Cervicovaginal Colonization Research Articles

A REVIEW OF GROUP B STREPTOCOCCUS (GBS) VAGINAL COLONIZATION AND ASCENDING INTRAUTERINE INFECTION: INTERACTION BETWEEN HOST IMMUNE RESPONSES AND GBS VIRULENCE FACTORS

Vaginal colonization with Group B streptococcus (GBS) or Streptococcus agalactiae can potentially cause ascending intrauterine infection among pregnant women, and hence it is known as one of the risk factors for preterm delivery. Ascending intrauterine infection may also cause the transmission of GBS to the fetus in utero and the newborn during delivery, leading to the development of early onset of neonatal infection. GBS are β-hemolytic, gram-positive bacteria that are opportunistic commensal of the gastrointestinal and urogenital tract of approximately 18% of pregnant women globally. Intrapartum antibiotic prophylaxis (IAP) only reduces the rate of early onset neonatal infection, but not the late onset neonatal infection. Thus, the development of GBS vaccine is thought to be important to decrease the rate of preterm delivery and neonatal infections particularly in low-and-middle income countries where IAP program is not feasible. Vaccination can also be cost-effective for the healthcare system when executed together with IAP program. The aim of the current review is to summarize the mechanisms on how the GBS virulence factors interact with host immune components in the gestational tissues, leading to cervicovaginal colonization and ascending intrauterine infection. The elucidation of these mechanisms is essential for expediting the development of vaccines and novel therapeutic measures targeting these GBS virulence factors that will hamper the vaginal colonization, ascending intrauterine infection and conceptus tissue invasion by GBS. These strategies are crucial to potentially reduce the rate of preterm delivery and subsequent serious complications in the newborn.

Does bacterial colonization during embryo transfer have an impact on pregnancy rate in ICSI? : Tunisian preliminary results

IntroductionEmbryos’ transfer into the uterine cavity remains a limiting factor in the success of intracytoplasmic sperm injection (ICSI). This study aimed to evaluate the impact of cervico-vaginal colonization on ICSI outcomes. Materiel and methodsLongitudinal, prospective and analytical study, conducted from February 1 st to October 31 st, 2017. On the day of embryos’ transfer, patients with the following criteria were included: Age ≤ 40, normal uterine ultrasound and hysteroscopy, first or second attempt of ICSI, use of fresh semen and transfer of at least one good quality embryo. Three samples were done for microbiological analysis: vaginal secretions, cervical mucus and the tip of the transfer catheter. ResultsThe study included 40 patients. Pregnancy rate was 52.5 %. Catheter contamination occurred in nine cases (22.5 %). The most frequently isolated bacteria were Streptococcus anginosus (37 % of cases), Gardnerella vaginalis (27 % of cases) and Streptococcus agalactiae (18 % of cases). In all cases of contamination, the same bacteria were found also in the vagina and cervical mucus. In cases of contamination with Gardnerella vaginalis, the study of vaginal flora showed bacterial vaginosis. No pregnancy was obtained when contamination of the transfer catheter occurred. In the absence of contamination, pregnancy rate was 61.2 % (ρ = 0.003). Both populations (patients with catheter contamination and patients without catheter contamination) were comparable regarding epidemiological characteristics and ICSI attempt data. ConclusionContamination of the transfer catheter by cervical-vaginal bacteria appears to affect IVF results. Systematic antibiotic prophylaxis could be proposed to reduce this negative impact.

Non-human Primate Papillomaviruses Share Similar Evolutionary Histories and Niche Adaptation as the Human Counterparts.

Given high genetic diversity of papillomaviruses (PV) and complex scenario of virus-host interaction, the genetic basis underlying the mechanisms of HPV carcinogenicity is not well understood. In an effort to evaluate the origin and evolution of PV pathogenicity, we collected paired oral, perianal, and genital swabs from a wild macaque population. Of the 117 surveyed macaques, 88 (75.2%) were positive for PV DNA in one or more sites, mostly common from genital swabs, followed by oral and perianal sites. All putative macaque PV types phylogenetically clustered into the genera Alpha-, Beta-, and Gammapapillomavirus, with a strong phylogeny-tropism association as observed in HPVs. Using a Bayesian Markov Chain Monte Carlo framework, we demonstrated ancient intra-host divergence of primate PVs in which multiple ancestors had split and adapted to specific host ecosystems at least 41 million years ago, prior to the speciation events of primate host species. Following subsequent divergence and niche adaptation, distinct but phylogenetically related PV types were transmitted to similar host ecosystems by closely related host animals when host speciation occurred, which may explain in part the origin of carcinogenicity of HPV type 16 (HPV16) and Macaca fascicularis PV type 3 (MfPV3) that evolved from a most recent common ancestor containing the determinants for cervicovaginal colonization and cervical cancer. The findings identifying evolutionary and biological relatedness between human and non-human primate PVs lay a genetic foundation for research on parasite-host interactions and carcinogenic outcomes, which will prove useful in further study of viral pathogenesis and host specificity.STUDY IMPORTANCETo better understand the origin and evolution of PV carcinogenicity associated with cervical cancer, we applied a combination of phylogenetic and bioinformatic analyses to investigate the genetic diversity of macaque papillomaviruses, and estimate divergence times of human and non-human primate PVs. The majority of both human and non-human primate PVs cluster into α-, β-, and γ-PVs, sharing similar evolutionary histories and biological properties to each other. The strong phylogeny-tropism association of primate PVs indicates an important role of niche adaptation and virus-host codivergence shaping the diversity of viral genomics, host specificity, immune exposure, and pathogenic property. Understanding the evolution of the family Papilloamviridae in general and the primate papillomaviruses in specific in relevant to virus-host interactions should provide important implications for viral pathogenesis and disease prevention.

Colonization of the cervicovaginal space with Gardnerella vaginalis leads to local inflammation and cervical remodeling in pregnant mice.

The role of the cervicovaginal (CV) microbiome in regulating cervical function during pregnancy is poorly understood. Gardnerella vaginalis (G. vaginalis) is the most common bacteria associated with the diagnosis of bacterial vaginosis (BV). While BV has been associated with preterm birth (PTB), clinical trials targeting BV do not decrease PTB rates. It remains unknown if G. vaginalis is capable of triggering molecular, biomechanical and cellular events that could lead to PTB. The objective of this study was to determine if cervicovaginal colonization with G. vaginalis, in pregnant mice, induced cervical remodeling and modified cervical function. CD-1 timed-pregnant mice received a 5X108 CFU/mL intravaginal inoculation of G. vaginalis or control on embryonic day 12 (E12) and E13. On E15, the mice were sacrificed and cervicovaginal fluid (CVF), amniotic fluid (AF), cervix, uterus, placentas and fetal membranes (FM) were collected. Genomic DNA was isolated from the CVF, placenta, uterus and FM and QPCR was performed to confirm colonization. IL-6 was measured in the CVF and AF and soluble e-cadherin (seCAD) was assessed in the CVF by ELISA. RNA was extracted from the cervices to evaluate IL-10, IL-8, IL-1β, TNF-α, Tff-1, SPINK-5, HAS-1 and LOX expression via QPCR. Mucicarmine and trichrome staining was used to assess cervical mucin and collagen. Biomechanical properties of the cervix were studied using quasi-static tensile load-to-failure biomechanical tests. G. vaginalis successfully colonized the CV space. This colonization induced immune responses (increased IL-6 levels in CVF and AF, increased mRNA expression of cervical cytokines), altered the epithelial barrier (increased seCAD in the CVF), induced cervical remodeling (increased mucin production, altered collagen) and altered cervical biomechanical properties (a decrease in biomechanical modulus and an increase in maximum strain). The ability of G. vaginalis to induce these molecular, immune, cellular and biomechanical changes suggests that this bacterium may play a pathogenic role in premature cervical remodeling leading to PTB.

Both MisR (CpxR) and MisS (CpxA) Are Required for Neisseria gonorrhoeae Infection in a Murine Model of Lower Genital Tract Infection.

During infection, Neisseria gonorrhoeae senses and responds to stress; such responses may be modulated by MisRS (NGO0177 and NGO0176), a two-component system that is a homolog of CpxRA. In Escherichia coli, CpxRA senses and responds to envelope stress; CpxA is a sensor kinase/phosphatase for CpxR, a response regulator. When a cpxA mutant is grown in medium containing glucose, CpxR is phosphorylated by acetyl phosphate but cannot be dephosphorylated, resulting in constitutive activation. Kandler and coworkers (J. L. Kandler, C. L. Holley, J. L. Reimche, V. Dhulipala, J. T. Balthazar, A. Muszyński, R. W. Carlson, and W. M. Shafer, Antimicrob Agents Chemother 60:4690-4700, 2016, https://doi.org/10.1128/AAC.00823-16) showed that MisR (CpxR) is required for the maintenance of membrane integrity and resistance to antimicrobial peptides, suggesting a role in gonococcal survival in vivo Here, we evaluated the contributions of MisR and MisS (CpxA) to gonococcal infection in a murine model of cervicovaginal colonization and identified MisR-regulated genes using RNA sequencing (RNA-Seq). The deletion of misR or misS severely reduced the capacity of N. gonorrhoeae to colonize mice or maintain infection over a 7-day period and reduced microbial fitness after exposure to heat shock. Compared to the wild type (WT), the inactivation of misR identified 157 differentially regulated genes, most of which encoded putative envelope proteins. The inactivation of misS identified 17 differentially regulated genes compared to the WT and 139 differentially regulated genes compared to the misR mutant, 111 of which overlapped those differentially expressed in the comparison of the WT versus the misR mutant. These data indicate that an intact MisRS system is required for gonococcal infection of mice. Provided the MisR is constitutively phosphorylated in the misS mutant, the data suggest that controlled but not constitutive activation is required for gonococcal infection in mice.

Prolonged progesterone administration is associated with less frequent cervicovaginal colonization by Ureaplasma urealyticum during pregnancy — Results of a pilot study

BackgroundPreterm birth is a leading cause of perinatal mortality and morbidity. Heavy cervicovaginal Ureaplasma colonization is thought to play a role in the pathogenesis of preterm birth. The administration of vaginal progesterone has been shown to reduce the incidence of preterm birth in women with short cervical length. Steroid hormones seem to modulate the presence of microorganisms in the vagina. The aim of this study was to assess whether the treatment with vaginal progesterone could reduce the incidence of preterm birth and cervicovaginal colonization by Ureaplasma urealyticum in a cohort of pregnant women with threatened preterm labor. MethodsA cohort of 63 females who presented with regular contractions and/or short cervical length between 24–32 weeks of gestation were recruited into a prospective study. 70% of patients had been treated with vaginal progesterone prior to recruitment and these patients continued with the treatment until birth. All patients were tested for the presence of cervicovaginal Ureaplasma urealyticum colonization at admission. The primary endpoint was preterm birth before 37 weeks. ResultsThe incidence of preterm delivery was significantly increased in patients who tested positive for Ureaplasma urealyticum. Prolonged vaginal progesterone administration was associated with less frequent cervicovaginal colonization by U. urealyticum. Cervicovaginal colonization by U. urealyticum and absence of progesterone treatment were identified as two independent risk factors for preterm delivery. ConclusionsOur results demonstrate the beneficial effects of progesterone administration in reducing the incidence of cervicovaginal colonization by Ureaplasma urealyticum.

Comparison of cervico-vaginal colonization among sexually active women by intrauterine device use.

In this study we aimed to evaluate the effect of intrauterine devices (IUDs) on cervico-vaginal colonization. Cervico-vaginal samples of 96 patients with vaginal discharge were included in the study. Microscopic evaluation, bacteriological and fungal culture, and antigen testing for Chlamydia trachomatis using an immunochromatographic test method were performed. Trichomonas vaginalis was not detected by wet mount examination. Gram smear revealed that seven patients (7.3%) had Candida spp. and five (5.2%) had clue cell. Of the 96 swabs tested for conventional culture, pathogenic microorganisms were isolated from 24 patients. While Neisseria gonorrhoeae was not found in any of the sample, five (5.2%) were positive for Gardnerella vaginalis. Five (5.2%) were positive for C. trachomatis antigen, while three positivity only for C. trachomatis antigen, one had G. vaginalis additionally, and the other had a mixed infection. Chlamydial antigen positivity was higher among women over 30 years of age (p = 0.157). Increase in polymorphonuclear leukocytes (PNL) was detected 40% and 35.2% of samples, positive and negative, for chlamydial antigen, respectively (p = 1.000). Among IUD+ cases, increase in PNL, fungal elements, E. coli and Gram-positive bacteria and decrease in Lactobacillus spp. were observed, compared to IUD-cases. No statistically significant relationship was detected between IUD and chlamydial antigen with the reported rates of 4.8% and 5.6% for IUD+ or IUD-, respectively (p > 0.05). Statistically significant relationship was not detected between IUD and cervico-vaginal colonization. More comprehensive studies using specific test methods should be conducted to better understand the relationship.

Group B streptococcal serine-rich repeat proteins promote interaction with fibrinogen and vaginal colonization.

Group B streptococcus (GBS) can cause severe disease in susceptible hosts, including newborns, pregnant women, and the elderly. GBS serine-rich repeat (Srr) surface glycoproteins are important adhesins/invasins in multiple host tissues, including the vagina. However, exact molecular mechanisms contributing to their importance in colonization are unknown. We have recently determined that Srr proteins contain a fibrinogen-binding region (BR) and hypothesize that Srr-mediated fibrinogen binding may contribute to GBS cervicovaginal colonization. In this study, we observed that fibrinogen enhanced wild-type GBS attachment to cervical and vaginal epithelium, and that this was dependent on Srr1. Moreover, purified Srr1-BR peptide bound directly to host cells, and peptide administration in vivo reduced GBS recovery from the vaginal tract. Furthermore, a GBS mutant strain lacking only the Srr1 "latching" domain exhibited decreased adherence in vitro and decreased persistence in a mouse model of GBS vaginal colonization, suggesting the importance of Srr-fibrinogen interactions in the female reproductive tract.

Colonization of the lower urogenital tract with Ureaplasma parvum can cause asymptomatic infection of the upper reproductive system in women: a preliminary study

PurposeGenital ureaplasmas are considered opportunistic pathogens of human genitourinary tract involved in adverse pregnancy sequelae and infertility. While association of Ureaplasma urealyticum with urogenital tract infections is well established, the role of Ureaplasma parvum in these infections is still insufficient. In the study, we compared how often cervicovaginal colonization with U. parvum is associated with the presence of these microorganisms in the upper genitourinary tract of fertile and infertile women.MethodsWe used PCR assay to determine the prevalence of U. parvum and U. urealyticum in pairs of specimens, i.e., vaginal swabs and Douglas’ pouch fluid samples from consecutive 40 women with no symptoms of genital tract infection.ResultsIn total, 19 (47.5 %) of the 40 samples were positive for ureaplasmas. U. parvum was simultaneously detected in pairs of samples in five (55.5 %) of the nine (47.4 %) women positive in PCR assay. As many as 5 (18.5 %) of the 27 infertile women and 1 (7.7 %) of the 13 fertile women showed infection of the upper genital tract with U. parvum.ConclusionThe results of the study demonstrated that colonization of the lower genital tract with U. parvum can produce asymptomatic infection of the upper reproductive system in women. These findings also imply that U. parvum may be present in the upper genital tract at the time of conception and might be involved in adverse pregnancy outcomes.

Can group B streptococci cause symptomatic vaginitis?

Background Maternal cervicovaginal colonization with Lancefield group B streptococci (GBS) is an important risk factor for neonatal morbidity and mortality. About 15% of women are carriers of GBS. Usually, they are asymptomatic. Cases We describe two patients with symptomatic vaginitis for which no apparent cause was found. Both patients were heavily colonized with GBS. After antibiotic treatment, both became asymptomatic and culture negative, but after recolonization with GBS, symptoms resumed. This phenomenon was repeatedly observed. After emergence of resistance to antibiotics, local application of chlorhexidine appeared to be the only useful treatment. Conclusion We hypothesize that GBS-vaginitis may be a possible disease entity. Although at present it is not clear why some patients become symptomatic, we speculate that the immunologic response is somehow selectively hampered in such patients. Infect. Dis. Obstet. Gynecol. 7:206–209, 1999. © 1999 Wiley-Liss, Inc.

Can Group B Streptococci Cause Symptomatic Vaginitis?

Background Maternal cervicovaginal colonization with Lancefield group B streptococci (GBS) is an important risk factor for neonatal morbidity and mortality. About 15% of women are carriers of GBS. Usually, they are asymptomatic. Cases We describe two patients with symptomatic vaginitis for which no apparent cause was found. Both patients were heavily colonized with GBS. After antibiotic treatment, both became asymptomatic and culture negative, but after recolonization with GBS, symptoms resumed. This phenomenon was repeatedly observed. After emergence of resistance to antibiotics, local application of chlorhexidine appeared to be the only useful treatment. Conclusion We hypothesize that GBS-vaginitis may be a possible disease entity. Although at present it is not clear why some patients become symptomatic, we speculate that the immunologic response is somehow selectively hampered in such patients. Infect. Dis. Obstet. Gynecol. 7:206–209, 1999. © 1999 Wiley-Liss, Inc.

Colonization with group B streptococci in pregnancy and adverse outcome

OBJECTIVE: Our purpose was to study the association of cervicovaginal colonization with group B streptococci with pregnancy and neonatal outcome. STUDY DESIGN: A prospective study was conducted at seven medical centers between 1984 and 1989. Genital tract cultures were obtained at 23 to 26 weeks' gestation and at delivery. Prematurity and neonatal sepsis rates were compared between group B streptococci positive and negative women. RESULTS: Group B streptococci was recovered from 2877 (21%) of 13,646 women at enrollment. Heavy colonization was associated with a significant risk of delivering a preterm infant who had a low birth weight (odds ratio = 1.5, 95% confidence interval 1.1 to 1.9). Heavily colonized women given antibiotics effective against group B streptococci had little increased risk of a preterm, low-birth-weight birth. Women with light colonization were at the same risk of adverse outcome as the uncolonized women. Neonatal group B streptococci sepsis occurred in 2.6 of 1000 live births in women with and 1.6 of 1000 live births in women without group B streptococci at 23 to 26 weeks' gestation ( p = 0.11). However, sepsis occurred in 16 of 1000 live births to women with and 0.4 of 1000 live births to women without group B streptococci at delivery ( p < 0.001). CONCLUSIONS: Heavy group B streptococci colonization at 23 to 26 weeks' gestation was associated with an increased risk of delivering a preterm, low-birth-weight infant. Cervicovaginal colonization with group B streptococci at 23 to 26 weeks' gestation was not a reliable predictor of neonatal group B streptococci sepsis. Colonization at delivery was associated with sepsis. (A M J O BSTET G YNECOL 1996;174:1354-60.)