AIMS:Increased iron is associated with type 2 diabetes, dyslipidemia, and high blood pressure. Therefore, serum ferritin may be a suitable biomarker to detect metabolic syndrome (MetS). We investigated the relationship between serum ferritin, and the prevalence of MetS and insulin resistance (IR). METHODS:This cross-sectional study assessed 2,786 Chinese participants, aged 25-75 years. MetS was defined using the 2006 International Diabetes Federation guidelines. IR was assessed with homeostasis model assessment estimated IR (HOMA-IR). Regression analysis was used to estimate the association between serum ferritin and the prevalence of MetS and IR. RESULTS:MetS prevalence within each serum ferritin quartile (Q1-4) was 31.7%, 37.1%, 43.6%, and 55.4%, respectively in men (P<0.001), and 30.1%, 34.8%, 48.2%, and 66.9%, respectively in women (P<0.001). Increased serum ferritin correlated with the number of MetS components (P<0.001). The odds ratio for MetS in the ferritin Q4 group was 1.95 (1.39-2.73) for men and 1.66(1.12-2.47) for women, compared with Q1. Serum ferritin correlated positively with HOMA-IR in men (regression coefficient: 0.058, P=0.009) and women (regression coefficient: 0.082, P=0.001). CONCLUSION:MetS prevalence increased with elevated serum ferritin levels, and serum ferritin levels were independently associated with MetS and IR.

Vitamin D is known to regulate innate and adaptive immune processes at the cellular level, but the role of vitamin D status on associated inflammatory processes across pregnancy is unclear. Our primary objective was to evaluate the relationships between serum biomarkers of inflammation (interleukin [IL]-6, IL-10, tumor necrosis factor [TNF]-α), acute-phase proteins (C-reactive protein and hepcidin) and vitamin D status, 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)D), measured across pregnancy and in the neonate at birth. A second objective was to identify associations between vitamin D status and clinically diagnosed infections. In this study, 158 racially and ethnically diverse pregnant adolescents were recruited from the Rochester Adolescent Maternity Program (RAMP) in Rochester, NY. Serum 1,25(OH)D was significantly lower in adolescents and neonates with IL-6 concentrations above the 75th percentile at delivery ( P = .04) and at birth ( P = .004), respectively. After adjusting for other potential covariates of inflammation, maternal serum 1,25(OH)D was significantly positively associated with TNF-α during pregnancy ( P = .02), but at delivery 1,25(OH)D and TNF-α were inversely associated with one another ( P = .02). Teens with 25(OH)D concentrations <30 ng/mL were more likely to test positive for candida ( P = .002) and bacterial vaginosis ( P = .02) during pregnancy. African Americans exhibited significantly lower TNF-α concentrations at both mid-gestation ( P = .009) and delivery ( P = .001) compared to the Caucasian adolescents. These results suggest that lower maternal vitamin D status may increase risk of infection across gestation.

BACKGROUND:Vaginal infections are a risk factor for preterm delivery. In this study, we sought to evaluate the vaginal flora of pregnant women receiving opioid maintenance therapy (OMT) in comparison to non-dependent, non-maintained controls. METHODS:A total of 3763 women with singleton pregnancies who underwent routine screening for asymptomatic vaginal infections between 10 + 0 and 16 + 0 gestational weeks were examined. Vaginal smears were Gram-stained, and microscopically evaluated for bacterial vaginosis, candidiasis, and trichomoniasis. In a retrospective manner, data of 132 women receiving OMT (cases) were matched for age, ethnicity, parity, education, previous preterm delivery, and smoking status to the data of 3631 controls. The vaginal flora at antenatal screening served as the primary outcome measure. Secondary outcome measures were gestational age and birth weight. RESULTS:In the OMT group, 62/132 (47 %) pregnant women received methadone, 39/132 (29.5 %) buprenorphine, and 31/132 (23.5 %) slow-release oral morphine. Normal or intermediate flora was found in 72/132 OMT women (54.5 %) and 2865/3631 controls [78.9 %; OR 0.49 (95 % CI, 0.33-0.71); p < 0.001]. Candidiasis occurred more frequently in OMT women than in controls [OR 2.11 (95 % CI, 1.26-3.27); p < 0.001]. Findings were inconclusive regarding bacterial vaginosis (± candidiasis) and trichomoniasis. Compared to infants of the control group, those of women with OMT had a lower mean birth weight [MD -165.3 g (95 % CI, -283.6 to -46.9); p = 0.006]. CONCLUSIONS:Pregnant women with OMT are at risk for asymptomatic vaginal infections. As recurrent candidiasis is associated with preterm delivery, the vulnerability of this patient population should lead to consequent antenatal infection screening at early gestation.

PURPOSE:More than 370 million women will experience recurrent vulvovaginal candidiasis (RVVC) during their lifetime. However, RVVC is often trivialized as clinically insignificant and not worthy of research funding. We evaluated the influence of RVVC on the quality of life in affected women. METHODS:The validated World Health Organization Quality of Life Abbreviated Assessment (WHOQOL-Bref) questionnaire was administered to 100 women with RVVC and to 101 epidemiologically matched women with no history of vulvovaginal candidiasis. RVVC was defined as at least four episodes of clinical and culture-positive vaginal candidiasis within a 1 year period. Data were analyzed by Chi square, Student t test and analysis of variance. Internal consistency of responses to questions was evaluated by Cronbach alpha. RESULTS:The Cronbach alpha coefficient was > 0.80 for responses to generalized questions and > 0.65 for answers to more specific questions, indicating substantial internal consistency. Perception of quality of life and satisfaction with their health was greatly reduced in the RVVC group (p < 0.001). Diminished responses to physical and psychological well-being were also reported by women with RVVC (p < 0.001). Various aspects of social relations including sexual activity were similarly reduced (p < 0.001) as were satisfaction with issues such as home environment, financial resources and employment (p < 0.001). CONCLUSION:RVVC affects multiple aspects of a woman's well-being. Women with this condition deserve serious attention from clinicians and research into susceptibility, prevention and treatment of this infection deserves much greater emphasis.

We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC), including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI). Yeasts were isolated from 71 (26%) women: 23 (32.4%) with a positive culture but without symptoms (COL), 22 (31%) in an acute episode (VVC), and 26 (36.6%) with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture) comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC) than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels) and reduced antioxidant capacity can be host predisposing factors to RVVC.

BACKGROUND:Self-reported unprotected vaginal sex seems to increase risk of bacterial vaginosis (BV). However, the validity of self-reports is questionable, given their inconsistency with more objective measures of recent semen exposure such as detection of prostate-specific antigen (PSA). We examined whether recent unprotected sex, as measured both by PSA detection on vaginal swabs and by self-report, was associated with increased BV recurrence. METHODS:We analyzed randomized trial data from nonpregnant, BV-positive adult women recruited from a sexually transmitted disease clinic. Participants received BV therapy at enrollment and were scheduled to return after 4, 12, and 24 weeks. Bacterial vaginosis (by Nugent score) and PSA were measured at each visit. We used Cox proportional hazards models to examine the association between PSA positivity and recurrent BV. We also evaluated associations between self-reported unprotected sex (ever/never since the last visit and in the last 48 hours, analyzed separately) and recurrent BV. RESULTS:Prostate-specific antigen and BV results were available for 96 women who contributed 226 follow-up visits. Prostate-specific antigen positivity was associated with increased BV recurrence (adjusted hazard ratio [aHR], 2.32; 95% confidence interval [CI], 1.28-4.21). In contrast, we observed no significant increase in BV recurrence among women self-reporting unprotected sex since the last visit (aHR, 1.63; 95% CI, 0.77-3.43) or in the last 48 hours (aHR, 1.28; 95% CI, 0.70-2.36). CONCLUSIONS:Estimates from earlier studies linking self-reported unprotected sex and BV may be biased by misclassification. Biomarkers can improve measurement of unprotected sex, a critical exposure variable in sexual health research.

The purpose of this study was to prospectively evaluate the impact of the use of L. plantarum I1001 applied vaginally on Vulvovaginal Candidiasis (VVC) time-until-recurrence after treatment with single-dose vaginal clotrimazole. This was a clinical open-label, prospective study of two non-randomized parallel cohorts with symptomatic acute VVC: (1) 33 sexually active women 18-50 years old, prescribed a standard single-dose 500 mg vaginal tablet of clotrimazole followed by vaginal tablets with L. plantarum I1001 as adjuvant therapy, and (2) 22 women of similar characteristics but prescribed single-dose clotrimazole only. Use of the probiotic and factors that might influence recurrence risk (age, recurrent VVC within previous year, antibiotic prior to study enrolment, diaphragm or IUD contraception, among others) were included in a multivariate Cox regression model to adjust for potential between-cohort differences. Probiotic use was associated with a three-fold reduction in the adjusted risk of recurrence (HR [95 %CI]: 0.30 [0.10-0.91]; P = 0.033). Adjusted free-survival recurrence was 72.83 % and 34.88 % for the probiotic and control groups, respectively. A higher cumulative recurrence was also observed in cases with use of antibiotics prior to enrolment (HR [95 %CI]: 10.46 [2.18-50.12]; P = 0.003). Similar findings were found at six months after azole treatment in women with RVVC. Overall, good compliance with the probiotic was reported for 91.3 % of women. The study suggests that follow-up therapy with vaginal tablets with L. plantarum I1001 could increase the effectiveness of single-dose 500 mg clotrimazole at preventing recurrence of VVC, an effect that was also observed in women with recurrent vulvovaginal candidiasis (RVVC) after six months of azole treatment.

Bacterial vaginosis (BV) is a common but treatable condition, with a number of effective available treatments, including oral and intravaginal metronidazole and clindamycin and oral tinidazole. However, as many as 50% of women with BV experience recurrence within 1 year of treatment for incident disease. Some reasons for recurrence include the persistence of residual infection, resistance, and possibly reinfection from either male or female partners. Persistence may occur due to the formation of a biofilm that protects BV-causing bacteria from antimicrobial therapy. Poor adherence to treatment among patients with genitourinary infections may lead to resistance. However, the underlying mechanisms of recurrent etiology of BV are not known. Recommended treatment for recurrent BV consists of an extended course of metronidazole treatment (500 mg twice daily for 10-14 days); if ineffective, metronidazole vaginal gel 0.75% for 10 days, followed by two times per week for 3-6 months, is an alternate treatment regimen. Past studies of clindamycin and tinidazole in the treatment of recurrent BV have focused on patients with evidence of metronidazole resistance. Secnidazole may be an attractive new option due to one-time dosing. Initial studies on biofilm disruption, use of probiotics and prebiotics, and botanical treatments have shown some promise, but must be studied further before use in the clinic. Despite limitations, antimicrobial therapy will remain the mainstay of treatment for recurrent BV for the foreseeable future.

Vulvovaginal candidiasis (VVC) is a hormonal-dependent infection but in contrast to sporadic VVC, therapy of recurrent vulvovaginal candidiasis (RVVC) is still unsolved. Long-term administration of medroxyprogesterone acetate was evaluated for the management of RVVC. Overall, 20 patients were treated with Depo-Provera; 14 patients were treated with Provera. Gestagen therapy was evaluated based on visual analogue scale (VAS), the frequency of attacks, the side effects of gestagens and the consumption of antifungals. There was a reduced symptomatology in both of the groups and substantial reduction in antifungal drug consumption during the second year of gestagen use. Twenty-four patients (70.6%) evaluated their condition regarding the vulvovaginal area as improvement (VAS decrease of 3-5 points). Five patients (14.7%) mentioned minimal or no improvement. Further, a number of antifungal drug-treated episodes dropped dramatically during the study period. Both regimes provided similar results, but five patients from the Depo-Provera group had to withdraw from gestagen therapy. Gestagen supplementation ameliorated the quality of life for the majority of patients with RVVC and suggested a potential role in the management of this syndrome, even if beneficial effect was evident after longer application, and some patients met with side effects that led to an interruption of therapy.

Recurrent vulvovaginal candidiasis (RVVC) is an important pathological and infectious condition that can greatly impact a woman's health and quality of life. Clinical and epidemiological studies show that different types of therapies are able to eliminate the signs and symptoms of mycotic vaginitis in the acute phase, but so far none of these has proved able to significantly reduce the risk of long-term recurrence. In this review, based on the available literature and original data from a preliminary in-vitro microbiological study on the compatibility between fluconazole, clotrimazole and metronidazole a new therapeutic approach to RVVC is discussed and presented. The treatment proposed is a combined scheme using both systemic antimicrobial drug therapy with oral fluconazole 200 mg and topical drug therapy using the association metronidazole 500 mg and clotrimazole 100 mg (vaginal ovules) with adjuvant oral probiotic therapy. In detail, at the time of diagnosis in the acute symptom phase, we propose the following treatment scheme: fluconazole 200 mg on day 1, 4, 11, 26, then 1 dose/month for 3 months at the end of the menstrual cycle; plus metronidazole/clotrimazole ovules 1/day for 6 days the first week, then 1 ovule/day for 3 days the week before the menstrual cycle for 3 months; plus probiotic 1 dose/day for 10 days for 3 months starting from the second month to the end of the menstrual cycle. This scheme aims to address the recurrent infection aggressively from the outset by attempting not only to treat acute symptoms, but also to prevent a new event by countering many of the potential risk factors of recurrence, such as the intestinal Candida reservoir, the mycotic biorhythm, the formation of biofilm, the phenotype switching and the presence of infections complicated by the presence of C. non albicans or G. Vaginalis, without interfering, but rather favoring the restoration of the vaginal lactobacillus species. Future clinical studies will be useful to confirm the proposed scheme.

Recurrent vulvovaginal candidiasis (RVVC) is a major health problem for sexually active women because of its severe effect on their quality of life. A thorough knowledge of their epidemiology leads to their efficient management. Therefore, a cross-sectional study was conducted in 2014 in women with leucorrhoea associated or not with other clinical signs. Recurrence was based on the occurrence of at least four annual episodes of Candida vulvo-vaginitis. An individual interview based on a questionnaire was conducted to identify the socio-demographic parameters that could be associated with the RVVC. Vaginal samples were collected at the obstetrical gynaecology department of the University Hospital of Cocody and at the Pasteur Institute of Côte d'Ivoire. On each sample, a direct examination and culture on Sabouraud-chloramphenicol medium with or without actidione were performed. Yeast identification was performed using chromogenic media (CandiSelect4 [Bio-Rad]) and the study of sugar assimilation using the Auxacolor 2 gallery (Bio-Rad). A total of 400 patients were included. The average age was 29.2 years (SD=7.2 years). Of these, 94 had recurrent vulvovaginal candidiasis, with a prevalence of 23.5% (CI: 19.49-28.02). Five species of the genus Candida have been identified: Candida albicans (59.6%), Candida glabrata (19.1%), Candida tropicalis (16%), Candida krusei (4.2%) and Candida inconspicua (1.1%). Some factors such as education level, history of sexually transmitted infection, type of underwear used, frequency of personal hygiene and type of product used for these hygiene have been associated with the occurrence of RVVCs. The occurrence of RVVCs is relatively high in our study population. Non-albicansCandida species occupy a significant place in this disease epidemiology. By addressing the factors associated with the occurrence and/or persistence of RVVCs, it will be possible to reduce their incidence in sexually active women.

Vulvovaginitis (VV) is one of the most commonly encountered problems by a gynecologist. Many women frequently self-treat with over-the-counter medications, and may present to their health-care provider after a treatment failure. Vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis may occur as discreet or recurrent episodes, and have been associated with significant treatment cost and morbidity. We present an update on diagnostic capabilities and treatment modalities that address recurrent and refractory episodes of VV.

Recurrent vulvovaginal candidiasis (RVVC) is a common cause of significant morbidity in women in all strata of society affecting millions of women worldwide. Previously, RVVC occurrence was limited by onset of menopause but the widespread use of hormone replacement therapy has extended the at-risk period. Candida albicans remains the dominant species responsible for RVVC, however optimal management of RVVC requires species determination and effective treatment measures are best if species-specific. Considerable progress has been made in understanding risk factors that determine susceptibility to RVVC, particularly genetic factors, as well as new insights into normal vaginal defense immune mechanisms and their aberrations in RVVC. While effective control of RVVC is achievable with the use of fluconazole maintenance suppressive therapy, cure of RVVC remains elusive especially in this era of fluconazole drug resistance. Vaccine development remains a critical challenge and need.

With vaginitis remaining a common condition that leads women to seek care, it is not surprising that some women develop chronic vulvovaginal problems that are difficult to diagnose and treat. With a differential diagnosis that encompasses vulvar disorders and infectious and noninfectious causes of vaginitis, accurate diagnosis is the cornerstone of choosing effective therapy. Evaluation should include a symptom-specific history, careful vulvar and vaginal examination, and office-based tests (vaginal pH, amine test, saline and 10% potassium hydroxide microscopy). Ancillary tests, especially yeast culture with speciation, are frequently crucial to obtaining a correct diagnosis. A heavy but normal physiologic discharge can be determined by excluding other causes. With vulvovaginal candidiasis, differentiating between Candida albicans and non-albicans Candida infection has important treatment ramifications. Most patients with C albicans infections can be successfully treated with maintenance antifungal therapy, usually with fluconazole. Although many non-albicans Candida, particularly Candida glabrata, may at times be innocent bystanders, vaginal boric acid therapy is an effective first choice for many true non-albicans Candida infections. Recurrent bacterial vaginosis, a difficult therapeutic challenge, can often be controlled with maintenance therapy. Multiple options, especially high-dose tinidazole, have been used for metronidazole-resistant trichomoniasis. With the aging of the U.S. population, atrophic vaginitis and desquamative inflammatory vaginitis, both associated with hypoestrogenism, are encountered frequently in women with persistent vaginitis.

Vaginal complaints are one of the most common reasons women seek the advice of a health care provider. Uncomplicated infections such as vulvovaginal candidiasis, bacterial vaginosis, or trichomoniasis are easy to diagnose and treat. However, about 8% of patients will have a more complicated course with failure to respond to treatment or rapid recurrence of symptoms. Understanding the need for a methodical, diagnostic approach to help these women with recurrent or refractory cases of vaginal symptoms will aid the clinician achieve successful patient outcomes.