Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women

Little is known about the dynamics of human papillomavirus (HPV) infection and subsequent development of high-grade cervical intraepithelial neoplasia (CIN2/3), particularly in women >30 years of age. This information is needed to assess the impact of HPV vaccines and consider new screening strategies. A cohort of 1728 women 15–85 years old with normal cytology at baseline was followed every 6 months for an average of 9 years. Women with squamous intraepithelial lesions were referred for biopsy and treatment. The Kaplan–Meier method was used to estimate the median duration of infection and Cox regression analysis was undertaken to assess determinants of clearance and risk of CIN2/3 associated with HPV persistence. No difference in the likelihood of clearance was observed by HPV type or woman's age, with the exception of lower clearance for HPV16 infection in women under 30 years of age. Viral load was inversely associated with clearance. In conclusion, viral load is the main determinant of persistence, and persistence of HPV16 infections carry a higher risk of CIN2/3

Human papillomavirus infection and use of oral contraceptives

Human papillomavirus (HPV) infection is thought to be a necessary but not sufficient cause of most cases of cervical cancer. Since oral contraceptive use for long durations is associated with an increased risk of cervical cancer, it is important to know whether HPV infection is more common in oral contraceptive users. We present a systematic review of 19 epidemiological studies of the risk of genital HPV infection and oral contraceptive use. There was no evidence for a strong positive or negative association between HPV positivity and ever use or long duration use of oral contraceptives. The limited data available, the presence of heterogeneity between studies and the possibility of bias and confounding mean, however, that these results must be interpreted cautiously. Further studies are needed to confirm these findings and to investigate possible relations between oral contraceptive use and the persistence and detectability of cervical HPV infection

Human papillomavirus infection in honduran women with normal cytology

Contains fulltext : 80440.pdf (publisher's version ) (Closed access)OBJECTIVE: This study was aimed at estimating type-specific HPV prevalence and its cofactors among Honduran women with normal cytology in order to provide valuable information to health policymakers about the epidemiology of this important sexually transmitted infection. METHODS: A total of 591 women with normal cytology from Tegucigalpa, Honduras were interviewed and tested for HPV using the SPF10 LiPA25. A structured epidemiological questionnaire was administered to each woman. RESULTS: The overall HPV prevalence was 51%. Twenty-three types of HPV were detected; HPV 16, 51, 31, 18, and 11 were the most common. The highest prevalence of cancer associated HPV types (15.0%) was found in the women less than 35 years. Besides the association with age, the main independent predictors of HPV infection were the lifetime number of sexual partners and having a low socioeconomic status and less than 5 previous Pap smears. CONCLUSIONS: In the population studied, there was a broad diversity of HPV infections, with high-risk types being the most common types detected. The establishment of a well-characterized population with regard to the community prevalence of type-specific HPV infection will provide a valuable baseline for monitoring population effectiveness of an HPV vaccine

Seroprevalence of 34 Human Papillomavirus Types in the German General Population

The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age- and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life

Supervivencia del fármaco a largo plazo y causas de interrupción del abatacept subcutáneo en la artritis reumatoide: resultados a 32 meses de un estudio de cohorte prospectivo

Background Survival time or time to discontinuation of medication is a surrogate of the long-term impact on the course of disease in real life. It reflects clinical effectiveness in the absence of significant adverse events [1]. Treatment discontinuation can result from loss of efficacy or safety concerns, but prognostic factors for patient retention have not been explored thoroughly despite data for abatacept and other biologics being available from national registries [2]. Objectives To assess drug survival of subcutaneous (SC) abatacept among patients with rheumatoid arthritis (RA) according to treatment background. Methods This was a prospective study in which well-characterized patients with RA (by 1987 ACR criteria) were assessed from April 2014 to December 2016. Each patient was evaluated by a rheumatologist in a single rheumatology outpatient private center in Bogotá, Colombia. Patients were stratified by treatment background: (n=54) biologic-naïve, (n=24) switched from IV to SC abatacept administration, and (n=51) inadequate response to at least 1 biologic disease-modifying antirheumatic drug. The Mantel-Haenszel test was used to test if there were any differences in the survival curves among groups. The test was performed by the survdiff function of the “survival” R package [3]. Results A total of 129 patients were included. Baseline characteristics of patients were as follows: female gender 86%, mean age 52±13 years, median disease duration 10 (IQR 11) years, Rheumatoid Factor positive 94%, Anti-Cyclic Citrullinated Peptide Antibodies 89%, and erosive phenotype 35%. At baseline, mean DAS28 and RAPID3 were 5.4±1.3 and 16.6±6.8, respectively. SC abatacept monotherapy was reported in 27%. Demographics and disease characteristics were similar in all groups, except for baseline DAS28 and RAPID3 in switch group (p<0.0001). According to the Mantel-Haenszel test (Fig.1), there were not significant differences between survival curves (p=0.158). Forty-three patients (33%) discontinued treatment. The most frequent reasons for drug suspension were loss of efficacy in 25%, insurance-related problems (i.e., access to medication/specialist) and adverse drug reactions in 16%. Other causes include lack of efficacy, surgeries (i.e., articular replacement), patient preference, and pregnancy

Supervivencia del fármaco a largo plazo y causas de interrupción del abatacept subcutáneo en la artritis reumatoide: resultados a 32 meses de un estudio de cohorte prospectivo

Background Survival time or time to discontinuation of medication is a surrogate of the long-term impact on the course of disease in real life. It reflects clinical effectiveness in the absence of significant adverse events [1]. Treatment discontinuation can result from loss of efficacy or safety concerns, but prognostic factors for patient retention have not been explored thoroughly despite data for abatacept and other biologics being available from national registries [2]. Objectives To assess drug survival of subcutaneous (SC) abatacept among patients with rheumatoid arthritis (RA) according to treatment background. Methods This was a prospective study in which well-characterized patients with RA (by 1987 ACR criteria) were assessed from April 2014 to December 2016. Each patient was evaluated by a rheumatologist in a single rheumatology outpatient private center in Bogotá, Colombia. Patients were stratified by treatment background: (n=54) biologic-naïve, (n=24) switched from IV to SC abatacept administration, and (n=51) inadequate response to at least 1 biologic disease-modifying antirheumatic drug. The Mantel-Haenszel test was used to test if there were any differences in the survival curves among groups. The test was performed by the survdiff function of the “survival” R package [3]. Results A total of 129 patients were included. Baseline characteristics of patients were as follows: female gender 86%, mean age 52±13 years, median disease duration 10 (IQR 11) years, Rheumatoid Factor positive 94%, Anti-Cyclic Citrullinated Peptide Antibodies 89%, and erosive phenotype 35%. At baseline, mean DAS28 and RAPID3 were 5.4±1.3 and 16.6±6.8, respectively. SC abatacept monotherapy was reported in 27%. Demographics and disease characteristics were similar in all groups, except for baseline DAS28 and RAPID3 in switch group (p<0.0001). According to the Mantel-Haenszel test (Fig.1), there were not significant differences between survival curves (p=0.158). Forty-three patients (33%) discontinued treatment. The most frequent reasons for drug suspension were loss of efficacy in 25%, insurance-related problems (i.e., access to medication/specialist) and adverse drug reactions in 16%. Other causes include lack of efficacy, surgeries (i.e., articular replacement), patient preference, and pregnancy

Cellular Composition and Fractional β-Cell Viability Assay Protocol at the Diabetes Research Institute – University of Miami

Cell Transplant Center Diabetes Research Institute University of Miami School of Medicine th 1450 NW 10 Avenue (R134) Miami, FL 33136 SOP: Cellular Composition and Fractional β-Cell Viability Assay Page 1 of 12 Original Version: 05/2005 Updated Version: 07/2014 CellR4 2014; 2 (4): e1121 – www.cellr4.org – ISSN: 2329-7042 Original Version: 05/2005 Attachments: N/A Cellular Composition and Fractional β-Cell Viability Assay PURPOSE: To outline the procedure for assessment of cellular composition and fractional beta cell viability for purified islets of Langerhans