Human Genital Tract Research Articles

Ureaplasma and Mycoplasma in kidney allograft recipients-A case series and review of the literature.

Ureaplasma urealyticum and Mycoplasma hominis are common inhabitants of the human genital tract. Increasingly, serious and sometimes fatal infections in immunocompromised hosts have been reported, highlighting their pathogenic potential. We reviewed the clinical impact of positive Ureaplasma spp. and Mycoplasma spp. urine cultures in 10 renal allograft recipients who presented with sterile leukocyturia. Five recipients remained asymptomatic. Five patients were symptomatic with dysuria or pain at the graft site. Three patients developed biopsy-proven acute graft pyelonephritis with graft dysfunction. One of these patients additionally showed a renal abscess as demonstrated by magnetic resonance imaging (MRI). All were successfully treated. A literature search revealed a substantial number of case reports with severe and sometimes fatal Ureaplasma spp. or Mycoplasma spp. infections in immunocompromised patients. Colonization rate is high in renal transplant patients. A subset of patients is at risk for invasive disease.

17 - Screening for anal dysplasia in women with a history of human papillomavirus related lower genital tract pathology

Background Women with a human papillomavirus related history of cervical, vaginal or vulvar high-grade dysplasia or cancer are at increased risk to develop anal dysplasia or anal cancer. Screening for anal cancer precursors (squamous intraepithelial lesions (SIL)) with high resolution anoscopy (HRA) in high-risk populations is subject of debate. In this study we evaluated standardized intra-anal SIL screening using HRA in high-risk female patients. Methods A retrospective observational study was performed to evaluate the prevalence of intra-anal SIL in women with a history of vulvar high-grade SIL (HSIL) and perianal HSIL diagnosed at the Netherlands Cancer Institute, who were referred for intra-anal SIL screening using HRA in the MC Slotervaart between 2015 and 2017. Results 22 female patients were screened for anal SIL using HRA. 19 females had a history of biopsy proven vulvar HSIL and 19 females had a history of biopsy proven perianal HSIL. Eleven (50%) patients had a history of multizonal HSIL at three or more perianogenital locations. No anal cancer was found at screening, 7 (32%) patients were diagnosed with anal HSIL and 7 (32%) patients with low-grade anal SIL. Conclusions We found a high prevalence of anal HSIL in women with HPV related lower genital tract dysplasia. Intra-anal SIL screening using HRA in this high risk population seems to be justified. However, HRA is an invasive screening method. Studying other, less invasive screening methods remains important.

Toll-like receptor 3 (TLR3) promotes the resolution of Chlamydia muridarum genital tract infection in congenic C57BL/6N mice.

Chlamydia trachomatis urogenital serovars primarily replicate in epithelial cells lining the reproductive tract. Epithelial cells recognize Chlamydia through cell surface and cytosolic receptors, and/or endosomal innate receptors such as Toll-like receptors (TLRs). Activation of these receptors triggers both innate and adaptive immune mechanisms that are required for chlamydial clearance, but are also responsible for the immunopathology in the reproductive tract. We previously demonstrated that Chlamydia muridarum (Cm) induces IFN-β in oviduct epithelial cells (OE) in a TLR3-dependent manner, and that the synthesis of several cytokines and chemokines are diminished in Cm-challenged OE derived from TLR3-/- 129S1 mice. Furthermore, our in vitro studies showed that Cm replication in TLR3-/- OE is more efficient than in wild-type OE. Because TLR3 modulates the release inflammatory mediators involved in host defense during Cm infection, we hypothesized that TLR3 plays a protective role against Cm-induced genital tract pathology in congenic C57BL/6N mice. Using the Cm mouse model for human Chlamydia genital tract infections, we demonstrated that TLR3-/- mice had increased Cm shedding during early and mid-stage genital infection. In early stage infection, TLR3-/- mice showed a diminished synthesis of IFN-β, IL-1β, and IL-6, but enhanced production of IL-10, TNF-α, and IFN-γ. In mid-stage infection, TLR3-/- mice exhibited significantly enhanced lymphocytic endometritis and salpingitis than wild-type mice. These lymphocytes were predominantly scattered along the endometrial stroma and the associated smooth muscle, and the lamina propria supporting the oviducts. Surprisingly, our data show that CD4+ T-cells are significantly enhanced in the genital tract TLR3-/- mice during mid-stage Chlamydial infection. In late-stage infections, both mouse strains developed hydrosalpinx; however, the extent of hydrosalpinx was more severe in TLR3-/- mice. Together, these data suggest that TLR3 promotes the clearance of Cm during early and mid-stages of genital tract infection, and that loss of TLR3 is detrimental in the development hydrosalpinx.

Mycoplasma hominis impacts gene expression in Trichomonas vaginalis

In Europe, up to 90% of isolated Trichomonas vaginalis strains are naturally infected with Mycoplasma hominis, a facultative pathogen of the human genital tract. The consequences of this endosymbiosis are not yet well understood. The aim of the current study was to evaluate the impact of natural and artificial infections with M. hominis on the RNA expression levels of metronidazole susceptibility-associated genes of T. vaginalis. Three T. vaginalis strains (TVSS10−, TVSS25−, G3) without M. hominis, as well as the same strains naturally (TVSS10+, TVSS25+) and artificially (G3-MhSS25, TVSS25-MhSS25) infected with M. hominis, were investigated for their expression profiles of three genes associated with metronidazole resistance (ferredoxin, flavin reductase 1 and pyruvate:ferredoxin oxidoreductase). The minimal inhibitory concentrations (MICs) of metronidazole were evaluated for all combinations and the respective M. hominis-free T. vaginalis strains were used as controls. The sole presence of M. hominis led to a down-regulation of metronidazole susceptibility-associated genes in all T. vaginalis strains tested. Interestingly, the effect was more prominent in the artificial symbioses. Moreover, a twofold enhancement of metronidazole tolerability was observed in three infected T. vaginalis strains, compared to the respective strains without M. hominis. In conclusion, M. hominis had an impact on gene expression in all T. vaginalis strains and on metronidazole MIC in all but one strain tested.

Candida albicans Hyphae: From Growth Initiation to Invasion

Candida albicans is a commensal resident of the human gastrointestinal and genital tracts. Under conditions such as dysbiosis, host immune perturbances, or the presence of catheters/implanted medical devices, the fungus may cause debilitating mucosal or fatal systemic infections. The ability of C. albicans to grow as long filamentous hyphae is critical for its pathogenic potential as it allows the fungus to invade the underlying substratum. In this brief review, I will outline the current understanding regarding the mechanistic regulation of hyphal growth and invasion in C. albicans.

Production of a chimeric protein and its potential application in sero-diagnosis of Mycoplasma hominis infection

IntroductionMycoplasma hominis is an opportunistic pathogen of the human genital tract. Detection of antibodies against this organism in human serum or plasma is theoretically unreliable because of high variation in bacterial surface antigens. In this study, we applied the bioinformatics tools to design a chimeric protein constructed of specific, conserved and predicted immuno-dominant epitopes from two different membrane proteins, P120 and P80. Material and methodsLinear B-cell epitopes of P120 and P80 were predicted and evaluated by bioinformatics tools and the designed chimeric protein was expressed in Escherichia coli. The chimeric protein, Mh128, was further analyzed in terms of immuno-reactivity by western blotting and enzyme immuno-sorbent assay (ELISA). ResultsWe found eight specific, conserved and immuno-dominant epitopes within P120 and P80 based on the bioinformatic studies. The constructed chimeric protein showed immuno-reaction in both western-blotting and ELISA tests. DiscussionBecause of extensive variation of genomic and antigenic structure, diagnosis of M. hominis infection is difficult. Mh128 as a predicted specific and conserved recombinant protein can be potentially used for sero-diagnosis of M. hominis infection. We plan to develop an immuno-assay based on Mh128 and further evaluate the clinical specificity and sensitivity of the method.

'Anaerococcus mediterraneensis' sp. nov., a new species isolated from human female genital tract.

We report the principal characteristics of ‘Anaerococcus mediterraneensis’ strain Marseille P2765, a new member of the Anaerococcus genus. Strain Marseille P2765 was isolated in a vaginal sample of a 26-year-old patient with bacterial vaginosis.

Mollicutes in vaginal microbiology: Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma genitalium

Mycoplasma hominis was isolated in 1937 from the human genital tract, followed 17 years later by Ureaplasma urealyticum and 27 years after that by Mycoplasma genitalium. The first two proved relatively easy to culture but the latter required a polymerase chain reaction assay for further studies. In sexually mature women, M. hominis may be found in the vagina/cervix of about 20–50%, ureaplasmas in 40–80% and M. genitalium in 0–5%. Some heterogeneity has been found among strains of all these species, sufficient to divide ureaplasmas into two species, namely U. urealyticum and Ureaplasma parvum. Studies in female mice show that sex hormones have a profound influence on colonization, multiplication and persistence of mycoplasmas/ureaplasmas in the genital tract and provoke the question, unanswered, of whether there is such an effect in the human tract. In women, there is no evidence that any of the mycoplasmal species stimulate an inflammatory vaginitis. M. hominis organisms increase hugely in number in the case of bacterial vaginosis (BV), and to a lesser extent so do ureaplasmas. Despite this, they have not been incriminated as a sole cause of BV. Evidence for the involvement of M. genitalium remains controversial. The strong association of BV with preterm birth raises the possibility that the genital mycoplasmas might play a part, but assurance that any do will be difficult to obtain. Detailed examination of the vaginal microbiome has not yet provided an answer.

Anal study in immunocompetent women with human papillomavirus related lower genital tract pathology

ObjetiveTo estimate the prevalence of anal dysplasia in immunocompetent women with cervical intraepithelial dysplasia. Study designWe did a prospective cohort study, in which we enrolled 166 women with gynecological pathology related to human papilloma virus (HPV) infection. All patients underwent an anal cytology and HPV detection. Statistical analysis with a 95% confidence interval was used for prevalence calculations. A Χ2 test and Fisher’s exact one were used to determine differences between groups of qualitative variables. Differences between normally distributed and non-normally distributed groups in quantitative variables were accounted for using Student’s t-test or Mann-Whitney’s U test, respectively. ResultsOut of the 166 patients studied, high risk HPV in the anal canal was detected in 107 (64.46%) cases. The most prevalent genotype observed was non 16/18 high risk HPV, present in 54 (50.47%) patients. There was no a significant association with smoking, use of condom, anal intercourse, or anal benign pathology. However, a significant correlation between the presence of high risk HPV in the anal canal and the antecedent of condylomas was observed (p=0.047) (CI95%: 1.00%–12.58%). Women with cervical intraepithelial neoplasia (CIN) grade 1 had a significantly increased presence of high risk HPV in the anal canal (p=0.044). Out of the 166 women, 6 (3.61%) had abnormal anal cytology results, and were referred to high-resolution anoscopy. Anal biopsy was performed in these six cases. In 2 patients the biopsy reported low-grade Anal Intraepithelial Neoplasia: 1.20% (0.15%–4.28%). ConclusionsWomen with cervical intraepithelial dysplasia have 1.20% prevalence of anal intraepithelial neoplasia, so that it does not seem necessary to screen this population.

Persistent Chlamydia trachomatis genital infection: laboratory diagnosis and treatment

If Chlamydia trachomatis (Ct) can not be cleared in time after invading human genital tract, it tends to cause persistent infection and induce severe sequelae, such as tubal infertility. Laboratory examination is of great value in the diagnosis of persistent Ct infection. Combined detection of antibodies to CT443 and CT381, or antibodies to Ct heat shock protein 60 (HSP60) , CT376, CT557 and CT443, can predict female tubal infertility with a specificity of 100% and a high sensitivity. Nucleic acid amplification techniques can be used to detect low Ct loads and to increase detection rates of Ct in patients with persistent infection. In clinic, antibacterial agents are the mainstay of treatment for Ct infection. Azithromycin in combination with metronidazole for 5 days or doxycycline combined with metronidazole for 7 days can be recommended for the treatment of persistent or recurrent nongonococcal urethritis. However, further studies are needed to confirm the efficacy of tryptophan metabolism-related drugs and glucocorticoids in the auxiliary treatment of persistent Ct infection. Key words: Chlamydia trachomatis; Reproductive tract infections; Clinical laboratory techniques; Diagnosis; Therapeutic uses

Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract.

Local mucosal cellular immunity is critical in providing protection from HSV-2. To characterize and quantitate HSV-2-reactive mucosal T cells, lymphocytes were isolated from endocervical cytobrush and biopsy specimens from 17 HSV-2-infected women and examined ex vivo for the expression of markers associated with maturation and tissue residency and for functional T cell responses to HSV-2. Compared to their circulating counterparts, cervix-derived CD4+ and CD8+ T cells were predominantly effector memory T cells (CCR7−/CD45RA−) and the majority expressed CD69, a marker of tissue residency. Co-expression of CD103, another marker of tissue residency, was highest on cervix-derived CD8+ T cells. Functional HSV-2 reactive CD4+ and CD8+ T cells responses were detected in cervical samples and a median of 17% co-expressed CD103. HSV-2 reactive CD4+ T cells co-expressed IL-2 and were significantly enriched in the cervix compared to blood. This first direct ex vivo documentation of local enrichment of HSV-2 reactive T cells in the human female genital mucosa is consistent with the presence of antigen-specific tissue-resident memory T cells. Ex vivo analysis of these T cells may uncover tissue-specific mechanisms of local control of HSV-2 to assist the development of vaccine strategies that target protective T cells to sites of HSV-2 infection.

“Collinsella vaginalis” sp. nov., a new bacterial species cultivated from human female genital tract

We present a brief description of “Collinsella vaginalis” strain P2666 (=CSUR P2666), a new bacterium that was cultivated from the vaginal sample of a 26-year-old woman affected from bacterial vaginosis.

"Ezakiella massiliensis" sp. nov., a new bacterial species isolated from human female genital tract.

We report the primary characteristics of “Ezakiella massiliensis” strain Marseille P2951 (= DSM 103122 = CSUR P2951), a new member of the Ezakiella genus. Strain Marseille P2951 was isolated from a vaginal sample taken from an asymptomatic 20-year-old woman who had sex with another woman who had bacterial vaginosis.

Group B Streptococcus (GBS) Bacteremia Likely From Infected Vaginal Pessary Causing Epidural Abscess, Endocarditis, and Septic Embolic Stroke

SESSION TITLE: Student/Resident Case Report Poster - Critical Care IV SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: GBS is a gram positive coccus that colonizes in the human gastrointestinal and genital tracts (1). The reported annual incidence of GBS infection in the general population of non-pregnant adults is between 4 and 8 per 100,000 (1,2,3). In population- based surveys, invasive GBS bacteremias are responsible for 2 to 9% of heart infections and 4% of central nervous system infections (3). Indeed, 20 to 60% of invasive GBS bacteremias are fatal (3). CASE PRESENTATION: A 75 year old female with a history of Diabetes presented with 1 week of body aches, an episode of fever, and 1 to 2 days of altered mental status. Vital signs were normal. Patient was oriented, but falling to sleep during the conversation. Positive physical examination findings included 4/5 motor strength in bilateral lower extremities. Laboratory evaluation showed leukocytosis at 16,800/ microliter. Patient was started on Vancomycin and Ceftriaxone after obtaining blood cultures. CT of the head and MRI of the spine did not show any acute pathology. Cerebrospinal fluid analysis showed nucleated cells as 311 (79% neutrophils), glucose as 133 and protein as 122. Blood cultures came back as positive for Penicillin sensitive GBS with MIC of < 0.12, so the antibiotics were changed to Penicillin. Patient continued to have persistent GBS bacteremia on repeated blood cultures, so Gentamicin was added. A Trans Esophageal Echocardiogram showed small vegetation on the aortic valve. Patient's daughter visited her mother a few days after admission and revealed that patient had been having significant discomfort from vaginal pessary for a few months. Repeated blood cultures did not grow any organisms after removal of vaginal pessary, and a culture of pessary grew rare GBS. Patient's mentation and lower extremity weakness significantly deteriorated over time. Repeat MRI of brain and spine revealed acute infarction of left posterior parietal region and epidural abscess extending from T 12 to L3. Patient was emergently taken to the operating room, and epidural abscess was drained. Patient completely recovered after finishing the course of antibiotics and rehabilitation. DISCUSSION: No case of GBS bacteremia leading to epidural abscess, endocarditis, and septic embolic stroke secondary to vaginal pessary has been reported so far. In our patient, the likely source of infection was vaginal pessary; however we could not completely conclude that source, as GBS colonizes in the genital tract. CONCLUSIONS: Despite new advancements in medical technologies, a medical practitioner should never ignore the importance of history and the physical examination. Reference #1: Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med. 2000;342(1):15. Reference #2: Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA. 2008;299(17):2056. Reference #3: A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults. N Engl J Med. 1993;328(25):1807. DISCLOSURE: The following authors have nothing to disclose: Mohana Krishna Loya No Product/Research Disclosure Information

"Vaginella massiliensis" gen. nov., sp. nov., a new genus cultivated from human female genital tract.

We relate the main characteristics of “Vaginella massiliensis” strain Marseille P2517 (= DSM 102346 = CSUR P2517), a new member of the Flavobacteriaceae family. The strain Marseille P2517 was cultivated from a vaginal swab from a healthy 22-year-old woman.

Vaginosis bacteriana

Bacterial vaginosis (BV) is the main cause of vaginal dysbacteriosis in the women during the reproductive age. It is an entity in which many studies have focused for years and which is still open for discussion topics. This is due to the diversity of microorganisms that cause it and therefore, its difficult treatment. Bacterial vaginosis is probably the result of vaginal colonization by complex bacterial communities, many of them non-cultivable and with interdependent metabolism where anaerobic populations most likely play an important role in its pathogenesis. The main symptoms are an increase of vaginal discharge and the unpleasant smell of it. It can lead to serious consequences for women, such as an increased risk of contracting sexually transmitted infections including human immunodeficiency virus and upper genital tract and pregnancy complications. Gram stain is the gold standard for microbiological diagnosis of BV, but can also be diagnosed using the Amsel clinical criteria. It should not be considered a sexually transmitted disease but it is highly related to sex. Recurrence is the main problem of medical treatment. Apart from BV, there are other dysbacteriosis less characterized like aerobic vaginitis of which further studies are coming slowly but are achieving more attention and consensus among specialists.

'Peptoniphilus vaginalis' sp. nov., a new species isolated from human female genital tract.

We relate here the main characteristics of ‘Peptoniphilus vaginalis’, strain KHD2 (= CSUR P0125 = DSM 101742), a new member of the Peptoniphilus genus, cultivated from a vaginal sample of a woman with bacterial vaginosis.

‘ Peptoniphilus pacaensis ’ sp. nov., a new species isolated from human female genital tract

We relate here the primary characteristics of ‘Peptoniphilus pacaensis’ strain KHD5 (= CSUR P2271), a new member of the Peptoniphilus genus. Strain KHD5 was isolated from a vaginal sample of a 33-year-old woman exhibiting a bacterial vaginosis.

'Lascolabacter vaginalis' strain KHD1, a new bacterial species cultivated from human female genital tract.

We present the major characteristics of ‘Lascolabacter vaginalis’ strain KHD1 (= CSUR P0109 = DSM 101752), a new member of the family Prevotellaceae that was cultivated from a vaginal sample of a 33-year-old woman with bacterial vaginosis.

'Peptoniphilus raoultii' sp. nov., a new species isolated from human female genital tract.

We report the principal characteristics of ‘Peptoniphilus raoultii’ strain KHD4 (= CSUR P0110), a new member of the Peptoniphilus genus. Strain KHD4 was isolated from the vaginal flora of a 33-year-old woman with bacterial vaginosis.