Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.
Journal - The New England journal of medicine (United States )
BACKGROUND: A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus (HPV) types 6, 11, 16, and 18. METHODS: In this randomized, placebo-controlled, double-blind trial involving 5455 women between the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1, month 2, and month 6. The coprimary composite end points were the incidence of genital warts, vulvar or vaginal intraepithelial neoplasia, or cancer and the incidence of cervical intraepithelial neoplasia, adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data for the primary analysis were collected for a per-protocol susceptible population of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1 month after administration of the third dose. RESULTS: The women were followed for an average of 3 years after administration of the first dose. In the per-protocol population, those followed for vulvar, vaginal, or perianal disease included 2261 women (83%) in the vaccine group and 2279 (83%) in the placebo group. Those followed for cervical disease included 2241 women (82%) in the vaccine group and 2258 (83%) in the placebo group. Vaccine efficacy was 100% for each of the coprimary end points. In an intention-to-treat analysis, including those with prevalent infection or disease caused by vaccine-type and non-vaccine-type HPV, vaccination reduced the rate of any vulvar or vaginal perianal lesions regardless of the causal HPV type by 34% (95% confidence interval [CI], 15 to 49), and the rate of cervical lesions regardless of the causal HPV type by 20% (95% CI, 8 to 31). CONCLUSIONS: The quadrivalent vaccine significantly reduced the incidence of HPV-associated anogenital diseases in young women. (ClinicalTrials.gov number, NCT00092521 [ClinicalTrials.gov].).Copyright 2007 Massachusetts Medical Society.
|ISSN : ||1533-4406|
|Mesh Heading : ||Adenocarcinoma Adolescent Adult Carcinoma in Situ Condylomata Acuminata DNA, Viral Double-Blind Method Female Follow-Up Studies Genital Neoplasms, Female Humans Papillomavirus Infections prevention & control genetics isolation & purification epidemiology epidemiology blood epidemiology adverse effects|
|Mesh Heading Relevant : ||Alphapapillomavirus Papillomavirus Vaccines prevention & control prevention & control prevention & control prevention & control|
An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women.
Journal - International journal of STD & AIDS (England )
Our objective was to determine the optimal duration of treatment with imiquimod for external genital warts over 4, 8, 12 or 16 weeks. A total of 120 women with a history of genital warts for a median of 3-6 months and prior alternative treatments in 73% were evaluated for total clearance rates. There was no statistically significant difference in complete clearance rates after 16-week follow-up across treatment groups: four weeks (40.0%), eight weeks (48.4%), 12 weeks (39.3%) and 16 weeks (51.6%). Imiquimod was well tolerated, and in those treated for four weeks there was a lower incidence of local skin reactions such as erythema and erosion, and no incidences of pain. These preliminary results suggest that a four-week treatment course of imiquimod applied thrice weekly for women with external genital warts may provide a reasonable approach with comparable efficacy and compliance, and minimal adverse events, drug costs and clinic visits.
|ISSN : ||0956-4624|
|Mesh Heading : ||Administration, Topical Adolescent Adult Aminoquinolines Condylomata Acuminata Female Genital Diseases, Female Humans Interferon Inducers Middle Aged Time Factors Treatment Outcome adverse effects therapeutic use adverse effects therapeutic use|
|Mesh Heading Relevant : ||administration & dosage drug therapy drug therapy administration & dosage|
Human papillomavirus update with a particular focus on cervical disease.
Journal - Pathology (England )
Human papillomavirus (HPV) is a common viral infection of squamous epithelial tissues, but its importance has only recently been recognised by the medical community. HPVs are now realised to consist of many genotypes and are associated with a diverse spectrum of clinical manifestations. Within the genital tract, some diseases have been recognised since antiquity; for example, genital warts which are caused by HPV types distinct from those causing genital cancer. However, others (such as cervical cancer), although recognised centuries ago as linked to sexual activity, have only been associated with oncogenic HPVs relatively recently, with the tools of molecular biology. We now understand that genital HPV infections are the most common sexually transmitted viral infections, are largely transient, asymptomatic and of no consequence. This virus manifests as more than just benign warts. Chronic carriage of with oncogenic genotypes (over years and in a minority of patients), together with other cofactors (host and/or exogenous) in complex pathways not totally understood, result in severe dysplasia or, ultimately, carcinogenesis. As it takes time for precursor lesions to develop and there are effective screening programmes for their detection and treatment, HPV-related neoplastic disease of the cervix is largely a preventable reproductive health issue of women. Yet, on a global scale, cervical cancer is the second most common cancer of women, with the majority of cases occurring in developing countries. Although HPV is noncultivatable by traditional diagnostic virological methods, successfully applied molecular biology techniques have underpinned development of vaccines which are now in phase II/III clinical trials. Successful vaccination ultimately has the greatest potential to impact upon the global burden of disease from genital HPV infection. However, the outcome from reduction in incidence of dysplasia and neoplasia will take years to eventuate; consequently, various cervical cancer prevention strategies still need to be endorsed and maintained in the meantime.
|ISSN : ||0031-3025|
|Mesh Heading : ||Animals Female Humans Papillomaviridae Papillomavirus Infections Tumor Virus Infections Uterine Cervical Neoplasms classification genetics pathology pathology pathology prevention & control|
|Mesh Heading Relevant : ||pathogenicity complications complications virology|
Mechanisms, organisms and markers of infection in pregnancy.
Journal - Journal of reproductive immunology (Ireland )
Premature delivery is still a significant problem in Obstetrics. It has multiple causes, with around 50% thought due to infection. Of note infection as a pathogenesis is more likely in those pre-term births occurring <30 weeks gestation and is largely sub-clinical. Potential pathogens largely arise from the ascending route and from the endogenous vaginal flora, causing chorioamnionitis. Resultant morbidity from the release of endo+/exotoxins from such pathogens, the stimulation and production of inflammatory cytokine pathways, prostaglandins, metalloproteinases includes maternal sepsis (chorioamnionitis, septicaemia, post-partum endometritis), pre-term delivery (infant pre-maturity and its consequences, increased susceptibility to cerebral palsy and neonatal sepsis). As well, infection increases mortality due to fetal loss (extreme pre-maturity) as well as severe neonatal sepsis.
|ISSN : ||0165-0378|
|Mesh Heading : ||Biological Markers Cerebral Palsy Female Humans Infant, Newborn Obstetric Labor, Premature Pregnancy Pregnancy Complications, Infectious Streptococcal Infections Streptococcus agalactiae Trichomonas Vaginitis Vaginosis, Bacterial etiology etiology immunology microbiology prevention & control immunology microbiology complications immunology pathogenicity complications immunology complications immunology|
|Mesh Heading Relevant : ||etiology|
Imiquimod 5% cream is a safe and effective self-applied treatment for anogenital warts--results of an open-label, multicentre Phase IIIB trial.
Journal - International journal of STD & AIDS (England )
Our objective was to determine the efficacy and safety of imiquimod 5% cream in the treatment of external genital/perianal warts in an open-label Phase IIIB trial. Patients applied imiquimod 5% cream 3 times per week, for up to 16 weeks. Those who cleared their warts were monitored during a 6-month follow-up period. If their warts recurred, or new warts developed during this time, patients could be re-treated for up to 16 additional weeks. Patients who experienced partial clearance during the initial treatment period entered an extended treatment period of up to an additional 16 weeks. A total of 943 patients from 114 clinic sites in 20 countries participated in this study. Complete clinical clearance was observed in 451/943 (47.8%) patients (intent-to-treat (ITT) analysis) during the initial treatment period, with clearance in an additional 52 (5.5%) patients during the extended treatment period beyond 16 weeks. The overall clearance rate for the combined treatment periods was 53.3%. In a treatment failure analysis, the overall clearance rate was 65.5%; a greater proportion of female patients (75.5%) experienced complete clearance than male patients (56.9%). Low recurrence rates, of 8.8% and 23.0%, were observed at the end of the 3- and 6-month follow-up periods, respectively. The sustained clearance rates (patients who cleared during treatment and remained clear at the end of the follow-up period) after 3 and 6 months were 41.6% and 33.0% (ITT analysis), respectively. Local erythema occurred in 67% of patients. In the majority of patients local skin reactions were of mild to moderate severity. In conclusion, imiquimod 5% cream is an effective self-applied treatment for external genital/perianal warts when applied for up to 16 weeks and is well tolerated for up to 32 weeks.
|ISSN : ||0956-4624|
|Mesh Heading : ||Adolescent Adult Aged Aminoquinolines Anti-Infective Agents Condylomata Acuminata Consumer Product Safety Demography Female Follow-Up Studies Health Personnel Humans Male Middle Aged Questionnaires Recurrence Self Administration Treatment Outcome Vaginal Creams, Foams, and Jellies administration & dosage adverse effects administration & dosage adverse effects methods|
|Mesh Heading Relevant : ||therapeutic use therapeutic use drug therapy|
Assessment of Chlamydia trachomatis prevalence by PCR and LCR in women presenting for termination of pregnancy.
Journal - Sexually transmitted infections (ENGLAND )
OBJECTIVES: To determine the prevalence of Chlamydia trachomatis in a patient population presenting for legal termination of pregnancy by polymerase chain reaction (PCR) and ligase chain reaction (LCR), from first catch urine and self administered tampons, and comparing with the traditionally collected endocervical swab tested by both PCR and culture. METHODS: Consecutive women attending for legal termination of pregnancy were screened for chlamydia by patient collected first catch urine and tampon, and physician collected endocervical swab. RESULTS: Of 1175 patients with complete samples, there were 33 (2.8%) in whom chlamydia was detected by two or more assays from one or more sample site. Chlamydia was detected equally well by both PCR and LCR in first catch urine (p = 0.25), tampon (p = 0.5), and endocervical swab (p = 0.5). However, both PCR and LCR were significantly better than culture of an endocervical swab (p = 0.0005) for detection of C trachomatis. CONCLUSION: The prevalence of chlamydia in patients presenting for termination of pregnancy was 2.8%. A simple efficient way of performing screening for chlamydia for women presenting for termination of pregnancy is by first catch urine or tampon, which can be tested by the highly sensitive amplification assays, PCR or LCR.
|ISSN : ||1368-4973|
|Mesh Heading : ||Abortion, Legal Chlamydia Infections Chlamydia trachomatis Cohort Studies Female Genital Diseases, Female Humans Ligases Polymerase Chain Reaction Pregnancy Prevalence diagnosis urine metabolism|
|Mesh Heading Relevant : ||diagnosis urine isolation & purification methods|
Is antenatal group B streptococcal carriage a predictor of adverse obstetric outcome?
Journal - Infectious diseases in obstetrics and gynecology (UNITED STATES )
OBJECTIVES: While early-onset neonatal GBS sepsis is positively associated with premature birth and prolonged rupture of membranes, there is debate in the literature as to whether maternal GBS colonization is a predictor of adverse obstetric outcome. This is a critical issue to resolve for appropriate management (expectant vs. interventional management) of the patient presenting with premature rupture of membranes, who has no overt signs of sepsis, but who is colonized with GBS. METHODS: Since 1981 it has been hospital policy to screen all public patients antenatally for genital carriage of GBS by collection of a low vaginal swab at 28-32 weeks. All patients colonized with GBS antenatally are given penicillin as intrapartum chemoprophylaxis. Review of all GBS-colonized antenatal patients for a 12-month period (580 of 4,495 patients) and a randomized (every fourth consecutive antenatal patient) number of noncolonized patients (958) was made. Lower vaginal GBS colonization and other risk factors for preterm delivery were assessed using univariate and multivariate generalized linear modeling. RESULTS: In the study group, the maternal GBS colonization rate was 12.9%. When cofounding variables were controlled in a multivariate analysis, the association between antepartum GBS colonization and preterm labor and preterm rupture of membranes was not significant. CONCLUSION: Maternal antenatal carriage of GBS does not predict preterm labor. Therefore it is appropriate that expectant management occur for a GBS-colonized woman who ruptures her membranes, is not in labor, and has no evidence of sepsis.
|ISSN : ||1064-7449|
|Mesh Heading : ||Australia Female Fetal Membranes, Premature Rupture Forecasting Humans Obstetric Labor, Premature Pregnancy Prenatal Diagnosis Risk Factors Streptococcal Infections Streptococcus agalactiae Vagina microbiology epidemiology epidemiology microbiology|
|Mesh Heading Relevant : ||Carrier State Pregnancy Outcome microbiology microbiology complications isolation & purification|
Do antepartum herpes simplex virus cultures predict intrapartum shedding for pregnant women with recurrent disease?
Journal - Infectious diseases in obstetrics and gynecology (UNITED STATES )
OBJECTIVE: To examine antenatal screening as a predictor of intrapartum shedding of herpes simplex virus (HSV) and to determine its usefulness in guiding the appropriate route of delivery for patients with recurrent HSV in pregnancy. METHODS: A population of 198 pregnant women with a history of recurrent genital HSV were cultured in the last weeks of their pregnancy by specially-trained personnel and intrapartum by their delivering attendants. RESULTS: Of cultures from a total of 906 antenatal visits, 17% were culture positive, with an asymptomatic shedding rate of 3.4%. Asymptomatic shedding occurred in 12.6% of women. Over the 8-week antepartum period, viral culture-positivity rates for each visit ranged from 11% to 19.5%. This provided an expected delivery culture-positivity rate of 15.3%. However, actual intrapartum viral culture positivity occurred in only three of 191 women (1.5%; P < 0.001). Because previous studies have suggested antepartum culture positivity fails to predict intrapartum viral shedding, evaluations, including cultures, as well as predictive values for subsequent culture positivities, were determined under the supervision of an infectious disease specialist. Under these conditions, positive predictive values were 59% when the interval between visits was 2 days, but only 19% when days between visits were >2 (P < 0.0001). No cases of neonatal herpes were seen in this population, although cesarean deliveries were performed in 31% of the patient population, with genital herpes as the indication for 56% of those. CONCLUSIONS: Antepartum serial screening by viral culture is not predictive of an infant's risk of intrapartum viral exposure when conducted at weekly intervals. However, more frequent assessments of patients can be predictive of an infant's exposure risk to HSV; for patients with frequent recurrent disease near term or primary infection in pregnancy, frequent late antepartum screening may be appropriate.
|ISSN : ||1064-7449|
|Mesh Heading : ||Adolescent Adult Antibodies, Viral Colony Count, Microbial Female Herpes Genitalis Humans Infant, Newborn Infant, Newborn, Diseases Infectious Disease Transmission, Vertical Mass Screening Predictive Value of Tests Pregnancy Pregnancy Complications, Infectious Prenatal Care Recurrence Risk Assessment Simplexvirus diagnosis prevention & control virology virology immunology|
|Mesh Heading Relevant : ||Virus Shedding analysis diagnosis transmission prevention & control methods diagnosis isolation & purification|
External Quality Assessment Program for Chlamydia trachomatis Diagnostic Testing by Nucleic Acid Amplification Assays
Journal - Journal of Clinical Microbiology
We report the results from 57 Australian diagnostic laboratories testing two external quality assessment panels using either the Roche Amplicor Chlamydia trachomatis test (R-PCR) or the Abbott LCx Chlamydia trachomatis assay (A-ligase chain reaction [LCR]). Panel samples were either normal urine spiked with Chlamydia trachomatis antigen or clinical urine specimens. There was no significant difference between laboratories or between assays in detection of C. trachomatis-positive clinical samples. Only at the lower limit of detection of the assays did the R-PCR demonstrate increased sensitivity over the A-LCR in the detection of C. trachomatis antigen. However, it was found that single-sample testing could lead to decreased test sensitivity. Detection of the presence of inhibitors of nucleic acid amplification differed between laboratories.