Candida species isolated from women diagnosed with recurrent vulvovaginal candidiasis (RVVC) and their partners; and to evaluate the fluconazole (FLZ) susceptibility of the isolates. In a period of six years, among 172 patients diagnosed with vulvovaginal candidiasis, 13 women that presented RVVC and their partners were selected for this investigation. The isolates were obtained using Chromagar Candida medium, the species identification was performed by phenotypic and molecular methods and FLZ susceptibility was evaluated by E-test. Among 26 strains we identified 14 Candida albicans , six Candida duobushaemulonii, four Candida glabrata , and two Candida tropicalis . Agreement of the isolated species occurred in 100% of the couples. FLZ low susceptibility was observed for all isolates of C. duobushaemulonii (minimal inhibitory concentration values from 8-> 64 μg/mL), two C. glabrata isolates were FLZ-resistant and all C. albicans and C. tropicalis isolates were FLZ-susceptible. This report emphasises the importance of accurate identification of the fungal agents by a reliable molecular technique in RVVC episodes besides the lower antifungal susceptibility profile of this rare pathogen C. duobushaemulonii to FLZ.

Improved treatment of vulvovaginal candidiasis with fluconazole plus probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14

To determine the ability of probiotic lactobacilli to improve the treatment of vulvovaginal candidiasis (VVC) using a randomized, double-blind and placebo-controlled trial. Fifty-five women diagnosed with VVC by vaginal discharge positive for Candida spp. (according to culture method) associated with at least one of the symptoms (itching and burning vaginal feeling, dyspareunia and dysuria), were treated with single dose of fluconazole (150 mg) supplemented every morning for the following 4 weeks with two placebo or two probiotic capsules (containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14). At 4 weeks, the probiotic treated group showed significantly less vaginal discharge associated with any of the above mentioned symptoms (10.3%vs 34.6%; P = 0.03) and lower presence of yeast detected by culture (10.3%vs 38.5%; P = 0.014). This study has shown that probiotic lactobacilli can increase the effectiveness of an anti-fungal pharmaceutical agent in curing disease. This novel finding of probiotic lactobacilli augmenting the cure rate of yeast vaginitis, not only offers an alternative approach to a highly prevalent condition that adversely affects the quality of life of women around the world, but also raises the question of how this combination works.

Evaluation of Syngonanthus nitens (Bong.) Ruhl. extract as antifungal and in treatment of vulvovaginal candidiasis

The purpose of this study was to evaluate the in vitro anticandidal activity of a methanolic extract of Syngonanthus nitens scapes against different Candida species and clinical isolates from patients with vulvovaginal candidiasis (VVC), and its effect in vivo in the treatment of vaginal infection. Chemical characterization of the extract was performed by HPLC-UV analyses and showed the presence of flavones derivatives. The extract was effective against several Candida strains from our collection and species recovered from VVC patients, and was able to inhibit the yeast-hyphal transition. No cytotoxic activity against human female reproductive tract epithelial cells and no hemolytic activity against human red blood cells were observed. In the in vivo model of VVC, we evaluated the efficacy of the intravaginal treatment with a cream containing the extract at doses of 0.5, 1.0 and 2.0%. The treatment eradicated the vaginal fungal burden in infected rats after 8 days of treatment. S. nitens extract could be considered as an effective and non-toxic natural antifungal agent in the treatment of vulvovaginal candidiasis. © 2013 ISHAM.

Epidemiologic Features of Vulvovaginal Candidiasis among Reproductive-Age Women in India

Background. Vulvovaginal candidiasis is characterized by curd-like vaginal discharge and itching, and is associated with considerable health and economic costs. Materials and Methods. We examined the incidence, prevalence, and risk factors for vulvovaginal candidiasis among a cohort of 898 women in south India. Participants completed three study visits over six months, comprised of a structured interview and a pelvic examination. Results. The positive predictive values for diagnosis of vulvovaginal candidiasis using individual signs or symptoms were low (<19%). We did not find strong evidence for associations between sociodemographic characteristics and the prevalence of vulvovaginal candidiasis. Women clinically diagnosed with bacterial vaginosis had a higher prevalence of vulvovaginal candidiasis (Prevalence 12%, 95% CI 8.2, 15.8) compared to women assessed to be negative for bacterial vaginosis (Prevalence 6.5%, 95% 5.3, 7.6); however, differences in the prevalence of vulvovaginal candidiasis were not observed by the presence or absence of laboratory-confirmed bacterial vaginosis. Conclusions. For correct diagnosis of vulvovaginal candidiasis, laboratory confirmation of infection with Candida is necessary as well as assessment of whether the discharge has been caused by bacterial vaginosis. Studies are needed of women infected with Candida yeast species to determine the risk factors for yeast’s overgrowth.

Association between vaginal bacterial microbiota and the presence and clinical presentation of vulvovaginal candidiasis

Thesis (Master's)--University of Washington, 2016-08

Aspectos de patogenicidade e relacionamento genético de isolados clínicos vaginas e anais de Candida albicans oriundos de pacientes com candidíase vulvovaginal

Vulvovaginal candidiasis (VVC) is one of the most common causes of vaginitis and affects about 75% of women of reproductive age. The majority of cases (80 to 90%) are due to C. albicans, the most virulent species of the genus Candida. Virulence attributes are scarcely investigated and the source of infection remains uncertain. Objective: This study aimed to evaluate the virulence factors and genotypes of clinical isolates of C. albicans sequentially obtained from the anus and vagina of patients with sporadic and recurrent VVC. Materials and methods: We analyzed 62 clinical isolates of C. albicans (36 vaginal and 26 anal strains). Direct examination of vaginal and anal samples and colony forming units (CFU) counts were performed. Yeasts were identified using the chromogenic media CHROMagar Candida® and by classical methodology, and phenotypically characterized regarding to virulence factors, including the ability to adhere to epithelial cells, proteinase activity, morphogenesis and biofilm formation. The genotypes of the strains were investigated with ABC genotyping, microsatellite genotyping with primer M13 and RAPD. Results: We found 100% agreement between direct examination and culture of vaginal samples. Filamentous forms were present in most of the samples of vaginal secretion, which presented CFU counts significantly higher than the samples of anal secretion. There was no statistically significant difference between virulence factors of infecting vaginal isolates and those presented by colonizing anal isolates; as well as for the comparison of the vaginal isolates from patients with different clinical conditions (sporadic or recurrent VVC). There was a decrease in the ability to adhere to HBEC, morphogenesis and biofilm formation of the vaginal isolates during the progress of infection. There was an association between the ability to express different virulence factors and the clinical manifestations presented by the patients. Genotype A was the most prevalent (93.6%), followed by genotype C (6.4%). We found maintenance of the same ABC genotype and greater prevalence of microevolution for the vaginal strains of C. albicans sequentially obtained. Vaginal and anal isolates of C. albicans obtained simultaneously from the same patient presented the same ABC genotype and high genetic relatedness. Conclusion: It is noteworthy that the proliferation of yeast and bud-to-hypha transition are important for the establishment of CVV. The expression of virulence factors is important for the pathogenesis of VVC, although it does not seem to be determinant in the transition from colonization to infection or to the installation of recurrent condition. Genotype A seems to be dominant over the others in both vaginal and anal isolates of patients with VVC. The most common scenario was microevolution of the strains of C. albicans in the vaginal environment. It is suggested that the anal reservoir constituted a possible source of vaginal infection, in most cases assessed

Analysis of vaginal lactobacilli from healthy and infected Brazilian women

Culture-dependent PCR-amplified rRNA gene restriction analysis and culture-independent (PCR-denaturing gradient gel electrophoresis) methodologies were used to examine vaginal lactobacilli from Brazilian women who were healthy or had been diagnosed with vulvovaginal candidiasis (VVC) or bacterial vaginosis. Only Lactobacillus crispatus was detected accordingly by both methods, and H2O2-producing lactobacilli were not associated with protection against VVC.

Efficacy and tolerance of metronidazole and miconazole nitrate in treatment of vaginitis

Objective: To evaluate the efficacy and tolerability of a vaginal pessary containing 750 mg of metronidazole and 200 mg of miconazole nitrate used daily for 7 days in the treatment of vaginitis. Methods: Ninety-two women with vaginitis participated in this phase 3 study using one vaginal pessary daily for 7 days. Gynecological and microbiological evaluations were carried out prior to and following treatment. Results: Reductions occurred in symptoms and signs of vaginitis. Clinical cure rate was 87.7%, while the cure rates according to microscopy and Candida albicans culture were 81.8% and 73.9%, respectively. The cure rate for bacterial vaginosis was 75% and culture of Gardnerella vaginalis turned negative in 63.6% of cases following treatment. The medication was well tolerated. Conclusion: Use of a combination of 750 mg of metronidazole and 200 mg of miconazole in a single daily application was found to be effective in the treatment of the most common causes of vaginitis. (c) 2008 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

First characterization of Candida albicans by random amplified polymorphic DNA method in Nicaragua and comparison of the diagnosis methods for vaginal candidiasis in Nicaraguan women

A total of 106 women with vaginitis in Nicaragua were studied. The positive rate for the identification of Candida species was 41% (44 positive cultures out of 106 women with vaginitis). The sensitivity of microscopic examination of wet mount with the potassium hydroxide (KOH) was 61% and 70% with Gram's stain when using the culture of vaginal fluid as gold standard for diagnosis of candidiasis. Among the 44 positives cultures, isolated species of yeast from vaginal swabs were C. albicans (59%), C. tropicalis (23%), C. glabrata (14%) and C. krusei (4%). This study reports the first characterization of 26 C. albicans stocks from Nicaragua by the random amplified polymorphic DNA method. The genetic analysis in this small C. albicans population showed the existence of linkage disequilibrium, which is consistent with the hypothesis that C. albicans undergoes a clonal propagation.

Investigação micológica do fluido vaginal de mulheres adultas da região de São José do Rio Preto

Pós-graduação em Microbiologia - IBILCE

Syngonanthus nitens (Bong.) Ruhland: caracterização biológica e prospecção terapêutica do extrato metanólico incorporado ou não em sistema nanoestruturado para aplicação no tratamento da candidíase vulvovaginal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)