Gert Bellen

Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy.

Introduction  Abnormal vaginal flora (AVF) before 14 gestational weeks is a risk factor for preterm birth (PTB). The presence of aerobic microorganisms and an inflammatory response in the vagina may also be important risk factors.

Dynamics of Vaginal Bacterial Communities in Women Developing Bacterial Vaginosis, Candidiasis, or No Infection, Analyzed by PCR-Denaturing Gradient Gel Electrophoresis and Real-Time PCR

ABSTRACT The microbial flora of the vagina plays a major role in preventing genital infections, including bacterial vaginosis (BV) and candidiasis (CA). An integrated approach based on PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR was used to study the structure and dynamics of bacterial communities in vaginal fluids of healthy women and patients developing BV and CA. Universal eubacterial primers and Lactobacillus genus-specific primers, both targeted at 16S rRNA genes, were used in DGGE and real-time PCR analysis, respectively. The DGGE profiles revealed that the vaginal flora was dominated by Lactobacillus species under healthy conditions, whereas several potentially pathogenic bacteria were present in the flora of women with BV. Lactobacilli were the predominant bacterial population in the vagina for patients affected by CA, but changes in the composition of Lactobacillus species were observed. Real-time PCR analysis allowed the quantitative estimation of variations in lactobacilli associated with BV and CA diseases. A statistically significant decrease in the relative abundance of lactobacilli was found in vaginal fluids of patients with BV compared to the relative abundance of lactobacilli in the vaginal fluids of healthy women and patients with CA.

Aerobic vaginitis in pregnancy.

Please cite this paper as: Donders G, Bellen G, Rezeberga D. Aerobic vaginitis in pregnancy. BJOG 2011; DOI: 10.1111/j.1471‐0528.2011.03020.x.

Individualized decreasing-dose maintenance fluconazole regimen for recurrent vulvovaginal candidiasis (ReCiDiF trial)

OBJECTIVE Although many women with recurrent vulvovaginal candidiasis initially benefit from prophylactic intermittent treatment with antimycotics, most of them experience relapse after cessation of therapy, and often they return to the pretreatment recurrence rate. The purpose of this study was to demonstrate the efficacy and safety of an individualized, degressive, prophylactic regimen in 136 women with recurrent vulvovaginal candidiasis. STUDY DESIGN After an induction dose of 600 mg fluconazole during the first week, 117 women started maintenance therapy: 200 mg fluconazole weekly for 2 months, followed by 200 mg biweekly for 4 months, and 200 mg monthly for 6 months, according to their individual response to therapy. All women were tested for recurrences monthly with wet mount microscopy and vaginal culture during the first 6 months and bimonthly during the next 6 months. Patients were allowed to move on to the next level of maintenance therapy only if they were symptom free and microscopy and culture negative. RESULTS Of the women who were cured successfully after the induction phase, 101 women (90%) were disease-free after 6 months of maintenance therapy with this degressive regimen, and 80 women (77%) were disease-free after 1 year. The weekly incidence of the first clinical relapse was 0.5% during any period of the maintenance phase, and the rate of all new relapses, which included evidence of mycologic or microscopic colonization, was 1% per week. Women who experienced several relapses (poor responders) had experienced more relapses before entering the study compared with the optimal responders (odds ratio, 4.9; 95% CI,1.8-13.7; P = .002), experienced the disease for a longer period of time (6.5 vs 3.7 years; P = .06), and harbored significantly more Candida non-albicans during maintenance therapy (P = .001). No serious side-effects were noted. CONCLUSION Individualized, degressive, prophylactic maintenance therapy with oral fluconazole is an efficient treatment regimen to prevent clinical relapses in women with recurrent vulvovaginal candidiasis.

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.

Change in knowledge of women about cervix cancer, human papilloma virus (HPV) and HPV vaccination due to introduction of HPV vaccines

OBJECTIVES Test knowledge of HPV, cervix cancer awareness and acceptance of HPV vaccination of women now and a year ago. STUDY DESIGN Questionnaires were filled out by 305 women visiting four gynaecologists of the Regional Hospital Heilig Hart, Tienen, Belgium during two subsequent weeks. Fisher T or Chi(2) were used as statistical methods to compare the data with the survey of 381 women exactly one year before. RESULTS Knowledge about HPV as a cause of cervix cancer and the presence of a vaccine rose from roughly 50% in 2007 to over 80% in 2008 (p<0.0001). Level of education and having daughters, sons or no children no longer influenced the level of knowledge or willingness to accept the vaccine. Most parents favor the age group 12-16 years as an ideal time for vaccination. In contrast with the 2007 survey, women below 26 years had now acquired almost equivalent knowledge to older women about the virus, cervix cancer and the vaccine, but they were far less likely to accept the vaccine due to its cost, unless it would be reimbursed (OR 4.2 (1.6-11) p=0.0055). CONCLUSION One year after introduction of the first two HPV vaccines, over 75% of women attending an ambulatory gynaecology clinic know HPV causes cervix cancer and that you can get vaccinated against it. Compared with a year earlier, young and lower educated women had dramatically improved their knowledge. However, women below 26 years are less prepared to pay the cost for vaccination if it is not reimbursed.

Management of recurrent vulvo-vaginal candidosis as a chronic illness.

For sporadic acute Candida vaginitis, any oral or local antifungal therapy can be used. For women with recurrent vulvo-vaginal candidosis (RVC), on the other hand, such simple approaches are insufficient, regardless of the product chosen. Instead, RVC should be managed as any other chronic disease and requires long-term, prophylactic, suppressive antifungal treatment. A regimen using individualized, decreasing doses of oral fluconazole (the ReCiDiF regimen) was proven to be highly efficient and offered great comfort to the patients. During this regimen, it is crucial that patients are carefully examined by anamnestic, clinical, microscopic and culture-proven absence of Candida. If a relapse occurs, the medication is adjusted and efforts are taken to find a possible triggering factor for the reactivation of the infection. Care has to be taken not to accumulate ‘don’t do’s’, unless the efficiency of a measure has been proven, by trying to eliminate one risk factor at a time for 2 months. Known possible triggers to be kept in mind are (1) antibiotic use, (2) use of specific contraceptives, especially combined contraceptive pills, (3) disturbed glucose metabolism, (4) the use of personal hygienic products, and (5) tight clothing or plastic panty liners. In therapy-resistant cases, non-albicans infection must be ruled out, and alternative therapies should be tried. Boric acid is proven to be efficient in most of these resistant cases, but other non-azoles like amphotericin B, flucytosine, gentian violet, and even caspofungin may have to be tried. As a final remark it has to be said that many patients feel poorly understood and inefficiently managed by many care-givers, increasing their feelings of guilt and sexual inferiority. Therefore, attention has to be given to take the disease seriously, follow strict treatment regimens, and advise precisely and based on individual evidence concerning any possible risk factors for recurrence. In case of therapy-resistant vulvo-vaginitis, reconsider your diagnosis and/or consider referral to specialized therapists.

Cream with cutaneous fibroblast lysate for the treatment of provoked vestibulodynia: a double-blind randomized placebo-controlled crossover study.

Objective Is treatment of provoked localized vulvodynia with cutaneous lysate skin cream containing human cytokines effective? Methods This is a double-blind placebo-controlled randomized crossover trial with a study and a placebo cream applied twice daily for 3 months, 1-week washout, followed by a 3-month crossover medication in 30 patients experiencing provoked localized vulvodynia with visible vulvar erythema. Tolerability of the product, sexual functioning, and clinical findings were the main outcomes. A linear model for repeated measures was used for all visits. Effect after 4 weeks of treatment, effect after 12 weeks of treatment, and, finally, carryover effects of first and second order were estimated. A Wilcoxon signed rank test was used to evaluate 4- and 12-week changes within a group, and Mann-Whitney U test was used to evaluate 4- and 12-week changes between groups. Results Tolerability of the cream was excellent and not different from that of placebo. During the first 12 weeks, use of the active cream resulted in a significant reduction in pain during sexual activity after 4 and 12 weeks (p < .05); however, use of the placebo cream did not. When analyzing the entire pain data with the statistical model for crossover clinical study design, the active cream resulted in a decrease of 1.1 points (95% confidence interval = −0.6 to 2.8, p = .20) and 1.3 points (95% confidence interval = 0.1 to 2.5, p = .037) in the visual analog scale score compared with that of placebo after 4 and 12 weeks of treatment, respectively. There was evidence for a second-order carryover effect (p = .024). The pain reduction was most evident for women with secondary dyspareunia. Erythema was reduced after use of the cream at 4 (p = .03) and 12 (p = .01) weeks but not after placebo. Conclusions As opposed to placebo, use of cutaneous lysate cream was more effective in reducing focal redness and pain while having intercourse in patients with provoked localized vulvodynia with erythema.

Vaginal flora changes on Pap smears after insertion of levonorgestrel-releasing intrauterine device.

BACKGROUND The levonorgestrel intrauterine system (LNG-IUS) combines a uterine foreign body and the continuous release of low-dose levonorgestrel for contraception. Its influence on the rate of vulvovaginal infections and flora disturbance is insufficiently known, but important for contraceptive advice in women, especially those who develop recurrent vaginosis or Candida vulvovaginitis. STUDY DESIGN Slides of 286 women who had a Pap smear taken before and 1 to 2 years after placement of a LNG-IUS were blindly reviewed for the presence of abnormal vaginal flora (AVF), bacterial vaginosis (BV), aerobic vaginitis (AV) and Candida vaginitis (CV). RESULTS Prior to insertion, there were no differences in vaginal flora abnormalities between women using different kinds of contraception. LNG-IUS users did not have different rates of AVF, BV, AV or CV, but the general risk to develop any infection was increased. Uterine bleeding after insertion did not seem to predict a different flora type. CONCLUSION We found that Pap smears suggested more vaginal infections after 1 year of LNG-IUS use than prior to insertion of the device.

Sialidase activity in aerobic vaginitis is equal to levels during bacterial vaginosis

OBJECTIVE To evaluate levels of proinflammatory cytokines and sialidase activity in aerobic vaginitis (AV) in relation to normal vaginal flora and bacterial vaginosis (BV). STUDY DESIGN In this cross-sectional study, a total of 682 consecutive non-pregnant women attending the gynecology service were assessed and 408 women were included. Vaginal rinsing samples were collected from 223 women with microscopic finding of BV (n=98), aerobic vaginitis (n=25) and normal flora (n=100). Samples were tested for interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and sialidase activity. RESULTS Compared to women with normal flora, vaginal levels of IL-1β were highly increased in both BV and AV (p<0.0001). Significantly higher vaginal IL-6 was detected in AV (p<0.0001) but not in BV, in relation to normal flora. Women with AV also presented increased IL-8 levels (p<0.001), while those with BV presented levels similar to normal flora. Sialidase was increased in BV and AV compared with the normal group (p<0.0001) but no difference in sialidase activity was observed between BV and AV. CONCLUSION A more intense inflammatory host response occurs for AV than for BV when compared with normal flora. Furthermore, the increased sialidase activity in AV and BV indicates that both abnormal vaginal flora types can be harmful to the maintenance of a healthy vaginal environment.