HPV infection and vaginal microecological disorders in women with intrauterine adhesion: cross-sectional study in a Chinese population.

BACKGROUND: The purpose of this study was to evaluate the vaginal microecology and the distribution of human papillomavirus (HPV) subtypes in patients with uterine adhesions and explore the correlation between HPV infection and vaginal microecology imbalance and the occurrence of intrauterine adhesion (IUA). METHODS: A total of 479 women were enrolled in the study, including 259 in the normal group and 220 in the IUA group. Vaginal microecological and HPV analyses were performed on all participants. Significant differences between the two groups were analyzed, and Spearman correlation analysis was performed. RESULTS: The incidence of IUA in patients between 31 and 40 years of age was high. The I-II degree of vaginal cleanliness in the IUA group was significantly lower than that in the normal group, and the number of III-IV degree was significantly higher than that in the normal group. Moreover, the incidences of VVC (vulvovaginal candidiasis) and vaginal disorders and infections with HPV 16 and HPV 52 subtypes were significantly higher in the IUA group than in the normal group. The incidence of high-risk HPV infection combined with vaginal disorders in the IUA group was higher than that in the normal group. Correlation analysis showed that the occurrence of IUAs was positively correlated with HPV infection and negatively correlated with PH and vaginal microecological imbalance. CONCLUSION: The HPV infection rate and vaginal microecology disorders affect the occurrence of IUAs. For patients with IUAs, control of the HPV infection rate and the prevention of vaginal microecological disorders should be improved.

Acceptability and efficacy of vaginal self-sampling for genital infection and bacterial vaginosis: A cross-sectional study.

BACKGROUND & AIM: Screening for genital infection (GI) such as bacterial vaginosis (BV) and yeast infection, for sexually transmitted infection (STI), and for asymptomatic carriage of group B streptococcus (GBS) in pregnant women are common reason for medical appointments. The diagnosis and control of GIs, STIs, and GBS are major issues, for fertility and overall well-being of affected women. Conventional testing is performed using vaginal/cervical classical sampling (VCS); this procedure requires pelvic examination performed by health care professionals which raises concerns among women. Vaginal-self-sampling (VSS), as an alternative to VCS, might capture more women. The aim was first to show non-inferiority of VSS compared with VCS to screen for GIs, STIs, and GBS; second to determine the feasibility of VSS. METHODS: VSS and VCS from 1027 women were collected by health care professionals and simultaneously carried out on each patient. GIs, STIs, and GBS were systematically screened in both paired VSS and VCS samples. Non-inferiority of VSS compared with VCS was assessed using z statistic for binomial proportions. RESULTS: Prevalence of GIs were 39.7% using VSS and 38.1% using VCS (p = 0.0016). Prevalence of STIs was 8.5% (VSS) vs 8.1% (VCS) (p = 0.0087). Prevalence of GBS was 13.4% (VSS) and 11.5% (VCS) (p = 0.0001). Most participants (84%) recommended the use of VSS. CONCLUSIONS: This study shows that VSS was not inferior to VCS for the detection of GIs, STIs, and GBS. This study provides evidence that VSS can be used as a universal specimen for detection of lower genital tract infections in women. STUDY IDENTIFICATION NUMBER: ID-RCB 2014-A01250-4.

Association of Vaginal Microbiota With Signs and Symptoms of the Genitourinary Syndrome of Menopause Across Reproductive Stages.

The genitourinary syndrome of menopause (GSM) describes signs and symptoms resulting from effects of estrogen deficiency on the female genitourinary tract, including the vagina, labia, urethra, and bladder. Signs/symptoms associated with GSM may occur during any reproductive stage from multiple etiologies but are most common during menopause due to low estrogen. Vaginal microbiota, particularly Lactobacillus spp., are beneficial to the female genital tract; however, their abundance declines during menopause. We aimed to longitudinally assess vaginal microbiota characterized by 16S rRNA gene amplicon sequencing and GSM-associated endpoints across reproductive stages. In a 2-year cohort study of 750 women aged 35-60 years at enrollment and 2 111 semiannual person-visits, low-Lactobacillus vaginal microbiota communities were observed at 21.2% (169/798), 22.9% (137/597), and 49.7% (356/716) of person-visits among pre-, peri-, and postmenopausal women, respectively (p < .001). Compared to communities that have high Gardnerella vaginalis relative abundance and diverse anaerobes, the following communities were associated with a lower covariate-adjusted odds of vaginal atrophy: L crispatus-dominated communities among postmenopausal women (odds ratio [OR] = 0.25; 95% confidence interval [CI]: 0.08, 0.81), L gasseri/L jensenii (OR = 0.21; 95% CI: 0.05, 0.94) and L iners (OR = 0.21; 95% CI: 0.05, 0.85) among perimenopausal women, and L iners-dominated communities (OR = 0.18; 95% CI: 0.04, 0.76) among premenopausal women. Postmenopausal women with L gasseri/L jensenii-dominated communities had the lowest odds of vaginal dryness (OR = 0.36; 95% CI: 0.12, 1.06) and low libido (OR = 0.28; 95% CI: 0.10, 0.74). Findings for urinary incontinence were inconsistent. Associations of vaginal microbiota with GSM signs/symptoms are most evident after menopause, suggesting an avenue for treatment and prevention.

A primary Chlamydia trachomatis genital infection of rhesus macaques identifies new immunodominant B-cell antigens.

To identify immunodominant antigens that elicit a humoral immune response following a primary and a secondary genital infection, rhesus monkeys were inoculated cervically with Chlamydia trachomatis serovar D. Serum samples were collected and probed with a protein microarray expressing 864/894 (96.4%) of the open reading frames of the C. trachomatis serovar D genome. The antibody response to the primary infection was analyzed in 72 serum samples from 12 inoculated monkeys. The following criteria were utilized to identify immunodominant antigens: proteins found to be recognized by at least 75% (9/12) of the infected monkeys with at least 15% elevations in signal intensity from week 0 to week 8 post infection. All infected monkeys developed Chlamydia specific serum antibodies. Eight proteins satisfied the selection criteria for immunodominant antigens: CT242 (OmpH-like protein), CT541 (mip), CT681 (ompA), CT381 (artJ), CT443 (omcB), CT119 (incA), CT486 (fliY), and CT110 (groEL). Of these, three antigens, CT119, CT486 and CT381, were not previously identified as immunodominant antigens using non-human primate sera. Following the secondary infection, the antibody responses to the eight immunodominant antigens were analyzed and found to be quite different in intensity and duration to the primary infection. In conclusion, these eight immunodominant antigens can now be tested for their ability to identify individuals with a primary C. trachomatis genital infection and to design vaccine strategies to protect against a primary infection with this pathogen.

The International Society for the Study of Vulvovaginal Disease Vaginal Wet Mount Microscopy Guidelines: How to Perform, Applications, and Interpretation.

OBJECTIVES: The aims of the study were to assess the available literature concerning the indications, performance, technique, and classification of wet mount microscopy (WMM) and to establish evidence-based recommendations. METHODS: Literature review from the main scientific databases was performed by the ad hoc "Vaginitis and Microbiome Committee" of the International Society for the Study of Vulvovaginal Disease. The document was approved by the executive council and membership of the International Society for the Study of Vulvovaginal Disease. RESULTS: Available data are limited and usually of low level of evidence. Nevertheless, it shows that WMM is capable of reducing misdiagnosis, overtreatment, and undertreatment of vaginal conditions. It has an excellent performance for the diagnosis of bacterial vaginosis and variable performance for trichomoniasis and candidiasis. It is the gold standard for aerobic vaginitis/desquamative inflammatory vaginitis. Currently, there is no recommendation to use WMM in the screening of asymptomatic women.The use of phase contrast is recommended to improve performance and reproducibility. Sampling location, devices, and technique have an impact on the results.Available scoring and classification scores have significant limitations. CONCLUSIONS: Wet mount microscopy is a point-of-care, inexpensive, and fast technique that, with practice, can be mastered by office clinicians. It should be considered a basic skill in the curricula of gynecology and obstetrics residencies. Recommendations are provided on sampling, reading, and scoring.

Vaginal tuberculosis as differential diagnosis of cancer: A case report.

Tuberculosis remains a worrying public health problem. But if pulmonary tuberculosis's symptomatology is well known by the medical profession, this is not the case of genital tuberculosis. We take advantage of a case of vaginal tuberculosis to review the international literature about clinical diagnosis, further tests, and treatment of this extremely rare tuberculosis localization.

Persistence of group B Streptococcus vaginal colonization and prevalence of hypervirulent CC-17 clone correlate with the country of birth: a prospective 3-month follow-up cohort study.

To identify factors associated with vaginal colonization and persistence by group B Streptococcus (GBS) and by the hypervirulent neonatal CC-17 clone in late pregnancy and after delivery, a multicentre prospective observational cohort with 3-month follow-up was established in two university hospitals, Paris area, France. Pregnant women were recruited when antenatal screening for GBS vaginal colonization at 34-38 weeks of gestational age was positive. Vaginal samples were analysed by conventional culture methods at antenatal screening, delivery, and 21 and 60 days following delivery. Identification of the hypervirulent neonatal GBS CC-17 was performed. Colonization was defined as persistent when all vaginal samples were positive for GBS. A total of 754 women were included. GBS vaginal colonization was persistent in 63% of the cases (95% CI 59%-67%). Persistent colonization was more likely in women born in Sub-Saharan Africa compared with women born in France (OR = 1.88, 95% CI 1.05-3.52), and GBS CC-17 was overrepresented in women born in Sub-Saharan Africa (OR = 2.09, 95% CI 1.20-3.57). Women born in Sub-Saharan Africa are at higher risk for GBS vaginal persistence than women born in France. This observation correlates with an increased prevalence of the hypervirulent GBS CC-17 in the former group, which likely reflect variations linked to ethnicity and vaginal community-state types and might account for the increased susceptibility of black neonates to GBS infections.

Vaginal microbiota evaluation and prevalence of key pathogens in ecuadorian women: an epidemiologic analysis.

Vaginal infection is a gynecological problem in women of reproductive age with multiple health outcomes. The most common forms of infection include bacterial vaginosis (BV), vulvovaginal candidiasis (VC), and aerobic vaginitis (AV). Our main goals were to evaluate different types of vaginal infections in Ecuadorian women in a large urban area (Quito) and to characterize the vaginal microbiota colonization by opportunistic species. We collected vaginal swabs and epidemiological surveys from 414 women from June 2016 to July of 2017. We analyzed vaginal samples for the presence of any vaginal infection. The microbiological examination was done through Gram-stain, wet mount smears, and polymerase chain reaction (PCR) assays using primers for target genes, such as 16S rRNA (Atopobium vaginae, Mobiluncus mulieris, and Gardnerella species), ddl (Enterococcus faecalis), adk (Escherichia coli) and KER1 (Candida albicans) genes. Most women showed a healthy vaginal microbiota (66.7%). Nearly one-tenth (10.4%) of the participants had intermediate microbiota, and the remaining women (22.9%) had a single vaginal infection (BV, AV, or VC) or coinfections. From the 95 participants that had an infection, AV was the main diagnosed vaginal infection (51.6%), followed by BV (24.2%) and finally VC (7.4%). The remaining women (16.8%) showed coinfections, being BV and AV the most common coinfection. Using univariable logistic regression analyses we found an increased odds of healthy microbiota in women with a sexual partner (P = 0.02, OR = 1.64). Also, women in a free union relationship (P = 0.000, OR = 16.65) had an increased odds of having coinfections. On the other hand, the use of birth control (condom OR = 0.388 or other contraceptive method OR = 0.363) was associated with significantly lower odds of intermediate microbiota (P ≤ 0.05). We found no statistically significant differences between women with infection and a particular group age. Using multivariate logistic regression analyses we initially found an increased odds of having BV in women with M. mulieris (P = 0.020, OR = 4.98) and Gardnerella species (P = 0.010, OR = 4.16). Women with E. coli showed an increased odds of having AV (P = 0.009, OR = 2.81). The presence of C. albicans in women showed an increased odds of having VC (P = 0.007, OR = 17.94). Finally, women with M. mulieris showed a reverse odds of having healthy microbiota (P = 0.008, OR = 0.06). We found no statistically significant differences between women with symptomatic and asymptomatic infections or the presence of Enterococcus faecalis. We found using logistic regression analyses that M. mulieris was the most prevalent opportunistic pathogen among women with vaginal infection. Further studies should evaluate the possibility to use M. mulieris as a potential key predictor for vaginal infections.

Society for Maternal-Fetal Medicine Special Statement: Reducing the risk of transmitting infection by transvaginal ultrasound examination.

Recent surveys have shown widespread lapses in the procedures used to reduce the risk of transmitting infection via medical devices. Transvaginal ultrasound examination has the potential to transmit vaginal infections, including human papillomavirus. Areas of particular concern are the use of probe covers with high rates of leakage, disinfectants that are not effective against human papillomavirus, and coupling gel from multiple-use containers. We reviewed these issues, and we recommend 4 steps to reduce the risk of transmitting infection. First, during every transvaginal ultrasound exam, the probe should be covered with a sterile, single-use "viral barrier" cover or a condom. Second, sterile, single-use ultrasound gel packets should be used. Third, after every examination, the probe should be cleaned to remove any visible gel or debris. Finally, after cleaning, the probe should undergo high-level disinfection using an agent with proven efficacy against the human papillomavirus, including hydrogen peroxide, hypochlorite, or peracetic acid. Glutaraldehyde, orthophthalaldehyde, phenols, and isopropyl alcohol have virtually no efficacy against the human papillomavirus.

Genome-Wide Screens Identify Group A Streptococcus Surface Proteins Promoting Female Genital Tract Colonization and Virulence.

Group A streptococcus (GAS) is a major pathogen that impacts health and economic affairs worldwide. Although the oropharynx is the primary site of infection, GAS can colonize the female genital tract and cause severe diseases, such as puerperal sepsis, neonatal infections, and necrotizing myometritis. Our understanding of how GAS genes contribute to interaction with the primate female genital tract is limited by the lack of relevant animal models. Using two genome-wide transposon mutagenesis screens, we identified 69 GAS genes required for colonization of the primate vaginal mucosa in vivo and 96 genes required for infection of the uterine wall ex vivo. We discovered a common set of 39 genes important for GAS fitness in both environments. They include genes encoding transporters, surface proteins, transcriptional regulators, and metabolic pathways. Notably, the genes that encode the surface-exclusion protein (SpyAD) and the immunogenic secreted protein 2 (Isp2) were found to be crucial for GAS fitness in the female primate genital tract. Targeted gene deletion confirmed that isogenic mutant strains ΔspyAD and Δisp2 are significantly impaired in ability to colonize the primate genital tract and cause uterine wall pathologic findings. Our studies identified novel GAS genes that contribute to female reproductive tract interaction that warrant translational research investigation.

Antifungal, anti-inflammatory and antioxidant activity of bi-herbal mixtures with medicinal plants from Argentinean highlands.

ETHNOPHARMACOLOGICAL RELEVANCE: Argentinean medicinal plants such as Larrea divaricata Cav., Larrea cuneifolia Cav., Larrea nitida Cav., Zuccagnia punctata Cav. and Tetraglochin andina Ciald. are used alone and in combination in traditional medicine by inhabitants from northwestern Argentina to solve mycosis, vaginal infections, gastrointestinal, respiratory, and inflammatory processes. AIM OF THE STUDY: To assess the effect of interactions between hydroalcoholic extracts of these five species of medicinal plants against yeast strains isolated from vaginal infections, select the most active mixtures and evaluate anti-inflammatory and antioxidant activities. MATERIAL AND METHODS: Synergy between the plant extracts was studied by using a broth microdilution assay by means of the checkerboard method against Saccharomyces cerevisiae, Candida albicans, and non albicans strains. The inhibitory effect on lipoxygenase and the antioxidant capacity in cell-free and cell systems were studied. The chemical profile was evaluated by qualitative and quantitative screening, whereas chemical markers were quantified by HPLC-DAD. RESULTS: A synergistic antifungal effect was observed in some binary combinations. Z. punctata/L. divaricata, Z. punctata/L. cuneifolia, and Z. punctata/L. nitida were the most active mixtures. Nordihydroguaiaretic acid and 2',4'-dihydroxychalcone, two antifungal compounds, present in these extracts, were identified and quantified by HPLC-DAD. Both single extracts and bi-herbal mixtures showed antioxidant activity (in cellular and in cell-free systems) and were active on pro-inflammatory enzymes (LOX). CONCLUSIONS: Our results indicated that the most active combinations of these species extracts could be useful in the treatment of vaginal infectious diseases caused by Saccharomyces cerevisiae and Candida spp. strains and in associated oxidative and inflammatory processes, supporting its traditional use. In addition, the results highlighted the phyto-therapeutic potential of total phytochemical compounds present in these medicinal plants.

Infectious disease symptoms and microbial carriage among French medical students travelling abroad: A prospective study.

BACKGROUND: In France, no previous studies have focused specifically on health problems among medical students during internships abroad including the clinical symptoms suggestive of infectious diseases and the acquisition of pathogen carriage. METHODS: Clinical follow up and qPCR based respiratory, gastrointestinal and vaginal pathogen carriage before and after travel were prospectively assessed in a cohort of medical students departing from Marseille, France. RESULTS: 134 students were included. 73.9%, 38.8% and 5.0% of students reported gastrointestinal, respiratory and vaginal symptoms, respectively. The acquisition rate of Enteroaggregative Escherichia coli (EAEC) and Enteropathogenic E. coli (EPEC) was 53% and 41%, respectively. The acquisition of respiratory viruses was low but associated with persisting symptoms, while bacterial acquisition ranged from 3.3% for Streptococcus pyogenes to 15.0% for Haemophilus influenzae. Gardnerella vaginalis and Atopobium vaginae acquisition rates were 7.7% and 14.3% respectively. Five students (5.1%) had molecular quantification criteria for bacterial vaginosis on return. CONCLUSION: This preliminary study demonstrates that besides the known risk of gastrointestinal and respiratory infections and associated changes in intestinal and respiratory microbiota, medical students abroad may also experience changes in vaginal microbiota leading, in some cases, to clinical symptoms or the acquisition of bacterial vaginosis, which may be asymptomatic.

Diversity of vaginal microbiome and metabolome during genital infections.

We characterized the vaginal ecosystem during common infections of the female genital tract, as vulvovaginal candidiasis (VVC, n = 18) and Chlamydia trachomatis infection (CT, n = 20), recruiting healthy (HC, n = 21) and bacterial vaginosis-affected (BV, n = 20) women as references of eubiosis and dysbiosis. The profiles of the vaginal microbiome and metabolome were studied in 79 reproductive-aged women, by means of next generation sequencing and proton based-nuclear magnetic resonance spectroscopy. Lactobacillus genus was profoundly depleted in all the genital infections herein considered, and species-level analysis revealed that healthy vaginal microbiome was dominated by L. crispatus. In the shift from HC to CT, VVC, and BV, L. crispatus was progressively replaced by L. iners. CT infection and VVC, as well as BV condition, were mainly characterised by anaerobe genera, e.g. Gardnerella, Prevotella, Megasphaera, Roseburia and Atopobium. The changes in the bacterial communities occurring during the genital infections resulted in significant alterations in the vaginal metabolites composition, being the decrease of lactate a common marker of all the pathological conditions. In conclusion, according to the taxonomic and metabolomics analysis, we found that each of the four conditions is characterized by a peculiar vaginal microbiome/metabolome fingerprint.

Estimated burden of Chlamydia trachomatis female infection and consequent severe pelvic inflammatory disease, Italy, 2005-2016.

Chlamydia trachomatis (Ct) is the leading sexually transmitted infection (STI) across Europe. In Italy, Ct prevalence is low in general population, but predominance of asymptomatic infections, passive voluntary reporting, variable diagnostic criteria and coding practices can lead to considerable underestimation, preventing assessment of real burden of disease and health intervention. We analysed data on female genital Ct infection registered in STI sentinel surveillance systems in Italy from 2005 through 2016 and found 3305 women. Among them, those aged 20-24 years had the highest disability-adjusted life years (DALYs) estimation equal to 106.77 DALYs per 100 000-stratum specific population. Through the study period, incidence rate (IR) for female Ct infection increased significantly from 2.9 to 7.1 per 100 000 resident population. Besides, we analysed data on pelvic inflammatory disease (PID) reported from the National Hospital Information system (NHIS) in the same period. We found 287 women hospitalised with concurrent PID and Ct infection. We recommend targeted screening programmes in women aged 20-24, definition of nationwide active surveillance system, standardisation of diagnostic criteria and ICD-9CM coding practices.

Prospective study of bidet toilet use: Association of abnormal vaginal colonization and preterm birth in high-risk pregnant women.

AIM: This study aimed to evaluate the association of bidet toilet use with abnormal vaginal microbial colonization and preterm birth (PTB) in high-risk pregnancies. METHODS: This is a prospective cohort study of 208 women, who were admitted to a high-risk pregnancy unit, due to preterm labor, preterm premature rupture of the membrane, or short cervical length, in two tertiary hospitals from April 2015 to July 2017. Responses to a questionnaire about using bidet toilet and vaginal culture were obtained upon admission. Maternal baseline characteristics, vaginal culture results, and pregnancy and neonatal outcomes were compared between bidet toilet users and nonusers. RESULTS: Among the 204 subjects, 67 (32.8%) women were identified as bidet toilet users. Overall, bidet toilet use was associated with a higher rate of abnormal vaginal microbial colonization, compared to the nonusers (60.7% vs 44.2%, P = 0.036). Notably, Escherichia coli colonization rate was significantly higher in bidet toilet users than nonusers (13.1% vs 3.3%, P = 0.023). Bidet toilet users had a significantly higher rate of PTB before 37 weeks of gestation, compared to the nonusers (87.3% vs 73.0%, P = 0.040). CONCLUSION: Our study suggests that chronic use of a bidet toilet is associated with a higher rate of abnormal vaginal colonization by Gram-negative bacteria and PTB in high-risk pregnancies.

Randomized, open-label, multicenter study of azithromycin compared with doxycycline for treating anorectal Chlamydia trachomatis infection concomitant to a vaginal infection (CHLAZIDOXY study).

BACKGROUND: Chlamydia trachomatis can lead to a persistent infection in the lower gastrointestinal tract, suggesting a potential role of autoinoculation of cervical chlamydial infection from the rectal site, contributing to repeat infections. Moreover, around 75% of women with urogenital C. trachomatis have concurrent anorectal infection. Current treatment guidelines for urogenital C. trachomatis infection recommend either a single 1 g dose of azithromycin or doxycycline 100 mg twice daily for 7 days. Doxycycline appears to be more effective in treating anorectal infections as suggested in a population of men who have sex with men, but no randomized controlled trial (RCT) had directly compared azithromycin with doxycycline for the treatment of rectal infections. We propose an open-label RCT to compare the microbial cure obtained with a single 1 g dose of azithromycin versus 100 mg of doxycycline twice daily for 7 days, for the treatment of anorectal C. trachomatis infection concurrent to urogenital infection in women. METHODS AND STUDY DESIGN: A total of 460 women with C. trachomatis urogenital infection will be enrolled in the study. Women will be asked to provide self-collected anorectal swabs and will be randomized to receive either a 1 g single dose of azithromycin or doxycycline 100 mg twice daily for 7 days. Clinical and biological data will be collected and patients will complete questionnaires about their sexual behavior. The primary outcome is the microbial cure rate, defined as a C. trachomatis negative nucleic acid amplification test (NAAT) result in the anorectal specimens 6 weeks after treatment initiation among women with a C. trachomatis positive urogenital and anorectal NAAT result at the baseline. The secondary outcome is autoinoculation from the rectum to the vagina, which will be evaluated based on the number of women with the same C. trachomatis genotype profile that will be identified in an anorectal-positive specimen obtained 6 weeks after treatment initiation and in a vaginal-positive specimen obtained four months after treatment. DISCUSSION: The results of this trial will establish which treatment is more efficacious against anorectal infection and could affect recommendations for the treatment of urogenital C. trachomatis infection, taking into account concurrent anorectal infection. TRIAL REGISTRATION NUMBERS: EudraCT number: 2017-002595-15. CLINICALTRIALS. GOV IDENTIFIER: NCT03532464. Date of registration: May 31, 2018. WORLD HEALTH ORGANISATION INTERNATIONAL CLINICAL TRIALS REGISTRY: NTC03532464. Secondary ID: CHUBX 2016/26. Date of registration: May 09, 2018.

Different degrees of maternal Ureaplasma colonization and its correlation with bronchopulmonary dysplasia in <32 weeks' preterm infants.

BACKGROUND: Ureaplasma spp. is a known risk factor for bronchopulmonary dysplasia (BPD). However, little is known about the effect of different degrees of maternal Ureaplasma colonization and their adverse outcomes. Hence, the aim of this study was to determine the effects of different degrees of maternal Ureaplasma colonization on BPD. METHODS: A retrospective cohort study of preterm infants delivered at <32 weeks' gestational age (GA) was performed. The infants were divided according to maternal Ureaplasma status as follows: high-colonization (≥104 CCU/ml, UUH), low-colonization (<104 CCU/ml, UUL), and noncolonization (controls). Subgroup analysis according to neonatal respiratory Ureaplasma (n-UU) was also performed to evaluate vertical transmission. RESULTS: In total, 245 infants were included in this study (UUH = 105, UUL = 47, controls = 93). The rates of preterm labor and histological chorioamnionitis were significantly different. The rate of BPD was significantly high in UUH (P = 0.044). The transmission rate of n-UU colonization was 36% in UUH and 32% in UUL (P = 0.609). The rate of BPD was 78% in n-UU (+) of UUH but 43% in n-UU (-) of UUL (P = 0.027). CONCLUSIONS: High-degree colonization of maternal Ureaplasma was associated with preterm labor, histological chorioamnionitis, and neonatal BPD. The incidence of BPD was significantly higher in Ureaplasma-colonized infants born to women with high-degree colonization.

Ascending Vaginal Infection Using Bioluminescent Bacteria Evokes Intrauterine Inflammation, Preterm Birth, and Neonatal Brain Injury in Pregnant Mice.

Preterm birth is a serious global health problem and the leading cause of infant death before 5 years of age. At least 40% of cases are associated with infection. The most common way for pathogens to access the uterine cavity is by ascending from the vagina. Bioluminescent pathogens have revolutionized the understanding of infectious diseases. We hypothesized that bioluminescent Escherichia coli can be used to track and monitor ascending vaginal infections. Two bioluminescent strains were studied: E. coli K12 MG1655-lux, a nonpathogenic laboratory strain, and E. coli K1 A192PP-lux2, a pathogenic strain capable of causing neonatal meningitis and sepsis in neonatal rats. On embryonic day 16, mice received intravaginal E. coli K12, E. coli K1, or phosphate-buffered saline followed by whole-body bioluminescent imaging. In both cases, intravaginal delivery of E. coli K12 or E. coli K1 led to bacterial ascension into the uterine cavity, but only E. coli K1 induced preterm parturition. Intravaginal administration of E. coli K1 significantly reduced the proportion of pups born alive compared with E. coli K12 and phosphate-buffered saline controls. However, in both groups of viable pups born after bacterial inoculation, there was evidence of comparable brain inflammation by postnatal day 6. This study ascribes specific mechanisms by which exposure to intrauterine bacteria leads to premature delivery and neurologic inflammation in neonates.