Vaginal community state types (CSTs) alter environmental cues and production of the Staphylococcus aureus toxic shock syndrome toxin-1 (TSST-1).

Menstrual toxic shock syndrome (mTSS) is a rare but life-threatening disease associated with the use of high-absorbency tampons. The production of the Staphylococcus aureus toxic shock syndrome toxin-1 (TSST-1) superantigen is involved in nearly all cases of mTSS and is tightly controlled by regulators responding to the environment. In the prototypic mTSS strain S. aureus MN8, the major repressor of TSST-1 is the carbon catabolite protein A (CcpA), which responds to glucose concentrations in the vaginal tract. Healthy vaginal Lactobacillus species also depend on glucose for both growth and acidification of the vaginal environment through lactic acid production. We hypothesized that interactions between the vaginal microbiota [herein referred to as community state types (CSTs)] and S. aureus MN8 depend on environmental cues and that these interactions subsequently affect TSST-1 production. Using S. aureus MN8 ΔccpA growing in various glucose concentrations, we demonstrate that the supernatants from different CSTs grown in vaginally defined medium (VDM) could significantly decrease tst expression. When co-culturing CST species with MN8 ∆ccpA, we show that Lactobacillus jensenii completely inhibits TSST-1 production in conditions mimicking healthy menstruation or mTSS. Finally, we show that growing S. aureus in "unhealthy" or "transitional" CST supernatants results in higher interleukin 2 (IL-2) production from T cells. These findings suggest that dysbiotic CSTs may encourage TSST-1 production in the vaginal tract and further indicate that the CSTs are likely important for the protection from mTSS.IMPORTANCEIn this study, we investigate the impact of the vaginal microbiota against Staphylococcus aureus in conditions mimicking the vaginal environment at various stages of the menstrual cycle. We demonstrate that Lactobacillus jensenii can inhibit toxic shock syndrome toxin-1 (TSST-1) production, suggesting the potential for probiotic activity in treating and preventing menstrual toxic shock syndrome (mTSS). On the other side of the spectrum, "unhealthy" or "transient" bacteria such as Gardnerella vaginalis and Lactobacillus iners support more TSST-1 production by S. aureus, suggesting that community state types are important in the development of mTSS. This study sets forward a model for examining contact-independent interactions between pathogenic bacteria and the vaginal microbiota. It also demonstrates the necessity of replicating the environment when studying one as dynamic as the vagina.

Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

New Aspects in the Study of Lactobacillus iners.

A cultural microbiological study of the vaginal microbiota of patients of reproductive age was carried out to isolate the species Lactobacillus iners with subsequent study of phenotypic features. The presence of two phenotypically different species variants was found in patients with bacterial vaginosis.

Glycogen availability and pH variation in a medium simulating vaginal fluid influence the growth of vaginal Lactobacillus species and Gardnerella vaginalis.

BACKGROUND: Glycogen metabolism by Lactobacillus spp. that dominate the healthy vaginal microbiome contributes to a low vaginal pH (3.5-4.5). During bacterial vaginosis (BV), strict and facultative anaerobes including Gardnerella vaginalis become predominant, leading to an increase in the vaginal pH (> 4.5). BV enhances the risk of obstetrical complications, acquisition of sexually transmitted infections, and cervical cancer. Factors critical for the maintenance of the healthy vaginal microbiome or the transition to the BV microbiome are not well defined. Vaginal pH may affect glycogen metabolism by the vaginal microflora, thus influencing the shift in the vaginal microbiome. RESULTS: The medium simulating vaginal fluid (MSVF) supported growth of L. jensenii 62G, L. gasseri 63 AM, and L. crispatus JV-V01, and G. vaginalis JCP8151A at specific initial pH conditions for 30 d. L. jensenii at all three starting pH levels (pH 4.0, 4.5, and 5.0), G. vaginalis at pH 4.5 and 5.0, and L. gasseri at pH 5.0 exhibited the long-term stationary phase when grown in MSVF. L. gasseri at pH 4.5 and L. crispatus at pH 5.0 displayed an extended lag phase over 30 d suggesting inefficient glycogen metabolism. Glycogen was essential for the growth of L. jensenii, L. crispatus, and G. vaginalis; only L. gasseri was able to survive in MSVF without glycogen, and only at pH 5.0, where it used glucose. All four species were able to survive for 15 d in MSVF with half the glycogen content but only at specific starting pH levels - pH 4.5 and 5.0 for L. jensenii, L. gasseri, and G. vaginalis and pH 5.0 for L. crispatus. CONCLUSIONS: These results suggest that variations in the vaginal pH critically influence the colonization of the vaginal tract by lactobacilli and G. vaginalis JCP8151A by affecting their ability to metabolize glycogen. Further, we found that L. jensenii 62G is capable of glycogen metabolism over a broader pH range (4.0-5.0) while L. crispatus JV-V01 glycogen utilization is pH sensitive (only functional at pH 5.0). Finally, our results showed that G. vaginalis JCP8151A can colonize the vaginal tract for an extended period as long as the pH remains at 4.5 or above.

Review of the evidence of the effects of human papillomavirus infection and Gardnerella vaginalis, and their co-infection on infertility.

A prevalent sexually transmitted infection, the human papillomavirus (HPV) is typically obtained just after the first sexual activity. The majority of HPV infections are asymptomatic and temporary. Cervical, anal, penile, vaginal, vulvar, and oropharyngeal cancers can occur due to recurrent infections with high-risk (hr)-HPV strains, generally decades later. Infections with HPV are significantly associated with reproductive function abnormalities. Per recent research, HPV infections may result in male infertility by reducing sperm motility. The hr-HPV infection was a risk factor for miscarriage, and the indiscriminate HPV genotype increased the probability of premature labor unexpectedly. Women's endometrial trophoblastic cell implantation is decreased by HPV. Gardnerella vaginalis (GV), an anaerobic bacterium that is a component of the natural vaginal flora, can be associated with bacterial vaginosis (BV) when it starts to overgrow and emerge as the dominant species. Reduced Lactobacillus species abundance and GV are linked to female infertility. Data from in vitro studies suggests that sialidase produced by GV may facilitate the entry and growth of papilloma and other sexually transmitted viruses. Also, based on some studies conducted in the past, it can be said that GV and BV are associated with the development of uterine cancer. However, there is still not enough information about the exact mechanism of GV and HPV in causing infertility, which requires more research.

Gardnerella pickettii sp. nov. (formerly Gardnerella genomic species 3) and Gardnerella greenwoodii sp. nov. (formerly Gardnerella genomic species 8) isolated from female urinary microbiome.

During an ongoing female urinary microbiome research study, strains c17Ua_112T and c31Ua_26T isolated from urine samples of a patient diagnosed with overactive bladder and a healthy postmenopausal woman, respectively, could not be allocated to any Gardnerella species with valid names. In this work, we aimed to characterize these strains. The 16S rRNA gene sequences confirmed that these strains are members of the genus Gardnerella. Phylogenetic analysis based on cpn60 strongly supported two clades, one encompassing c17Ua_112T and nine other strains from the public database, and the other including c31Ua_26T and three other strains, which were distinct from currently recognized species of the genus Gardnerella. Likewise, the phylogenomic tree also showed that strains c17Ua_112T and c31Ua_26T formed independent and robust clusters. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between c17Ua_112T and c31Ua_26T were 79.27 and 27.4 %, respectively. Strain c17Ua_112T showed the highest ANI (94.8 %) and dDDH values (59.8 %) with Gardnerella piotii UGent 18.01T, and strain c31Ua_26T revealed highest ANI (84.2 %) and dDDH (29.1 %) values with Gardnerella swidsinskii GS 9838-1T. Based on the data presented here, the two strains c17Ua_112T and c31Ua_26T represent two novel species of the genus Gardnerella, for which the names Gardnerella pickettii (c17Ua_112T=DSM 113414T=CCP 71T) and Gardnerella greenwoodii (c31Ua_26T=DSM 113415T=CCP 72T) are proposed.

Characterization of Gardnerella vaginalis isolates: correlations among clades, biofilm formation and cytokine stimulation.

We characterized 61 Gardnerella vaginalis (GV) strains isolated from women with bacterial vaginosis. GV clade 1 was the most commonly found (52.5%), followed by clade 4 (36.1%). All the strains were susceptible to ampicillin and clindamycin, whereas 96.7% and 6.6% of strains showed metronidazole and tetracycline resistance, respectively. Isolates within clade 4 tended to possess the highest ability to form biofilm. Strains resistant to metronidazole and tetracycline were all intermediate or high biofilm producers. All GV clades significantly upregulated the production of pro-inflammatory cytokines by HeLa cells, especially IL-8 and IL-6. Clade 4 induced a significantly higher production of IL-1ß compared to other clades.

Cervical and Vaginal Microbiomes in Early Miscarriages and Ongoing Pregnancy with and without Dydrogesterone Usage.

Emerging evidence suggests that the reproductive tract microbiota is a key modulator of local inflammatory and immune pathways throughout pregnancy and may subsequently impact pregnancy outcomes. In this study, our objective was to analyze the cervical and vaginal microbiomes during early pregnancy among three groups: women with healthy ongoing pregnancies, women undergoing dydrogesterone treatment, and those who experienced miscarriages. The experiment involved 51 women at 8-11 weeks of gestation. The microbiome was examined using 16S rRNA sequencing on the Ion Torrent PGM platform. Across all groups, Lactobacillus iners was predominant, suggesting that the vaginal community type CST III is common among the majority of participants. Notably, our data highlighted the significant roles of Gardnerella vaginalis and Mycoplasma girerdii in the pathogenesis of early miscarriage. Conversely, L. iners and Bifidobacterium longum have a protective effect in early pregnancy. Moreover, dydrogesterone intake appeared to influence notable differences between the cervical and vaginal microbiomes. Overall, our study enhanced our understanding of the cervical and vaginal microbiome composition in the eastern European population during early pregnancy.

Lacticaseibacillus rhamnosus Lcr35 Stimulates Epithelial Vaginal Defenses upon Gardnerella vaginalis Infection.

Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria, such as Gardnerella vaginalis, and low levels of "healthy" lactobacilli leads to bacterial vaginosis (BV), usually associated with a low-grade inflammatory process. Despite appropriate antibiotic treatment, G. vaginalis-associated BV is characterized by significant recurrence. The use of probiotics could be an interesting alternative therapy due to their ability to rebalance vaginal microbiota. In this study, we investigated the effects of a well-characterized probiotic strain, Lacticaseibacillus rhamnosus Lcr35, on epithelial vaginal and dendritic cell (DC) immune responses after G. vaginalis infection. In an in vitro coculture model with human monocyte-derived dendritic cells and a vaginal epithelial cell (VEC) monolayer, the Lcr35 strain induced DC activation, as evidenced by the induction of maturation and synthesis of interleukin-8 (IL-8) and CCL-20 chemokines upon apical challenge of the VECs by G. vaginalis. Analysis of the vaginal epithelial response showed that the presence of Lcr35 significantly increased the production of the proinflammatory cytokines IL-8 and IL-1ß and human ß-defensin 2 (HBD-2), whereas the concentration of secretory leukocyte protease inhibitor (SLPI) was decreased in G. vaginalis-infected vaginal epithelial cells. Treatment with recombinant SLPI was associated with upregulation of Lcr35-stimulated IL-8 and HBD-2 production. These results suggest that inhibition of SLPI by Lcr35 in vaginal epithelial cells contributes to the host defense response against G. vaginalis infection.

Inhibitory effect of Lactobacillus gasseri CCFM1201 on Gardnerella vaginalis in mice with bacterial vaginosis.

Gardnerella vaginalis is the core pathogen of bacterial vaginosis (BV), the most common vaginal infection in women. G. vaginalis exerts pathogenicity through various factors, such as biofilm formation and the local host immune response stimulation. Therefore, this study aimed to evaluate the inhibitory effect of Lactobacillus gasseri CCFM1201 on G. vaginalis using experimental BV models. We evaluated L. gasseri in vitro to inhibit pathogen biofilm formation and adhesion capacity in HeLa cells using crystal violet staining. Further in vivo studies were conducted to assess the inhibitory effects of L. gasseri CCFM1201 on BV induced by G. vaginalis. L. gasseri exhibited strain-specific adhesion and inhibition of pathogen biofilm formation in vitro. L. gasseri CCFM1201 significantly reduced G. vaginalis in mice (p < 0.05), inhibited sialidase activity, modulated tumor necrosis factor-α and interleukin-1ß expression, and reduced myeloperoxidase activity (p < 0.05). Histopathological examination indicated that L. gasseri CCFM1201 improved inflammatory cell infiltration of vaginal tissue and restored its structure. Vaginal epithelial cell exfoliation, the main clinical feature of BV, was significantly improved by L. gasseri CCFM1201 intervention (p < 0.05). Thus, L. gasseri CCFM1201 is a potential candidate for treating G. vaginalis-induced vaginal diseases.

Gardnerella vaginalis purulent meningitis in an adolescent male: a case report.

BACKGROUND: We report a rare case of Gardnerella vaginalis found in the cerebrospinal fluid of a young boy. CASE PRESENTATION: A 14-year-old boy was admitted to hospital with headache, vomiting, fever, drowsiness and positive meningeal irritation signs on examination. Cerebrospinal fluid (CSF) shows white blood cell and protein were elevated, and glucose was low. Traditional aerobic and anaerobic culture of CSF did not grow any organisms. However, metagenomic next-generation sequencing (mNGS) reveals G. vaginalis in his CSF. The patient was diagnosed with purulent meningitis, and treated with intravenous meropenem and linezolid for a week, followed by oral administration of amoxicillin for two weeks. He recovered without sequelae. CONCLUSIONS: Purulent meningitis caused by Gardnerella vaginalis is extremely rare. Metagenomic next-generation sequencing of CSF should be highlighted for early diagnosis. With effective antibiotic treatment, the prognosis was excellent.

Vaginal microbiota as an unusual cause of spondylodiscitis.

The incidence of extra pelvic infections due to vaginal microflora bacteria has increased as growth media and methods of isolation have improved. However, bone infections seem to be still relatively rare, and little is known about their risk factors, clinical presentation, treatment and final outcome. We describe here a spondylodiscitis due to Gardnerella vaginalis, Atopobium vaginae, Peptostreptococcus indolicus and Prevotella amnii, anaerobic bacteria from vaginal microbiota. Our patient had no obvious predisposing factor and recovered after antibiotic treatment. To our knowledge, this case is the first reported spondylodiscitis caused by polymicrobial vaginal flora in a healthy, immunocompetent woman.

SERS-PLSR Analysis of Vaginal Microflora: Towards the Spectral Library of Microorganisms.

The accurate identification of microorganisms belonging to vaginal microflora is crucial for establishing which microorganisms are responsible for microbial shifting from beneficial symbiotic to pathogenic bacteria and understanding pathogenesis leading to vaginosis and vaginal infections. In this study, we involved the surface-enhanced Raman spectroscopy (SERS) technique to compile the spectral signatures of the most significant microorganisms being part of the natural vaginal microbiota and some vaginal pathogens. Obtained data will supply our still developing spectral SERS database of microorganisms. The SERS results were assisted by Partial Least Squares Regression (PLSR), which visually discloses some dependencies between spectral images and hence their biochemical compositions of the outer structure. In our work, we focused on the most common and typical of the reproductive system microorganisms (Lactobacillus spp. and Bifidobacterium spp.) and vaginal pathogens: bacteria (e.g., Gardnerella vaginalis, Prevotella bivia, Atopobium vaginae), fungi (e.g., Candida albicans, Candida glabrata), and protozoa (Trichomonas vaginalis). The obtained results proved that each microorganism has its unique spectral fingerprint that differentiates it from the rest. Moreover, the discrimination was obtained at a high level of explained information by subsequent factors, e.g., in the inter-species distinction of Candida spp. the first three factors explain 98% of the variance in block Y with 95% of data within the X matrix, while in differentiation between Lactobacillus spp. and Bifidobacterium spp. (natural flora) and pathogen (e.g., Candida glabrata) the information is explained at the level of 45% of the Y matrix with 94% of original data. PLSR gave us insight into discriminating variables based on which the marker bands representing specific compounds in the outer structure of microorganisms were found: for Lactobacillus spp. 1400 cm-1, for fungi 905 and 1209 cm-1, and for protozoa 805, 890, 1062, 1185, 1300, 1555, and 1610 cm-1. Then, they can be used as significant marker bands in the analysis of clinical subjects, e.g., vaginal swabs.

Gardnerella vaginalis promotes group B Streptococcus vaginal colonization, enabling ascending uteroplacental infection in pregnant mice.

BACKGROUND: Group B Streptococcus is a common vaginal bacterium and the leading cause of invasive fetoplacental infections. Group B Streptococcus in the vagina can invade through the cervix to cause ascending uteroplacental infections or can be transmitted to the neonate during vaginal delivery. Some studies have found that women with a "dysbiotic" polymicrobial or Lactobacillus-depleted vaginal microbiota are more likely to harbor group B Streptococcus. Gardnerella vaginalis is often the most abundant bacteria in the vaginas of women with dysbiosis, while being detected at lower levels in most other women, and has been linked with several adverse pregnancy outcomes. Mouse models of group B Streptococcus and Gardnerella vaginalis colonization have been reported but, to the best of our knowledge, the two have not been studied together. The overarching idea driving this study is that certain members of the dysbiotic vaginal microbiota, such as Gardnerella vaginalis, may directly contribute to the increased rate of group B Streptococcus vaginal colonization observed in women with vaginal dysbiosis. OBJECTIVE: We used a mouse model to test the hypothesis that vaginal exposure to Gardnerella vaginalis may facilitate colonization and/or invasive infection of the upper reproductive tract by group B Streptococcus during pregnancy. STUDY DESIGN: Timed-pregnant mice were generated using an allogeneic mating strategy with BALB/c males and C57Bl/6 females. Dams were vaginally inoculated at gestational day 14 with group B Streptococcus alone (using a 10-fold lower dose than previously reported models) or coinoculated with group B Streptococcus and Gardnerella vaginalis. Bacterial titers were enumerated in vaginal, uterine horn, and placental tissues at gestational day 17. The presence (Fisher exact tests) and levels (Mann-Whitney U tests) of bacterial titers were compared between mono- and coinoculated dams in each compartment. Relative risks were calculated for outcomes that occurred in both groups. Tissue samples were also examined for evidence of pathophysiology. RESULTS: Inoculation of pregnant mice with 107 group B Streptococcus alone did not result in vaginal colonization or ascending infection. In contrast, coinoculation of group B Streptococcus with Gardnerella vaginalis in pregnant mice resulted in a 10-fold higher risk of group B Streptococcus vaginal colonization (relative risk, 10.31; 95% confidence interval, 2.710-59.04; P=.0006 [Fisher exact test]). Ascending group B Streptococcus infection of the uterus and placenta occurred in approximately 40% of coinoculated animals, whereas none of those receiving group B Streptococcus alone developed uterine or placental infections. Immunofluorescence microscopy revealed group B Streptococcus in both the maternal and fetal sides of the placenta. Histologic inflammation and increased proinflammatory cytokines were evident in the setting of group B Streptococcus placental infection. Interestingly, placentas from dams exposed to group B Streptococcus and Gardnerella vaginalis, but without recoverable vaginal or placental bacteria, displayed distinct histopathologic features and cytokine signatures. CONCLUSION: These data suggest that Gardnerella vaginalis vaginal exposure can promote group B Streptococcus vaginal colonization, resulting in a greater likelihood of invasive perinatal group B Streptococcus infections. These findings suggest that future clinical studies should examine whether the presence of Gardnerella vaginalis is a risk factor for group B Streptococcus vaginal colonization in women. Because Gardnerella vaginalis can also be present in women without bacterial vaginosis, these findings may be relevant both inside and outside of the context of vaginal dysbiosis.

Sex is associated with the persistence of non-optimal vaginal microbiota following treatment for bacterial vaginosis: a prospective cohort study.

OBJECTIVE: Determine the associations between factors and sexual practices and the composition of the vaginal microbiome (VM) of women treated for bacterial vaginosis (BV). DESIGN: Prospective cohort study. SETTING: The Melbourne Sexual Health Centre, Melbourne, Australia. POPULATION: Seventy-five reproductive-age women diagnosed with clinical BV, treated with first-line antibiotics and followed for up to 6 months. METHODS: Women self-collected vaginal swabs and completed questionnaires at enrolment, the day following antibiotics and monthly for up to 6months until BV recurrence or no BV recurrence (n = 430 specimens). Bacterial composition was determined using 16S rRNA gene amplicon sequencing. The effects of ongoing factors on VM composition (utilising 291 monthly specimens) were assessed using generalised estimating equations population-averaged models, which accounted for repeated measures within individuals. MAIN OUTCOME MEASURES: The relative abundance of vaginal bacterial taxa. RESULTS: Women who reported ongoing sex with a regular sexual partner (RSP) had a VM comprised of increased relative abundance of non-optimal BV-associated bacteria (Adjusted co-efficient [Adjusted co-eff] = 11.91, 95% CI 3.39to20.43, P = 0.006) and a decreased relative abundance of optimal, Lactobacillus species (Adjusted co-eff = -12.76, 95% CI -23.03 to -2.49, P = 0.015). A history of BV was also associated with a decreased relative abundance of Lactobacillus spp. (Adjusted co-eff = -12.35, 95% CI -22.68, P = 0.019). The relative abundance of Gardnerella, Atopobium and Sneathia spp. increased following sex with an RSP. CONCLUSIONS: Sex with an untreated RSP after BV treatment was associated with a VM comprised of non-optimal BV-associated bacteria. BV treatment approaches may need to include partner treatment if they are to achieve a sustained optimal VM associated with improved health outcomes. TWEETABLE ABSTRACT: Sex drives a return to a 'non-optimal' vaginal microbiota after antibiotics for bacterial vaginosis.

Syndromic surveillance of female sexually transmitted infections in primary care: a descriptive study in Monastir, Tunisia, 2007─2017.

BACKGROUND: Sexually Transmitted Infections (STIs) are a public health problem, especially for reproductive-age women. The aim of this study was to determine the incidence and trend of STIs during 11 years in Tunisia (2007-17). METHODS: We conducted a descriptive study including all women with curable STIs (chlamydia, gonorrhea, syphilis and trichomoniasis) diagnosed with the syndromic approach in all basic health care centers of the Governorate of Monastir (Tunisia) from 2007 to 2017. Syndromes included, Pelvic Pain (PP), Vaginal Discharge (VD) and Genital Ulceration (GU). RESULTS: We analyzed 40,388 episodes of curable STIs with a crude incidence rate and age standardized incidence rate of 1393 (95% Confidence Interval (CI); 1348-1438) / 100,000 Person Year (PY) and 1328 (95%CI; 1284-1372) /100,000 PY respectively. The incidence rate showed a positive trend over 11 years for all age groups and syndromes. VD was the most common syndrome with a crude incidence rate of 1170/100,000 PY. For all syndromes, women aged 20 to 39 were the most affected age group (p < 0.001). CONCLUSION: In conclusion, the incidence rate of STIs episodes among women diagnosed with the syndromic approach was high, consistent with the global evidence. Focusing on reviewing STIs surveillance system in low and middle-income countries could allow the achievement of the ending of STIs epidemics by 2030.

Influence of Lactobacillus crispatus, Lactobacillus iners and Gardnerella vaginalis on bacterial vaginal composition in pregnant women.

PURPOSE: To investigate associations between bacterial species in the vagina in mid-trimester pregnant women from Brazil. METHODS: The vaginal microbiome in 613 subjects was identified by analysis of the V1-V3 region of bacterial 16S ribosomal RNA and the relative prevalence of individual bacteria were determined. RESULTS: The bacterial species present in the greatest number of women were Lactobacillus crispatus (306 women), L. iners (298 women) and Gardnerella vaginalis (179 women). When present in the vagina, L. crispatus was the most abundant bacterium more than 85% of the time. In contrast, L. iners and G. vaginalis were most abundant in 63% and 41% of women who were positive for these microorganisms, respectively (p < 0.0001 vs. L. crispatus). The proportion of L. crispatus was negatively associated with the proportions of L. iners, L. jensenii, L. gasseri, G. vaginalis, Megasphaera, Atopobium vaginae and Prevotella (p < 0.0001). In contrast, the proportion of G. vaginalis was positively associated with levels of Megasphaera, A. vaginae and Prevotella (p < 0.0001) while L. iners proportion was unrelated to the proportion of L. jensenii, G. vaginalis, Megasphaera, A. vaginae or Prevotella. CONCLUSION: The composition of the vaginal microbiota in mid-trimester pregnant women is influenced by the relative concentrations of L. crispatus, L. iners and G. vaginalis.

Detection of co-infection of Gardnerella vaginalis and Atopobium vaginae using qualitative PCR: A better predictor of bacterial vaginosis.

The present study aimed to determine the utility of detection of co-infection of Gardnerella vaginalis and Atopobium vaginae using qualitative PCR for diagnosing bacterial vaginosis (BV). Vaginal samples (n = 385) categorized as positive (n = 108) or negative (n = 208) for bacterial vaginosis based on the Nugent scoring system, were analyzed for the presence of G. vaginalis and A. vaginae by conventional PCR. We compared the sensitivity, specificity, positive predictive value, negative predictive value and odds ratio for the detection of each bacterium alone with the combination of the two bacteria for diagnosing BV. The detection of co-infection of the two bacteria demonstrated a sensitivity of 96%, a specificity of 82.9%, a positive predictive value of 68.5%, a negative predictive value of 98.2% with an odds ratio of 116 (CI -32 - 409). In our study, we found a high sensitivity, specificity, negative predictive value and odds ratio for the detection of co-infection of A. vaginae and G. vaginalis for the diagnosis of BV.

Gardnerella vaginalis in urinary tract infections, are men spared?

Gardnerella vaginalis in association with anaerobes has been linked to bacterial vaginosis in women, while urinary tract infections (UTIs) in men have rarely been reported. The aim of the review was to reveal the significance of G. vaginalis UTIs in men. Prevalence of G. vaginalis UTIs in men varied from 0.5 to >27% according to patients' groups. Most patients had comorbidity such as urolithiasis or stents, transplants, tumors and diabetes, however, infections can also affect immunocompetent patients. We observed G. vaginalis-associated bacteriuria and leukocyturia in a kidney transplant man. Complications of the UTIs such as bacteremia (in 9/11 cases), hydronephrosis (4/11) and abscesses or septic emboli have been reported. Bacterial vaginosis in female partners has been a risk factor for UTIs in males. In women, biofilm Gardnerella phenotype, stabilized by Atopobium vaginae and Prevotella bivia was linked to ≥6-fold higher antibiotic resistance rates compared with the planktonic phenotype. Non-susceptibility to metronidazole and levofloxacin was found also in males. Therefore, if aerobic urine cultures are negative, urine and blood samples from male patients with predisposing factors and clinical signs of UTIs and bacteremia, can be taken. Plates should be incubated for 2-4 days in capnophilic/microaerophilic conditions, however only anaerobic incubation can help with detecting G. vaginalis strains which grow only anaerobically. Susceptibility testing of the isolates is highly important. Briefly, adherent G. vaginalis phenotype can be sexually transmissible. Despite the infrequency of G. vaginalis UTIs in men, the infections should be considered since they are often linked to severe complications.

Vaginal Lactobacilli and Vaginal Dysbiosis-Associated Bacteria Differently Affect Cervical Epithelial and Immune Homeostasis and Anti-Viral Defenses.

Persistent infection with High Risk-Human Papilloma Viruses (HR-HPVs) is a primary cause of cervical cancer worldwide. Vaginal-dysbiosis-associated bacteria were correlated with the persistence of HR-HPVs infection and with increased cancer risk. We obtained strains of the most represented bacterial species in vaginal microbiota and evaluated their effects on the survival of cervical epithelial cells and immune homeostasis. The contribution of each species to supporting the antiviral response was also studied. Epithelial cell viability was affected by culture supernatants of most vaginal-dysbiosis bacteria, whereas Lactobacillus gasseri or Lactobacillus jensenii resulted in the best stimulus to induce interferon-γ (IFN-γ) production by human mononuclear cells from peripheral blood (PBMCs). Although vaginal-dysbiosis-associated bacteria induced the IFN-γ production, they were also optimal stimuli to interleukin-17 (IL-17) production. A positive correlation between IL-17 and IFN-γ secretion was observed in cultures of PBMCs with all vaginal-dysbiosis-associated bacteria suggesting that the adaptive immune response induced by these strains is not dominated by TH1 differentiation with reduced availability of IFN-γ, cytokine most effective in supporting virus clearance. Based on these results, we suggest that a vaginal microbiota dominated by lactobacilli, especially by L. gasseri or L. jensenii, may be able to assist immune cells with clearing HPV infection, bypasses the viral escape and restores immune homeostasis.