Detection and Clearance of Type-Specific and Phylogenetically Related Genital Human Papillomavirus Infections in Young Women in New Heterosexual Relationships.

BACKGROUND: Understanding the natural history of human papillomavirus (HPV) infections is essential to cervical cancer prevention planning. We estimated HPV type-specific infection detection and clearance in young women. METHODS: The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) study is a prospective cohort of 502 college-age women who recently initiated a heterosexual relationship. We tested vaginal samples collected at 6 clinical visits over 24 months for 36 HPV types. Using rates and Kaplan-Meier analysis, we estimated time-to-event statistics with 95% confidence intervals (CIs) for detection of incident infections and clearance of incident and present-at-baseline infections (separately). We conducted analyses at the woman- and HPV-levels, with HPV types grouped by phylogenetic relatedness. RESULTS: By 24 months, we detected incident infections in 40.4% (CI, 33.4%-48.4%) of women. Incident subgenus 1 (43.4; CI, 33.6-56.4), 2 (47.1; CI, 39.9-55.5), and 3 (46.6; CI, 37.7-57.7) infections cleared at similar rates per 1000 infection-months. We observed similar homogeny in HPV-level clearance rates among present-at-baseline infections. CONCLUSIONS: Our analyses provide type-specific infection natural history estimates for cervical cancer prevention planning. HPV-level analyses did not clearly indicate that high oncogenic risk subgenus 2 infections persist longer than their low oncogenic risk subgenera 1 and 3 counterparts.

The effect of training given using three different methods on genital hygiene behaviours after medical curettage.

This research was conducted to determine the effect of genital hygiene training given with three different methods after medical curettage on genital hygiene behaviours. A randomised semi-experimental study was performed with 90 patients who underwent medical curettage at a university hospital in Turkey. The participants were divided into three equal groups: verbal training, training with written materials, and demonstration only. Data was collected using the Patient Information Form and the Genital Hygiene Behaviour Scale. There was no difference between mean pre-training and post-training Genital Hygiene Behaviours Scale total and sub-dimension scores in the verbal group (p > .05). There was a difference between the groups after the training between the mean total and sub-dimensions of the Genital Hygiene Behaviour Scale scores (p < .05). The study findings showed that the demonstration method in genital hygiene training given to participants who underwent medical curettage was more effective in improving genital hygiene behaviours than other methods.IMPACT STATEMENTWhat is already known on this subject? It is seen that verbal education alone is not effective in providing and developing genital hygiene behaviours. Although studies are investigating the effectiveness of education on genital hygiene behaviours of women, there is no study investigating the effectiveness of education methods.What do the results of this study add? The demonstration method for the development of genital hygiene behaviours is more effective than verbal and written education methods.What are the implications of these findings for clinical practice and/or further research? This study provides evidence for the effectiveness of training methods for the development of genital hygiene behaviours. Nurses' preference for demonstration methods in genital hygiene education programs may contribute to the protection and development of health by facilitating the teaching of correct health behaviours.

The Reaction of Innate Lymphoid Cells in the Mouse Female Genital Tract to Chlamydial Infection.

Innate lymphoid cells (ILCs) comprise five distinct subsets. ILCs are found at mucosal barriers and may fight invading pathogens. Chlamydia is an intracellular bacterium that infects the mucosa of the genital tract and can cause severe tissue damage. Here, we used a mouse infection model with Chlamydia muridarum to measure the reaction of genital tract ILCs to the infection. Tissue-resident natural killer (NK) cells were the largest group in the uninfected female genital tract, and their number did not substantially change. Conventional NK cells were present in the greatest numbers during acute infection, while ILC1s continuously increased to high numbers. ILC2 and ILC3s were found at lower numbers that oscillated by a factor of 2 to 4. The majority of ILC3s transdifferentiated into ILC1s. NK cells and ILC1s produced gamma interferon (IFN-γ) and, rarely, tumor necrosis factor (TNF), but only early in the infection. Lack of B and T cells increased ILC numbers, while the loss of myeloid cells decreased them. ILCs accumulated to a high density in the oviduct, a main site of tissue destruction. ILC subsets are part of the inflammatory and immune reaction during infection with C. muridarum and may contribute to tissue damage during chlamydial infection.

In Vitro and In Vivo Activity, Tolerability, and Mechanism of Action of BX795 as an Antiviral against Herpes Simplex Virus 2 Genital Infection.

Herpes simplex virus type 2 (HSV-2) causes recurrent lesions in the anogenital area that may be transmitted through sexual encounters. Nucleoside analogs, such as acyclovir (ACV), are currently prescribed clinically to curb this infection. However, in some cases, reduced efficacy has been observed due to the emergence of resistance against these drugs. In our previous study, we reported the discovery of a novel anti-HSV-1 small molecule, BX795, which was originally used as an inhibitor of TANK-binding kinase 1 (TBK1). In this study, we report the antiviral efficacy of BX795 on HSV-2 infection in vaginal epithelial cells in vitro at 10 µM and in vivo at 50 µM. Additionally, through biochemical assays in vitro and histopathology in vivo, we show the tolerability of BX795 in vaginal epithelial cells at concentrations as high as 80 µM. Our investigations also revealed that the mechanism of action of BX795 antiviral activity stems from the reduction of viral protein translation via inhibition of protein kinase B phosphorylation. Finally, using a murine model of vaginal infection, we show that topical therapy using 50 µM BX795 is well tolerated and efficacious in controlling HSV-2 replication.

Mycoplasma genitalium Detection in Urogenital Specimens from Symptomatic and Asymptomatic Men and Women by Use of the cobas TV/MG Test.

Mycoplasma genitalium (MG) infections are a growing concern within the field of sexually transmitted infections. However, diagnostic assays for M. genitalium have been limited in the United States. As most infections are asymptomatic, individuals can unknowingly pass the infection on, and the prevalence is likely to be underestimated. Diagnosis of M. genitalium infection is recommended using a nucleic acid test. This multicenter study assessed the performance of the cobas Trichomonas vaginalis (TV)/MG assay (cobas) for the detection of M. genitalium, using 22,150 urogenital specimens from both symptomatic and asymptomatic men and women collected at geographically diverse sites across the United States. The performance was compared to a reference standard of three laboratory-developed tests (LDTs). The specificity of the cobas assay for M. genitalium ranged from 96.0% to 99.8% across symptomatic and asymptomatic men and women. The sensitivities in female vaginal swabs and urine samples were 96.6% (95% confidence interval [CI], 88.5 to 99.1%) and 86.4% (95% CI, 75.5 to 93.0%), respectively. The sensitivities in male urine and meatal swab samples were 100% (95% CI, 94.0 to 100%) and 85.0% (95% CI, 73.9 to 91.9%), respectively. This study demonstrated that the cobas assay was highly sensitive and specific in all relevant clinical samples for the detection of M. genitalium.

Recent clinical relevance of mono-genital colonization/infection by Ureaplasma parvum.

Ureaplasma parvum is the most prevalent genital mycoplasma in women of childbearing age. There is debate around the relevance of its presence in male or female genitals for disease development and as a cofactor. The objective of this study was to determine the prevalence of colonization/infection by U. parvum and its possible relationship with reproductive tract infections. We retrospectively analyzed the presence of U. parvum in patients referred by specialist clinicians for suspicion of genitourinary tract infection. U. parvum was detected in 23.8% of samples, significantly more frequently in females (39.9%) than in males (6%). Among the males, U. parvum was found alone in 68.4% of episodes, with Ct < 30. Among the females, U. parvum was detected in 88.6% of cases, with Ct < 30, including 22 cases with premature rupture of membranes and 6 cases with threat of preterm labor. Co-infection was significantly more frequent in females (62.6%) than in males (31.6%). Given the high prevalence of U. parvum as sole isolate in males and females with genitourinary symptoms, it should be considered in the diagnosis and treatment of genital infections, although its pathogenic role in some diseases has not been fully elucidated.

Characterization of the Horizontal and Vertical Sexual Transmission of Chlamydia Genital Infections in a New Mouse Model.

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide, and there is a need to control this epidemic. So far there is no established animal model in which both the horizontal and the vertical transmission of Chlamydia can be studied. To implement a horizontal sexual transmission model, male mice were inoculated in the meatus urethra with Chlamydia muridarum and they were caged with naive female mice. Urine and vaginal swab specimens were collected for culture. To study vertical transmission, newborns were euthanized and specimens were cultured. As controls, females were mated with sham-infected male mice. All C. muridarum-inoculated male mice had positive urine cultures. As determined by serology, all females caged with C. muridarum-inoculated males became infected, and 93% of them had positive vaginal swab specimen cultures. More females mated with C. muridarum-infected male mice (35%) than females mated with sham-infected male mice (0%) were infertile (P < 0.05). Also, C. muridarum-infected females delivered significantly fewer pups (3.8 ± 3.2/mouse) than control females (6.3 ± 1.6/mouse) (P < 0.05). Of the newborn mice, 32% were C. muridarum positive either in the lungs or in the intestines. Female mice housed with sham-infected males had no positive vaginal swab specimen cultures or C. muridarum-positive pups. This new mouse model of horizontal and vertical sexual transmission of Chlamydia closely parallels C. trachomatis sexual transmission in humans and may be a good model system to better understand the pathogenesis of these infections.

Evaluation of the Performance of the Cobas CT/NG Test for Use on the Cobas 6800/8800 Systems for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in Male and Female Urogenital Samples.

The clinical performance of the Cobas CT/NG assay on the Cobas 6800/8800 systems (Cobas) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae was established in a multisite, prospective collection study using male and female urogenital specimens; supportive data from archived specimens were also included. The results obtained with the Cobas assay were compared with the patient infected status derived from a combination of U.S. Food and Drug Administration-approved nucleic acid amplification tests to determine the sensitivity and specificity of detection from each sample type. The sensitivity of Cobas for the detection of C. trachomatis in female specimens was 95.6% (95% confidence interval [CI], 92.4% to 97.4%) for urine; 98.6% (95% CI, 95.2% to 99.6%) and 99.2% (95% CI, 95.4% to 99.9%) for clinician- and self-collected vaginal swab specimens, respectively; 93.3% (95% CI, 89.6% to 95.7%) for endocervical swabs; and 92.5% (95% CI, 88.7% to 95.1%) for cervical swab samples in PreservCyt. The specificity for the detection of C. trachomatis was ≥98.8% for all female sample types. Sensitivity and specificity estimates of Cobas for the detection of C. trachomatis in male urine samples were 100% (96.8% to 100.0%) and 99.7% (95% CI, 99.2% to 99.9%), respectively. The sensitivity of Cobas for the detection of N. gonorrhoeae in female specimens was 94.8% (95% CI, 89.6% to 97.4%) for urine; 100.0% (95% CI, 87.9% to 100.0%) and 100.0% (95% CI, 87.9% to 100.0%) for clinician- and self-collected vaginal swab specimens, respectively; 97.0% (95% CI, 91.5% to 99.0%) for endocervical swabs; and 96.6% (95% CI, 90.6% to 98.8%) for cervical samples in PreservCyt; the specificity for all female sample types was >99.0%. The sensitivity and specificity of Cobas for detecting N. gonorrhoeae in male urine were 100.0% (95% CI, 95.8% to 100.0%) and 99.5% (95% CI, 98.8% to 99.8%), respectively. Fully automated assays help fill the clinical need for a sensitive, high-throughput screening tool to aid public health efforts to control C. trachomatis and N. gonorrhoeae infections.

Emergent genital infection by Leptotrichia trevisanii.

We report the first case of an association between Leptotrichia trevisanii and an episode of pelvic inflammatory disease (PID) and the second case of the isolation of this infection in the cervical canal. A 45-yr-old woman was admitted to our emergency department with clinical and radiological signs and symptoms compatible with an episode of PID. She was hospitalized for intravenous antibiotic control and treatment and the subsequent surgical drainage of abscesses. Cultures were taken throughout the process, but only cultures from cervical canal exudate were positive, with the growth of L. trevisanii species. It appears important to carry out a complete microbiological screening, not limited to conventional agents, on adequate clinical samples to detect possible infectious agents that may be missed in these cases.

Pasteurella multocida multiple intrapelvic abscesses in a young woman with uterine cervical cancer.

Pasteurella multocida, a zoonotic pathogen in humans, is known to be associated with skin and soft tissue infections following animal bites, but rarely causes visceral infections. We report a case of P. multocida-associated multiple intrapelvic abscesses in a young woman with uterine cervical cancer. A 29-year-old unmarried woman was referred to us because of prolonged high fever accompanying abdominal pain with muscular guarding. She had a domestic cat but denied of any bites or scratches before that. Computed tomography demonstrated ascites and multiple abscesses around her uterus. Her condition did not improve with an initial treatment with flomoxef, clindamycin, and azithromycin. Further, we performed percutaneous pus drainage and switched the antimicrobial therapy to a combination of piperacillin/tazobactam and minocycline for 10 days. Although P. multocida was isolated from vaginal culture, no organisms were isolated from the pus culture. However, further investigation with specimen-direct 16S rDNA analysis diagnosed P. multocida as possibly a single pathogen responsible for the intrapelvic infection. After taking oral levofloxacin for two weeks, no recurrence was reported. Although P. multocida is known as an animal-related pathogen, it can transmit to humans without apparent bites or scratches. The present case illustrates that P. multocida can cause intrapelvic abscess as a result of ascending genital infection.

The first reported case of pelvic inflammatory disease caused by Actinobaculum massiliense.

We report the first case of pelvic inflammatory disease (PID) caused by Actinobaculum massiliense. A 53-year-old woman attended the emergency department with symptoms compatible with a PID episode, finally resolved by intramuscular antibiotic treatment. Actinobaculum sp. was isolated by culture, and A. massiliense was confirmed by matrix assisted laser desorption time-of-flight mass spectrometry and 16S rRNA gene sequencing. Only a few cases of A. massiliense infections have been reported, and the pathogenesis of infections by these bacteria is poorly understood. The introduction of new diagnostic methods into hospital routines will improve the detection of new and little-studied pathogens.

Human Papillomavirus (HPV) Prevalence in Male Adolescents 4 Years After HPV-16/18 Vaccination.

We assessed human papillomavirus (HPV) prevalence among HPV-16/18-vaccinated and unvaccinated Finnish male adolescents participating in chlamydia screening 4 years after vaccination with AS04-adjuvanted HPV-16/18 vaccine in 2007-2009. Previously vaccinated (n = 395) or unvaccinated (n = 149) male adolescents were enrolled in 12 municipalities. First-void urine samples were tested for HPV types 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 59, 66, and 68, and prevalence rates for HPV-16/18, and HPV-11/16/18/31/33/45 were reduced profoundly (0% vs 2.1% [P = .02] and 0.8% vs 5.3 [P = .002], respectively). Overall HPV DNA prevalence was also significantly reduced among HPV-16/18-vaccinated (4.1%) compared with unvaccinated subjects (10.1%) (P = .01). In this post hoc study, a highly significant reduction in HPV prevalence 4 years after vaccination suggests that the bivalent HPV-16/18 vaccine has protective efficacy in men.

Chlamydia trachomatis Biovar L2 Infection in Women in South Africa.

We detected Chlamydia trachomatis biovar L2 in vaginal swab specimens of 7 women with vaginal discharge in South Africa. Whole-genome sequencing directly from clinical specimens identified a closely related cluster of strains. The clinical role of this infection in the context of syndromic management should be clarified.

Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: A meta-analysis of randomized controlled trials.

AIMS: To evaluate the effects of different sodium-glucose co-transporter 2 (SGLT2) inhibitors on the risk of urinary tract infections (UTIs) and genital infections in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We systematically searched PubMed, Embase, CENTRAL, and ClinicalTrials.gov from inception to October 9, 2016 to identify randomized controlled trials (RCTs) reporting the occurrence of UTIs and genital infections in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Meta-regression was performed to assess explanatory factors that might influence effect size. RESULTS: A total of 52 RCTs involving 36 689 patients were eligible for our meta-analysis. Canagliflozin, dapagliflozin and empagliflozin were associated with a higher risk of genital infections than placebo, with ORs ranging from 3.21 (95% CI 2.08-4.93) for dapagliflozin 2.5 mg to 5.23 (95% CI 3.86-7.09) for canagliflozin 300 mg. Only dapagliflozin 10 mg led to significantly more UTIs than placebo. The increased risk of UTIs and genital infections seemed to have a dose-response relationship for dapagliflozin only. No factors that had a significant modification effect on these infectious events were detected in meta-regression analysis. CONCLUSIONS: The present study found that canagliflozin, dapagliflozin and empagliflozin were associated with a significantly higher risk of genital infections compared with placebo and other active treatments. Only dapagliflozin had a dose-response relationship with UTIs and genital infections.

Genitourinary infections in diabetic patients in the new era of diabetes therapy with sodium-glucose cotransporter-2 inhibitors.

AIMS: To review prevalence and significance of urinary tract (UTI) and genital infections (GI) in diabetes and the effects of sodium glucose cotransporter 2 (SGLT-2) inhibitors on these complications. DATA SYNTHESIS: The prevalence of asymptomatic bacteriuria (ASB) is 2-3 times higher in diabetic than in non-diabetic women. The treatment of ASB has no impact on the development of UTIs and/or a decline in renal function. Therefore, there is no indication for screening for and/or treatment of ASB. The incidence of UTI is higher and frequently complicated in diabetic patients, particularly in those with longer duration of disease and of older age. There is no consistent evidence of an association between A1c levels, glycosuria and the risk of ASB and/or UTIs. Diabetes is a known risk factor for Candida colonization and GI, and a poor glycemic control is associated with a higher risk. While patients treated with SGLT-2 inhibitors may have a non-significant increased risk of UTI, they have a clearly increased risk of GI; most of these infections are mild, easy to treat, and the rate of recurrence is low. CONCLUSION: Diabetic patients are at high risk of UTIs and of GI. Only GI are associated with poor glycemic control. Although patients treated with SGLT-2 inhibitors have an increased 3-5 fold risk of GI, proper medical education can reduce this risk.

Risk factors in ectopic pregnancy and differences between adults and adolescents, is consanguinity important?

The aim of the study was to determine the risk factors of ectopic pregnancy (EP) and to compare them between women over and under 20 years of age. 308 cases of EP (case group) were compared with 616 cases of normal pregnancy. Smoking [Ad OR =5.7 (CI 95%=2.8-11.6), p < 0.001], previous EP [Ad OR= 11.4 (CI 95%=3-42.4), p = 0.000], previous STD [Ad OR =3.2 (CI 95%=2.1-4.9), p < 0.001], previous use of IUD [Ad OR =4.1 (CI 95%=2.1-8), p < 0.001], history of infertility [Ad OR= 1.8 (CI 95%=1.1-3), p = 0.01], previous caesarean delivery [Ad OR= 1.5 (CI 95%=1.1-2.3), p = 0.03] and consanguinity [Ad OR =2.2 (CI 95%=1.3-3.6), p = 0.002] were considered as risk factors for EP. Prior abortion [p = 0.000], prior STD [p = 0.004], previous caesarean delivery [p = 0.000] and consanguinity [p = 0.04] were more in the >20-year-old group. Negative Rh [p = 0.02], good economic status [p = 0.000] and prior STD [p = 0.03] were more common in Afghan women. However, previous caesarean delivery [p = 0.04] was more in Iranian women. Smoking, previous EP, history of STD, IUD, infertility, previous caesarean delivery and consanguinity are all risk factors for EP.

Tumor Necrosis Factor (TNF) Receptor Superfamily Member 1b on CD8+ T Cells and TNF Receptor Superfamily Member 1a on Non-CD8+ T Cells Contribute Significantly to Upper Genital Tract Pathology Following Chlamydial Infection.

BACKGROUND: We demonstrated previously that tumor necrosis factor α (TNF-α)-producing Chlamydia-specific CD8(+) T cells cause oviduct pathological sequelae. METHODS: In the current study, we used wild-type C57BL/6J (WT) mice with a deficiency in genes encoding TNF receptor superfamily member 1a (TNFR1; TNFR1 knockout [KO] mice), TNF receptor superfamily member 1b (TNFR2; TNFR2 KO mice), and both TNFR1 and TNFR2 (TNFR1/2 double KO [DKO] mice) and mix-match adoptive transfers of CD8(+) T cells to study chlamydial pathogenesis. RESULTS: TNFR1 KO, TNFR2 KO, and TNFR1/2 DKO mice displayed comparable clearance of primary or secondary genital Chlamydia muridarum infection but significantly reduced oviduct pathology, compared with WT animals. The Chlamydia-specific total cellular cytokine response in splenic and draining lymph nodes and the antibody response in serum were comparable between the WT and KO animals. However, CD8(+) T cells from TNFR2 KO mice displayed significantly reduced activation (CD11a expression and cytokine production), compared with TNFR1 KO or WT animals. Repletion of TNFR2 KO mice with WT CD8(+) T cells but not with TNFR2 KO CD8(+) T cells and repletion of TNFR1 KO mice with either WT or TNFR1 KO CD8(+) T cells restored oviduct pathology to WT levels in both KO groups. CONCLUSIONS: Collectively, these results demonstrate that TNFR2-bearing CD8(+) T cells and TNFR1-bearing non-CD8(+) T cells contribute significantly to oviduct pathology following genital chlamydial infection.

Time trends in ophthalmia neonatorum and dacryocystitis of the newborn in England, 2000-2011: database study.

AIMS: To investigate English national trends in ophthalmia neonatorum and dacryocystitis (ON) of the newborn and the completeness of statutory notification of this serious infection. DESIGN: Analysis of hospital episode statistics (HES) from 2000 to 2011. MATERIALS AND METHODS: Using linked HES, numbers of neonates hospitalised with ON were identified from 2000 to 2011. The numbers of hospitalised cases were compared with numbers of statutory notifications for ON published by the Notifications of Infectious Diseases (NOIDS). RESULTS: The national incidence rate of hospitalised cases showed a gradual decline from 464 (95% CI 447 to 482) per 100,000 live births in 2000 to 216 (204 to 228) per 100,000 live births in 2005. It then gradually increased to 471 (455 to 487) per 100,000 live births in 2010, but dropped to 257 (245 to 269) per 100,000 in 2011. From 2000 to 2009, when NOIDS data were available, the NOIDS data showed only 1006 cases compared with 20,505 cases in HES, and thus the notification system captured only about 1 case in 20. CONCLUSIONS: As shown by hospital statistics, there were marked cyclical fluctuations in ON over the study period. The annual figures for ON reported during the study period, under statutory health protection regulations, underestimated the actual occurrence of this disease by a very substantial amount. Linked hospital data should be used routinely to monitor the national incidence of ON.

Herpes simplex virus 2-induced activation in vaginal cells involves Toll-like receptors 2 and 9 and DNA sensors DAI and IFI16.

OBJECTIVE: The pathway by which herpes simplex virus 2 (HSV2) triggers the innate immune system in the urogenital system has not as yet been fully elucidated. In this study, we aimed to determine which pattern recognition receptors (PRRs) recognize HSV2 in primary vaginal epithelial cells. Once we deciphered the receptors involved, we aimed to target them to immunomodulate innate responses as a prophylactic or therapeutic intervention for early HSV2 infection. STUDY DESIGN: To determine which PRRs are involved, receptor silencing as well as confocal microscopy was utilized. For immunomodulation, PRR agonists were utilized to induce a strong, local response to limit the infection, and we used 2 quantitative methods, flow cytometry and plaque assays, to determine their effect on HSV2 replication. RESULTS: Our results show that HSV2 is detected by a plethora of PRRs: Toll-like receptors (TLR) 2 as well as deoxyribonucleic acid (DNA) sensors TLR9, DNA-dependent activator of interferon regulatory factors, and to a lesser extent interferon-inducible 16, which trigger cytokine secretion to protect the host. Using PRR agonists, such as lipoproteins, CpG DNA, and cyclic dinucleotides, we could significantly limit HSV2 replication. CONCLUSION: Different PRRs are strategically placed in different cell locations to detect virus invasion. Use of agonists that target and activate these PRRs appeared to be effective in preventing primary HSV2 infection in vaginal cells and could provide new insights in defense against HSV2 urogenital infections.