An Update on the COGiTATE Phase II Study: Feasibility and Safety of Targeting an Optimal Cerebral Perfusion Pressure as a Patient-Tailored Therapy in Severe Traumatic Brain Injury.

INTRODUCTION: Monitoring of cerebral autoregulation (CA) in patients with a traumatic brain injury (TBI) can provide an individual 'optimal' cerebral perfusion pressure (CPP) target (CPPopt) at which CA is best preserved. This potentially offers an individualized precision medicine approach. Retrospective data suggest that deviation of CPP from CPPopt is associated with poor outcomes. We are prospectively assessing the feasibility and safety of this approach in the COGiTATE [CPPopt Guided Therapy: Assessment of Target Effectiveness] study. Its primary objective is to demonstrate the feasibility of individualizing CPP at CPPopt in TBI patients. The secondary objectives are to investigate the safety and physiological effects of this strategy. METHODS: The COGiTATE study has included patients in four European hospitals in Cambridge, Leuven, Nijmegen, and Maastricht (coordinating centre). Patients with severe TBI requiring intracranial pressure (ICP)-directed therapy are allocated into one of two groups. In the intervention group, CPPopt is calculated using a published (modified) algorithm. In the control group, the CPP target recommended in the Brain Trauma Foundation guidelines (CPP 60-70 mmHg) is used. RESULTS: Patient recruitment started in February 2018 and will continue until 60 patients have been studied. Fifty-one patients (85% of the intended total) have been recruited in October 2019. The first results are expected early 2021. CONCLUSION: This prospective evaluation of the feasibility, safety and physiological implications of autoregulation-guided CPP management is providing evidence that will be useful in the design of a future phase III study in severe TBI patients.

The use of 3 selected lactobacillary strains in vaginal probiotic gel for the treatment of acute Candida vaginitis: a proof-of-concept study.

In vitro studies suggest that certain probiotic bacterial strains have potential activity against opportunistic infections such as Candida. There are few in vivo trials using probiotics as a single treatment for acute Candida vulvovaginitis (CV). In this open-label, proof-of-concept study, selected Lactobacillus strains were tested in women with acute Candida vaginitis. Twenty women diagnosed with proven, symptomatic CV were instructed to administer a vaginal probiotic gel with L. plantarum YUN-V2.0, L. pentosus YUN-V1.0 and L. rhamnosus YUN-S1.0 for 10 consecutive days. Vaginal rinsing fluid, vaginal culture swab and vaginal smear for fresh wet-mount microscopy were collected before and 7, 14 and 28 days after start of treatment. On average, participating women were 39 years old and had an history of 5 vaginal infections of which 95% was CV. Nine women (45%) completed the study without the need of rescue medication. Women who needed rescue treatment experienced twice as much Candida infections in the past. A negative correlation was found between the clinical composite score and the time to use rescue medication (R2 = 0.127). Seventy-four per cent of participants found the study gel comfortable to use, and 42% of all women would use the tested gel again for this indication. Forty-five per cent of women were treated successfully for acute CV with a novel vaginal gel containing 3 selected Lactobacillus strains. Patients needing rescue treatment were suffering from more severe and long-standing disease. These results warrant for further testing of this new product, especially of its potential in cases with mild to moderate severity, as an adjuvant to antimycotics or as a preventive measure in women with recurrent vulvovaginal candidosis.

Treatment Attitudes for Belgian Women With Persistent Trichomonas vaginalis Infection in the VlaResT Study.

BACKGROUND: Because of its increasing prevalence worldwide, its sexual transmissibility and its facilitation of human immunodeficiency virus transmission, Trichomonas vaginalis (TV) infection constitutes an important public health concern. THE AIM OF THE STUDY: While searching for possible resistant TV cases, adequacy of management of TV-infected women was assessed. METHODS: Cervical cytology between July 2007 and July 2014 was tested with TV polymerase chain reaction, and 304 women expressed repeatedly positive results, 718 in total. For each of these positive results, a questionnaire about treatment decisions was sent to the 182 Belgian physicians treating these women. RESULTS: From the 346 returned questionnaires by their physician it was evident that 58.1% of women with repeatedly positive TV had received no treatment. TV was overlooked in 31.5%, and in 17.6% the test result was seen but ignored. Upon seeing the positive result, 23.9% of physicians decided that this finding was not important enough to institute treatment, and/or requested confirmatory tests. Adequate treatment was prescribed in 38.4%. Retreatment after failed therapy was given in only 29.3% of the cases. And 60% of the partners of women with persistent TV infection were not traced, nor treated. CONCLUSION: Most of the repeatedly positive TV infection may not be due to antibiotics resistance. The low awareness, poor attention, failure of contact tracing, and low rates of proper treatment provided by treating physicians question the adequacy of the current management of TV infection and requires renewed education campaigns and increased surveillance.

Abnormal vaginal microbioma is associated with severity of localized provoked vulvodynia. Role of aerobic vaginitis and Candida in the pathogenesis of vulvodynia.

Localized provoked vulvodynia (LPV) causes introital dyspareunia in up to 14% of premenopausal women. Vaginal infections like candidosis may play a initiating role. The aim of this study was to test a possible association of vaginal microbiota alternations such as Candida vaginitis (CV), aerobic vaginitis (AV) and bacterial vaginosis (BV) with severity of vulvodynia and painful intercourse. In an observational study, Q-tip touch test (score 1 (no pain) to 10 (worst possible pain)) was performed on seven vestibular locations in 231 LPV patients presenting in the Vulvovaginal Disease Clinics in Tienen, Leuven and Antwerp, Belgium. Severity of pain upon attempting sexual intercourse was recorded in a similar scale. Both scales were compared to results from fresh wet mount phase contrast microscopy on vaginal fluid smears tested for abnormal vaginal flora (AVF), BV, AV and CV according the standardized microscopy method (Femicare). Fisher's exact test was used. Average age was 31.3 ± 11.6 years, and 58.8% (n = 132) had secondary vestibulodynia. There was an inverse relation between the presence of Candida in the vaginal smears and pain score (p = 0.03). There was no relation of pain score, nor Q-tip score with BV. LPV patients with Q-tip score above 7 at 5 and/or 7 o'clock or at 1 and/or 11 o'clock had more often AV than women with lower pain scores (30 vs 14.5%, p = 0.01, and 39 vs 14.7%, p < 0.005, respectively). Detailed study of the vaginal microflora in patients demonstrates that the most severe patients suffer more from AV and less from Candida. These abnormalities need to be actively looked for and corrected before considering surgery or other therapies.

Sexual behaviour and extra-genital colonisation in women treated for recurrent Candida vulvo-vaginitis.

OBJECTIVE: This study analyses a relation between sexual habits and the presence of Candida in extra-genital locations as well as a potential effect on therapy response. MATERIAL AND METHODS: Candida cultures were obtained from mouth, nose, anus, urine and perineum of 117 women enrolled in a RVVC treatment trial (ReCiDiF). Sexual behaviour and carriage rates of extra-genital Candida of women responding well to treatment were compared to that of non-responders. RESULTS: Most respondents were heterosexual. All but one practiced vaginal sex. Regular receptive oral sex was not related to multiple site colonisation with Candida (OR = 1.27; CI95% 0.36-4.48), nor to non-response to therapy (OR = 1.3; CI 95% 0.41-4.73). Also, masturbation was not related to response to therapy (OR 0.8; CI95% 0.31-1.84), nor was anal sex (OR = 0.54; CI95% 0.11-2.72). CONCLUSION: Neither oral nor casual anal sex, nor masturbation can be held responsible for the association of the multiple site/anal colonisation with Candida and inferior response to fluconazole maintenance therapy. Changing sexual behaviour during fluconazole maintenance treatment for RVVC in otherwise healthy women should not be advocated. Also, treatment of asymptomatic sexual partners of women with RVVC is not recommended.

Non-response to fluconazole maintenance treatment (ReCiDiF regimen) for recurrent vulvovaginal candidosis is not related to impaired glucose metabolism.

Is non-response to maintenance treatment for recurrent vulvovaginal candidosis (RCVV) related to the impaired glucose metabolism? In the ReCiDiF trial, women with RCVV were given a degressive regimen with fluconazole according to their clinical, microscopic and mycologic response. Data obtained from optimal, suboptimal and non-reponding patients were used for secondary analysis of medical history, physical status and family history for potential glucose impairment. Results were presented in means and percentages. Pearson chi-square, Fisher exact, Mann-Whitney U, Kruskal-Wallis and Spearman's correlation coefficient was calculated. P<.05 were interpreted as statistically significant. Sociodemographic characteristics and family and personal history of diabetes were not different between optimal, suboptimal and non-responders. The average HbA1c concentration was 5.1±0.3% in optimal, 5.0±0.4% in sub-optimal, and 5.1±0.3% in non-responding patients (P=1.0). There are no statistical differences between optimal, sub-optimal and non-respondents to treatment in all deciles of HbA1c among patients with recurrent candidosis (P=1.0). There was no difference among groups in fasting glucose concentration, nor after 30 min, 60 min or 120 min during the oral glucose tolerance test (OGTT) (P=.6). Area under the OGTT curve did not differ within groups (P=.8), nor was the deviation from the normal cut-off value any different (P=.8). Glucose concentration in vaginal rinsing fluid showed no correlation with responsiveness to treatment (P=.7). Glucose metabolism, BMI, personal or family history of diabetes are not related to non-response to maintenance treatment with fluconazole for patients with RVVC.

Mycoplasma/Ureaplasma infection in pregnancy: to screen or not to screen.

Mycoplasmata have been linked to pregnancy complications and neonatal risk. While formerly a limited number of species could be discovered by cultures, molecular biology nowadays discovers both lower quantities and more diverse species, making us realize that mycoplasmata are ubiquitous in the vaginal milieu and do not always pose a danger for pregnant women. As the meaning of mycoplasmata in pregnancy is not clear to many clinicians, we summarized the current knowledge about the meaning of different kinds of mycoplasmata in pregnancy and discuss the potential benefits and disadvantages of treatment. Currently, there is no general rule to screen and treat for mycoplasmata in pregnancy. New techniques seem to indicate that Ureaplasma parvum (Up), which now can be distinguished from U. urealyticum (Uu), may pose an increased risk for preterm birth and bronchopulmonary disease in the preterm neonate. Mycoplasma hominis (Mh) is related to early miscarriages and midtrimester abortions, especially in the presence of abnormal vaginal flora. Mycoplasma genitalium (Mg) is now recognized as a sexually transmitted infection (STI) that is involved in the causation of cervicitis, pelvic inflammatory disease (PID) in non-pregnant, and preterm birth and miscarriages in pregnant women, irrespective of the presence of concurrent other STIs, like Chlamydia or gonorrhoea. Proper studies to test for efficacy and improved pregnancy outcome are scarce and inconclusive. Azythromycin is the standard treatment now, although, for Mg, this may not be sufficient. The role of clarithromycin in clinical practice still has to be established. There is a stringent need for new studies based on molecular diagnostic techniques and randomized treatment protocols with promising and safe antimicrobials.

Genital Tract Infections in an Isolated Community: 100 Women of the Príncipe Island.

Objective: To characterize the vaginal microbiome and the rate of sexually transmitted infections (STIs) in the women of Príncipe (São Tomé and Príncipe). Methods: Cross-sectional study of 100 consecutive women, invited for a free appointment and cervical cancer screening. A vaginal slide (wet mount microscopy) and a cervical sample (ThinPrep®) (Pap test, high risk human papillomavirus [HR-HPV], N. gonorrhea [NG], T. vaginalis [TV], and C. trachomatis [CT]) were obtained. Results: TV, NG, CT, and HIV were found in 8.0%, 2.0%, 3.0%, and 2.0%, respectively, and were more prevalent in younger women. HR-HPV was positive in 36.7%; 2 were positive for HPV18, but none for HPV16. Coinfection of HPV with other STIs was 8.3%. Prevalence of abnormal vaginal flora (AVF) was 82.5%, mostly bacterial vaginosis (BV) 54.6%, and moderate/severe aerobic vaginitis (msAV) 25.8%. HR-HPV was not related to BV (p = 0.67). The association of abnormal Pap test with msAV was not significant (p = 0.08). Conclusion: The prevalence of NG, CT, TV, and HR-HPV was according to expected, while that of HR-AVF was higher. The surprisingly low prevalence of HPV16 and HPV18 must be considered in the design of programs for prevention and vaccination; this setting can be useful as a model for postvaccination scenarios.

Effect of short training on vaginal fluid microscopy (wet mount) learning.

OBJECTIVE: Is it feasible to learn the basics of wet mount microscopy of vaginal fluid in 10 hours? MATERIALS AND METHODS: This is a pilot project wherein 6 students with different grades of education were invited for being tested on their ability to read wet mount microscopic slides before and after 10 hours of hands-on training. Microscopy was performed according to a standard protocol (Femicare, Tienen, Belgium). Before and after training, all students had to evaluate a different set of 50 digital slides. Different diagnoses and microscopic patterns had to be scored. κ indices were calculated compared with the expert reading. RESULTS: All readers improved their mean scores significantly, especially for the most important types of altered flora (p < .0001). The mean increase in reading concordance (κ from 0.64 to 0.75) of 1 student with a solid previous experience with microscopy did not reach statistical significance, but the remaining 5 students all improved their scores from poor performance (all κ < 0.20) to moderate (κ = 0.53, n = 1) to good (κ > 0.61, n = 4) concordance. Reading quality improved and reached fair to good concordance on all microscopic items studied, except for the detection of parabasal cells and cytolytic flora. CONCLUSIONS: Although further improvement is still possible, a short training course of 10 hours enables vast improvement on wet mount microscopy accuracy and results in fair to good concordance of the most important variables of the vaginal flora compared to a reference reader.

Utility of microscopic techniques and quantitative real-time polymerase chain reaction for the diagnosis of vaginal microflora alterations.

OBJECTIVE: The aim of the study was to evaluate the diagnostic value of Nugent score, wet mount microscopy, and polymerase chain reaction (PCR) test developed in Russia for bacterial vaginosis (BV) diagnosis. MATERIALS AND METHODS: One hundred Caucasian women were enrolled in this study. Three vaginal samples were taken from each participant: 1 for PCR analysis, 1 for Nugent score evaluation, and 1 for wet mount microscopy. The smears for microscopy were air-dried and sent to Femicare, Tienen, Belgium, for blinded analysis by microscopy. Multiplex real-time PCR was performed using primers and probes targeting Gardnerella vaginalis, Atopobium vaginae, Lactobacillus species, and total quantity of bacterial DNA (16SrRNA gene). RESULTS: Agreement among the 3 methods was 72 (73.5%) of 98 samples. Agreement between Nugent score and PCR results was 77 (78.6%) of 98 samples; between wet mount microscopy and PCR, 81 (82.65%) of 98 samples; between wet mount microscopy and Nugent score, 84 (85.7%) of 98 samples. The sensitivity and specificity of the methods studied were as follows: 75% (21/28) and 97.1% (68/70) for Nugent score, 96.4% (27/28) and 94.3% (66/70) for wet mount microscopy, 92.8% (26/28) and 85.7% (60/70) for PCR, respectively. CONCLUSIONS: This study demonstrated that wet mount microscopy is a superior method for BV diagnosis. The PCR test under study showed a high sensitivity and can be used for discrimination between normal flora and BV.

Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor(®)) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study.

Phase I pharmacokinetic (PK) study assessed circulating estrogens in breast cancer (BC) patients on a non-steroidal aromatase inhibitor (NSAI) with vaginal atrophy using vaginal ultra-low-dose 0.03 mg estriol (E3) and Lactobacillus combination vaginal tablets (Gynoflor(®)). 16 women on NSAI with severe vaginal atrophy applied a daily vaginal tablet of Gynoflor(®) for 28 days followed by a maintenance therapy of 3 tablets weekly for 8 weeks. Primary outcomes were serum concentrations and PK of E3, estradiol (E2), and estrone (E1) using highly sensitive gas chromatography-mass spectrometry. Secondary outcomes were clinical measures for efficacy and side effects; microscopic changes in vaginal epithelium and microflora; and changes in serum FSH, LH, and sex hormone-binding globulin. Compared with baseline, serum E1 and E2 did not increase in any of the women at any time following vaginal application. Serum E3 transiently increased after the first application in 15 of 16 women, with a maximum of 168 pg/ml 2-3 h post-insertion. After 4 weeks, serum E3 was slightly increased in 8 women with a maximum of 44 pg/ml. The vaginal atrophy resolved or improved in all women. The product was well tolerated, and discontinuation of therapy was not observed. The low-dose 0.03 mg E3 and Lactobacillus acidophilus vaginal tablets application in postmenopausal BC patients during AI treatment suffering from vaginal atrophy lead to small and transient increases in serum E3, but not E1 or E2, and therefore can be considered as safe and efficacious for treatment of atrophic vaginitis in BC patients taking NSAIs.

Assessing severity of pain in women with focal provoked vulvodynia: are von Frey filaments suitable devices?

OBJECTIVE: To determine whether von Frey filaments are effective in the standardized assessment of the severity of focal provoked vulvodynia (FPV) syndrome. STUDY DESIGN: The data of 30 women with FPV attending monthly at our vulvovaginal disease clinic, for a collective total of 141 visits over 6 months, were analyzed. At each visit sensitivity tests at the vulvar vestibule were performed at the 5 and 7 o'clock area, totaling 282 measurements. A questionnaire, blinded to the examining physician, and a visual analogue score (VAS) of pain ranging from 1 (no pain) to 10 (maximal pain) was obtained of the discomfort felt when attempting sexual intercourse. RESULTS: The VAS, the investigator assessment of redness, and the 1 to 10 score result of the cotton swab touch test at 5 and 7 o'clock were superior diagnostic tools for assessing the severity of the pain when compared to the use of von Frey filaments. CONCLUSION: Although elegant because of the promise of objective, semiquantitative measurements, von Frey filaments are less suitable devices to assess severity of disease and response to treatment than are cotton swab 1 to 10 pain scores and clinical parameters like subjective pain (VAS) and objective focal redness.

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.

Self-elimination of risk factors for recurrent vaginal candidosis.

Women suffering from recurrent vulvo-vaginal candidosis (RVC) often follow medical and non-medical advices to diminish the severity and frequency of the recurrences, but the impact of such interventions is unclear. The aim of this study was to identify differences in life style habits of women with RVC compared with normal women and to define which changes have influenced the frequency of recurrences in these women. Fifty-one women with RVC and 51 age-matched control women without a history of RVC were sent a questionnaire. History of allergic disease (OR 2.8) and use of corticoids (OR 5) were more frequent in patients with RVC than controls. When interrogated about beneficial changes introduced in their life style habits, lowering the intake of sugars, preventing perineum humidity and stopping contraceptive pills were factors offering substantial improvement. Apart from an increased risk of having an allergic constitution, no differences in the medical history or life style habits were evident between women with RVC and healthy women. However, women with RVC have introduced several changes in life style habits that proved beneficial to them. Among these changes, lowering intake of sugars, preventing perineum humidity and stopping oral contraceptives were the most important.

Association between abnormal vaginal flora and cervical length as risk factors for preterm birth.

AIM.: To study the relationship between abnormal vaginal flora (AVF) in the first trimester as a risk factor for shortening cervix length (CL) at second and third trimester, and to assess the combination of these factors in predicting preterm delivery. METHODS.: 1026 unselected low risk women seen before 16 weeks of pregnancy underwent sampling of vaginal fluid for wet mount microscopy at a central laboratory blinded to clinical data. Disappearance of lactobacilli and bacterial vaginosis (BV) were scored according to standardized definitions. Specific cultures were performed for M hominis, U urealyticum, aerobic vaginitis (AV) and vaginal colonization with Candida. CL was measured by transvaginal ultrasound at 10-14, 20-24 and at 30-34 weeks, and gestational age at delivery was recorded. RESULTS.: Short cervix (CL below the lower quartile) at 10-14 weeks is related to a lower CL at 20-24 and 30-34 weeks of gestation (p=0.01, p=0.005 respectively). Short cervix at 20-24 weeks, but not at 10-14 weeks, was predictive for preterm birth. In patients with M. hominis and/or with severe AV at 10-14 weeks, the cervix appeared shorter at 20-24 and at 30-34 weeks than in other women. Increased risk for preterm birth in women with a shorter cervix at 10-14 weeks and AVF could not be proved by this study. DISCUSSION.: Presence of AV or M. hominis is associated with a shorter cervix at 20-24 and 30-34 weeks. Although a short cervix at 10-14 weeks increases the likelihood of having a short cervix later in pregnancy, it was not a prerequisite for AVF to be associated with preterm delivery. Therefore, in the pathogenesis of preterm birth, certain types of AVF may be involved directly in the process of cervical shortening, rather than being exposed to the intrauterine cavity more readily by a short cervix in the early stages of pregnancy. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.

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.

Easiness of use and validity testing of VS-SENSE device for detection of abnormal vaginal flora and bacterial vaginosis.

Accessing vaginal pH is fundamental during gynaecological visit for the detection of abnormal vaginal flora (AVF), but use of pH strips may be time-consuming and difficult to interpret. The aim of this study was to evaluate the VS-SENSE test (Common Sense Ltd, Caesarea, Israel) as a tool for the diagnosis of AVF and its correlation with abnormal pH and bacterial vaginosis (BV). The study population consisted of 45 women with vaginal pH ≥ 4.5 and 45 women with normal pH. Vaginal samples were evaluated by VS-SENSE test, microscopy and microbiologic cultures. Comparing with pH strips results, VS-SENSE test specificity was 97.8% and sensitivity of 91%. All severe cases of BV and aerobic vaginitis (AV) were detected by the test. Only one case with normal pH had an unclear result. Concluding, VS-SENSE test is easy to perform, and it correlates with increased pH, AVF, and the severe cases of BV and AV.

Vaginal pH and microbiota during fluconazole maintenance treatment for recurrent vulvovaginal candidosis (RVVC).

BACKGROUND: It is commonly stated that Candida in the vagina prefers a low pH to develop infection. However, mixed infections of Candida with bacterial vaginosis (BV) and aerobic vaginitis (AV) are rather common and may challenge the rule that Candida should only be looked for in low vaginal pH settings. In this study we tested whether the vaginal pH in acute vaginal candidosis is lower than in women successfully treated to prevent Candida recurrences. METHODS: Vaginal pH and microscopy findings of vaginal microbiota were recorded during 12 visits over 1.5 years in 117 patients medically monitored during a degressive fluconazole maintenance regimen for proven recurrent vulvovaginal candidosis (ReCiDiF trial). The fluctuation of the mean pH of and microscopic findings of the vaginal smears were studied before, during and after the treatment. RESULTS: The mean vaginal pH of women with acute infection before or after ending maintenance treatment was (4.7±0.8 and 4.8 ±1.0, respectively, p>0.05). During maintenance treatment with fluconazole, the pH dropped significantly to 4.5±0.8 (p=0.01). Depression of Lactobacilli spp. (increased lactobacillary grades) was more frequent during the acute, pre-treatment period (30.0%) than during the treatment period (23.1%, p=0.03). Aerobic vaginitis type flora was also more prevalent pre-treatment than during treatment (30.0% vs 22.2%, OR=0.7 (95%CI 0.5-0.9), p=0.01). DISCUSSION: In women with RVVC, acute vaginal Candida infection is associated with an increased pH, and disturbed vaginal bacterial microbiota. During fluconazole maintenance treatment, the pH drops to normal levels and the lactobacillary grade improves. CONDENSATION: Acute Candida vulvovaginitis can be associated with a disturbance of the vaginal microbiota. In patients with recurrent vulvovaginal candidosis, decrease of pH, and increase of Lactobacilli spp. were observed during fluconazole maintenance treatment. This pH drop was seen in all response groups. This contradicts the common belief that active vaginal Candida infection is related to low pH.

The Dwindling Microbiota of Aerobic Vaginitis, an Inflammatory State Enriched in Pathobionts with Limited TLR Stimulation.

While bacterial vaginosis (BV) is a well-known type of vaginal dysbiosis, aerobic vaginitis (AV) is an inflammatory condition that remains understudied and under-recognised. It predisposes women to serious complications including urogenital infections and pregnancy problems. Here, we investigated the bacterial community in AV to explore its possible role in AV pathogenesis. We collected vaginal lavage fluid samples of women (n = 58) classified by wet-mount microscopy as suffering from AV or BV and included an asymptomatic reference group without signs of AV or BV. AV samples showed reduced absolute abundances of bacteria in general and specifically of lactobacilli by qPCR, but 16S rRNA gene sequencing and amplicon sequence variant analysis revealed that Lactobacillus remained the dominant taxon in 25% of the AV samples studied. The other AV samples showed high relative abundances of Streptococcus agalactiae and, unexpectedly, the anaerobes Gardnerella vaginalis and Prevotella bivia in more than half of the AV samples studied. Yet, despite increased relative abundance of these potential pathogens or pathobionts in the AV bacterial communities, the AV samples only slightly stimulated Toll-like receptor 4 and showed reduced activation of Toll-like receptor 2/6, receptors of two pathways central to mucosal immunity. Our findings indicate that the reduced total bacterial abundance with associated enrichment in certain pathobionts in AV might be mainly a consequence of the inflammatory conditions and/or altered hormonal regulation rather than bacteria being a major cause of the inflammation.

Impact of a lactobacilli-containing gel on vulvovaginal candidosis and the vaginal microbiome.

Vulvovaginal candidosis (VVC) is a common condition with severe symptoms and high recurrence rates. Probiotic lactobacilli are explored as alternatives to azole treatments. Although the vaginal microbiota is generally not depleted in lactobacilli during VVC, studies indicate that the functionality and antimicrobial activity of the lactobacilli is impaired. We selected three strains from the Lactobacillus genus complex (L. rhamnosus GG, L. pentosus KCA1 and L. plantarum WCFS1) based on in vitro evaluation and formulated them in a gel for vaginal application. This gel was evaluated in 20 patients suffering from acute VVC, who were followed for four weeks including a 10-day treatment period. The microbiome was assessed through 16S rRNA (bacteria) and internal transcribed spacer (ITS; fungi) amplicon sequencing, supplemented with quantitative PCR, culture and microscopy for Candida evaluation. 45% of women did not require rescue medication (3×200 mg fluconazole), implying an improvement of their symptoms. These women showed similar end concentrations of fungi as women treated with fluconazole. Moreover, fluconazole appeared to reduce numbers of endogenous lactobacilli. Our study points towards important aspects for future selection of lactobacilli for probiotic use in VVC and the need to investigate possible negative influences of azoles on the vaginal bacterial community.