Differences in Vaginal Microbiota, Host Transcriptome, and Proteins in Women With Bacterial Vaginosis Are Associated With Metronidazole Treatment Response.

BACKGROUND: Bacterial vaginosis (BV) treatment failures and recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy. METHODS: Women with BV (Bronx, New York and Thika, Kenya) received 7 days of oral metronidazole at enrollment (day 0) and underwent genital tract sampling of microbiome (16S ribosomal RNA gene sequencing), transcriptome (RNAseq), and immune mediator concentrations on day 0, 15, and 35. RESULTS: Bronx participants were more likely than Thika participants to clinically respond to metronidazole (19/20 vs 10/18, respectively, P = .0067) and by changes in microbiota composition and diversity. After dichotomizing the cohort into responders and nonresponders by change in α-diversity between day 35 and day 0, we identified that transcription differences associated with chemokine signaling (q = 0.002) and immune system process (q = 2.5 × 10-8) that differentiated responders from nonresponders were present at enrollment. Responders had significantly lower levels of CXCL9 in cervicovaginal lavage on day 0 (P < .007), and concentrations of CXCL9, CXCL10, and monocyte chemoattractant protein 1 increased significantly between day 0 and day 35 in responders vs nonresponders. CONCLUSIONS: Response to metronidazole is characterized by significant changes in chemokines and related transcripts, suggesting that treatments that promote these pathways may prove beneficial.

Host-vaginal microbiota interactions in the pathogenesis of bacterial vaginosis.

PURPOSE OF REVIEW: The cause of bacterial vaginosis, the most common cause of vaginal discharge in women, remains controversial. We recently published an updated conceptual model on bacterial vaginosis pathogenesis, focusing on the roles of Gardnerella vaginalis and Prevotella bivia as early colonizers and Atopobium vaginae and other bacterial vaginosis-associated bacteria (BVAB) as secondary colonizers in this infection. In this article, we extend the description of our model to include a discussion on the role of host-vaginal microbiota interactions in bacterial vaginosis pathogenesis. RECENT FINDINGS: Although G. vaginalis and P. bivia are highly abundant in women with bacterial vaginosis, neither induce a robust inflammatory response from vaginal epithelial cells. These early colonizers may be evading the immune system while establishing the bacterial vaginosis biofilm. Secondary colonizers, including A. vaginae, Sneathia spp., and potentially other BVAB are more potent stimulators of the host-immune response to bacterial vaginosis and likely contribute to its signs and symptoms as well as its adverse outcomes. SUMMARY: Elucidating the cause of bacterial vaginosis has important implications for diagnosis and treatment. Our current bacterial vaginosis pathogenesis model provides a framework for key elements that should be considered when designing and testing novel bacterial vaginosis diagnostics and therapeutics.

Vaginal Microbiota and Mucosal Immune Markers in Women With Vulvovaginal Discomfort.

BACKGROUND: Up to 30% of women with vaginal symptoms are not assigned a diagnosis after standard diagnostic assessment. METHODS: We compared premenopausal women with idiopathic vaginitis (IV) or vulvodynia (VVD) to healthy controls. Microbiota were characterized using rRNA sequencing. Cytokines/chemokines (IL-10, IL-1α, IL-1ß, IL-6, IL-8, IL-2, IL-18, IL-4, IL-9, and IL-13) were measured in vaginal lavage fluid using the Meso Scale Discovery platform or ELISA (IL-1ra). Immunoglobulins were measured in vaginal lavage fluid using a bead-based immunoassay (Millipore). Cases and controls were compared using Kruskal-Wallis, analysis of variance, and linear regression or (for microbiome composition) the Bray-Curtis dissimilarity statistic. RESULTS: We compared 20 women with IV, 30 with VVD, and 52 controls. Most (80%) had greater than 90% 16S rRNA gene sequences from Lactobacillus crispatus, L. jensenii, L. gasseri, or L. iners. In analyses adjusted for age and hormonal contraception (HC), Gardnerella vaginalis was less prevalent and abundant in women with VVD (2/30, 7%) versus controls (16/52, 31%) or IV (5/20, 25%) (P = 0.030). Bray-Curtis dissimilarity was not significantly different between IV and controls or VVD. Fungal sequences were only detected in 5 participants: 2 control, 1 IV, 2 VVD. In univariate analysis, cytokines were not associated with diagnosis. Median vaginal concentration of IgE (but not other immunoglobulins) was lower in women with VVD (P = 0.006). CONCLUSIONS: Minimal differences in vaginal microbiota and inflammatory markers between women with IV, VVD or controls suggest no striking association between vaginal bacteria, fungi or inflammation and diagnosis in these women.

Is bacterial vaginosis associated with autoimmune antibody positivity?

OBJECTIVE: To evaluate the association between bacterial vaginosis (BV) and autoimmune antibody positivity. METHOD: We evaluated Papanicolaou-stained cervicovaginal smears of 210 patients with poor obstetric history who were admitted to a special preconception counselling programme. Cytological specimens with various types of microorganisms except for BV, epithelial cell abnormalities and other non-neoplastic findings, including inflammation were excluded from the cohort in addition to patients with autoimmune and chronic inflammatory diseases. The remaining study population (n = 121) was divided into two groups of patients with autoimmune antibody positivity (study group, n = 80) and patients without antibody positivity (control group, n = 41). RESULTS: The rate of BV was demonstrated to be 13.8% and 2.4% in the study and control groups respectively (P = .042). We also demonstrated that the anti-nuclear antibody was positive in 58.3% of the cases with BV. CONCLUSION: BV was found more frequently in patients with autoimmune antibody positivity to a statistically significant degree.

Differential Expression of Local Immune Response Genes in the Vagina: Implication for the Diagnosis of Vaginal Infections.

Transcription profiles of genes of local immune response were determined in the vagina of women with bacterial vaginosis, aerobic vaginitis, and vulvovaginal candidosis for detection of the most specific immune markers for these vaginal infections. Laboratory diagnosis of the vaginal infections was performed microscopically; the inflammatory reaction in the vagina (leukorrhea) was defined as the presence of >10 white blood cells per field of view. Transcription profiles of IL1b, IL10, IL18, TNFα, TLR4, GATA3, and CD68 were determined using reverse-transcription quantitative real-time PCR. The strongest predictors of aerobic vaginitis were increased levels of IL1b and IL10 mRNA. Bacterial vaginosis was strongly associated with reduced levels of IL18 and GATA3 mRNA. Increased levels of IL1b and TLR4 transcripts showed significant discriminatory power for vulvovaginal candidosis and leukorrhea. The results of this study suggest differential expression of local immune response genes in the vagina of women with different vaginal infections. Detection of specific immune markers in the vagina using reverse-transcriptase PCR could supplement PCR detection of abnormal vaginal microflora for the diagnosis of vaginal infections.

Inflammation Mediators Regulate the Microbiota Resistance to Adverse Factors.

We studied the effects of IL-1ß, IL-8, TNFα, and prostaglandin E2α in concentrations typically observed in health and during inflammation on the growth of vaginal microbiota and its resistance to factors inhibiting the synthesis of proteins, nucleic acids, and peptidoglycans. An increase in the cytokine levels, characteristic of inflammation, inhibits the growth of Lactobacillus population and improves its resistance to adverse factors. The growth of the population of opportunistic microorganisms (S. aureus, E. coli) is stimulated under these conditions, while their resistance to adverse factors decreases. Hence, it seems that the cytokines regulate the behavior of the host cells and of its bacterial symbionts.

Characterization of the Genital Mucosa Immune Profile to Distinguish Phases of the Menstrual Cycle: Implications for HIV Susceptibility.

BACKGROUND: Inflammation and immune activation are key factors in sexual transmission of human immunodeficiency virus (HIV). We sought to define the impact of hormonal cycling on the mucosal immune environment and HIV risk in sex workers with a natural menstrual cycle. METHODS: We compared soluble mucosal immune factors and cervical mononuclear cells during hormone titer-defined phases of the menstrual cycle among 37 sex workers from Nairobi, Kenya. Systemic and mucosal samples were collected 14 days apart to distinguish the follicular and luteal phases of the menstrual cycle, and phases were confirmed by hormone measurements. Vaginal concentrations of 19 immune modulators and cervical T-cell activation markers were measured. RESULTS: The follicular phase signature was characterized by an elevated CCL2 level, decreased interleukin 1α and interleukin 1ß cervical concentrations, and a significant increase in the proportion of CD4+ T cells that expressed CD69. The genital concentration of CCL2 was the best marker to distinguish the follicular from the luteal phase in univariate and multivariate analyses and remained independent of elevated genital inflammation and bacterial vaginosis. CONCLUSION: The follicular phase of the menstrual cycle was associated with an elevated CCL2 level and retention of resident memory CD4+ T cells, which has implications for increased susceptibility to HIV infection.

Impact of Standard Bacterial Vaginosis Treatment on the Genital Microbiota, Immune Milieu, and Ex Vivo Human Immunodeficiency Virus Susceptibility.

BACKGROUND: Genital immunology is a key determinant of human immunodeficiency virus (HIV) susceptibility. Both factors are modulated by bacterial vaginosis (BV) and, to some extent, by Lactobacillus iners, the genital Lactobacillus spp. that predominates in African, Caribbean, and other Black (ACB) women. We conducted a clinical trial to assess the impact of oral metronidazole treatment on the genital immune parameters of HIV acquisition risks in Kenyan women with BV. METHODS: The primary endpoint was ex vivo cervical CD4+ T-cell HIV susceptibility after 1 month; secondary endpoints included genital cytokine/chemokine levels, cervical immune cell populations, and the composition of the cervico-vaginal microbiota by 16S ribosomal RNA gene amplicon sequencing. RESULTS: BV resolved (Nugent score ≤ 3) at 1 month in 20/45 participants, and cervical CD4+ T-cell HIV entry was moderately reduced in all participants, regardless of treatment outcome. Resolution of BV and reduced abundances of BV-associated gram-negative taxa correlated with reduced genital interleukin (IL)-1α/ß. However, BV resolution and the concomitant colonization by Lactobacillus iners substantially increased several genital chemokines associated with HIV acquisition, including interferon-γ inducible protein (IP)-10, macrophage inflammatory protein (MIP)-3α, and monokine induced by gamma interferon (MIG). In an independent cohort of ACB women, most of whom were BV-free, vaginal chemokines were again closely linked with L. iners abundance, though not other Lactobacillus spp. CONCLUSIONS: BV treatment reduced genital CD4+ T-cell HIV susceptibility and IL-1 levels, but dramatically increased the genital chemokines that may enhance HIV susceptibility; the latter effect was related to the restoration of an Lactobacillus iners-dominated microbiota. Further studies are needed before treatment of asymptomatic BV can be recommended for HIV prevention in ACB communities.

Inflammatory cytokine biomarkers of asymptomatic sexually transmitted infections and vaginal dysbiosis: a multicentre validation study.

OBJECTIVES: Vaginal dysbiosis and STIs are important drivers of the HIV epidemic and reproductive complications. These conditions remain prevalent, partly because most cases are asymptomatic. We have shown that inflammatory cytokines interleukin (IL)-1α, IL-1ß and interferon-γ-induced protein (IP)-10 are biomarkers for detecting asymptomatic STIs and vaginal dysbiosis (bacterial vaginosis (BV) or intermediate microbiota). This study aimed to validate the performance of these biomarkers in African women recruited regardless of symptoms. METHODS: IL-1α, IL-1ß and IP-10 were measured in menstrual cup secretions, endocervical, lateral vaginal wall and vulvovaginal swabs from 550 women from Pretoria, Soweto and Cape Town, South Africa and Bondo, Kenya using Luminex and ELISA. STIs were assessed by PCR, BV by Nugent scoring and vaginal microbiota by 16S rRNA sequencing. RESULTS: Across four study populations and four types of genital specimens, the performance of IL-1α, IL-1ß and IP-10 for identification of women with STIs, BV or intermediate microbiota was consistent. Of the genital samples assessed, biomarkers measured in lateral vaginal wall swabs performed best, correctly classifying 76%(95% CI 70% to 81%) of women according to STI, BV or intermediate microbiota status (sensitivity 77%, specificity 71%) and were more accurate than clinical symptoms (sensitivity 41%, specificity 57%) (p=0.0003). Women incorrectly classified as STI/BV positive using the biomarkers had more abundant dysbiosis-associated bacteria, including Prevotella bivia and Gardnerella sp, detected by 16S rRNA sequencing, but not Nugent scoring. Including vaginal pH with the cytokine biomarkers improved the accuracy of the test (82% (95% CI 75% to 88%) correctly classified), although pH alone had poor specificity (61%). CONCLUSIONS: An inexpensive, point-of-care screening test including IL-1α, IL-1ß and IP-10 (and potentially pH) could be used in resource-limited settings to identify women with asymptomatic STIs and dysbiosis. These women could then be referred for aetiological testing, followed by specific treatment.

Therapeutic effects of probiotic Clostridium butyricum WZ001 on bacterial vaginosis in mice.

AIMS: To observe the therapeutic effects of vaginal infusion of probiotic Clostridium butyricum WZ001 on bacterial vaginosis (BV) in mice. METHODS AND RESULTS: Female ICR mice were used to establish the model of BV by infecting oestrogen-treated mice with Escherichia coli, and then treated with high- and low dose of C. butyricum. Clinical indexes of mice in the C. butyricum-treated groups were significantly improved and comparable to those in the antibiotic group. Pap staining showed that neutrophil count was significantly increased after modelling and largely decreased after C. butyricum treatment (P < 0·01). Dynamic observation of E. coli and Lactobacillus showed that the number of E. coli significantly decreased in the C. butyricum-treated groups or in the antibiotic group with prolonged treatment (P < 0·01). Besides, the number of E. coli in the low-dose C. butyricum group was higher than that in either its high-dose counterpart or the antibiotic group respectively (P < 0·01). The number of Lactobacillus decreased evidently in the antibiotic group (P < 0·01), while that in the C. butyricum groups remained consistent. Moreover, C. butyricum inhibited the proliferation of E. coli by the experiment in vitro. The phosphorylation of nuclear factor-kappa B (NF-κB) p65 in vaginal tissue and the serum levels of inflammatory cytokines, IL-1ß, TNF-α and IL-6, increased after modelling and significantly decreased after treated with C. butyricum (P < 0·01), with no difference found when compared with the antibiotic group. CONCLUSION: Clostridium butyricum inhibits the growth of pathogenic bacteria as well as the inflammatory response induced by E. coli and promotes the growth of Lactobacillus to maintain the vaginal micro-ecological balance. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest that probiobitc C. butyricum WZ001 has a great potential in the clinical treatment of BV.

The Human Microbiome during Bacterial Vaginosis.

Bacterial vaginosis (BV) is the most commonly reported microbiological syndrome among women of childbearing age. BV is characterized by a shift in the vaginal flora from the dominant Lactobacillus to a polymicrobial flora. BV has been associated with a wide array of health issues, including preterm births, pelvic inflammatory disease, increased susceptibility to HIV infection, and other chronic health problems. A number of potential microbial pathogens, singly and in combinations, have been implicated in the disease process. The list of possible agents continues to expand and includes members of a number of genera, including Gardnerella, Atopobium, Prevotella, Peptostreptococcus, Mobiluncus, Sneathia, Leptotrichia, Mycoplasma, and BV-associated bacterium 1 (BVAB1) to BVAB3. Efforts to characterize BV using epidemiological, microscopic, microbiological culture, and sequenced-based methods have all failed to reveal an etiology that can be consistently documented in all women with BV. A careful analysis of the available data suggests that what we term BV is, in fact, a set of common clinical signs and symptoms that can be provoked by a plethora of bacterial species with proinflammatory characteristics, coupled to an immune response driven by variability in host immune function.

The Vaginal Microbiome: Current Understanding and Future Directions.

This article summarizes the highlights of the expert technical consultation on bacterial vaginosis (BV), sponsored by the National Institute of Allergy and Infectious Disease and held in Washington, DC, on 8-9 April 2015. Many issues touched on in this article are discussed in much greater detail in the 6 preceding articles in this supplement to The Journal of Infectious Diseases There was a consensus among the meeting attendees concerning the most important research issues in the field: the pathogenesis of the syndrome, way to optimize treatment, and the relative roles of sexual transmission and endogenous infection in BV epidemiology. This article concludes with a listing of BV and genitourinary tract research priorities that were discussed and agreed on by attendees. The most important of these included better characterization of vaginal microbiome community state subtypes, application of advanced "-omic" technologies to improve understanding of BV pathogenesis, further investigation of the relationships between the male and female genitourinary tract microbiomes, and the development of new drugs for BV treatment.

The Interplay of Host Immunity, Environment and the Risk of Bacterial Vaginosis and Associated Reproductive Health Outcomes.

Bacterial vaginosis (BV) is one of the most common causes of vaginal symptoms in US women, but its causal mechanism has not yet been defined. BV is more prevalent in women who are immunosuppressed, and several risk factors for the development of BV are associated with lower quantities of immune mediators in vaginal fluid. In contrast, the poor reproductive health outcomes associated with BV, such as preterm birth and human immunodeficiency virus type 1 acquisition, are associated with increased levels of proinflammatory immune mediators in the genital tract. In this article, we discuss how variations in the host immune profile and environmental effects on host immunity may influence the risk of BV, as well as the risk of complications associated with BV.

The Cervicovaginal Microbiota and Its Associations With Human Papillomavirus Detection in HIV-Infected and HIV-Uninfected Women.

BACKGROUND: Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status. METHODS: 16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4+ T-cell count of > 500 cells/mm3, and 20 were HIV infected with progressive immunosuppression. Vaginal pH was serially measured. RESULTS: The relative abundances of Lactobacillus crispatus and other Lactobacillus species were inversely associated with vaginal pH (all P < .001). High (vs low) L. crispatus relative abundance was associated with decreased HPV detection (odds ratio, 0.48; 95% confidence interval, .24-.96; Ptrend = .03) after adjustment for repeated observation and multiple covariates, including pH and study group. However, there were no associations between HPV and the relative abundance of Lactobacillus species as a group, nor with Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii individually. CONCLUSIONS: L. crispatus may have a beneficial effect on the burden of HPV in both HIV-infected and HIV-uninfected women (independent of pH).

Hydrogen Peroxide-Producing Lactobacilli Are Associated With Lower Levels of Vaginal Interleukin-1ß, Independent of Bacterial Vaginosis.

BACKGROUND: The presence of hydrogen peroxide (H2O2)-producing lactobacilli in the vagina is associated with decreased rates of preterm birth and HIV acquisition. We hypothesize that this is due to immunomodulatory effects of these species. METHODS: Concentrations of interleukin (IL)-1ß, IL-6, IL-8, secretory leukocyte protease inhibitor, and human ß-defensin 2 were quantified from vaginal swabs from 4 groups of women: women with and without bacterial vaginosis (BV) by Nugent score, further stratified by detection of H2O2-producing lactobacilli by semiquantitative culture. Ten quantitative polymerase chain reaction assays characterized the presence and quantity of select Lactobacillus and BV-associated species in each group. Levels of immune markers and bacteria were compared between the 4 groups using analysis of variance, Kruskal-Wallis, Mann-Whitney U, or χ tests. RESULTS: Swabs from 110 women from 4 groups were included: 26 had a normal Nugent score (BV-), and no H2O2-producing lactobacilli detected (H2O2-); 47 were BV-, H2O2+; 27 BV+, H2O2-; and 10 BV+, H2O2+. The groups were similar in age, marital status, and reproductive history, but not ethnicity: the BV-, H2O2- group had more white participants (P = 0.02). In women with and without BV, IL-1ß was lower in the H2O2+ groups. Human ß-defensin 2 was lowest in BV+ H2O2- women and highest in BV-, H2O2-. Secretory leukocyte protease inhibitor was lower in women with BV and did not differ by the presence of H2O2-producing lactobacilli. In regression analysis, higher quantities of Lactobacillus crispatus were associated with lower quantities of IL-1ß. Detection and quantity of BV-associated species by quantitative polymerase chain reaction was significantly different between women with and without BV, but not between women with and without H2O2-producing lactobacilli within those groups. CONCLUSIONS: The presence of H2O2-producing lactobacilli is associated with lower levels of some vaginal proinflammatory cytokines, even in women with BV.

Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner.

BACKGROUND: Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health. METHODS: To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia). RESULTS: Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1ß, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8. CONCLUSIONS: We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis.

Intermediate vaginal flora and bacterial vaginosis are associated with the same factors: findings from an exploratory analysis among female sex workers in Africa and India.

OBJECTIVES: Several recent studies suggest that intermediate vaginal flora (IVF) is associated with similar adverse health outcomes as bacterial vaginosis (BV). Yet, it is still unknown if IVF and BV share the same correlates. We conducted a cross-sectional and exploratory analysis of data from women screened prior to enrolment in a microbicide trial to estimate BV and IVF prevalence and examine their respective correlates. METHODS: Participants were interviewed, examined and provided blood and genital samples for the diagnosis of IVF and BV (using Nugent score) and other reproductive tract infections. Polytomous logistic regressions were used in estimating respective ORs of IVF and BV, in relation to each potential risk factor. RESULTS: Among 1367 women, BV and IVF prevalences were 47.6% (95% CI 45.0% to 50.3%) and 19.2% (95% CI 17.1% to 21.2%), respectively. Multivariate polytomous analysis of IVF and BV showed that they were generally associated with the same factors. The respective adjusted ORs were for HIV 1.98 (95% CI 1.37 to 2.86) and 1.62 (95% CI 1.20 to 2.20) (p=0.2248), for gonorrhoea 1.25 (95% CI 0.64 to 2.4) and 2.01 (95% CI 1.19 to 3.49) (p=0.0906), for trichomoniasis 3.26 (95% CI 1.71 to 6.31) and 2.39 (95% CI 1.37 to 4.33) (p=0.2630), for candidiasis 0.52 (95% CI 0.36 to 0.75) and 0.59 (95% CI 0.44 to 0.78) (p=0.5288), and for hormonal contraception 0.65 (95% CI 0.40 to 1.04) and 0.62 (95% CI 0.43 to 0.90) (p=0.8819). In addition, the association between vaginal flora abnormalities and factors such as younger age, HIV, gonorrhoea trichomoniasis and candidiasis were modified by the study site (all p for interaction ≤0.05). CONCLUSIONS: IVF has almost the same correlates as BV. The relationship between some factors and vaginal flora abnormalities may be site-specific.

Bacterial vaginosis and the risk of trichomonas vaginalis acquisition among HIV-1-negative women.

BACKGROUND: The vaginal microbiota may play a role in mediating susceptibility to sexually transmitted infections, including Trichomonas vaginalis (TV). METHODS: Data were analyzed from HIV-1-seronegative women participating in HIV Prevention Trials Network Protocol 035. At quarterly visits for up to 30 months, participants completed structured interviews and specimens were collected for genital tract infection testing. T. vaginalis was detected by saline microscopy. Bacterial vaginosis (BV) was characterized by Gram stain using the Nugent score (BV = 7-10; intermediate = 4-6; normal = 0-3 [reference group]). Cox proportional hazards models stratified by study site were used to assess the association between Nugent score category at the prior quarterly visit and TV acquisition. RESULTS: In this secondary analysis, 2920 participants from Malawi, South Africa, United States, Zambia, and Zimbabwe contributed 16,259 follow-up visits. Bacterial vaginosis was detected at 5680 (35%) visits, and TV was detected at 400 (2.5%) visits. Adjusting for age, marital status, hormonal contraceptive use, unprotected sex in the last week and TV at baseline, intermediate Nugent score, and BV at the prior visit were associated with an increased risk of TV (intermediate score: adjusted hazard ratio [aHR], 1.73; 95% confidence interval [CI], 1.21-2.19; BV: aHR, 2.40; 95% CI, 1.92-3.00). Sensitivity analyses excluding 211 participants with TV at baseline were similar to those from the full study population (intermediate score: aHR, 1.54; 95% CI, 1.10-2.14; BV: aHR, 2.23; 95% CI, 1.75-2.84). CONCLUSIONS: Women with a Nugent score higher than 3 were at an increased risk for acquiring TV. If this relationship is causal, interventions that improve the vaginal microbiota could contribute to reductions in TV incidence.

Bacterial vaginosis in the context of lichen sclerosus in a prepubertal girl.

Group A beta-hemolytic streptococcus cause most vulvovaginal infections seen in prepubertal girls. Bacterial vaginosis is a common cause of abnormal vaginal discharge in women of childbearing age but is rare in children. Data are insufficient to suggest that bacterial vaginosis is an exclusively sexually transmitted disease. We report a 10-year-old girl with no history or suspicion of sexual abuse who developed bacterial vaginosis in the context of a lichen sclerosus being treated with tacrolimus ointment. Secondary bacterial infection in lichen sclerosus is uncommon. We speculate that the immunosuppressive effect of topical tacrolimus could have triggered the infection.

Role of innate immunity in pregnant patients with vulvovaginal infections in the development of intrauterine infection in the newborn.

A total of 115 pregnant women were examined: 59 patients with opportunistic vulvovaginal infections and 56 without infection. Congenital immunity parameters (TLR-2, NF-κB, and IL-2 receptors in placental tissue) were studied by immunohistochemical methods. Realization of congenital infection was associated with activation of IL-6 receptors and TLR-2 in the placenta and an increase of NF-κB level. These changes seemed to reflect the strained status of congenital immunity and were responsible for the intensity of local inflammatory response.