Vaginal prevention of Candida albicans: synergistic effect of lactobacilli and mannan oligosaccharides (MOS).

Vulvovaginal candidiasis (VVC) affects approximately 30-50% of women at least once during their lifetime, causing uncomfortable symptoms and limitations in their daily quality of life. Antifungal therapy is not very effective, does not prevent recurrencies and usually causes side effects. Therefore, alternative therapies are urgently needed. The goal of this work was to investigate the potential benefits of using mannan oligosaccharides (MOS) extracts together with a Lactobacillus sp. pool, composed by the most significant species present in the vaginal environment, to prevent infections by Candida albicans. Microbial growth of isolated strains of the main vaginal lactobacilli and Candida strains was assessed in the presence of MOS, to screen their impact upon growth. A pool of the lactobacilli was then tested against C. albicans in competition and prophylaxis studies; bacterial and yeast cell numbers were quantified in specific time points, and the above-mentioned studies were assessed in simulated vaginal fluid (SVF). Finally, adhesion to vaginal epithelial cells (HeLa) was also evaluated, once again resorting to simultaneous exposure (competition) or prophylaxis assays, aiming to measure the effect of MOS presence in pathogen adherence. Results demonstrated that MOS extracts have potential to prevent vaginal candidiasis in synergy with vaginal lactobacilli, with improved results than those obtained when using lactobacilli alone. KEY POINTS: Potential benefits of MOS extracts with vaginal lactobacilli to prevent C. albicans infections. MOS impacts on growth of vaginal lactobacilli pool and C. albicans in SVF. MOS extracts in synergy with L. crispatus inhibit C. albicans adhesion in HeLa cells.

Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein.

Candida causes an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused by Candida albicans, which, in this setting, triggers nonprotective neutrophil infiltration, aggressive local inflammation, and symptomatic disease. Despite its prevalence, little is known about the molecular mechanisms underpinning the immunopathology of this fungal infection. In this study, we describe the molecular determinant of VVC immunopathology and a potentially straightforward way to prevent disease. In response to zinc limitation, C. albicans releases a trace mineral binding molecule called Pra1 (pH-regulated antigen). Here, we show that the PRA1 gene is strongly up-regulated during vaginal infections and that its expression positively correlated with proinflammatory cytokine concentrations in women. Genetic deletion of PRA1 prevented vaginal inflammation in mice, and application of a zinc solution down-regulated expression of the gene and also blocked immunopathology. We also show that treatment of women suffering from recurrent VVC with a zinc gel prevented reinfections. We have therefore identified a key mediator of symptomatic VVC, giving us an opportunity to develop a range of preventative measures for combatting this disease.

ROS mediated anticandidal efficacy of 3-Bromopyruvate prevents vulvovaginal candidiasis in mice model.

Candidal infections, particularly vulvovaginal candidiasis (VVC), necessitate effective therapeutic interventions in clinical settings owing to their intricate clinical nature and elusive understanding of their etiological mechanisms. Given the challenges in developing effective antifungal therapies, the strategy of repurposing existing pharmaceuticals has emerged as a promising approach to combat drug-resistant fungi. In this regard, the current study investigates molecular insights on the anti-candidal efficacy of a well-proven anticancer small molecule -3-bromopyruvate (3BP) against three clinically significant VVC causing Candida species viz., C. albicans, C. tropicalis and C. glabrata. Furthermore, the study validates 3BP's therapeutic application by developing it as a vaginal cream for the treatment of VVC. 3BP exhibited phenomenal antifungal efficacy (killing >99%) with minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of 256 µg/mL against all tested Candida spp. Time killing kinetics experiment revealed 20 min as the minimum time required for 3BP at 2XMIC to achieve complete-killing (99.9%) in all Candida strains. Moreover, the ergosterol or sorbitol experiment explicated that the antifungal activity of 3BP does not stem from targeting the cell wall or the membrane component ergosterol. Instead, 3BP was observed to instigate a sequence of pre-apoptotic cascade events, such as phosphatidylserine (PS) externalization, nuclear condensation and ROS accumulations, as evidenced by PI, DAPI and DCFH-DA staining methods. Furthermore, 3BP demonstrated a remarkable efficacy in eradicating mature biofilms of Candida spp., achieving a maximum eradication level of 90%. Toxicity/safety profiling in both in vitro erythrocyte lysis and in vivo Galleria mellonella survival assay authenticated the non-toxic nature of 3BP up to 512 µg/mL. Finally, a vaginal cream formulated with 3BP was found to be effective in VVC-induced female mice model, as it significantly decreasing fungal load and protecting vaginal mucosa. Concomitantly, the present study serves as a clear demonstration of antifungal mechanistic action of anticancer drug -3BP, against Candida species. This finding holds significant potential for mitigating candidal infections, particularly VVC, within healthcare environments.

Impact of Lactobacillus crispatus-containing oral and vaginal probiotics on vaginal health: a randomised double-blind placebo controlled clinical trial.

Health of reproductive tract is tightly associated with balance of microbial communities in this area. Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) represent common disturbances of vaginal communities. Vaginal discharge due to BV or VVC is a very frequent reason for visiting gynaecologist. We aimed to evaluate the impact of the novel evidence-based probiotics on BV and VVC patients. The study group included 89 BV and 93 VVC patients (aged 18-50 years) who were recruited into randomised double-blind placebo-controlled two-arm parallel trial. The patients of each diagnosis group received oral or vaginal probiotic capsules, or placebo capsules during 3 months. A probiotic capsule contained two (DSM32717 and DSM32720, in case of BV) or three (DSM32720, DSM32718 and DSM32716, in case of VVC) Lactobacillus crispatus strains. Vaginal, intestinal and general health was monitored weekly by questionnaire. Blood analyses were done in the beginning and at the end of trial. Vaginal samples were collected monthly, microscopic and molecular analyses were performed. The study revealed that both oral and vaginal capsules reduced the signs and symptoms in BV patients. Remarkable improvement was noted in Nugent score, amount and smell of discharge, but also in itching/irritation. Consumption of vaginal probiotics significantly increased the lactobacilli counts in their vagina while mean proportion of some BV-related bacteria decreased. In VVC patients, both oral and vaginal capsules lowered the combined score of two most important symptoms, amount of discharge and itching/irritation. In conclusion, the novel formulations of evidence-based well-focused probiotic L. crispatus strains are effective against BV and VVC being suitable for both vaginal and oral administration. Clinical trial registration: ISRCTN34840624, BioMed Central.

Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis.

Resistance to antifungal agents in vulvovaginal candidiasis has resulted in increasing morbidity among women globally. It is therefore crucial that new antimycotic agents are developed to counter this rising challenge. Q-Griffithsin (Q-GRFT) is a red algal lectin, manufactured in Nicotiana benthamiana. Griffithsin has well characterized broad spectrum antiviral activity and has demonstrated potent in vitro activity against multiple strains of Candida, including C. albicans. We have been working to incorporate Q-GRFT into topical microbicide products to prevent HIV-1 and HSV-2 transmission. The goal of this study was to evaluate the efficacy of a prototype Q-GRFT dosage form in prophylactic and therapeutic murine models of vaginal candidiasis, through microbiologic, histopathologic, and immune studies. In a preventive model, in comparison with infected controls, Q-GRFT treatment resulted in a lower fungal burden but did not alter the number of vaginal neutrophils and monocytes. In a therapeutic model, Q-GRFT enhanced fungal clearance when compared with infected untreated controls. Finally, histopathology demonstrated lower vaginal colonization with C. albicans following Q-GRFT treatment. Our results demonstrate that Q-GRFT has significant preventive and therapeutic activity in vaginal candidiasis offering additional benefit as a topical microbicide for prevention of HIV-1 and HSV-2 transmission.

Vulvovaginal Candidiasis: A Review of the Evidence for the 2021 Centers for Disease Control and Prevention of Sexually Transmitted Infections Treatment Guidelines.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common cause of vulvovaginal itching and discharge. This article discusses the latest CDC STI Treatment Guidelines for VVC. METHODS: A literature search of relevant topics was performed, and a team of experts was convened to discuss (1) diagnosis/testing modalities; treatment of (2) uncomplicated VVC , (3) complicated VVC, and (4) VVC caused by non-albicans yeast; (5) alternative treatment regimens; (6) susceptibility testing of yeast; Special Populations: (7) pregnancy and (8) HIV and VVC. RESULTS: Yeast culture remains the gold standard for diagnoses. Newer molecular assays have been developed for the diagnosis of VVC and perform well. Azole antifungals remain the treatment of choice for uncomplicated VVC. Two new drugs, TOL-463 and recently FDA-approved ibrexafungerp, appeared promising in clinical trials. For recurrent VVC, oteseconazole, not yet commercially available, may represent a new option. For non-albicans yeast infections in symptomatic patients, boric acid appears useful. No evidence supports the use of alternative treatments, including probiotics. Fluconazole during pregnancy may be associated with spontaneous abortion and craniofacial and heart defects. In women with HIV infection, lower CD4+ T-cell counts are associated with increased rates of VVC, and VVC is associated with increased viral shedding. Treatment measures in women with HIV infection are identical to those women without HIV infection. CONCLUSIONS: There has been significant new knowledge generated about VVC since the 2015 CDC Guidelines which have led to changing recommendations.

Lactobacilli reduce recurrences of vaginal candidiasis in pregnant women: a randomized, double-blind, placebo-controlled study.

AIMS: The aim of this study was to investigate the effects of lactobacilli strains in preventing the recurrences of vaginal candidiasis (VC) in 78 pregnant women with VC (lactobacilli, n = 39; placebo, n = 39) and the potential benefits on quality of life. METHODS AND RESULTS: The lactobacilli putative probiotic (SynForU-HerCare; two capsules/day of 9·5 log CFU per capsule) or placebo was administered for 8-weeks in a randomized, double-blind, placebo-controlled study. Subjects were assessed for vaginal and gut health conditions at baseline, week-4 and week-8 via questionnaires. The vulvovaginal symptom questionnaire not only covered aspects pertaining to vulvovaginal symptoms but also the quality of life impacts such as emotional, social and sexual. The administration of lactobacilli reduced symptoms of irritation (P = 0·023) and discharge (P = 0·011) starting week-4 and continued after week-8 (P < 0·05), accompanied by reduced symptoms for burning after week-8 (P = 0·046) as compared to the placebo. Patients consuming lactobacilli also showed reduced concern about symptoms after week-4 (P = 0·010) and continued after week-8 (P = 0·001), accompanied by reduced impairment of daily activities attributed to vulvovaginal symptoms (P = 0·012) and continued after week-8 (P = 0·026). Insignificant differences were observed for sexual impacts between treatment groups. The administration of lactobacilli also reduced recurrences of both emotional and social stress as compared to the placebo at both week-4 and week-8 (P < 0·05). Patients consuming lactobacilli showed higher defecation times per week at week-4 (P = 0·010) and week-8 (P = 0·001) as compared to the placebo group, indicating the potential to reduce risks of pregnancy-induced constipation. CONCLUSIONS: Lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated the preventive and modulatory roles of lactobacilli strains against VC in pregnant women. Taken altogether, our present data illustrated that lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC, thus could be a potential strategy for the maintenance of vaginal health during pregnancy.

Development of bifunctional vaginal suppositories by joint use terconazole and probiotic for treatment and prophylaxis of vulvovaginal candidiasis.

OBJECTIVE: The objective of this article is the creation and investigation of bifunctional suppositories that are endowed with antifungal and probiotic properties intended for the treatment of vulvovaginal candidiasis (VVC) and colonization of the vaginal cavity by powerful lactobacilli. MATERIALS AND METHODS: Freeze-dried Lactobacillus delbrueckii MH10 was used as a probiotic, which is an active producer of H2O2 isolated from a healthy woman's vagina. Hydrophilic PEG 4000/400, amphiphilic Suppocire AP, and lipophilic Novata ABPH bases were used for the preparation of vaginal suppositories and each included 80 mg terconazole and 25 mg (∼109 CFU) lactobacilli. The release kinetic of active agents from suppositories was studied using the British Pharmacopeia's basket dissolution method, and the physicochemical properties were studied using known methods. Bioadhesion of suppositories was evaluated by flow rate from polyacrylamide substrate inclined at 60°. Antagonism of lactobacillus against fungi was studied using the disk diffusion method and joint cultivation in simulated vaginal fluid. RESULTS: The release rate of active ingredients from the suppositories was PEG 4000/400 > Suppocire AP > Novata ABPH in decreasing order. Suppositories made of Suppocire AP possessed higher adhesion ability to artificial mucosa and longer shelf life. It was revealed that during joint cultivation L. delbrueckii MH10 kills more than 90% of C. albicans population. CONCLUSIONS: Due to its physicochemical, biopharmaceutical, and bioadhesive properties, the base Suppocire AP is preferable for manufacturing vaginal bifunctional suppositories. Lactobacilli kill C. albicans by coaggregating and direct releasing hydrogen peroxide onto target cells.

Prophylactic and Therapeutic Role of Vitamin D3 in Combination with Fluconazole Against Vaginal Candidiasis in a Murine Model.

OBJECTIVE: In the present study, we assessed the adjunct effect of vitamin D3 in combination with Fluconazole (FLZ) against Vulvovaginal Candidiasis (VVC) in mice. METHODS: Prophylactic effect was assessed by pretreating mice with vitamin D3 before exposure of mice with 2 X 106 CFUs of Candida albicans followed by treatment with FLZ. To determine the combined therapeutic efficacy, C. albicans infected mice were treated with a combination of vitamin D3 (10 µg/kg) and FLZ (10 and 20 mg/kg). The efficacy of the treatment was assessed by analyzing the fungal load and blood cell count. Moreover, the levels of inflammatory cytokines, including IL- 1ß, IL-17 and TNF-α, were analyzed in the vaginal tissues. The histological analysis of the vaginal tissue from the untreated and treated mice was performed to assess the efficacy of the treatment. RESULTS: Prophylactic treatment with vitamin D3 (10 and 20 µg/kg) significantly increased the therapeutic effect of FLZ against VVC. In a therapeutic experiment, mice in the infected control group showed the highest vaginal fungal load of 83627 ± 10058 CFUs. Treatment with FLZ at a dose of 10 mg/kg reduced fungal load to 55523 ± 14823 CFUs, whereas the mice treated with a combination of vitamin D3 and FLZ (10 mg/kg) had the fungal burden of 12156 ± 3219. Similarly, treatment with FLZ (20 mg/kg) reduced fungal load to 36394 ± 5648 CFUs, whereas the addition of vitamin D3 to FLZ (20 mg/kg) further reduced the fungal burden to 2179 ± 1188. The leukocyte numbers in the infected mice increased to 9802 ± 505 as compared to 5152 ± 778 in normal control mice. Whereas, a combination of vitamin D3 with FLZ (10 and 20 mg/kg) reduced leukocyte numbers to 7284 ± 607 and 5739 ± 1126. The histological analysis data revealed epithelial necrosis, shedding and ulceration in the vaginal wall. Treatment with FLZ or a combination of FLZ and vitamin D3 brought regenerative changes in the vaginal epithelium and lamina proparia. CONCLUSION: The results of the present work recommend that the addition of vitamin D3 may be considered to increase the efficacy of FLZ against VVC.

Prevention and Management of Genital Mycotic Infections in the Setting of Sodium-Glucose Cotransporter 2 Inhibitors.

OBJECTIVE: To review the incidence, risk factors, prevention, and management of genital mycotic infections (GMIs) associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors. DATA SOURCES: A literature search of PubMed and Reactions Weekly was performed in February 2020 with updated searches monthly through July 2020 to identify relevant data regarding SGLT2 inhibitors and GMIs. Manufacturers of each agent were contacted, and clinical practice guidelines were consulted. STUDY SELECTION AND DATA EXTRACTION: All available literature was evaluated for inclusion based on relevance to the research question, timeliness of the publication, validity, and impact on current practice. A date limit was not set; however, publications from 2010 to July 2020 were prioritized. DATA SYNTHESIS: The 3- to 4-fold increased incidence of GMIs is considered a classwide effect of SGLT2 inhibitors. Female sex and a prior history of GMIs are factors associated with the highest risk, whereas circumcised males are at the lowest risk of SGLT2 inhibitor-induced GMI. Personal hygiene advice can reduce the infection risk. When candidiasis occurs, it is often mild and responsive to treatment and often does not require discontinuation of the medication. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This narrative review can assist in shared decision-making discussions with patients who may benefit from SGLT2 inhibitors and provides guidance for health care professionals managing SGLT2 inhibitor-associated GMIs. CONCLUSIONS: SGLT2 inhibitors predispose patients to developing mild GMIs. Strong consideration should be given to avoid SGLT2 inhibitors in female patients with a history of severe, recurrent infections. Preventive strategies are optimized diabetes management and personal hygiene advice.

ß-cyclodextrin polymer/Soluplus® encapsulated Ebselen ternary complex (EßpolySol) as a potential therapy for vaginal candidiasis and pre-exposure prophylactic for HIV.

Epidemiological findings have discussed recurrent and persistent vulvovaginal candidiasis to be a major manifestation of HIV infected women. Conversely, women with vulvovaginal candidiasis have higher risk of acquiring HIV transmitted during intercourse. Common treatments for such conditions include combined antiretroviral and antifungal therapy. Drug-Drug interaction is a major problem encountered due to common CYP450 metabolic pathway of azoles and antiretroviral drugs. Ebselen (EB), lipophilic, organo-selenium compound has demonstrated promising anti-HIV and anti-fungal activity. The aim of current research was to develop and characterize a rapidly soluble and non-cytotoxic vaginal film of ebselen which could serve dual purpose of treating vulvovaginal candidiasis and pre-exposure prophylactic (PrEP) against HIV. Ebselen/cyclodextrin polymer/Soluplus® (1:10:10) ternary complex (EßpolySol) showed 200 fold enhancement in aqueous solubility and no degradation of EB in thermogravimetry analysis. EßpolySol film with tensile strength of 33.12 ± 1.98 N/cm2 disintegrated within 30 sec, presented instant drug release with no apparent precipitation in simulated vaginal fluid. EßpolySol film showed compatibility with HEC-1A monolayer and HeLa cells compared to VCF®. EßpolySol film showed MIC of 20 µM against Candida species and IC50 of 0.71 µM against HIV.

The role of diet and probiotics in prevention and treatment of bacterial vaginosis and vulvovaginal candidiasis in adolescent girls and non-pregnant women.

The article raises important issues regarding the use of diet and probiotics in prevention and treatment of vaginitis. Vaginitis is defined as any condition with symptoms of abnormal vaginal discharge. The most common causes of vaginitis are vulvovaginal candidiasis (VVC), trichomoniasis and bacterial vaginosis (BV). Vaginitis has been linked to itching, burning, pain, discharge, irritation and also adverse reproductive and obstetric health outcomes. Moreover, microorganisms that build vaginal flora in the state of bacterial vaginosis are a source of cervicitis and endometritis (often in subclinical forms) and pelvic inflammatory disease (PID) The proper diet and probiotics consumption may influence the composition of the gut microbiota, improve gut integrity, and have an impact on maintaining and recovering the normal vaginal microbiota. Future studies and reviews investigating the role of diet and probiotics in changes to gut and vaginal microbiome need to focus on deciphering the mechanismus of host bacteria interaction in vulvovaginal health.

Recovery of Saccharomyces cerevisiae CNCM I-3856 in Vaginal Samples of Healthy Women after Oral Administration.

Bacterial vaginosis and vulvovaginal candidiasis are common causes of impaired health and quality of life for women. Although antimicrobial agents remain the main strategy for the treatment of vaginal infections, their repeated use involves high rates of resistance and recurrence. Alternative approaches such as probiotics are studied. Saccharomyces cerevisiae CNCM I-3856 already demonstrated beneficial effects in experimental models of vaginal infections. This randomized, double-blind, placebo-controlled clinical study was performed to evaluate the recovery of S. cerevisiae CNCM I-3856 in vaginal samples in healthy women after oral consumption. Sixty healthy women were randomized to receive a daily dose of S. cerevisiae CNCM I-3856 or a placebo for 4 weeks. Subcultures and quantitative polymerase chain reaction (qPCR) were used to detect the strain in vaginal and stool samples. A safety assessment was carried out throughout the study. Fifty-seven women completed the study. Over the 4-week supplementation phase, S. cerevisiae CNCM I-3856 has been detected in the vaginal samples of 21% of women (n = 4/19) in the 500 mg Probiotic group and 16% of women (n = 3/19) in the 1000 mg Probiotic group. The strain was detected in the faeces of 90% of women consuming the probiotic. This is the first clinical study demonstrating the migration of yeast from intestine to vagina where it may exert its benefits.

Biosurfactant from vaginal Lactobacillus crispatus BC1 as a promising agent to interfere with Candida adhesion.

BACKGROUND: Lactobacillus spp. dominating the vaginal microbiota of healthy women contribute to the prevention of urogenital and sexually transmitted infections. Their protective role in the vagina can be mediated by Lactobacillus cells themselves, metabolites or bacterial components, able to interfere with pathogen adhesion and infectivity. Vulvovaginal candidiasis (VVC) is a common genital infection, caused by the overgrowth of opportunistic Candida spp. including C. albicans, C. glabrata, C. krusei and C. tropicalis. Azole antifungal drugs are not always efficient in resolving VVC and preventing recurrent infections, thus alternative anti-Candida agents based on vaginal probiotics have gained more importance. The present work aims to chemically characterize the biosurfactant (BS) isolated from a vaginal Lactobacillus crispatus strain, L. crispatus BC1, and to investigate its safety and antiadhesive/antimicrobial activity against Candida spp., employing in vitro and in vivo assays. RESULTS: BS isolated from vaginal L. crispatus BC1 was characterised as non-homogeneous lipopeptide molecules with a critical micellar concentration value of 2 mg/mL, and good emulsification and mucoadhesive properties. At 1.25 mg/mL, the BS was not cytotoxic and reduced Candida strains' ability to adhere to human cervical epithelial cells, mainly by exclusion mechanism. Moreover, intravaginal (i.va.) inoculation of BS in a murine experimental model was safe and did not perturb vaginal cytology, histology and cultivable vaginal microbiota. In the case of i.va. challenge of mice with C. albicans, BS was able to reduce leukocyte influx. CONCLUSIONS: These results indicate that BS from vaginal L. crispatus BC1 is able to interfere with Candida adhesion in vitro and in vivo, and suggest its potential as a preventive agent to reduce mucosal damage occasioned by Candida during VVC.

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.

Lactobacilli-containing vaginal probiotics to cure or prevent bacterial or fungal vaginal dysbiosis: a systematic review and recommendations for future trial designs.

BACKGROUND: Vaginal probiotics claiming to cure and/or prevent bacterial and/or fungal vaginal dysbiosis are available on the market but, until recently, did not have to be approved as drugs for human use. OBJECTIVES: We evaluated the impact of vaginal probiotics on bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) cure and/or recurrence, as well as vaginal microbiota (VMB) composition and vaginal detection of probiotic strains. SEARCH STRATEGY: We performed a systematic literature search in MEDLINE and Embase up to 15 January 2019. SELECTION CRITERIA: There were no restrictions in probiotic strains/formulations, study populations, and designs. BV had to be diagnosed by Nugent or Ison-Hay Gram stain scoring, VVC by culture, wet mount or PCR, and VMB composition/detection by molecular techniques. DATA COLLECTION AND ANALYSIS: The authors independently extracted data. MAIN RESULTS: All 22 vaginal probiotics evaluated in the 34 eligible studies contained Lactobacillus strains, and some contained additional active ingredients. The probiotics hold promise for BV cure and prevention, but much less so for VVC cure and prevention. No major safety concerns were reported in any of the studies. Vaginal detection of probiotic strains never lasted long beyond the dosing period, suggesting that they did not colonise the vagina. However, findings are not definitive because heterogeneity was high and the quality of most studies suboptimal. CONCLUSIONS: Availability of vaginal probiotics for vaginal health indications will likely decline in 2020 because of regulatory changes. We urge the field to invest in clinical evidence-based product development and to conduct future trials more rigorously. TWEETABLE ABSTRACT: Lactobacilli-containing vaginal probiotics hold promise for bacterial vaginosis cure and prevention, but not for vulvovaginal candidiasis.

Mitos y creencias del cuidado e higiene íntima en mujeres peruanas jóvenes / Myths and beliefs of intimate care and hygiene in young peruvian women

Introducción: Muchas veces se propagan mitos y creencias sobre la higiene íntima femenina, que podrían traer consecuencias en muchos aspectos. Objetivo: Determinar la asociación entre los mitos y creencias del cuidado e higiene íntima y los cuidados reales de higiene íntima en mujeres peruanas jóvenes. Método: Se realizó un estudio transversal analítico, que presentó una revisión del tema para realizar una encuesta de 21 interrogantes, en temas comunes en la higiene íntima, post piloto, se preguntó de su realización y la frecuencia semanal; esta última se asoció a variables socio-educativas. Resultados: De las 600 mujeres jóvenes encuestadas, hubo diferencia en cuanto la edad según la percepción del uso de ropa interior de algodón (p=0,013), la limpieza de la zona íntima de adelante hacia atrás (p<0,001), el uso de ropa interior no muy ajustada (p<0,001), el uso de ropa sintética (p=0,045), el uso de jabón exclusivo para la zona íntima (p<0,001), la edad de inicio de relaciones sexuales (p=0,031) y el uso de métodos anticonceptivos como causantes de flujo (p=0,008). En cuanto al ser o no estudiantes, hubo diferencia en la percepción de que el rasurado del pubis para la limpieza (p=0,018) y que los ejercicios de relajación disminuyen el flujo vaginal (p=0,030). Conclusiones: Se describió algunos mitos y creencias en cuanto a la limpieza íntima; a su vez, se encontró que algunas prácticas de higiene tienen asociación con la edad y el ser estudiante. Esto debe ser estudiado a profundidad, ya que, esto podría llevar a problemas mayores.

Introduction: Myths and beliefs about female intimate hygiene are often spread, which could have consequences in many aspects. Objective: To determine the association between the myths and beliefs of intimate care and hygiene and the actual care of intimate hygiene in young Peruvian women. Method: An analytical cross-sectional study was conducted, which exposed a review of the topic to conduct a survey of 21 questions on common issues in intimate hygiene, post pilot, asked about its performance and weekly frequency; The latter was associated with socio-educational variables. Results: Of the 600 young women surveyed, there was a difference regarding age according to the perception of the use of cotton underwear (p = 0.013), the cleaning of the intimate area from front to back (p <0.001), the use of underwear not very tight (p <0.001), the use of synthetic clothing (p = 0.045), the use of exclusive soap for the intimate area (p <0.001), the age of onset of sexual intercourse (p = 0.031) and the use of contraceptive methods as causing flow (p = 0.008). Regarding whether or not they were students, there was a difference in the perception that shaving the pubis for cleaning (p = 0.018) and that relaxation exercises decrease vaginal discharge (p = 0.030). Conclusions: Some myths and beliefs regarding intimate cleansing were described; In turn, some hygiene practices were found to be associated with age and being a student. This should be studied in depth, as this could lead to bigger problems.

Cinnamaldehyde inhibits Candida albicans growth by causing apoptosis and its treatment on vulvovaginal candidiasis and oropharyngeal candidiasis.

The invasion of Candida albicans is one of the most common fungal infections seen in clinical practice, and serious drug resistance has been reported in recent years. Therefore, new anti-C. albicans drugs must be introduced. In this research, it was demonstrated that cinnamaldehyde (CA) shows strong antimicrobial activity, with 0.26 mg/mL CA being the minimum inhibitory concentration to manage C. albicans. Extraordinarily, we detected that CA accumulated the intracellular reactive oxygen species (ROS) and enhanced the calcium concentration in the cytoplasm and mitochondria through flow cytometry. In addition, we observed that C. albicans cells released Cytochrome c from the mitochondria to the cytoplasm, depolarized the mitochondrial membrane potential, and activated the metacaspase when exposed to 0.065, 0.13, 0.26, and 0.52 mg/mL CA. Furthermore, to confirm that CA introduces the C. albicans apoptosis, we discovered that when the phosphatidylserine was exposed, DNA damage and chromatin condensation occurred, which were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and periodic acid-Schiff (PAS) staining were conducted to prove that CA possessed the ability to treat oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). From the above, our research indicates that CA is a promising antifungal candidate when applied to C. albicans infections.

Salivary ABO antigens and risk of microbial vaginosis.

OBJECTIVE: To investigate the effect of blood group ABO antigens on the risk of vaginosis. METHODS: The cross-sectional study was conducted at the Department of Obstetrics and Gynaecology, Al-Yarmouk Teaching Hospital, Baghdad, Iraq, from April 2016 to June 2017. Two vaginal swabs and 1ml of stimulated saliva from women aged16-46 years were collected. The first swab was used for direct wet smear examination, while the second swab was cultured on aerobic and facultative anaerobic cultures on appropriate media. SPSS 25 was used for data analysis. RESULTS: Of the 269 patients with a mean age of 30.7}6.2 years, 52(19.3%) were positive and 217(80.7%) were negative for ABO antigen. The duration of vaginosis symptoms were observed after 7-13 days in both positive and negative groups (p=0.24).The main symptom in women with positive ABO was vaginal pain, while it was a foul smelling vaginal discharge and itching in women with the negative status (p=0.0001).Single bacterial species growth was obtained from 32(61.5%) positive patients and 81(37.3%) negative patients. CONCLUSIONS: ABO secretory status could increase defence against microbial vaginosis.