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Background Community-acquired pneumonia (CAP) is a major cause of mortality and morbidity in many countries but few recent large-scale studies have examined trends in its incidence. Methods Incidence of CAP leading to hospitalisation in one UK region (Oxfordshire) was calculated over calendar time using routinely collected diagnostic codes, and modelled using piecewise-linear Poisson regression. Further models considered other related diagnoses, typical administrative outcomes, and blood and microbiology test results at admission to determine whether CAP trends could be explained by changes in case-mix, coding practices or admission procedures. Results CAP increased by 4.2%/year (95% CI 3.6 to 4.8) from 1998 to 2008, and subsequently much faster at 8.8%/year (95% CI 7.8 to 9.7) from 2009 to 2014. Pneumonia-related conditions also increased significantly over this period. Length of stay and 30-day mortality decreased slightly in later years, but the proportions with abnormal neutrophils, urea and C reactive protein (CRP) did not change (p>0.2). The proportion with severely abnormal CRP (>100 mg/L) decreased slightly in later years. Trends were similar in all age groups. Streptococcus pneumoniae was the most common causative organism found; however other organisms, particularly Enterobacteriaceae , increased in incidence over the study period (p Conclusions Hospitalisations for CAP have been increasing rapidly in Oxfordshire, particularly since 2008. There is little evidence that this is due only to changes in pneumonia coding, an ageing population or patients with substantially less severe disease being admitted more frequently. Healthcare planning to address potential further increases in admissions and consequent antibiotic prescribing should be a priority.

Trichomonas vaginalis (TV) rates in women are increasing and many are asymptomatic. Nucleic acid amplification tests (NAATs) are becoming the ‘gold standard’ for diagnosis. We aimed to establish our asymptomatic TV rates by testing all women attending Oxfordshire’s Sexual Health service, regardless of symptoms, using the BD ProbeTec™ TV Qx NAATs (BDQx). During BDQx’s verification process, the sensitivity and specificity were calculated using results of 220 endocervical samples from symptomatic women, compared with culture. BDQx was subsequently implemented and prospectively evaluated over 6 months in female attendees. Wet mount microscopy was also performed in symptomatics. Demographic and clinical characteristics of those diagnosed were analysed. From 220 samples tested by BDQx and culture: 5 were positive on both and one solely using BDQx, giving a sensitivity and specificity of 100% and 99.53%, respectively. In the prospective cohort, of 5775 BDQx tests, 33 (0.57%) were positive. 11/33 (33%) patients were asymptomatic. All patients diagnosed had risk factors: age >25 years (85%), residence in a deprived area (79%) and black ethnicity (21%). Despite BDQx being highly sensitive and specific, with our low TV prevalence universal screening may not be justified. Targeted screening using local demographic data merits further investigation.

Trichomonas vaginalis (TV) rates in women are increasing and many are asymptomatic. Nucleic acid amplification tests (NAATs) are becoming the 'gold standard' for diagnosis. We aimed to establish our asymptomatic TV rates by testing all women attending Oxfordshire's Sexual Health service, regardless of symptoms, using the BD ProbeTec™ TV Q

Canonically, immunoglobulin E (IgE) mediates allergic immune responses by triggering mast cells and basophils to release histamine and type 2 helper cytokines. Here we found that in human systemic lupus erythematosus (SLE), IgE antibodies specific for double-stranded DNA (dsDNA) activated plasmacytoid dendritic cells (pDCs), a type of cell of the immune system linked to viral defense, which led to the secretion of substantial amounts of interferon-α (IFN-α). The concentration of dsDNA-specific IgE found in patient serum correlated with disease severity and greatly potentiated pDC function by triggering phagocytosis via the high-affinity FcɛRI receptor for IgE, followed by Toll-like receptor 9 (TLR9)-mediated sensing of DNA in phagosomes. Our findings expand the known pathogenic mechanisms of IgE-mediated inflammation beyond those found in allergy and demonstrate that IgE can trigger interferon responses capable of exacerbating self-destructive autoimmune responses.

Objective: Our purpose was to ascertain the prevalence, incidence, and predictors of gynecologic disorders among women infected with human immunodeficiency virus. Study Design: We serially assessed 292 women infected with human immunodeficiency virus and 681 uninfected women. Outcomes were incidence and prevalence of sexually transmitted diseases, viral shedding, findings of Papanicolaou smears, fungal infections, and menstrual disorders. Results: Women infected with the virus were more likely to have prevalent vulvovaginal candidiasis (odds ratio 1.80, 95% confidence interval 1.0-3.25, P = .05), oncogenic human papillomavirus (odds ratio 3.79, 95% confidence interval 2.43-5.91, P = .001), abnormal Papanicolaou smears (odds ratio 5.40, 95% confidence interval 3.35-8.78, P = .001), amenorrhea (4.8% vs 0%, P = .05), positive results on Treponema pallidum hemagglutination assay (odds ratio 1.83, 95% confidence interval 1.16-2.88, P = .01), infection with cytomegalovirus (odds ratio 4.2, 95% confidence interval 1.82-10.62, P = .001), and genital warts (odds ratio 6.93, 95% confidence interval 3.16-16.30, P = .001) but were less likely to have Chlamydia trachomatis infection (odds ratio 0.28, 95% confidence interval 0.10-0.66, P = .01). Annual incidence rates among women infected with human immunodeficiency virus were 4.0% for candidiasis, 22.0% for oncogenic human papillomavirus, 11.4% for genital warts, 1.7% for infection with C trachomatis , 1.7% for infection with Neisseria gonorrhoeae , 10.3% for Trichomonas vaginalis , 1.1% for positive results on T pallidum hemagglutination assay, 7.4% for an abnormal Papanicolaou smear, and 10.9% for infection with herpes simplex virus. Overall, 46.9% had at least 1 incident condition. Women infected with human immunodeficiency virus were more likely to have incident oncogenic human papillomavirus infection (odds ratio 2.0, 95% confidence interval 1.01-3.8), abnormal Papanicolaou smears (odds ratio 7.76, 95% confidence interval 2.08-42.8), and genital warts (odds ratio 9.32, 95% confidence interval 3.04-38.0). Incidence and prevalence of sexually transmitted diseases and oncogenic human papillomavirus infection increased with increased CD4 + cell counts. Conclusions: Women infected with the human immunodeficiency virus are significantly more likely to have prevalent and incident gynecologic disorders but not disorders related to risk taking (eg, incident sexually transmitted diseases). The latter disorders increased in women with CD4 + cell counts >500 cells/mm 3 . Clinicians should be aware of these patterns so that they can provide appropriate evaluation and treatment of gynecologic disorders. (Am J Obstet Gynecol 1999;180:824-36.)

Objective: To investigate the effect of human immunodeficiency virus (HIV) infection on vaginal yeast colonization and symptomatic vulvovaginitis and to explore the effects of immune compromise on these conditions in HIV-positive women. Methods: Between September 1991 and May 1993, 223 HIV-positive women without AIDS-defining conditions were enrolled for prospective follow-up and compared with 289 HIV-negative women enrolled in a concurrent study. Standardized gynecologic assessment was carried out. Results: Cultures from 81 of 223 (36%) HIV-positive women and 72 of 289 (25%) HIV-negative women were positive for any yeast. The most commonly isolated yeasts were Candida albicans and Torulopsis glabrata ; the proportion of non- C albicans isolates (26%) did not differ by serostatus. The rates of C albicans colonization and vulvovaginitis among immunocompetent (CD4 count at least 500 cells/mm 3 ) HIV-positive women did not differ from those among HIV-negative women. Among HIV-positive women, risks for colonization and for symptomatic vulvovaginitis were increased approximately threefold and fourfold, respectively, in women with CD4 counts below 200 cells/mm 3 compared with either immunocompetent HIVpositive women or HIV-negative women. Conclusion: The yeast species isolated from HIV-positive and HIV-negative women were similar. Rates of vaginal colonization and vaginitis were similar among nonimmunocompromised HIV-positive women and HIV-negative women. Elevated rates of yeast colonization and vaginitis were not seen among this population of HIV-infected women before immune compromise. Both vaginal colonization and symptomatic vaginitis increased with immune compromise among HIV-positive women, especially at CD4 counts below 200 cells/mm 3 .

Background The discovery of Immunoglobulin E (IgE) nearly 40 years ago was a breakthrough in the field of allergy research. IgE directed against parasitic worms and allergens binds mast cells and basophils, triggering an inflammatory response that is characterized by the release of histamine and Th2 cytokines. Here we report that double-stranded DNA (dsDNA)-specific IgE autoantibodies complexed to DNA activate plasmacytoid dendritic cells (pDC), an immune cell type linked to viral defense, leading to the secretion of substantial amounts of IFN-a. Although typical IgE mediated responses are not a hallmark of systemic lupus erythematosus (SLE), IFN-a producing pDCs are a key driver for loss of immune tolerance to host DNA in SLE. We, therefore, investigated this apparent paradox and found that even the small concentrations of circulating dsDNA-specific IgE found in SLE patients greatly potentiated pDC secretion of IFN-a by triggering phagocytosis via the Fc-epsilon receptor I (FceRI) and TLR9-mediated DNA sensing in the phagolysosome. Consequently, this potent pDC signaling mechanism reduces the threshold of pDC activation, which has the potential to expand anti-DNA responses and greatly exacerbate self-inflicted damage. These findings expand the known pathogenic mechanisms of IgE mediated inflammation beyond those found in allergies and demonstrate that, in addition to recognizing exogenous allergens, IgE can also bind to autoantigens and drive an aberrant and self-destructive anti-viral response. This previously unrecognized link between IgE and the interferon pathway provides additional insights into the pathological mechanisms underlying autoimmunity and may be useful in the rational design of therapies for the treatment of diseases such as SLE. Disclosure of Interest M. Sanjuan Employee of: Medimmune, J. Henault Employee of: Medimmune, J. Riggs Employee of: Medimmune, J. Karnell Employee of: Medimmune, V. Liarski: None declared, L. Shirinian Employee of: Medimmune, L. Xu Employee of: Medimmune, K. Casey Employee of: Medimmune, M. Smith Employee of: Medimmune, D. Khatry Employee of: Medimmune, L. Clarke Employee of: Medimmune, R. Herbst Employee of: Medimmune, R. Ettinger Employee of: Medimmune, M. Petri: None declared, M. Clark: None declared, T. Mustelin Employee of: Medimmune, R. Kolbeck Employee of: Medimmune

SummaryToll-like receptor-9 (TLR9) is largely responsible for discriminating self from pathogenic DNA. However, association of host DNA with autoantibodies activates TLR9, inducing the pathogenic secretion of type I interferons (IFNs) from plasmacytoid dendritic cells (pDCs). Here, we found that in response to DNA-containing immune complexes (DNA-IC), but not to soluble ligands, IFN-α production depended upon the convergence of the phagocytic and autophagic pathways, a process called microtubule-associated protein 1A/1B-light chain 3 (LC3)-associated phagocytosis (LAP). LAP was required for TLR9 trafficking into a specialized interferon signaling compartment by a mechanism that involved autophagy-related proteins, but not the conventional autophagic preinitiation complex, or adaptor protein-3 (AP-3). Our findings unveil a new role for nonconventional autophagy in inflammation and provide one mechanism by which anti-DNA autoantibodies, such as those found in several autoimmune disorders, bypass the controls that normally restrict the apportionment of pathogenic DNA and TLR9 to the interferon signaling compartment.

Regardless of the nontreponemal test used for the screening and diagnosis of syphilis, biological false-positive results (BFPs) are documented in 1%-2% of all cases. An association between BFPs and human immunodeficiency virus (HIV) infection in men has been suggested. We conducted a cohort study to determine whether a similar association between HIV seropositivity and BFPs exists for women. Among 156 HIV-seropositive women, 9 (5.8%) had a BFP for syphilis. Among 633 HIV-seronegative women, only 1 (0.2%) had a BFP. When the 25 HIV-seropositive patients and 55 HIV-seronegative patients with reactive rapid plasma reagin tests and microhemagglutination assays for antibodies to Treponema pallidum were excluded from the calculations, 6.9% and 0.2% of HIV-seropositive and HIV-seronegative women, respectively, had BFPs (P < .001; odds ratio, 39.45; 95% confidence interval, 6.4-879.0). An association was found between injection drug use and BFPs for the population of HIV-infected women but did not entirely account for the differences between this group and the HIV-seronegative group.

Culture is currently considered the "gold standard" for detecting Chlamydia trachomatis infections. We evaluated the Syva MicroTrak enzyme immunoassay (EIA) and Gen-Probe PACE 2 tests, which detect chlamydial antigens and rRNA, respectively. These assays were compared with each other and with culture for the detection of C. trachomatis in cervical specimens obtained from 217 women attending a clinic for sexually transmitted diseases. The prevalence of infection was 22.1% by culture. The sensitivity, specificity, and positive and negative predictive values were 79.2, 98.2, 92.6, and 94.3%, respectively, for EIA. For PACE 2, the respective values were 77.1, 97.6, 90.1, and 93.7%. After corrections for two false-negative cultures, the sensitivities and specificities were 80 and 99.4%, respectively, for the EIA and 78 and 98.8%, respectively, for the probe assay. Quantitative evaluation of the results showed that false-negative results with either assay were associated with cultures that had low inclusion counts or were negative without subpassage. Analysis of nonculture results revealed that 2.3% of the EIA results and 4.6% of the probe assay results were within +/- 30% of the respective assay cutoff values. These included four false-negative (one EIA and three probe) and two false-positive (one EIA and one probe) results. The Syva MicroTrak EIA and the Gen-Probe PACE 2 assay are comparable to but significantly less sensitive than culture. Use of a grey zone may help identify the need for repeat or confirmatory testing.

misses an important point regarding the potential of nutritional interventions to prevent pre-eclampsia.Steegers and colleagues state that an evidence-based review found no relation between calcium supple-mentation and risk reduction for pre-eclampsia, but that some reduction might be seen in populations that are calcium defi cient. The review cited was a US Food and Drug Administration (FDA) assessment

The recovery of cytomegalovirus from bronchoalveolar lavage (BAL) specimens was compared after inoculation of MRC-5 tube and shell vial cell cultures with four different BAL preparations. Analysis of culture results obtained with 55 cytomegalovirus culture-positive samples showed significant differences in the ability to isolate virus from the supernatant and cellular components of these specimens. There was a 52% reduction in cytomegalovirus recovery and a significant delay in the development of cytopathic effect in cultures inoculated with the cellular component of BAL specimens when compared to cultures inoculated with crude BAL cells and fluid. The mean time for detection of cytopathic effect was 11.8 days in tubes inoculated with crude BAL and 18.2 days for tubes inoculated with BAL cells. A similar effect was observed using a rapid shell vial culture technique. A 39% reduction in the number of isolates and a 57% reduction in the number of positive cells were observed in vials inoculated with cells when compared to cultures inoculated with crude BAL. By contrast, using cell-free BAL supernatant as inoculum did not reduce the number of positive cultures or delay development of cytopathic effect. The results suggest that in most BAL specimens, cytomegalovirus is associated with the cell-free, rather than the cellular, component. Although BAL cell concentrates frequently are used for cultivation of viruses from BAL, our results showed that the use of these preparations results in a significant number of false-negative cytomegalovirus cultures.

TLR9 compartmentalization is largely responsible for discriminating self from pathogenic DNA. However, association of host DNA with autoantibodies activates TLR9, inducing the secretion of large amounts of type I IFNs in plasmacytoid dendritic cells. Here, we show that TLR9-mediated production of IFN-α depends on the convergence of the phagocytic and autophagic pathways in response to DNA-containing immune complexes, a process called LC3-associated phagocytosis (LAP). LAP is required for TLR9 trafficking into a specialized IRF7-signaling compartment (ISC) by a mechanism that involves ATG7 but not the conventional autophagic pre-initiation complex. Progression to this compartment did not require AP-3, a protein that mediates TLR9 trafficking and IFN-α secretion in response to CpG oligonucleotides. Our findings unveil a new role for autophagy in inflammatory responses, and provide one of the mechanisms by which anti-DNA autoantibodies, such as those found in several autoimmune disorders, bypass the controls that normally restrict TLR9 activation to pathogenic DNA. Further, we have established phagosomal enrichment assays that will allow us to characterize precise nature ISC as well as the role of LAP in ISC regulation .

A 19-year-old woman with well-documented HIV-1 infection had persistently negative enzyme immunoassay (EIA) and Western blot serological tests. She has plasma HIV-1 RNA levels of480,000 copies/mL and T-helper cell counts of approximately 100/mm3. When treated with highly active antiretroviral therapy (HAART), the viral load became undetectable (400 copies/mL), the T-helper cell count increased to500/mm3 and EIA and Western blot tests became positive.

Lower genital tract specimens and endometrial biopsies from 147 women with pelvic inflammatory disease (PID) and surgical specimens (fallopian tubes, ovaries, or both) from 22 women with PID and 37 women without PID were cultured for cytomegalovirus (CMV) and herpes simplex virus (HSV), as well as for organisms commonly associated with PID. CMV was isolated from 39 cervical or endometrial samples from 30 (20.4%) of 147 women with PID and from ovaries or fallopian tubes from 5 (22.7%) of 22 women with PID, but CMV was not recovered from surgical specimens obtained from 37 women undergoing surgery for tubal ligation, ectopic pregnancy, or other gynecologic conditions (P = .005). HSV was isolated from cervical samples obtained from 5 (3.4%) of 147 women with PID but not from any endometrial or surgical specimens. These data suggest that CMV, but not HSV, may contribute to the pathogenesis of PID in some patients.

Cytomegalovirus (CMV) seroprevalence and genital tract shedding in human immunodeficiency virus (HIV)-seronegative and HIV-seropositive women from an urban minority community were investigated. CMV seropositivity was high in both groups : 181(95.2%) of 190 HIV-negative and 158 (90.3%) of 175 HIV-positive subjects. Cervicovaginal shedding was detected in 8 (4.4%) CMV-positive HIV-negative subjects and 31 (19.6%) HIV-positive subjects (odds ratio [OR], 5.28 ; P < .001). Multiple logistic regression analysis revealed that CMV shedding was independently associated with younger age (OR = 0.90 ; P

Background : Trichomonas vaginalis is a common sexually transmitted pathogen that has been linked to upper genital tract bacterial disease. Its association with upper tract chlamydial disease has not been assessed. Goal of this Study : This study was undertaken to determine whether women colonized with Chlamydia trachomatis who are also infected with Trichomonas vaginalis are at increased risk for having pelvic inflammatory disease. Study Design : A nested case control methodology was used to compare Trichomonas vaginalis rates between women colonized with Chlamydia trachomatis who had pelvic inflammatory disease (n = 24) and those who were colonized but did not have pelvic inflammatory disease (n = 47). Factors that might be related to the development of upper tract disease (e.g., douching, other sexually transmitted diseases) and factors linked to colonization with Trichomonas vaginalis (e.g. race, use of oral contraceptives) were assessed. Results : When exact logistic regression models were used and variables associated with pelvic inflammatory disease were considered, it was found that age (odds ratio = 0.73 ; P =.001) and Trichomonas vaginalis colonization (odds ratio = 4.72 ; P =.053) were significant. Conclusions : In this preliminary study of women colonized with Chlamydia trachomatis, an association was found between co-infection with Trichomonas vaginalis and evidence of upper tract disease.

The prevalence of untreated sexually transmitted diseases (STDs) was assessed in a cohort of 372 sexually active inner-city women (92% black, 49% US-born) with no history of injection drug use who were recruited in Brooklyn, New York, in 1990 and 1991. The presence of STDs was assessed via culture, serologic analyses, and medical history. Sexual and drug-use histories were obtained, as was a urine sample for toxicologic analysis. Thirty-five percent of the women had at least one STD (27% Trichomonas vaginalis, 6.8% Chlamydia trachomatis, 5.2% syphilis, 2.4% human immunodeficiency virus (HIV), and 1.4% Neisseria gonorrhoeae). US-born women were more likely than foreign-born (96% Caribbean) women to have an STD (50% vs. 22%; p < 0.001). Among US-born women, 61% of crack and/or cocaine users had an STD as opposed to 34% of non-users (OR = 2.9, 95% CI 1.6-5.5). Recent crack cocaine use was the strongest predictor of syphilis infection (OR = 12.8, p = 0.019), and was reported by each of the seven HIV-positive women. This study, based on a large sample with laboratory confirmation of both STDs and drug use, documents that women who use crack cocaine are at substantially higher risk of contracting an STD than other women. STD/HIV prevention programs in inner cities should target US-born women, particularly crack cocaine users.

Objective The aim of our study was to determine the prevalence of human immunodeficiency virus-1 (HIV-1) in an infertile population. Design The study design included a retrospective anonymous survey of clinical data and screening for HIV-1 antibody by enzyme-linked immunoabsorbent assay (ELISA) in stored sera. Samples that were ELISA-positive were further tested by Western blot assay. Frequency distributions were analyzed by Fisher's exact test. Setting University tertiary care center. Participants Based on availability of stored frozen sera, the total study population included 182 of 304 consecutively registered infertile couples. Results Seventy-five percent of the study population were found to have one or more risk factors for HIV infection. Of the 252 sera tested, 10 were repeatedly reactive by ELISA, and Western blot testing confirmed HIV-1 infection in one woman and two men. Conclusions This relatively high HIV-1 seroprevalence (male: 2.6%; female: 0.6%) in a low-middle class infertile population emphasizes the urgent need to implement on-site HIV-infection counseling aimed at preventing the spread of disease to the healthy partner and fetus and to discuss therapeutic and reproductive options.

To compare the prevalence of genital herpes simplex virus type 2 (HSV-2) shedding in human immunodeficiency virus (HIV)-seropositive women and HIV-seronegative women.Cross-sectional study.A major inner-city medical center.106 women who were HIV-seropositive and HSV-2-seropositive and 70 women who were HIV-seronegative and HSV-2-seropositive were enrolled from various primary care settings.Herpes simplex virus type 2 antibody determinations were done for all patients. Regardless of symptoms, vulvar and cervical HSV cultures were obtained from all HIV-seropositive women and from a randomly selected subgroup of HIV-seronegative women.The prevalence of HSV-2 shedding was nearly four times greater in HIV-seropositive than in HIV-seronegative women (13.2% compared with 3.6%; P = 0.04; odds ratio, 4.1 [95% CI, 1.0 to 27.4]) when the serum antibody for HSV-2 was present. Seventy-nine percent of viral shedding among HIV-seropositive women was asymptomatic. Overall viral shedding increased significantly as the CD4 cell count decreased.Women with HIV infection, particularly those with low CD4 cell counts, shed HSV-2 from the vulva and cervix more commonly than women not infected with HIV. Most of this shedding is asymptomatic.

Two hundred seventy nasopharyngeal aspirates were tested in duplicate with the Ortho Diagnostics, Inc. (Raritan, N.J.), respiratory syncytial virus antigen enzyme-linked immunosorbent assay. The test was sensitive (80 to 82%) and specific (96%) when compared with cell culture. The enzyme-linked immunosorbent assay detected seven antigen-positive specimens not among the 71 specimens that were positive for respiratory syncytial virus in cell culture. A blocking test confirmed those specimens as true positives (specificity, 100%).

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children. Rapid identification of RSV infections would allow for specific chemotherapy. We evaluated a means of rapid diagnosis, the Abbott enzyme immunoassay (EIA), by using 314 stored nasopharyngeal aspirates. RSV antigens were identified in 62 of 66 RSV culture-positive specimens. An additional 37 specimens from which RSV was not isolated were positive in the EIA. Of these, 29 were confirmed as truly positive by a blocking assay, for a total of 95 (66 + 29) positive specimens. The sensitivity of the EIA for total positive samples was 96% (91/95) versus 69% (66/95) for cell culture. The specificity of the EIA was 96% (211/219). In these stored specimens, Abbott EIA was superior to cell culture for the detection of RSV.

Immediate inoculation of HEp-2 cells is generally advocated for the isolation of respiratory syncytial virus. However, delayed laboratory inoculation of properly transported specimens obtained by aspiration of nasopharyngeal mucus provided an isolation rate similar to that obtained with immediate inoculation.