ORCID Profile
0000-0003-2459-0511
Current Organisations
Aarhus University
,
Aarhus University Hospital
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Publisher: Oxford University Press (OUP)
Date: 03-02-2014
Abstract: Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of 25(OH)D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma s les during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH)D levels and immunological/inflammatory markers. In sum, 250 patients were included. Median time between first and last s le and last s le and event was 44.6(interquartile range [IQR]: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval [CI], 2.0-70.0, P = .04) for a 2-fold increase in latest 25(OH)D level. There was no association between 25(OH)D and the occurrence of AIDS or non-AIDS-defining events (P > .05). In patients with current 25(OH)D <10 ng/mL, hsIL-6 concentration increased by 4.7%(95% CI, .2,9.4, P = .04) annually after adjustment for immunological/inflammatory markers, and no change in hsCRP rate was observed (P = .76). Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of vitamin D supplementation on inflammation and patient outcomes should be investigated.
Publisher: BMJ
Date: 10-1994
DOI: 10.1136/STI.70.5.300
Abstract: To evaluate the diagnostic efficacy of chlamydia culture, direct immunofluorescence (DFA), direct enzyme immunoassay (EIA), polymerase chain reaction (PCR) and serology by defining positive culture or at least two positive non-culture tests as true positive. Three gynaecological departments located in separate areas of Sweden. All pregnant women requesting abortion during a six month period were included. In cases with unconfirmed non-culture tests, reculture with multiple passage and PCR on the culture transport medium was performed for confirmation. Serum was analysed for chlamydial antibodies type IgG, IgM and IgA using microimmunofluorescence. 18 of 419 (4.3%) patients were positive for chlamydia according to the defined criteria. Twelve of 419 (2.9%) were positive in standard culture (primary inoculation). The sensitivity of standard culture, DFA, EIA and PCR were 66.7%, 77.8%, 64.7% and 71.4% respectively. The specificity 100% (by definition), 99.5%, 100%, 100% respectively. The positive predictive value 100% (by definition), 87.5%, 100%, 100% respectively. Negative predictive value 98.5%, 99.0%, 98.5%, 98.9% respectively. Serum IgG titre of > or = 64 and > or = 1024 gave positive predictive values of 10% and 21% respectively. When an expanded gold standard is used, the specificity and positive predictive value of the non-culture tests used are comparable with that of standard culture even in this low prevalence population. Standard culture underestimated the chlamydia prevalence by 33%. The prevalence found represents a decrease from 10 to 2.9% of culture verified chlamydia during four years in comparable populations. Chlamydial antibodies of certain immunological classes are not necessarily present in cases with chlamydia.
Publisher: Oxford University Press (OUP)
Date: 15-07-2008
DOI: 10.1086/589580
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-03-2014
Publisher: Oxford University Press (OUP)
Date: 07-2023
DOI: 10.1093/CID/CIAD402
Abstract: Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in in iduals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05–7.62). Antibody levels were further significantly boosted in all in iduals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in in iduals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09–1.57) and BA.3 (1.32, 1.09–1.59) antigens in in iduals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76–0.98), BA.4 (0.85, 0.75–0.97), and BA.5 (0.87, 0.76–0.99) antigens in in iduals with a prior infection. Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of Omicron variants.
Publisher: Mary Ann Liebert Inc
Date: 11-2012
Publisher: Elsevier BV
Date: 07-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-07-2011
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 08-2001
Publisher: Oxford University Press (OUP)
Date: 11-1997
DOI: 10.1086/516087
Abstract: In this study the polymerase chain reaction was used to test for the presence of Chlamydia pneumoniae DNA in 118 middle-ear aspirates from 20 children with acute otitis media (AOM) and 53 children with otitis media with effusion (OME). C. pneumoniae was detected in 8 s les obtained from 5 children with OME and, together with Streptococcus pneumoniae, in a s le from 1 child with AOM. The mean age of these five children (6.6 +/- 1.4 years) was significantly higher than that of the 48 children with OME in whom C. pneumoniae could not be detected (4.3 +/- 1.9 years). The presence of C. pneumoniae in 9.4% of the examined children with OME suggests that C. pneumoniae might be a significant supplementary factor in the etiology of this common children's disease.
Publisher: International Union Against Tuberculosis and Lung Disease
Date: 2017
Abstract: A suburban area of Bissau, the capital of Guinea-Bissau the study was conducted among presumptive pulmonary tuberculosis (prePTB) patients seeking medical care for signs and symptoms suggestive of PTB. To determine if a clinical TB score and a biomarker suPAR (soluble urokinase plasminogen activator receptor) have separate and composite ability to predict PTB diagnosis and mortality in prePTB patients. Observational prospective follow-up study conducted from August 2010 to August 2012. We included 1011 prePTB patients (mean age 34 years, 95%CI 33-35) 55% (n = 559) were female and 161 (16%) had human immunodeficiency virus (HIV) infection. Of all included patients, 10% (n = 101) were diagnosed with PTB. Mortality during follow-up was 5% (n = 48), with a mean survival time of 158 days (95%CI 27-289) in prePTB patients diagnosed with PTB vs. 144 days (95%CI 109-178) in those not diagnosed with PTB (P = 0.774). After adjusting for HIV status and age, the best separate predictor was suPAR 5 ng/ml, with a hazard ratio (HR) of 4.6 (95%CI 2.1-9.9) for mortality and 6.7 (95%CI 4.0-11.2) for TB diagnosis. All patients who died had a TBscore II + suPAR 7 the HR of the composite score for subsequent PTB diagnosis was 33.0 (95%CI 4.6-236.6). The proposed composite score of suPAR + TBscore II 7 can improve TB case finding and clinical monitoring.
Publisher: Springer Science and Business Media LLC
Date: 10-06-2016
Publisher: Oxford University Press (OUP)
Date: 18-05-2012
DOI: 10.1093/CID/CIS488
Abstract: Pneumonia is commonly diagnosed in immunosuppressed in iduals. The risk and attributable morbidity of first hospitalization for pneumonia among renal transplant candidates and recipients were compared to those of population controls. This population-based cohort study was conducted from 1 January 1990 to 31 December 2009. Each member of a Danish population-based, nationwide cohort of first-time renal transplant recipients was matched by age and sex with up to 19 population controls. Information on hospital discharge diagnosis, emigration, and mortality was obtained from nationwide administrative databases. In iduals were observed from diagnosis of end-stage renal disease until first hospitalization for pneumonia. Risk factors were assessed by Poisson regression. The study included 4729 renal transplant candidates and recipients and 81 757 controls, providing 25 546 and 704 329 person-years of observation, respectively. Compared with population controls, the incidence rate ratio of first hospitalization for pneumonia was 10.2 (95% confidence interval [CI], 8.74-11.8) for renal transplant candidates, 8.02 (95% CI, 7.29-8.83) for renal transplant recipients, and 13.7 (95% CI, 11.5-16.3) for patients with graft loss. Among renal transplant recipients, risk factors included male sex, age ≥50 years, diabetes, chronic interstitial nephritis, polycystic kidney disease, and 1-3 years of prior dialysis. Patients with pneumonia had a 78% (95% CI, 1.52-2.10) increased risk of graft loss. Thirty-day mortality of patients was comparable to that of the background population. The risk of first-time hospitalization for pneumonia remains high among renal transplant candidates and recipients. The attributable morbidity and mortality are of great clinical and public health concern and preventive measures are warranted.
Publisher: Public Library of Science (PLoS)
Date: 09-02-2011
Publisher: BMJ
Date: 09-11-1996
DOI: 10.1136/BMJ.313.7066.1186
Abstract: To compare urine and vaginal flush s les collected by women at home with endocervical and urethral swabs obtained by general practitioners for their efficacy in the diagnosis of urogenital Chlamydia trachomatis infection. Multipractice comparative study. 33 general practices and a central department of clinical microbiology in Aarhus County, Denmark. 222 women aged 18-25 years who for any reason had a gynaecological examination. Endocervical and urethral swabs were obtained by the women's general practitioners. The same women when at home then collected a first void urine s le, a midstream urine s le, and a vaginal flush s le (using a vaginal pipette) and mailed them to the laboratory. C trachomatis defected by the polymerase chain reaction and the ligase chain reaction. Eight tests for C trachomatis were performed for every woman. When two of the eight yielded positive results the patient was considered infected. The overall prevalence of C trachomatis infection was 11.2% (23/205 women). Test sensitivities in s les obtained by general practitioners, s les obtained at home subjected to polymerase chain reaction, and s les obtained at home subjected to ligase chain reaction were 91%, 96%, and 100% respectively. The corresponding specificities were 100%, 92.9%, and 99.5%. The diagnostic efficacy of s les obtained by women at home and mailed to the laboratory was as good as for s les obtained by a general practitioner when using the ligase chain reaction. This may have important implications for the practicability of screening for this common, often asymptomatic, and treatable infection.
Publisher: Springer Science and Business Media LLC
Date: 10-02-2022
DOI: 10.1186/S12879-022-07102-1
Abstract: COVID-19 is thought to be more prevalent among ethnic minorities and in iduals with low socioeconomic status. We aimed to investigate the prevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among citizens 15 years or older in Denmark living in social housing (SH) areas. We conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning risk factors associated with COVID-19. As a proxy for the general Danish population we accessed data on seroprevalence from Danish blood donors (total Ig ELISA assay) in same time period. Of the 13,279 included participants, 2296 (17.3%) were seropositive (mean age 46.6 (SD 16.4) years, 54.2% female), which was 3 times higher than in the general Danish population (mean age 41.7 (SD 14.1) years, 48.5% female) in the same period (5.8%, risk ratios (RR) 2.96, 95% CI 2.78–3.16, p 0.001). Seropositivity was higher among males (RR 1.1, 95% CI 1.05–1.22%, p = 0.001) and increased with age, with an OR seropositivity of 1.03 for each 10-year increase in age (95% CI 1.00–1.06, p = 0.031). Close contact with COVID-19-infected in iduals was associated with a higher risk of infection, especially among household members (OR 5.0, 95% CI 4.1–6.2 p 0,001). Living at least four people in a household significantly increased the OR of seropositivity (OR 1.3, 95% CI 1.0–1.6, p = 0.02) as did living in a multi-generational household (OR 1.3 per generation, 95% CI 1.1–1.6, p = 0.003). Only 1.6% of participants reported not following any of the national COVID-19 recommendations. Danish citizens living in SH areas of low socioeconomic status had a three times higher SARS-CoV-2 seroprevalence compared to the general Danish population. The seroprevalence was significantly higher in males and increased slightly with age. Living in multiple generations households or in households of more than four persons was a strong risk factor for being seropositive. Results of this study can be used for future consideration of the need for preventive measures in the populations living in SH areas.
Publisher: Wiley
Date: 2014
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 02-1998
DOI: 10.1016/S1078-5884(98)80138-X
Abstract: To investigate whether Chlamydia pneumoniae is present in symptomatic abdominal aortic aneurysms (AAA). After optimisation of DNA extraction procedures an inhibitor-controlled nested polymerase chain reaction (PCR) lifying fragments of the gene encoding the C. pneumoniae specific major outer membrane protein was performed on 124 wall-specimens from 20 patients with symptomatic AAA. None of the specimens contained C. pneumoniae-specific DNA. Minor inhibition of the PCR was noticed especially in media specimens. Using a sensitive and specific nested PCR, we were not able to detect C. pneumoniae in symptomatic AAA. The failure to detect C. pneumoniae in symptomatic AAA, combined with previously reported positive findings in atherosclerotic lesions, supports the hypothesis that AAA and atherosclerosis might be two different disease entities.
Publisher: BMJ
Date: 04-07-1998
Publisher: MDPI AG
Date: 10-12-2022
DOI: 10.3390/JCM11247338
Abstract: Background: Post-COVID Clinics were recommended for patients with persistent symptoms following COVID-19, but no specific tests were suggested for evaluation. This study aimed to present a post-COVID clinic patient cohort and evaluate the use of a post-COVID symptom questionnaire (PCQ) score. Methods: Patients were referred from a population of approximately 1 million citizens. PCQ and standardized health scales were registered. Descriptive analyses were performed to assess the prevalence of symptoms, and correlation analyses was undertaken to asses convergent and discriminant trends between PCQ scores and health scales. Results: Of 547 patients, 447 accepted inclusion. The median age was 47 years and 12% of the patients were hospitalized. At a median of 6.3 (IQR 4.4–9.9) months after the onset of symptoms, 82% of the patients reported both physical exhaustion and concentration difficulties. Functional disability and extreme fatigue were reported as moderate to severe by 33% and 62% of the patients, respectively. The PCQ score correlated significantly with each of the standardized health scales. Conclusion: Patients referred to a Post-COVID Clinic were previously generally healthy. At the time of diagnosis, they reported multiple symptoms with severely affected health. The PCQ score could be used as valid measure of Post-COVID severity.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 12-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-08-2022
Publisher: American Society for Microbiology
Date: 22-12-2021
DOI: 10.1128/SPECTRUM.01330-21
Abstract: To date, including 318,522 participants, this is the largest population-based study with broad national participation where tests and questionnaires have been sent to participants’ homes. We found that more emphasis from national and local authorities toward the risk of infection should be placed on age of tested in iduals, type of occupation, as well as exposure in local communities and households.
Publisher: Oxford University Press (OUP)
Date: 04-08-2015
DOI: 10.1093/JPIDS/PIV039
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.VACCINE.2008.08.075
Abstract: Development of meningococcal serogroups A, C, W-135 and Y conjugate vaccines could expand coverage against devastating meningococcal diseases. The immunogenicity of one dose of each one of five MenACWY-TT formulations versus a licensed ACWY polysaccharide vaccine was evaluated in 175 healthy subjects of 15-25 years. Serum bactericidal titers (rSBA) were evaluated before and after vaccination. The percentage of rSBA responders to each serogroup A, C, W-135 and Y did not statistically differ from the control for each of the five formulations except for serogroup A that was lower after administration of one formulation. In the 3-year follow-up of the first study where the latter formulation was assessed, bactericidal antibody persistence was similar to the licensed ACWY polysaccharide vaccine for MenA and MenC and higher for MenW-135 and MenY. Our results present five investigational MenACWY-TT conjugate vaccine formulations which are well tolerated and highly immunogenic in adolescents.
Publisher: Elsevier BV
Date: 08-2019
Publisher: Oxford University Press (OUP)
Date: 10-2000
DOI: 10.1086/318139
Abstract: We compared the efficacy of a screening program for urogenital Chlamydia trachomatis infections based on home s ling with that of a screening program based on conventional swab s ling performed at a physician's office. Female subjects, comprising students at 17 high schools in the county of Aarhus, Denmark, were ided into a study group (tested by home s ling) and a control group (tested in a physician's office). We assessed the number of new infections and the number of subjects who reported being treated for pelvic inflammatory disease (PID) at 1 year of follow-up 443 (51.1%) of 867 women in the intervention group and 487 (58.5%) of 833 women in the control group were available for follow-up. Thirteen (2.9%) and 32 (6.6%) new infections were identified in the intervention group and the control group, respectively (Wilcoxon exact value, P=.026). Nine (2.1%) women in the intervention group and 20 (4.2%) in the control group reported being treated for PID (P=.045), indicating that a screening strategy involving home s ling is associated with a lower prevalence of C. trachomatis and a lower proportion of reported cases of PID.
Publisher: SAGE Publications
Date: 10-2012
DOI: 10.3851/IMP2407
Abstract: The aim of this study was to determine whether there is a protective effect of combination anti-retroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression. A total of 3,780 patients from the EuroSIDA study under follow-up after 2001 with a current CD4 + T-cell count ≤200 cells/mm 3 were stratified into five groups: group 1, viral load (VL) copies/ml on cART group 2, VL 50-99,999 copies/ml on cART group 3, VL 50-99,999 copies/ml off cART group 4, VL≥100,000 copies/ml on cART and group 5, VL≥100,000 copies/ml off cART. Poisson regression was used to identify the risk of (non-fatal or fatal) AIDS- and non-AIDS-related events considered together (AIDS/non-AIDS) or separately as AIDS or non-AIDS events within each group. There were 428 AIDS/non-AIDS events during 3,780 person-years of follow-up. Compared with group 1, those in group 2 had a similar incidence of AIDS/ non-AIDS events (incidence rate ratio [IRR] 1.04 95% CI 0.79–1.36). Groups 3, 4 and 5 had significantly higher incidence rates of AIDS/non-AIDS events compared with group 1 incidence rates increased from group 3 (IRR 1.78 95% CI 1.25–2.55) to group 5 (IRR 2.36 95% CI 1.66–3.40), demonstrating the increased incidence of AIDS/non-AIDS events associated with increasing viraemia. After adjustment, the use of cART was associated with a 40% reduction in the incidence of AIDS/non-AIDS events in patients with VL 50–99,999 copies/ml (IRR 0.59 95% CI 0.41–0.85) and in those with a VL ,000 copies/ml (IRR 0.66 95% CI 0.44–1.00). Similar relationships were seen for non-AIDS events and AIDS events when considered separately. In patients with ongoing severe immuno-suppression, cART was associated with significant clinical benefits in patients with suboptimal virological control or virological failure.
Publisher: BMJ
Date: 10-2002
DOI: 10.1136/STI.78.5.389
Publisher: American Medical Association (AMA)
Date: 05-2010
DOI: 10.1001/ARCHPEDIATRICS.2010.9
Abstract: To investigate the association between hospitalization for infection in the perinatal/neonatal period or childhood and the diagnosis of autism spectrum disorders (ASDs). A population-based cohort study. Denmark. All children born in Denmark from January 1, 1980, through December 31, 2002, comprising a total of 1 418 152 children. Infection requiring hospitalization. The adjusted hazard ratio (HR) for ASDs among children hospitalized for infection compared with other children. A total of 7379 children were diagnosed as having ASDs. Children admitted to the hospital for any infectious disease displayed an increased rate of ASD diagnoses (HR, 1.38 [95% confidence interval, 1.31-1.45]). This association was found to be similar for infectious diseases of bacterial and viral origin. Furthermore, children admitted to the hospital for noninfectious disease also displayed an increased rate of ASD diagnoses (HR, 1.76 [95% confidence interval, 1.68-1.86]), and admissions for infection increased the rate of mental retardation (2.18 [2.06-2.31]). The association between hospitalization for infection and ASDs observed in this study does not suggest causality because a general association is observed across different infection groups. Also, the association is not specific for infection or for ASDs. We discuss a number of noncausal explanatory models.
Publisher: Oxford University Press (OUP)
Date: 03-2003
DOI: 10.1086/367663
Abstract: Serological analysis is often used for the diagnosis of chlamydial infections. However, an increase in Chlamydia antibodies has been reported in patients with parvovirus and Mycoplasma infections. Whether this antibody response is the result of dual infection or nonchlamydial antigen stimulation is unknown. In a randomized study, 48 healthy volunteers either were immunized against yellow fever, polio, diphtheria, and tetanus (the group receiving intervention with nonchlamydial antigen) or received saline injections (the placebo group). The change in antibody levels was compared between the 2 groups. The Chlamydia recombinant lipopolysaccharide enzyme-linked immunosorbent assay (Medac) showed an increase in the antibody titer in the intervention group, compared with that in the control group (for immunoglobulin M, P=.004 for immunoglobulin A, P=.038 and for immunoglobulin G, P=.056), but no differences between study groups was found when the C. pneumoniae enzyme immunoassay (EIA ThermoLabsystems), the C. pneumoniae EIA (Medac), and the microimmunofluorescence test (MRL) were used. An increase in antibodies to Chlamydia organisms can be measured after exposure to nonchlamydial antigens, depending on the test used.
Publisher: Oxford University Press (OUP)
Date: 23-11-2013
Abstract: We compared the immunogenicity and reactogenicity of Cervarix or Gardasil human papillomavirus (HPV) vaccines in adults infected with the human immunodeficiency virus (HIV). This was a double-blind, controlled trial randomizing HIV-positive adults to receive 3 doses of Cervarix or Gardasil at 0, 1.5, and 6 months. Immunogenicity was evaluated for up to 12 months. Neutralizing anti-HPV-16/18 antibodies were measured by pseudovirion-based neutralization assay. Laboratory tests and diary cards were used for safety assessment. The HPV-DNA status of the participants was determined before and after immunization. Ninety-two participants were included in the study. Anti-HPV-18 antibody titers were higher in the Cervarix group compared with the Gardasil group at 7 and 12 months. No significant differences in anti-HPV-16 antibody titers were found among vaccine groups. Among Cervarix vaccinees, women had higher anti-HPV-16/18 antibody titers compared to men. No sex-specific differences in antibody titers were found in the Gardasil group. Mild injection site reactions were more common in the Cervarix group than in the Gardasil group (91.1% vs 69.6% P = .02). No serious adverse events occurred. Both vaccines were immunogenic and well tolerated. Compared with Gardasil, Cervarix induced superior vaccine responses among HIV-infected women, whereas in HIV-infected men the difference in immunogenicity was less pronounced.
Publisher: Elsevier BV
Date: 07-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-07-2018
Publisher: Public Library of Science (PLoS)
Date: 31-03-2015
Publisher: Wiley
Date: 02-2009
DOI: 10.1111/J.1600-0463.2008.00024.X
Abstract: Monocytes/macrophages are known to represent a potential reservoir of human immunodeficiency virus type 1 (HIV-1), which ensures continuous replication of the virus in patients on highly active antiretroviral therapy (HAART). Infected macrophages are a highly productive source of HIV-1 during infections with common opportunistic pathogens. Previous studies report that toll like receptors (TLR)s play a role in HIV-1 replication in macrophages. Here, we investigate the three main pathways activated through TLR4 and the interactions with the HIV-1 long terminal repeat (LTR), using human embryonic kidney (HEK) 293 cells expressing TLR4 and transfected with a luciferase reporter under the control of the HIV-1 LTR. Here, we demonstrate, that TLR4-mediated activation of HIV-LTR is largely governed by the nuclear factor-kappaB pathway. Neither of the mitogen-activated protein kinases ERK1/2, JNK, or p38 nor the transcription factor interferon regulatory factor 3 were involved in the direct transactivation of HIV-LTR through stimulation of TLR4.
Publisher: Wiley
Date: 25-02-2015
DOI: 10.1111/HIV.12227
Publisher: The Endocrine Society
Date: 08-2004
DOI: 10.1210/ER.2003-0012
Publisher: Frontiers Media SA
Date: 04-08-2022
Abstract: We aimed to investigate and present cases of perimyocarditis and pericarditis verified by cardiovascular resonance (CMR) imaging in patients with a strong temporal association to SARS-CoV-2 vaccination. We sought to describe the clinical presentation including coronary artery angiography, CMR, transthoracic echocardiography, blood s les, electrocardiography, and symptoms. We included 10 patients admitted with chest pain shortly after vaccination for SARS-CoV-2, who were diagnosed with pericarditis or perimyocarditis by CMR. We reviewed the CMR, echocardiography, electrocardiography, blood s les, coronary artery angiography, vital signs and medical history. The updated Lake Louise Criteria were used to determine the diagnosis by CMR. Eight patients had perimyocarditis and two patients had pericarditis. The mean age was 22 ± 5 years (range 16 to 31 years), 90% were male. The median time from vaccination to hospital admission was 4 days (range 2 to 28 days). Admissions were seen after vaccination with three different SARS-CoV-2 vaccine manufacturers. Nine Patients had ST-elevation on the initial electrocardiography. Peak troponins varied from 357 to 23,547 ng/l, with a median of 4,304 ng/l. Two patients had an LVEF & % on echocardiography and four patients had left ventricular global longitudinal strain values & %. CMR revealed preserved left ventricular ejection fraction (LVEF), although one patient had decreased LVEF on CMR. The T1 and T2 mapping values were increased in all patients. Of the 8 patients with perimyocarditis, all patients had signs of myocardial injury in the lateral segments of the left ventricle. This case series of 10 patients supports the emerging evidence of an association between vaccination for SARS-CoV-2 and perimyocarditis and pericarditis, especially in young males. The temporal association was seen after vaccines from three different manufacturers. Imaging data from echocardiography and CMR displayed normal to mildly impaired cardiac function, usually with a mild disease course.
Publisher: Public Library of Science (PLoS)
Date: 14-09-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-10-2022
Publisher: Elsevier BV
Date: 10-2016
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.VACCINE.2010.10.071
Abstract: Combined vaccination with diphtheria-tetanus-pertussis (DTP) and measles vaccine (MV) has been associated with increased mortality in observational studies. Among children missing MV and a dose of DTP and oral polio vaccine (OPV), we conducted a randomised trial of providing MV+DTP+OPV simultaneously, as currently recommended, or MV+OPV only, and examined the effect on morbidity and growth. We hypothesised that the MV+OPV group would experience less morbidity and grow better. Due to previous observations of sex differences in the non-specific effects of vaccinations, we analysed all data stratified by sex. At the Bandim Health Project in Guinea-Bissau, 568 children who were due to receive MV and who were missing either DTP3 or DTP booster were enrolled in the study. A subgroup of 332 children was followed intensively to register adverse events and infections in the first month after vaccination. A subgroup of 276 children was followed every third month for a year to monitor growth. All children were followed for one year for infectious diseases, consultations, and hospitalisations. As expected, adverse events were more common in the MV+DTP+OPV group diarrhoea and use of medication were increased among girls but not among boys (both p=0.02, test of interaction between DTP and sex). Febrile disease with vesicular rash, as well as consultations and hospitalisations tended to be more common in the MV+DTP+OPV group than in the MV+OPV group the hazard ratio (HR) for febrile disease with vesicular rash was 1.86 (1.00 3.47). The strongest tendencies for more febrile diseases and hospitalisations in the MV+DTP+OPV group were found in girls. Overall, growth did not differ by randomisation group. However, results differed by sex. Girls in the MV+DTP+OPV group had a consistent pattern of worse z-scores for weight, height, and mid-upper-arm-circumference (MUAC) than girls in the MV+OPV group. The effect was opposite for boys, with boys in the MV+OPV group faring worse than those in the MV+DTP+OPV group, the interaction test for sex and DTP being significant for weight at 6 and 9 months, for MUAC at 12 months and for weight-for-height at 3 and 9 months after randomisation. This is the first randomised trial of the non-specific effects of DTP and supports that these effects may be sex-differential and of clinical and anthropometric importance. Combined vaccination with DTP+MV+OPV may be detrimental for girls.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/208412
Abstract: Macrophages play an important role in human immunodeficiency virus (HIV) pathogenesis and contribute to establishment of a viral reservoir responsible for continuous virus production and virus transmission to T cells. In this study, we investigated the differences between various monocyte-derived macrophages (MDMs) generated through different differentiation protocols and evaluated different cellular, immunological, and virological properties. We found that elevated and persistent HIV-1 pWT/BaL replication could be obtained only in MDMs grown in RPMI containing macrophage colony-stimulating factor (M-CSF). Interestingly, this MDM type was also most responsive to toll-like receptor stimulation. By contrast, all MDM types were activated to a comparable extent by intracellular DNA, and the macrophage serum-free medium-(Mac-SFM-)differentiated MDMs responded strongly to membrane fusion through expression of CXCL10. Finally, we found that HIV infection of RPMI/M-CSF-differentiated MDMs induced low-grade expression of two interferon-stimulated genes in some donors. In conclusion, our study demonstrates that the differentiation protocol used greatly influences the ability of MDMs to activate innate immune reactions and support HIV-1 replication. Paradoxically, the data show that the MDMs with the strongest innate immune response were also the most permissive for HIV-1 replication.
Publisher: Informa UK Limited
Date: 27-12-2011
DOI: 10.3109/00365548.2011.616223
Abstract: The software program InfCare HIV is a combined clinical decision support tool and database. This study investigated the usefulness of InfCare HIV for identifying and characterizing suboptimally treated HIV-infected patients at a Danish HIV clinic. This cross-sectional cohort study included data on all HIV-infected patients treated at the Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark on a specific date. InfCare HIV was used to identify and characterize suboptimally treated patients defined as patients with virological failure (VF) or untreated patients with a CD4 + count below 350 cells/μl. Patient characteristics were analyzed (i.e. age, sex, ethnicity, and nadir and latest CD4 + cell count). Treatment history and reasons for suboptimal treatment were also investigated. Among all 530 patients, 421 were receiving highly active antiretroviral therapy (HAART) and had undergone at least 48 weeks of treatment on 29 October 2010. Of these, 27 (6.4%) had ongoing VF. Four were untreated despite a CD4 + count below 350 cells/μl. Among patients on HAART, patients with VF were younger and had lower median nadir CD4 + cell counts than patients without VF. Further, 33.3% (6/18) of African Black men but only 4.1% (10/244) of Caucasian men on HAART had VF (p < 0.001). The primary reason for VF was non-adherence. Three untreated patients had refused HAART, and 1 was not treated because of concerns of non-adherence. InfCare HIV was successfully used to identify patients with suboptimal treatment. A surprisingly high percentage of African Black men had VF.
Publisher: Springer Science and Business Media LLC
Date: 05-1995
DOI: 10.1007/BF02114911
Abstract: To determine the types of patient safety incidents and associated harm in nuclear medicine practice. This study included 147 patient safety incidents related to nuclear medicine practice and submitted to the incident reporting system of a tertiary care nuclear medicine department between 2014 and 2019. The top-three incident types according to the International Classification for Patient Safety (ICPS) were medication/IV fluids (36/147, 24.5%), clinical administration (28/147, 19.0%), and clinical process rocedure (27/147, 18.4%), altogether comprising 61.9% of incidents. Within the medication/IV fluids domain, half of incident subtypes were attributable to supply/ordering, omitted medicine or dose, and wrong dose/strength of frequency. Within the clinical administration domain, appointment and wrong patient represented the majority of incident subtypes. Within the clinical process rocedure domain, the majority of incident subtypes fell in the categories: specimens/results and incomplete/inadequate. There was no patient harm in 145 (98.6%) of cases, mild patient harm in 1 (0.7%) case, and in 1 (0.7%) case, it remained unclear if there was patient harm. In 4 (2.7%) cases, a Prevention Recovery Information System for Monitoring and Analysis evaluation was performed because of the high risk of reoccurrence and patient harm. The majority of patient safety incidents in nuclear medicine occur in three main ICPS categories (medication/IV fluids, clinical administration, and clinical process rocedure, in order of decreasing frequency). These can be considered as key strategic areas for incident prevention and patient safety improvement. Nevertheless, the rate of actual patient harm was very low in our series.
Publisher: American College of Physicians
Date: 02-2022
DOI: 10.7326/M21-3507
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-01-2018
Publisher: Informa UK Limited
Date: 09-2003
DOI: 10.1080/00365510310002031
Abstract: to assess the age- and sex-specific prevalence of Chlamydia trachomatis infection according to the indications for testing. This was done as part of a health technology assessment to identify the populations that would benefit most from universal screening, and to identify ongoing potential superfluous testing that could liberate resources to be used for targeted screening programs. In Aarhus County, Denmark, population of 630,000, data were collected on 11,423 persons who were being tested for C. trachomatis (10,351 females and 1072 males). Indicated on the request slip were: the sex, the age and the reasons for testing (infected partner planned transcervical procedure symptoms consistent with C. trachomatis infection or routine testing). All s les were analyzed by the Ligase Chain Reaction. More than 90% of all the tests were conducted in women. The majority of tests were performed in the 21-25 years age group but the prevalence was highest in the 16-20 years age group (7.2% 95% CI: 5.4%-9.3%). A total of 25% of all tests were carried out in asymptomatic women above the age of 30 in whom the prevalence was only 1.3% (95% CI: 0.8%-1.9%). More than three times as many women (5.8%) than men (1.7%) were tested as sexual partners to C. trachomatis-infected index patients but the risk of infection was highest among men. In women who were tested prior to a transcervical procedure, the prevalence was highest (5.5% 95% CI: 1.8%-12.4%) in the 16-20 years age group, whereas most s les were obtained in women aged 31-35 years in whom the prevalence was only 0.8% (0.2%-2.3%). The prevalence of C. trachomatis infection justifies the screening of asymptomatic in iduals below 30 years of age. At present, however, 25% of all tests are requested in asymptomatic women above the age of 30. It might be advisable to use the resources for systematic universal screening of younger in iduals rather than to continue the current opportunistic screening of older women.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.ATHEROSCLEROSIS.2007.02.025
Abstract: The purpose was to investigate in a large, randomized, double-blinded, placebo-controlled trial, whether antibiotic treatment can prevent progression of peripheral arterial disease (PAD). Five hundred and seven patients were included all patients had an established diagnosis of PAD. Their mean age was 66 years (36-85), and 59% were males. Patients were randomized to Roxithromycin 300 mg daily for 28 days. Baseline investigations were ankle blood pressure, ankle-brachial blood pressure index (ABPI), walking distance, C. pneumoniae serology, cholesterol and medical history. Follow-up was performed every 6 months. Primary events were defined as death, peripheral revascularization and major lower limb utation. Secondary events were thrombosis, stroke, transient cerebral ischaemic attack and myocardial infarction. Change in ABPI was also investigated. Data were analyzed mainly by Cox regression and linear regression. Included patients with PAD were randomized. Two patients withdrew. Of the remaining, 248 received roxithromycin and 257 placebo. In the treatment group 55% were seropositive and 53% in the placebo group. Mean follow-up was 2.1 years (range 0.06-5.1 years). In the placebo group, 26 died and 80 primary events occurred in total. In the treatment group, 28 died and 74 primary events were observed. The hazard ratio of death was 1.13 (95% CI: 0.68 1.90), and of primary events 0.92 (95% CI: 0.67 1.26). Also on secondary events and ABPI changes, no significant differences were found. Long-term treatment with roxithromycin is ineffective in preventing death, utation, peripheral revascularization, myocardial infarction, stroke, transient cerebral ischaemic attack, thrombosis and decline in ABPI in patients with an established diagnosis of PAD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-01-2013
Publisher: European Respiratory Society (ERS)
Date: 07-2000
DOI: 10.1034/J.1399-3003.2000.16A19.X
Abstract: In a small uncontrolled study, persistent cough has recently been found to be associated with serological evidence of acute Chlamydia pneumoniae infection. In order to assess whether C. pneumoniae plays a role in chronic cough, the prevalence of C. pneumoniae infection in 201 adult patients with chronic cough was compared with the prevalence in 106 healthy blood donors without respiratory tract symptoms in the preceding 3 months. A microimmunofluorescence antibody test was used to determine C. pneumoniae antibodies in the immunoglobulin (Ig)M, IgG and IgA fractions. Further, nasopharyngeal aspirates from the 201 patients were examined for C. pneumoniae deoxyribonucleic acid by polymerase chain reaction (PCR). As judged by serology, nine patients (4%) and one control (1%) had acute C. pneumoniae infection, and 92 patients (46%) and 42 controls (40%) had previous or chronic C. pneumoniae infection. Of the nine patients with acute infection, three were C. pneumoniae PCR positive, and they all had an IgM antibody titre response. The remaining six patients had either an IgG antibody titre of > or =512 (five patients) or an IgA antibody titre of > or =512 (one patient). None of these six patients had detectable IgM antibodies. The mean cough period for the five IgG positive patients (10.8 weeks) was significantly longer than the mean cough period for the remaining patient population (6.4 weeks p=0.004). It is concluded that Chlamydia pneumoniae infection was not statistically significantly more prevalent in patients with chronic cough than in healthy blood donors, and that Chlamydia pneumoniae appears to have a minor role in patients with chronic cough. Direct detection of Chlamydia pneumoniae by polymerase chain reaction on nasopharyngeal aspirates is highly correlated with detectable immunoglobulin M antibodies, but in the late stages of prolonged cough serological testing of immunoglobulin G and immunoglobulin A may be more beneficial for obtaining a microbiological diagnosis.
Publisher: Frontiers Media SA
Date: 03-10-2022
Abstract: The SARS-CoV-2 pandemic has, as of July 2022, infected more than 550 million people and caused over 6 million deaths across the world. COVID-19 vaccines were quickly developed to protect against severe disease, hospitalization and death. In the present study, we performed a direct comparative analysis of four COVID-19 vaccines: BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford/AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen), following primary and booster vaccination. We focused on the vaccine-induced antibody-mediated immune response against multiple SARS-CoV-2 variants: wildtype, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and B.1.1.529 (Omicron). The analysis included the quantification of total IgG levels against SARS-CoV-2 Spike, as well as the quantification of antibody neutralization titers. Furthermore, the study assessed the high-throughput ACE2 competition assay as a surrogate for the traditional pseudovirus neutralization assay. The results demonstrated marked differences in antibody-mediated immune responses. The lowest Spike-specific IgG levels and antibody neutralization titers were induced by one dose of the Ad26.COV2.S vaccine, intermediate levels by two doses of the BNT162b2 vaccine, and the highest levels by two doses of the mRNA-1273 vaccine or heterologous vaccination of one dose of the ChAdOx1 vaccine and a subsequent mRNA vaccine. The study also demonstrated that accumulation of SARS-CoV-2 Spike protein mutations was accompanied by a marked decline in antibody neutralization capacity, especially for B.1.1.529. Administration of a booster dose was shown to significantly increase Spike-specific IgG levels and antibody neutralization titers, erasing the differences between the vaccine-induced antibody-mediated immune response between the four vaccines. The findings of this study highlight the importance of booster vaccines and the potential inclusion of future heterologous vaccination strategies for broad protection against current and emerging SARS-CoV-2 variants.
Publisher: BMJ
Date: 12-2001
DOI: 10.1136/STI.77.6.416
Abstract: To evaluate the effectiveness of a structured information c aign aiming to recruit young adults for a Chlamydia trachomatis test by use of a non-invasive, home obtained and mailed s le. All in iduals aged 21-23 living in Aarhus county, Denmark (30 000 young adults) were offered a mailed home s ling test for C trachomatis as part of a structured 14 week information c aign on chlamydia. The kit for home s ling could be requested by leaving a message on an answering machine or through a website on the internet. During the c aign 119 of 15 000 women (0.8%) and 64 of 15 000 men (0.4%) were tested. Prevalence of infection was 8.4% (10/119) and 7.8% (5/64) in females and males, respectively. Four infections in women (4/10=40%) and three infections in men (3/5=60%) were asymptomatic. The mass media c aign had only a limited effect, and there is a need for more effective outreach programmes to recruit young asymptomatic in iduals for C trachomatis testing.
Publisher: CSIRO Publishing
Date: 2011
DOI: 10.1071/SH10067
Abstract: Background: The aim of this study was to follow a cohort of HIV-positive in iduals for 3 years in order to assess changes in depression, adherence, unsafe sex and emotional strains from living with HIV. Methods: Participants were assessed for depression, adherence, emotional strain and unsafe sex via a questionnaire. The Beck Depression Inventory II (BDI) was used to assess the prevalence and severity of depressive symptoms. Patients with a BDI score of 20 or above (moderate to major depression) were offered a clinical evaluation by a consultant psychiatrist. Results: In 2005, 205 HIV-positive in iduals participated in the study. Symptoms of depression (BDI ) were observed in 77 (38%) and major depression (BDI ≥20) in 53 (26%) in iduals. In 2008, 148 participants were retested (72% of original s le). Depression (BDI ) was observed in 38 (26%) and symptoms of major depression (BDI ≥20) in 24 (16%) in iduals. Patients at risk of moderate to major depression were more likely to be non-adherent to medications, to practice unsafe sex and to suffer from emotional strains compared with patients not at risk of depression, both at baseline (2005) and follow-up (2008). Conclusion: This study demonstrated a decline in depression scores over time and an association between the risk of depression and low medication adherence, stress and unsafe sex. We recommend routine screening for depression to be conducted regularly to provide full evaluations and relevant psychiatric treatment.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2010
DOI: 10.1007/S10803-010-1006-Y
Abstract: Exposure to prenatal infection has been suggested to cause deficiencies in fetal neurodevelopment. In this study we included all children born in Denmark from 1980, through 2005. Diagnoses of autism spectrum disorders (ASDs) and maternal infection were obtained through nationwide registers. Data was analyzed using Cox proportional hazards regression. No association was found between any maternal infection and diagnosis of ASDs in the child when looking at the total period of pregnancy: adjusted hazard ratio = 1.14 (CI: 0.96-1.34). However, admission to hospital due to maternal viral infection in the first trimester and maternal bacterial infection in the second trimester were found to be associated with diagnosis of ASDs in the offspring, adjusted hazard ratio = 2.98 (CI: 1.29-7.15) and adjusted hazard ratio = 1.42 (CI: 1.08-1.87), respectively. Our results support prior hypotheses concerning early prenatal viral infection increasing the risk of ASDs.
Publisher: SAGE Publications
Date: 11-2016
Abstract: The incidence of bacteremia and fungemia (BAF) is largely unknown in end-stage renal disease (ESRD) patients initiating peritoneal dialysis (PD). The main objective was to estimate and compare incidence rates of first episodes of BAF in incident PD patients and a comparison cohort. A secondary objective was to compare causative agents and 30-day post-BAF mortality between PD patients and the comparison cohort. Design: Observational cohort study. Setting: Central and North Denmark regions. Participants: patients who initiated PD during 1995 – 2010. For each patient we s led up to 10 controls from the general population matched on age, sex, and municipality. Data on positive blood cultures were retrieved from electronic microbiology databases covering the 2 regions. We calculated incidence rates (IRs) of first-time BAF for PD patients and population controls. Incidence-rate ratios (IRRs) were calculated to compare these rates. Thirty-day mortality was estimated by Kaplan-Meier analysis. Among 1,024 PD patients and 10,215 population controls, we identified 75 and 282 episodes of BAF, respectively. Incidence rates of BAF were 4.7 (95% confidence interval [CI], 3.8 – 5.9) per 100 person-years of follow-up (PYFU) in PD patients and 0.5 (95% CI, 0.4 – 0.5) per 100 PYFU in population controls (IRR = 10.4 95% CI, 8.1 – 13.5). In PD patients, the most frequent microorganisms were Escherichia coli (18.7%) and Staphylococcus aureus (13.3%). Escherichia coli (27.3%) also ranked first among population controls. Thirty-day mortality following BAF was 20.8% (95% CI, 12.6 – 31.0) and 20.7% (95% CI, 16.3 – 25.9) among PD patients and population controls, respectively. Peritoneal dialysis patients are at markedly higher risk of BAF than population controls. Causative agents and the 30-day post-BAF mortality were similar in the 2 cohorts.
Publisher: Elsevier BV
Date: 12-2002
Abstract: The available diagnostic methods for Chlamydia trachomatis infection comprise serology (indirect detection) and culture, antigen detection and nucleic acid lification (direct detection). The rationale, applications, advantages and disadvantages of the methods and diagnostic targets are discussed. Compared to conventional methods, nucleic acid lification tests have increased sensitivity. This allows s les to be taken at home by the patient herself and mailed directly to the laboratory. Public health strategies implying home s ling for asymptomatic men and women result in a lower prevalence and a lower risk of short-term complications in terms of pelvic inflammatory disease (PID). The importance of predictive values and the association with prevalence are highlighted.
Publisher: Public Library of Science (PLoS)
Date: 08-07-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-03-2013
Publisher: Public Library of Science (PLoS)
Date: 24-04-2015
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1111/J.1469-0691.2009.02709.X
Abstract: Recent studies have suggested that procalcitonin (PCT) is a safe marker for the discrimination between bacterial and viral infection, and that PCT-guided treatment may lead to substantial reductions in antibiotic use. The present objective was to evaluate the effect of a single PCT measurement on antibiotic use in suspected lower respiratory tract infections (LRTIs) in a Danish hospital setting. In a randomized, controlled intervention study, 223 adult patients admitted to the hospital because of suspicion of LRTI were included with 210 patients available for analysis. Patients were randomized to either PCT-guided treatment or standard treatment. Antibiotic treatment duration in the PCT group was based on the serum PCT value at admission. The cut-off point for recommending antibiotic treatment was PCT > or =0.25 microg/L. Physicians could overrule treatment guidelines. The mean duration of hospital stay was 5.9 days in the PCT group vs. 6.7 days in the control group (p 0.22). The mean duration of antibiotic treatment during hospitalization in the PCT group was 5.1 days on average, as compared to 6.8 days in the control group (p 0.007). In a subgroup analysis of chronic obstructive pulmonary disease patients, the mean length of stay was reduced from 7.1 days in the control group to 4.8 days in the PCT group (p 0.009). It was concluded that the determination of a single PCT value at admission in patients with suspected LRTIs can lead to a reduction in the duration of antibiotic treatment by 25% without compromising outcome. No effect on the length of hospital stay was found.
Publisher: Informa UK Limited
Date: 1990
DOI: 10.3109/00365529009095525
Abstract: Simultaneous recordings of electromyography and manometry were obtained from rabbit sphincter of Oddi (SO) and duodenum. Three different patterns of activity were observed in SO and in duodenum: 1) a low- litude (less than 3 cm H2O) pattern of background oscillations with 2) superimposed high- litude (4-20 cm H2O) contractions and 3) occasional complex contractions consisting of an elevation of the basal pressure with superimposed smaller contractions. A certain SO autonomy was evident: 57.6% of SO pressure peaks could not be assigned to any duodenal activity. The distribution of SO pressure peak litudes could not be described by a simple normal distribution. The distribution of SO pressure peak litudes with concomitant duodenal activity differed from the overall distribution (p less than 0.001). Whereas a substantial part of SO pressure peaks greater than 4 cm H2O had no or low- litude corresponding duodenal pressure activity, duodenal pressure peaks greater than 4 cm H2O almost invariably were associated with SO pressure peaks. It is concluded that rabbit SO does possess a certain autonomy, but at the same time a close functional connection exists between the two compartments.
Publisher: Informa UK Limited
Date: 1990
DOI: 10.3109/00365529009095526
Abstract: Simultaneous recordings of pressure and slow-wave activity were obtained from the sphincter of Oddi (SO) and the duodenum in anesthetized rabbits. Histographic analysis of the recordings was performed when the following criteria were fulfilled: 1) slow waves must be present in the EMG recordings from both compartments and 2) only pressure recordings with sufficient pressure activity (greater than 50 peaks in 10 min) would be considered. Of 12 animals fulfilling the criteria for histographic analysis of 4 channels, a common basic-mode activity was found in all channels in 9 animals (75%). Of three animals fulfilling the criteria for histographic analysis of three channels, a common basic-mode activity was seen in all channels in all animals (100%). A correlation between the litude of the slow waves and the litude of the elicited pressure peaks in the SO was significant at a 5% level or better in 12 animals (80%). In some of the animals episodes of low- litude pressure activity was observed in the SO, occurring synchronously with slow waves devoid of spike activity. It is concluded that rabbit SO and duodenum are paced by slow waves with a common basic-mode activity in most animals. Slow waves may not only be the chief determinant of the contractile rhythm but may also have a certain influence on the force of the in idual SO contractions. It is suggested that slow waves per se may be able to mediate contractile activity.
Publisher: Oxford University Press (OUP)
Date: 04-2002
Publisher: SAGE Publications
Date: 29-07-2009
Abstract: Background: Antibodies against Chlamydia pneumoniae are associated with an increased rate of expansion of small abdominal aortic aneurysms (AAAs). Short-term follow-up trials have shown a transient reduction AAA growth rate, in macrolide treated compared with placebo. Therefore we analysed the influence of intermittent, long-term roxithromycin treatment on AAA expansion and referral for surgery. Methods: Eighty-four patients with small AAAs were randomized to either an annual 4 weeks’ treatment with roxithromycin or placebo, and followed prospectively. Results: Intermittent, long-term Roxithromycin-treatment reduced mean annual growth rate by 36% compared with placebo after adjustment for potential confounders. Long-term roxithromycin-treated patients had a 29% lower risk of being referred for surgical evaluation, increasing to 57% after adjusting for potential confounders. Conclusion: Annual 4 week treatment with 300 mg roxithromycin daily may reduce the progression of small AAAs, and later need for surgical repair. However, more robust studies are needed for confirmation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-11-2008
Publisher: Oxford University Press (OUP)
Date: 04-2003
DOI: 10.1086/368188
Abstract: Submission of s les from the home allows screening for Chlamydia trachomatis without preceding professional assessment of clinical risk factors. Therefore, a validation of self-reportable information for use as selective screening criteria is needed. We asked a total of 1175 women and 1033 men who participated in an in-home s ling screening study to provide information on behavior and sociodemographic characteristics. In a multivariate model, selective screening criteria were developed on the basis of information from a random part of the tested population (development group), and the validity was assessed for the remaining part of the tested population (validation group). To find all infections, 95% of the subjects had to be screened, and screening 63% of them would have detected 86% of infections. Low predictive values were found when selective screening criteria from other studies were assessed. Selective screening by means of in-home s ling strategies among men and women aged 21-23 years cannot be recommended in the area studied.
Publisher: Wiley
Date: 09-12-2021
DOI: 10.1111/HIV.13212
Abstract: Although direct‐acting antivirals (DAAs) can clear HCV in nearly all HIV/HCV‐coinfected in iduals, high rates of reinfection may h er efforts to eliminate HCV in this population. We investigated reinfection after sustained virological response (SVR) in HIV/HCV‐coinfected in iduals in Europe. Factors associated with odds of reinfection by 2 years after SVR in EuroSIDA participants with one or more HCV‐RNA test and 2 years follow‐up were assessed using logistic regression. Overall, 1022 in iduals were included. The median age was 50 (interquartile range: 43–54 years), and most were male (78%), injection drug users (52%), and received interferon (IFN)‐free DAAs (62%). By 24 months, 75 [7.3%, 95% confidence interval (CI): 5.7–8.9%] in iduals were reinfected. Among in iduals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN‐free and IFN‐based therapy. After adjustment, in iduals who had started treatment during or after 2014 with IFN‐free or IFN‐based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11–0.38 0.43, 95% CI: 0.22–0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis. Among HIV/HCV‐coinfected in iduals in Europe, 7.3% were reinfected with HCV within 24 months of achieving SVR, with evidence suggesting that this is decreasing over time and with use of newer HCV regimens. Harm reduction to reduce reinfection and surveillance to detect early reinfection with an offer of treatment are essential to eliminate HCV.
Publisher: Public Library of Science (PLoS)
Date: 03-01-2012
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.VACCINE.2011.11.051
Abstract: The co-administration of the tetravalent meningococcal conjugate vaccine, MenACWY-TT, with a licensed hepatitis A and B vaccine, HepA/B (Twinrix(®)), was compared to their separate administration in this open, randomised, controlled study. Healthy subjects 11-17 years of age (n=611) were randomised (3:1:1) to receive both vaccines, MenACWY-TT alone or HepA/B alone. The co-administration of both vaccines was shown to be non-inferior to their in idual administration. At seven months after the first vaccination, 99.4-100% of the subjects who received both vaccines co-administered showed seroprotection against all meningococcal serogroups and at least 99.1% of them were seropositive for hepatitis A and seroprotected against hepatitis B. This study suggests that MenACWY-TT vaccine could be co-administered with HepA/B without adversely impacting the immunogenicity, safety and reactogenicity of either of the vaccines.
Publisher: Oxford University Press (OUP)
Date: 25-10-2017
DOI: 10.1093/OFID/OFX228
Abstract: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. We performed a case-control (1:2 age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. We included 32 cases and 64 controls with a median age of 52 years 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M IQR, 0.13–0.40) than controls (0.12 IQR, 0.09–0.17 P ≤ .001). When ided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21–0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25–43.90). High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration. NCT01056185.
Publisher: Informa UK Limited
Date: 14-05-2013
DOI: 10.4161/HV.23800
Publisher: Springer Science and Business Media LLC
Date: 14-10-2012
Abstract: Innate recognition is essential in the antiviral response against infection by herpes simplex virus (HSV). Chemokines are important for control of HSV via recruitment of natural killer cells, T lymphocytes, and antigen-presenting cells. We previously found that early HSV-1-mediated chemokine responses are not dependent on TLR2 and TLR9 in human macrophages. Here, we investigated the role of the recently identified innate IFN-inducible DNA receptor IFI16 during HSV-1 infection in human macrophages. Peripheral blood mononuclear cells were purified from buffy coats and monocytes were differentiated to macrophages. Macrophages infected with HSV-1 were analyzed using siRNA-mediated knock-down of IFI16 by real-time PCR, ELISA, and Western blotting. We determined that both CXCL10 and CCL3 are induced independent of HSV-1 replication. IFI16 mediates CCL3 mRNA accumulation during early HSV-1 infection. In contrast, CXCL10 was induced independently of IFI16. Our data provide the first evidence of HSV-1-induced innate immune responses via IFI16 in human primary macrophages. In addition, the data suggest that at least one additional unidentified receptor or innate sensing mechanism is involved in recognizing HSV-1 prior to viral replication.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Wiley
Date: 09-12-2021
DOI: 10.1111/HIV.13210
Abstract: The aim of this study was to assess the impact of hepatitis B virus (HBV) infection on non‐liver malignancies in people living with HIV (PLWH). All persons aged ≥ 18 years with known hepatitis B virus (HBV) surface antigen (HBsAg) status after the latest of 1 January 2001 and enrolment in the EuroSIDA cohort (baseline) were included in the study persons were categorized as HBV positive or negative using the latest HBsAg test and followed to their first diagnosis of nonliver malignancy or their last visit. Of 17 485 PLWH included in the study, 1269 (7.2%) were HBV positive at baseline. During 151 766 person‐years of follow‐up (PYFU), there were 1298 nonliver malignancies, 1199 in those currently HBV negative [incidence rate (IR) 8.42/1000 PYFU 95% confidence interval (CI) 7.94–8.90/1000 PYFU] and 99 in those HBV positive (IR 10.54/1000 PYFU 95% CI 8.47–12.62/1000 PYFU). After adjustment for baseline confounders, there was a significantly increased incidence of nonliver malignancies in HBV‐positive versus HBV‐negative in iduals [adjusted incidence rate ratio (aIRR) 1.23 95% CI 1.00–1.51]. Compared to HBV‐negative in iduals, HBsAg‐positive/HBV‐DNA‐positive in iduals had significantly increased incidences of nonliver malignancies (aIRR 1.37 95% CI 1.00–1.89) and NHL (aIRR 2.57 95% CI 1.16–5.68). There was no significant association between HBV and lung or anal cancer. We found increased rates of nonliver malignancies in HBsAg‐positive participants, the increases being most pronounced in those who were HBV DNA positive and for NHL. If confirmed, these results may have implications for increased cancer screening in HIV‐positive subjects with chronic HBV infection.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.IJID.2018.08.010
Abstract: Denmark has a high incidence rate of candidaemia. A Nordic study suggested a higher Danish prevalence of haematological malignancies as an underlying reason. This nationwide study ascertained clinical characteristics of Danish candidaemia patients and investigated potential factors contributing to the high incidence and mortality. Microbiological and clinical data for candidaemia patients in 2010-2011 were retrieved. 30-day mortality was estimated by hazard ratios (HR) with 95% confidence intervals (CI, Cox regression). Data were available for 912/973 candidaemia episodes (93.7%). Intensive care unit (ICU) held the largest share of patients (43.2%). Prevalent host factors were multi-morbidity (≥2 underlying diseases, 74.2%) and gastrointestinal disease (52.5%). Haematological disease was infrequent (7.8%). Risk factors included antibiotic exposure (90.5%), CVC (71.9%) and Candida colonisation (66.7%). 30-day mortality was 43.4%, and 53.6% in ICU. Mortality was lower for patients with recent abdominal surgery (HR 0.70, 95% CI: 0.54-0.92). A substantial prevalence of multi-morbidity and a high 30-day mortality was found. We hypothesise, that an increasing population of severely ill patients with prolonged supportive treatment and microbiological testing may in part explain the high candidaemia incidence in Denmark. Nationwide studies are warranted to clarify this issue.
Publisher: American Society for Microbiology
Date: 2008
DOI: 10.1128/IAI.00856-07
Abstract: Excessive inflammation contributes to the pathogenesis of bacterial meningitis, which remains a serious disease despite treatment with antibiotics. Therefore, anti-inflammatory drugs have important therapeutic potential, and clinical trials have revealed that early treatment with dexamethasone significantly reduces mortality and morbidity from bacterial meningitis. Here we investigate the molecular mechanisms behind the inhibitory effect of dexamethasone upon the inflammatory responses evoked by Neisseria meningitidis and Streptococcus pneumoniae , two of the major causes of bacterial meningitis. The inflammatory cytokine response was dependent on Toll-like receptor signaling and was strongly inhibited by dexamethasone. Activation of the NF-κB pathway was targeted at several levels, including inhibition of IκB phosphorylation and NF-κB DNA-binding activity as well as upregulation of IκBα synthesis. Our data also revealed that the timing of steroid treatment relative to infection was important for achieving strong inhibition, particularly in response to S. pneumoniae . Altogether, we describe important targets of dexamethasone in the inflammatory responses evoked by N. meningitidis and S. pneumoniae , which may contribute to our understanding of the clinical effect and the importance of timing with respect to corticosteroid treatment during bacterial meningitis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2007
Publisher: Springer Science and Business Media LLC
Date: 08-01-2015
Publisher: Springer Science and Business Media LLC
Date: 12-1991
DOI: 10.1007/BF01984929
Publisher: Oxford University Press (OUP)
Date: 07-2010
DOI: 10.1086/653112
Abstract: Persons infected with human immunodeficiency virus (HIV) are often hyporesponsive to immunization, including pneumococcal vaccines. We hypothesized that adding CPG 7909, a toll-like receptor 9 (TLR9) agonist and vaccine adjuvant, to 7-valent pneumococcal conjugate vaccine (7vPnC) would increase its immunogenicity in HIV-infected adults. We performed a double-blind, placebo-controlled, phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC (Prevnar) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23 Pneumo Novum) at 9 months, with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses control patients had phosphate-buffered saline added instead. Immunogenicity and safety were evaluated for up to 10 months. The primary end point was the proportion of vaccine high responders at 9 months, defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes. Ninety-seven participants were included in the study. The proportion of vaccine high responders was higher in the experimental group (n = 48) than among controls (n = 49 48.8% vs 25.0% P = .02) at 9 months. Greater proportions of high responders were also observed at 3 (51.1% vs 39.6% P = .26), 4 (77.3% vs 56.3% P = .03), and 10 months (87.8% vs 51.1% P < .001). Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group (100% vs 81.3% P = .002). CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization. No adverse effects on CD4(+) cell count or organ functions occurred in either group. The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders. ClinicalTrials.gov identifier: NCT00562939 .
Publisher: BMJ
Date: 17-09-2012
DOI: 10.1136/BMJ.E5823
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2011
Publisher: Elsevier BV
Date: 10-2014
Publisher: Massachusetts Medical Society
Date: 11-03-2021
Publisher: Public Library of Science (PLoS)
Date: 13-04-2016
Publisher: Springer Science and Business Media LLC
Date: 08-2022
DOI: 10.1038/S41467-022-32254-8
Abstract: SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21–28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15–0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron.
Publisher: SAGE Publications
Date: 11-04-2011
Abstract: The purpose of this grounded theory study was to investigate how Danish HIV-positive persons live with their disease, focusing on HIV-related stressors. Using the Glaserian method, we analyzed textual data from in-depth interviews with 16 HIV-positive persons. Decisions about disclosure appeared to be a major concern and a determining factor for HIV-related stress. Consequently, we developed a substantive theory about disclosure decisions in which three different strategies could be identified: (a) disclosing to everyone (being open) (b) restricting disclosure (being partly open) and (c) disclosing to no one (being closed). Disclosure was a continuum none of the three strategies automatically relieved HIV-related stress. The theory describes the main determinants and consequences of each strategy. Our study demonstrates the importance of recurrent in idual considerations about disclosure choices and plans, and offers a theoretical basis for interventions designed to assist persons living with HIV to make the best possible in idual decisions regarding disclosure, and thereby reduce HIV-related stress.
Publisher: Wiley
Date: 22-08-2014
DOI: 10.1111/TMI.12378
Abstract: To calculate Tuberculosis (TB) incidence rates in Guinea-Bissau over an 8-year period. Since 2003, a surveillance system has registered all TB cases in six suburban districts of Bissau. In this population-based prospective follow-up study, 1205 cases of pulmonary TB were identified between January 2004 and December 2011. Incidence rates were calculated using census data from the Bandim Health and Demographic Surveillance System (HDSS). The overall incidence of pulmonary TB was 279 per 100,000 person-years of observation the male incidence being 385, and the female 191. TB incidence rates increased significantly with age in both sexes, regardless of smear or HIV status. Despite a peak with unknown cause of 352 per 100,000 in 2007, the overall incidence of pulmonary TB declined over the period. The incidence of HIV infected TB cases declined significantly from 108 to 39 per 100,000, while the incidence of smear-positive TB cases remained stable the overall figure was 188 per 100,000. Overall incidence of pulmonary TB in Guinea-Bissau has declined from 2004 to 2011. The decline was also seen in the subgroups of smear-negative and HIV-positive TB cases, probably due to antiretroviral treatment. Smear-positive TB incidence remains stable over the period.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Springer Science and Business Media LLC
Date: 18-11-2013
Publisher: Frontiers Media SA
Date: 23-11-2021
DOI: 10.3389/FIMMU.2021.779453
Abstract: Introduction of vaccines against COVID-19 has provided the most promising chance to control the world-wide COVID-19 pandemic. However, the adenovirus-vector based Oxford/AstraZeneca [ChAdOx1] (AZ) and Johnson & Johnson [Ad26.CoV2.S] COVID-19 vaccines have been linked with serious thromboembolic events combined with thrombocytopenia, denominated Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). The pathogenesis of COVID-19 VITT remain incompletely understood especially the initial events that trigger platelet activation, platelet factor (PF)4 release, complex formation and PF4 antibody production are puzzling. This is a prospective study investigating the impact of different COVID-19 vaccines on inflammation (CRP, TNF-α, IL-1β, IL-6, IL-8, IL-10), vascular endothelial activation (syndecan-1, thrombomodulin, E-selectin, ICAM-1, ICAM-3, VCAM-1), platelet activation (P-selectin, TGF-β, sCD40L) and aggregation (Multiplate ® impedance aggregometry), whole blood coagulation (ROTEM ® ), thrombin generation and PF4 antibodies to reveal potential differences between AZ and mRNA vaccines in in iduals without VITT. The study included 80 (55 AZ and 55 mRNA) vaccinated in iduals and 55 non-vaccinated age- and gender matched healthy controls. The main findings where that both vaccines enhanced inflammation and platelet activation, though AZ vaccination induced a more pronounced increase in several inflammatory and platelet activation markers compared to mRNA vaccination and that post-vaccination thrombin generation was higher following AZ vaccination compared to mRNA vaccination. No difference in neither the PF4 antibody level nor the proportion of in iduals with positive PF4 antibodies were observed between the vaccine groups. This is the first study to report enhanced inflammation, platelet activation and thrombin generation following AZ vaccination compared to mRNA vaccination in a head-to-head comparison. We speculate that specific components of the AZ adenovirus vector may serve as initial trigger(s) of (hyper)inflammation, platelet activation and thrombin generation, potentially lowering the threshold for a cascade of events that both trigger complications related to excessive inflammation, platelet and coagulation activation as observed in epidemiological studies and promote development of VITT when combined with high-titer functionally active PF4 antibodies.
Publisher: Wiley
Date: 2014
Publisher: Informa UK Limited
Date: 2006
DOI: 10.1080/00365540500434638
Abstract: The objective was to determine the incidence and prognosis of ventilator-associated pneumonia (VAP) in intensive care units (ICUs) in Melbourne (29-bed ICU), Australia and Aarhus and Aalborg (22-bed unit and 8-bed ICU, respectively), Denmark and to characterize participating ICUs with regard to prevalence of nosocomial type bacterial pathogens, antibiotic resistance and antibiotic consumption. In this prospective cohort study 25 patients in Melbourne and 32 patients in Aarhus + Aalborg had a first episode of VAP. The incidence of VAP per 1000 ventilator d was 6.2 in Melbourne and 9.5 in Aarhus + Aalborg. Case fatality during hospital admission was 28% and 59%, respectively (unadjusted odds ratio (OR) 0.3, 95% confidence interval (CI) 0.1-0.8). OR adjusted for age and APACHE II score was 0.2 (95% CI 0.1-1.0). Nosocomial type pathogens including methicillin resistant Staphylococcus aureus were more prevalent in Melbourne, and antibiotic consumption per VAP patient was 35% higher in Melbourne than in Aarhus + Aalborg. To judge from the present data, there seems to be a complicated interrelationship between prognosis on the 1 hand and antibiotic consumption and resistance on the other. A more favourable prognosis was found in Melbourne, where levels of antibiotic consumption and antimicrobial resistance were higher than in Aarhus + Aalborg.
Publisher: Informa UK Limited
Date: 09-2004
Publisher: Wiley
Date: 08-02-2019
DOI: 10.1111/HIV.12711
Abstract: The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected in iduals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173 81.3%), currently HCV RNA positive (3179 of 5173 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876 43.7%), completed HCV treatment (1598 of 3876 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876 30.8%), and cure (629 of 3876 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P < 0.0001). In the proposed HCV continuum of care for HIV/HCV-coinfected in iduals, we found major gaps at all stages, with almost 20% of anti-HCV-positive in iduals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.
Publisher: Elsevier BV
Date: 2016
Publisher: BMJ
Date: 06-2000
DOI: 10.1136/STI.76.3.169
Abstract: To evaluate the rate of recurrence of genital Chlamydia trachomatis infection after antibiotic therapy in a population of patients drawn from general practice, and to evaluate whether retesting after antibiotic therapy was advisable and, if so, whether it could be based on a strategy involving s les obtained at home and mailed to the laboratory for analysis. Prospective follow up study of 42 patients with genital C trachomatis infection drawn from general practice. Patients at or above the age of 18, with a positive urogenital swab s le obtained by a general practitioner were invited to participate. Follow up testing was based on LCR testing (LCx, Abbott diagnostics) of first void urinary and vaginal flush s les taken by the patients at home and mailed to the laboratory at weeks 2, 4, 8, 12, and 24 after antibiotic therapy. Cumulated incidence of recurrent infection was calculated to 29% (95% CI: 12%-46%) during the 24 weeks of follow up. Previous or present sexually transmitted diseases other than C trachomatis were significantly associated with recurrence (OR 6.1, p = 0.03). 89% of patients tested negative at week 2, and all patients tested negative at some point during the first 4-8 weeks. 84% of the test kits mailed to the patients were returned to the laboratory for analysis. Recurrence of C trachomatis after antibiotic treatment is a substantial problem. Retesting should be carried out, but not sooner than 12-24 weeks after treatment. Requiring patients to take tests at home appears to be a promising method for retesting.
Publisher: Elsevier BV
Date: 04-2023
Publisher: Informa UK Limited
Date: 05-2016
DOI: 10.2147/CLEP.S104379
Publisher: SAGE Publications
Date: 24-02-2022
DOI: 10.1177/09612033221080548
Abstract: Current treatment of Systemic Lupus Erythematosus (SLE) is suboptimal and causes broad immunosuppression. Therapeutic use of helminths or helminth products has been suggested for autoimmune diseases such as SLE. In the present study, we evaluated possible immunomodulating effects of adult body fluid (ABF) from Ascaris suum on peripheral blood mononuclear cells (PBMCs) from SLE patients in an ex vivo setup. PBMCs from SLE patients and healthy controls (HC) were isolated and stimulated ex vivo with ABF and Toll-like receptor agonists or activators of the stimulator of interferon genes (STING) or mitochondrial antiviral signaling protein (MAVS) pathways. After 24 h of incubation, the cytokine profile was analyzed using ELISA and Meso Scale Discovery techniques. ABF suppressed production of IL-6, TNF-α, CXCL10, and IL-10 by PBMCs from SLE patients and HCs following stimulation with specific agonists. ABF also reduced IFN-у production by stimulated PBMCs from HCs. Our data show that ABF has an immunomodulatory effect on the production of key cytokines in the pathogenesis of SLE. These results suggest that ABF or ABF components hold potential as a novel treatment option for SLE.
Publisher: Wiley
Date: 2014
Publisher: Public Library of Science (PLoS)
Date: 29-10-2020
Publisher: American Society for Microbiology
Date: 10-1995
DOI: 10.1128/JCM.33.10.2620-2623.1995
Abstract: A procedure for use of the Amplicor Chlamydia PCR with the Syva MicroTrak enzyme immunoassay (EIA) medium was developed, and the performance of the Syva MicroTrak EIA was evaluated by use of PCR and the Syva MicroTrak direct immunofluorescence assay (DFA) as confirmatory methods. PCR detected Chlamydia organisms at a 10-fold greater dilution than did DFA. Of 366 specimens, 119 specimens were positive by both PCR and DFA, 6 specimens were positive only by PCR, and 241 specimens were negative by both PCR and DFA. Subsequently, DFA and the developed PCR procedure were used prospectively for confirmation of EIA results in a defined negative gray zone between the cutoff value and 30% of the cutoff value (70% below the cutoff value). All specimens with results above the EIA cutoff value were also subjected to confirmation with DFA and PCR. EIA was performed on 7,748 endocervical swab specimens, of which 494 (6.4%) were subjected to confirmation, and on 968 male urethral swab specimens, of which 185 (19.1%) were subjected to confirmation. A "gold standard" was based on the findings by DFA and PCR, and ergent results were resolved by a major outer membrane protein-based PCR. Forty-five of 160 female specimens (28.1%) and 11 of 93 male specimens (11.8%) within the defined negative gray zone were found to be positive. Of 334 female specimens having absorbance unit (AU) values above the EIA cutoff value, 258 could be confirmed, thereby giving a positive predictive value of 77% (258/334). Accordingly, the positive predictive value with male specimens was 95% (87/92). The prevalence of Chlamydia trachomatis-positive specimens was 3.9% (303/7,748) in females and 10.1% (98/968) in males. All male specimens having AU values above 1.0 in the EIA were confirmed positive. In contrast to this, 16 females with AU values above 1.0 in the EIA could not be confirmed positive with either DFA or PCR. The mean age of these females was higher than that of patients testing negative for C. trachomatis (P 0.005). This might suggest an age-dependent change in vaginal colonization with an organism(s) crossreacting in the EIA. Thus, the PCR procedure developed can be used for confirmation of EIA results, testing specimens with AU values in the defined negative gray zone improves the sensitivity of EIA, and all specimens testing positive in EIA should be subjected to confirmation.
Publisher: Wiley
Date: 11-2004
Publisher: Elsevier BV
Date: 10-2020
Publisher: American Society for Clinical Investigation
Date: 17-08-2017
Publisher: Springer Science and Business Media LLC
Date: 17-10-2022
DOI: 10.1038/S41591-022-02023-7
Abstract: Attempts to reduce the human immunodeficiency virus type 1 (HIV-1) reservoir and induce antiretroviral therapy (ART)-free virologic control have largely been unsuccessful. In this phase 1b/2a, open-label, randomized controlled trial using a four-group factorial design, we investigated whether early intervention in newly diagnosed people with HIV-1 with a monoclonal anti-HIV-1 antibody with a CD4-binding site, 3BNC117, followed by a histone deacetylase inhibitor, romidepsin, shortly after ART initiation altered the course of HIV-1 infection ( NCT03041012 ). The trial was undertaken in five hospitals in Denmark and two hospitals in the United Kingdom. The coprimary endpoints were analysis of initial virus decay kinetics and changes in the frequency of CD4 + T cells containing intact HIV-1 provirus from baseline to day 365. Secondary endpoints included changes in the frequency of infected CD4 + T cells and virus-specific CD8 + T cell immunity from baseline to day 365, pre-ART plasma HIV-1 3BNC117 sensitivity, safety and tolerability, and time to loss of virologic control during a 12-week analytical ART interruption that started at day 400. In 55 newly diagnosed people (5 females and 50 males) with HIV-1 who received random allocation treatment, we found that early 3BNC117 treatment with or without romidepsin enhanced plasma HIV-1 RNA decay rates compared to ART only. Furthermore, 3BNC117 treatment accelerated clearance of infected cells compared to ART only. All groups had significant reductions in the frequency of CD4 + T cells containing intact HIV-1 provirus. At day 365, early 3BNC117 + romidepsin was associated with enhanced HIV-1 Gag-specific CD8 + T cell immunity compared to ART only. The observed virological and immunological effects of 3BNC117 were most pronounced in in iduals whose pre-ART plasma HIV-1 envelope sequences were antibody sensitive. The results were not disaggregated by sex. Adverse events were mild to moderate and similar between the groups. During a 12-week analytical ART interruption among 20 participants, 3BNC117-treated in iduals harboring sensitive viruses were significantly more likely to maintain ART-free virologic control than other participants. We conclude that 3BNC117 at ART initiation enhanced elimination of plasma viruses and infected cells, enhanced HIV-1-specific CD8 + immunity and was associated with sustained ART-free virologic control among persons with 3BNC117-sensitive virus. These findings strongly support interventions administered at the time of ART initiation as a strategy to limit long-term HIV-1 persistence.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-01-2009
Publisher: Springer Science and Business Media LLC
Date: 2008
Publisher: American Society for Microbiology
Date: 05-2012
DOI: 10.1128/IAI.00079-12
Abstract: Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs, CpG ODN, are Toll-like receptor 9 agonists (TLR9a), which have been used as adjuvants in pneumococcal vaccines to improve antibody responses in immunodeficient patients. Here, we examined whether the coadministration of TLR9a with pneumococcal CRM 197 -conjugate vaccine enhances protection against pneumococcal colonization, the levels of antipolysaccharide antibodies, and the CD4 + T-cell responses. Wild-type BALB/c mice and B-cell-deficient BALB/c Igh-J tm1Dhu mice were immunized twice with the following: (i) PCV alone (ii) simultaneous PCV and TLR9a (iii) PCV and then TLR9a, after a 48-h delay (iv) TLR9a alone and (v) phosphate-buffered saline. Nasopharyngeal protection, serum antibodies, CD4 + T-cell responses, and clearance of bacteremia after intraperitoneal challenge with Streptococcus pneumoniae 6B were evaluated. We found decreased nasopharyngeal protection against S. pneumoniae 6B colonization after simultaneous immunization with PCV and TLR9a compared to immunization with PCV alone in wild-type BALB/c mice ( P = 0.037). A similar trend was observed in B-cell-deficient BALB/c Igh-J tm1Dhu mice. Simultaneous administration did not enhance antibody levels and lowered the CRM 197 -specific cytokine release of gamma interferon, interleukin-2 (IL-2), IL-5 and IL-13. Immunization with PCV and then TLR9a, after a 48-h delay, significantly improved nasopharyngeal protection compared to simultaneous administration ( P = 0.011). Furthermore, delaying TLR9a delivery increased antibody titers compared to both simultaneous administration ( P = 0.001) and PCV immunization alone ( P = 0.026). In conclusion, the immunological and clinical impact of adjuvanting a pneumococcal conjugate vaccine (Prevnar Pfizer) with a TLR9a is highly depended on timing of the adjuvant administration. Thus, careful timing of adjuvant administration may improve novel vaccine formulations.
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/00365540801914833
Abstract: The main object was to examine the diagnostic performance of a novel combination of a specific real-time PCR (combined real-time PCR) for immediate and simultaneous detection of Streptococcus pneumoniae and Neisseria meningitidis and of a real-time PCR of the 16S rRNA gene (16S DNA). During 12 months, 1015 routine CSF s les were consecutively collected from patients in the County of Aarhus, Denmark. The s les were cultured, examined by microscopy, and, in parallel, CSF DNA was automatically purified and subjected to real-time PCR. Melting curve analysis discriminated between the 2 specific pathogens and 16S DNA positive s les were sequenced. Clinical data were extracted from patients having positive s les. Clinically, 35 of 46 (76%) patients with positive s les had bacterial meningitis. 18 of these 35 patients had a concomitant culture and real-time PCR-positive s le. The remaining 17 patients were either culture positive (n =7) or real-time PCR-positive (n = 10). The aetiology of bacterial meningitis was revealed by microscopy in 18/35 (51.4%), culture in 24/35 (68.6%) and combined real-time PCR in 27/35 (77.1%) patients, respectively. In conclusion, the combined real-time PCR strategy is superior to microscopy and a valuable supplement to routine culture to establish the aetiology of bacterial meningitis.
Publisher: Oxford University Press (OUP)
Date: 21-12-2022
DOI: 10.1093/OFID/OFAC679
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with persistent symptoms (“long COVID”). We assessed the burden of long COVID among nonhospitalized adults with polymerase chain reaction (PCR)–confirmed SARS-CoV-2 infection. In the fall of 2020, a cross-sectional survey was performed in the adult Danish general population. This included a self-administered point-of-care test for SARS-CoV-2 antibodies, the Short Form Health Survey (SF-12), and coronavirus disease 2019 (COVID-19)–associated symptom questions. Nonhospitalized respondents with a positive SARS-CoV-2 PCR test ≥12 weeks before the survey (cases) were matched (1:10) to seronegative controls on age, sex, and body mass index. Propensity score–weighted odds ratios (ORs) and ORs for risk factors were estimated for each health outcome. In total, 742 cases and 7420 controls were included. The attributable risk of at least 1 long-COVID symptom was 25.0 per 100 cases (95% confidence interval [CI], 22.2–27.4). Compared to controls, cases reported worse general health (OR, 5.9 [95% CI, 5.0–7.0]) and had higher odds for a broad range of symptoms, particularly loss of taste (OR, 11.8 [95% CI, 9.5–14.6]) and smell (OR, 11.2 [95% CI, 9.1–13.9]). Physical and Mental Component Summary scores were also significantly reduced with differences of −2.5 (95% CI, −3.1 to −1.8) and −2.0 (95% CI, −2.7 to −1.2), respectively. Female sex and severity of initial infection were major risk factors for long COVID. Nonhospitalized SARS-CoV-2 PCR–positive in iduals had significantly reduced physical and mental health, and 1 in 4 reported persistence of at least 1 long-COVID symptom.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2015
DOI: 10.1038/GENE.2015.46
Abstract: Herpes simplex encephalitis (HSE) in children has previously been linked to defects in type I interferon production downstream of Toll-like receptor (TLR)3. In the present study, we used whole-exome sequencing to investigate the genetic profile of 16 adult patients with a history of HSE. We identified novel mutations in IRF3, TYK2 and MAVS, molecules involved in generating innate antiviral immune responses, which have not previously been associated with HSE. Moreover, data revealed mutations in TLR3, TRIF, TBK1 and STAT1 known to be associated with HSE in children but not previously described in adults. All discovered mutations were heterozygous missense mutations, the majority of which were associated with significantly decreased antiviral responses to HSV-1 infection and/or the TLR3 agonist poly(I:C) in patient peripheral blood mononuclear cells compared with controls. Altogether, this study demonstrates novel mutations in the TLR3 signaling pathway in molecules previously identified in children, suggesting that impaired innate immunity to HSV-1 may also increase susceptibility to HSE in adults. Importantly, the identification of mutations in innate signaling molecules not directly involved in TLR3 signaling suggests the existence of innate immunodeficiencies predisposing to HSE beyond the TLR3 pathway.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JINF.2016.09.004
Abstract: We aimed to investigate the incidence and mortality of herpes simplex encephalitis (HSE) in a nationwide cohort. From the Danish National Patient Registry, we identified all adults hospitalised with a first-time diagnosis of HSE in Denmark during 2004-2014. The HSE diagnoses were verified using medical records and microbiological data. Patients were followed for mortality through the Danish Civil Registry System. We estimated age-standardised incidence rates of HSE and 30-day, 60-day, and 1-year cumulative mortality. Furthermore, we assessed whether calendar year, age, gender, level of comorbidity, virus type, and department type was associated with HSE mortality. We identified a total of 230 cases of HSE. Median age was 60.7 years (interquartile range: 49.3-71.6). The overall incidence rate was 4.64 cases per million population per year (95% confidence interval: 4.06-5.28). The cumulative mortality within 30 days, 60 days, and 1 year of the HSE admission was 8.3%, 11.3%, and 18.6%, respectively. Advanced age and presence of comorbidity were associated with increased 60-day and 1-year mortality. This nationwide study of verified HSE found a higher incidence than reported in previous nationwide studies. Presence of comorbidity was identified as a novel adverse prognostic factor. Mortality rates following HSE remain high.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Informa UK Limited
Date: 2001
DOI: 10.1080/00365540110076642
Abstract: We present a case of group A streptococcal pyomyositis of the thoraco-abdominal wall of an immunocompetent adult. This diagnosis was made when soft tissue swelling was seen on chest X-ray. Complete recovery followed drainage of the collection and short-course i.v. penicillin. The importance, diagnosis and treatment of pyomyositis are outlined.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1038/MI.2017.59
Publisher: Springer Science and Business Media LLC
Date: 30-09-2022
DOI: 10.1038/S41598-022-19629-Z
Abstract: Passive immunotherapy with convalescent plasma may be the only available agent during the early phases of a pandemic. Here, we report safety and efficacy of high-titer convalescent plasma for COVID-19 pneumonia. Double-blinded randomized multicenter placebo-controlled trial of adult patients hospitalized with COVID-19 pneumonia. The intervention was COVID-19 convalescent plasma and placebo was saline allocated 2:1. The primary outcome was clinical status 14 days after the intervention evaluated on a clinical ordinal scale. The trial was registered at ClinicalTrials.Gov, NCT04345289, 14/04/2020. The CCAP-2 trial was terminated prematurely due to futility. Of 147 patients randomized, we included 144 patients in the modified intention-to-treat population. The ordinal clinical status 14 days post-intervention was comparable between treatment groups (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.72–2.09). Results were consistent when evaluating clinical progression on an in idual level 14 days after intervention (OR 1.09 95% CI 0.46–1.73). No significant differences in length of hospital stay, admission to ICU, frequency of severe adverse events or all-cause mortality during follow-up were found between the intervention and the placebo group. Infusion of convalescent plasma did not influence clinical progression, survival or length of hospitalization in patients with COVID-19 pneumonia.
Publisher: Frontiers Media SA
Date: 13-05-2022
Abstract: Persistent cardiac symptoms are an increasingly reported phenomenon following COVID-19. However, the underlying cause of cardiac symptoms is unknown. This study aimed to identify the underlying causes, if any, of these symptoms 1 year following acute COVID-19 infection. 22 in iduals with persistent cardiac symptoms were prospectively investigated using echocardiography, cardiovascular magnetic resonance (CMR), 6-min walking test, cardio-pulmonary exercise testing and electrocardiography. A median of 382 days (IQR 368, 442) passed between diagnosis of COVID-19 and investigation. As a cohort their echocardiography, CMR, 6-min walking test and exercise testing results were within the normal ranges. There were no differences in left ventricular ejection fraction (61.45 ± 6.59 %), global longitudinal strain (19.80 ± 3.12 %) or tricuspid annular plane systolic excursion (24.96 ± 5.55 mm) as measured by echocardiography compared to a healthy control group. VO2 max (2045.00 ± 658.40 ml/min), % expected VO2 max (114.80 ± 23.08 %) and 6-minute distance walked (608.90 ± 54.51 m) exceeded that expected for the patient cohort, whilst Troponin I (5.59 ± 6.59 ng/l) and Nt-proBNP (88.18 ± 54.27 ng/l) were normal. Among a cohort of 22 patients with self-reported persistent cardiac symptoms, we identified no underlying cardiac disease or reduced cardiopulmonary fitness 1 year following COVID-19.
Publisher: Oxford University Press (OUP)
Date: 15-04-2008
DOI: 10.1086/586713
Abstract: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group, participants started ART when the CD4+ cell count was or= 6 months (n=228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death) (ii) OD (fatal or nonfatal) (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths and (iv) the composite of outcomes (ii) and (iii). A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for >or= 6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for 6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56 p=.02) outcome (ii), 3.26 (95% CI, 1.04-10.25 p=.04) outcome (iii), 7.02 (95% CI, 1.57-31.38 p=.01) and outcome (iv), 4.19 (95% CI, 1.69-10.39 p=.002 ). Initiation of ART at CD4+ cell counts >350 cells/microL compared with <250 cells/microL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial.
Publisher: Oxford University Press (OUP)
Date: 26-04-2015
Abstract: Data regarding the association between diabetes mellitus (DM) and tuberculosis (TB) in Africa are scare. We did a DM screening survey among TB patients and non-TB controls in Guinea-Bissau. The study was conducted at the Bandim Health Project (BHP) in the capital Bissau. From July 2010 to July 2011, newly diagnosed TB cases were identified through a TB notification system. Concurrently, non-TB controls were selected randomly from the BHP's demographic surveillance database and visited at home. Participants were tested using fasting blood glucose (FBG) measurements. DM was diagnosed as FBG ≥ 7 mmol/l. Our survey was linked to the patient database at the only existing Diabetes Clinic in Bissau. TB patients (n=110) were older than the controls (n=572) (35 vs 31 years p=0.02), more often male (55% vs 37% p<0.001) and had a lower body mass index (18.7 vs 24.2 kg/m(2) p<0.001). The prevalence of DM was 2.8% (3/107) for TB patients and 2.1% (11/531) for controls (p=0.64). Excluding two controls already receiving anti-diabetic treatment, the prevalence of DM was 2.8% (3/107) vs 1.7% (9/529) (p=0.44). The prevalence of DM was low, also among TB patients. No association between DM and TB was found.
Publisher: Informa UK Limited
Date: 2009
DOI: 10.1080/00365540902946536
Abstract: In this retrospective study of 332 cases of Legionnaires' disease (LD) in 4 Danish counties between 1995 and 2005 we aimed to compare the sensitivity of culture, PCR, urinary antigen testing, and serology to the mode of acquisition, serogroup, and severity of disease. Furthermore, we analyzed time to diagnosis. Laboratory confirmed cases of LD were found through the national Danish surveillance system and departments of clinical microbiology. In our study PCR was more sensitive (79.2%) than urinary antigen testing (70.4%), serology (54.8%), and culture (39.9%) (p<0.001).The sensitivity of Legionella urinary antigen test was higher among travel-associated cases (90.2%) compared to non-travel-associated cases (65.8%) and hospital acquired cases (45.7%) (p<0.001). Overall, the most common species and serogroup identified was L. pneumophila serogroup 1 (64.3% (110/171)). Community acquired cases with serogroup 1 were diagnosed earlier (mean 5 d, IQR: 4-9 d) than community acquired cases with other species or serogroups (mean 10.5 d, IQR: 5-19.5) (p<0.001). In conclusion, the urinary antigen test, PCR, and culture were conducive to the diagnosis of Legionella infection, and ordering of all 3 tests is recommended to ensure a definite and rapid diagnosis of Legionella.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Informa UK Limited
Date: 2000
DOI: 10.1080/003655400750045259
Abstract: A total of 11 HIV-1 positive patients, with CD4+ cell counts between 200 and 500/microl, who were in stable anti-retroviral therapy, were treated with subcutaneous recombinant human IL-2 thrice weekly administered on an out-patient basis in a dose-escalating manner. Subcutaneous IL-2 was well tolerated and associated with only mild to moderate constitutional symptoms and local inflammation at the injection site. CD4+ cell count increased from 404 +/- 48/microl at baseline to 639 +/- 88/microl at week 6, with proportionate increases in naive cells and memory cells. Increased doses of IL-2 were then needed to sustain the number of CD4+ cells. After discontinuation of IL-2 treatment, CD4+ cell count returned to baseline levels. IL-2 induced a reduction in the percentage of CD8+ CD38+ and CD8+ HLA-DR+ cells, an increase in the fraction of CD8+ CD25+ and CD8+ CD122+, and an elevation in the number of NK-cells. IL-2 did not induce any clinically significant change in plasma HIV-RNA. In conclusion, IL-2 can safely be administered subcutaneously on an out-patient basis to HIV-infected in iduals with CD4+ cell counts from 200/microl to 500/microl and with some improvement in immunological abnormalities. Continuous therapy, however, seems to result in the development of tachyphylaxia.
Publisher: Public Library of Science (PLoS)
Date: 27-02-2012
Publisher: Proceedings of the National Academy of Sciences
Date: 23-10-2013
Abstract: HIV-1 is a lentivirus and replicates through a replication cycle involving several DNA forms including ssDNA. Here we report that synthetic DNA oligos corresponding to DNA forms of the lentivirus replication cycle as well as viral DNA are detected by the immunological DNA sensor IFN-inducible protein 16 (IFI16) and stimulate innate immune responses through a pathway dependent on stimulator of IFN genes (STING). Moreover, we show that replication of HIV-1 is elevated in cells with decreased expression of IFI16 or STING. We suggest IFI16 is a sensor for lentivirus DNA in macrophages stimulating innate immune responses, which contribute to early control of the virus.
Publisher: American Medical Association (AMA)
Date: 06-04-2011
Publisher: Wiley
Date: 26-07-2010
DOI: 10.1002/CNCR.25311
Abstract: In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported on the relationship between immunodeficiency and the development of some non-AIDS-defining malignancies. A total of 14,453 patients from the prospective, multinational EuroSIDA cohort were included. Malignancies were classified as virus-related, non-virus-related epithelial, and other. The incidence of non-AIDS-defining malignancies was calculated stratified by current CD4 count. Poisson regression was used to investigate factors associated with the development of non-AIDS-defining malignancies. A total of 356 non-AIDS-defining malignancies occurred, with an incidence rate of 4.3 per 1000 person years of follow-up (95% confidence interval [CI], 3.8-4.7) 172 (48.3%) were virus-related, 135 (37.9%) were non-virus-related epithelial, and 49 (13.7%) were classified as other. Anal (69 cases), lung (31 cases), and melanoma (13 cases), respectively, were the most common non-AIDS-defining malignancies within each group. After adjustment, current CD4 was associated with virus-related non-AIDS-defining malignancies (incidence rate ratio [IRR], 0.81 per doubling 95% CI, 0.75-0.88 P < .0001) and non-virus-related epithelial non-AIDS-defining malignancies (IRR, 0.84 95% CI, 0.75-0.95 P = .004), but not with other non-AIDS-defining malignancies (IRR, 1.04 95% CI, 0.83-1.31 P = .73). Current CD4 count was also associated with anal cancer (IRR, 0.86 95% CI, 0.75-0.99 P = .03), Hodgkin lymphoma (n = 52 IRR, 0.83 95% CI, 0.73-0.95 P = .005), and lung cancer (IRR, 0.76 95% CI, 0.64-0.90 P = .0002). A low current CD4 count was associated with an increased incidence of certain non-AIDS-defining malignancies. Starting cART earlier to reduce the proportion of patients with a low CD4 count may decrease the rate of developing many common non-AIDS-related malignancies. A randomized trial to explore this strategy is urgently needed.
Publisher: MyJove Corporation
Date: 31-01-2019
DOI: 10.3791/60723
Publisher: Wiley
Date: 08-11-2010
DOI: 10.1111/J.1468-1293.2010.00892.X
Abstract: The effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV-23) in preventing pneumococcal disease in HIV-infected people is a subject of debate. We reviewed the clinical evidence for recommending PPV-23 for use in HIV-infected patients. A systematic search of peer-reviewed publications (EMBASE, the Cochrane Library, and PubMed/BioMed Central), the Internet and grey literature was conducted. Three hundred and eighteen documents were reviewed. Studies reporting risk estimates for all-cause pneumonia, all-pneumococcal disease, and/or invasive pneumococcal disease after PPV-23 immunization in HIV-infected adults were included. We identified one randomized trial and 15 observational studies. While the randomized trial found a 60% increased risk of all-cause pneumonia among vaccinees, 11 of the 15 observational studies found various degrees of disease protection associated with PPV-23 immunization. However, most studies suffered from limited confounder control in their multivariate analyses, despite study data suggesting substantial differences between the characteristics of exposed and unexposed in iduals. The current clinical evidence provides only moderate support for PPV-23 immunization of HIV-infected adults. More data are needed on the efficacy of newer conjugated pneumococcal vaccines, which may be more immunogenic and could potentially replace PPV-23 in the future.
Publisher: Elsevier BV
Date: 12-2016
Publisher: Informa UK Limited
Date: 11-04-2018
Publisher: Springer Science and Business Media LLC
Date: 06-08-2022
DOI: 10.1186/S12981-022-00457-0
Abstract: Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce. Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann–Whitney U test and Chi-square test. A logistic regression model was used to compare participants’ characteristics by treatment group. Kaplan–Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values 50 copies/mL). 1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3–5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p 0.001). Our estimates of VF 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS).
Publisher: Wiley
Date: 28-07-2015
DOI: 10.1111/HIV.12294
Abstract: The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of cardiovascular disease (CVD) and diabetes. We analysed data from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre-ART) to 1 year after initiation (continuous variable) in treatment-naïve in iduals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI [weight (kg)/(height (m))(2)] was categorized as underweight ( 30). Poisson regression models were fitted stratified for each pre-ART BMI category to allow for category-specific estimates of incidence rate ratio (IRR). Models were adjusted for pre-ART BMI and CD4 count, key known risk factors (time-updated where possible) and calendar year. A total of 97 CVD events occurred in 43,982 person-years (n = 9321) and 125 diabetes events in 43,278 person-years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre-ART BMI category, was: underweight, 0.90 (0.60-1.37) normal, 1.18 (1.05-1.33) overweight, 0.87 (0.70-1.10), and obese, 0.95 (0.71-1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre-ART BMI (P for interaction > 0.05). Short-term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre-ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre-ART BMI.
Publisher: American Society for Microbiology
Date: 05-2016
DOI: 10.1128/JVI.00222-16
Abstract: Toll-like receptor (TLR) agonists are potent enhancers of innate antiviral immunity and may also reverse HIV-1 latency. Therefore, TLR agonists have a potential role in the context of a “shock-and-kill” approach to eradicate HIV-1. Our extensive preclinical evaluation suggests that a novel TLR9 agonist, MGN1703, may indeed perform both functions in an HIV-1 eradication trial. Peripheral blood mononuclear cells (PBMCs) from aviremic HIV-1-infected donors on antiretroviral therapy (ART) that were incubated with MGN1703 ex vivo exhibited increased secretion of interferon alpha (IFN-α) ( P = 0.005) and CXCL10 ( P = 0.0005) in culture supernatants. Within the incubated PBMC pool, there were higher proportions of CD69-positive CD56 dim CD16 + NK cells ( P = 0.001) as well as higher proportions of CD107a-positive ( P = 0.002) and IFN-γ-producing ( P = 0.038) NK cells. Incubation with MGN1703 also increased the proportions of CD69-expressing CD4 + and CD8 + T cells. Furthermore, CD4 + T cells within the pool of MGN1703-incubated PBMCs showed enhanced levels of unspliced HIV-1 RNA ( P = 0.036). Importantly, MGN1703 increased the capacity of NK cells to inhibit virus spread within a culture of autologous CD4 + T cells assessed by using an HIV-1 p24 enzyme-linked immunosorbent assay (ELISA) ( P = 0.03). In conclusion, we show that MGN1703 induced strong antiviral innate immune responses, enhanced HIV-1 transcription, and boosted NK cell-mediated suppression of HIV-1 infection in autologous CD4 + T cells. These findings support clinical testing of MGN1703 in HIV-1 eradication trials. IMPORTANCE We demonstrate that MGN1703 (a TLR9 agonist currently undergoing phase 3 clinical testing for the treatment of metastatic colorectal cancer) induces potent antiviral responses in immune effector cells from HIV-1-infected in iduals on suppressive antiretroviral therapy. The significantly improved safety and tolerability profiles of MGN1703 versus TLR9 agonists of the CpG-oligodeoxynucleotide (CpG-ODN) family are due to its novel “dumbbell-shape” structure made of covalently closed, natural DNA. In our study, we found that incubation of peripheral blood mononuclear cells with MGN1703 results in natural killer cell activation and increased natural killer cell function, which significantly inhibited the spread of HIV in a culture of autologous CD4 + T cells. Furthermore, we discovered that MGN1703-mediated activation can enhance HIV-1 transcription in CD4 + T cells, suggesting that this molecule may serve a dual purpose in HIV-1 eradication therapy: enhanced immune function and latency reversal. These findings provide a strong preclinical basis for the inclusion of MGN1703 in an HIV eradication clinical trial.
Publisher: Public Library of Science (PLoS)
Date: 18-06-2013
Publisher: Wiley
Date: 08-06-2023
Abstract: The treatment of implant‐associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic‐tolerant persister cells. This need is addressed herein through an engineering of antibody‐drug conjugates (ADCs) that contain an anti‐neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non‐specific counterpart, in suspension and within biofilms, in vitro, and in an implant‐associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms.
Publisher: Elsevier BV
Date: 2023
Publisher: Oxford University Press (OUP)
Date: 06-2001
DOI: 10.1086/320718
Abstract: Chlamydia pneumoniae has been associated with cardiovascular diseases, and C. pneumoniae infection is treatable with macrolides. In this comparative cohort study, 634 users of macrolides and 3827 users of penicillins were identified from the Danish Health Service Registry of Prescriptions and followed up for an average of 6 months. The patients were then linked to the Regional Hospital Discharge Registry to assess the outcome of hospitalization for cardiovascular disease. In the first 3 months, the relative risk (RR) of admission for a cardiovascular disease was 0.48 (95% confidence interval, 0.27-0.88) in users of macrolides compared with users of penicillins. No difference was seen after 3 months. Interaction analyses indicated that the lower risk seen in users of macrolides could be more pronounced in patients without versus those with a previous cardiovascular disease (RR, 0.39 vs. 0.52), in patients >or=60 versus <60 years old (RR, 0.39 vs. 0.64), and in men versus women (RR, 0.35 vs. 0.67).
Publisher: Springer Science and Business Media LLC
Date: 03-2003
DOI: 10.1007/S11908-003-0052-4
Abstract: During the past several years, research related to screening for Chlamydia trachomatis has flourished, with new diagnostic tests, new methods for specimen collection, and new prevalence data in different populations. Public health endorsements for screening are now more specific than ever, yet several important clinical and laboratory questions remain, including questions concerning who to screen and how often to screen. Additional important research is addressing issues related to assay validity, efficacy of screening in different populations, and feasibility of screening on the level of the in idual patient and the level of the community and health care system. This article discusses major research findings related to chlamydial screening from the past several years and suggests areas in which additional research is needed.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Wiley
Date: 16-10-2006
DOI: 10.1111/J.1365-3083.2006.01856.X
Abstract: Neisseria meningitidis causes acute severe diseases, including sepsis and meningitis, and more benign manifestations such as chronic meningococcemia or colonization of the upper respiratory tract. The inflammatory response, which contributes to the pathogenesis of meningococcal disease, is initiated by pattern recognition receptors, among which Toll-like receptors (TLR)s have been ascribed a particularly important role. We have previously demonstrated that N. meningitidis induce proinflammatory cytokine expression through TLR2 and TLR4. Here we characterize the molecular basis for differential activation of the inflammatory response by two N. meningitidis strains. This difference was due to differential ability to activate signal transduction through TLR4, as HEK293 cells expressing TLR4 produced significantly different levels of interleukin-8 in response to these strains. At the level of signal transduction, the two strains differed substantially in their ability to activate the pathway to nuclear factor kappaB in HEK293-TLR4/MD2 cells at late, but not early, time points. TLR4 activates two signal transduction pathways: one dependent on the adaptor molecule MyD88 and one independent of MyD88, and these pathways induce distinct patterns of gene expression in response to TLR4 ligands. By using macrophages from TLR2-/- mice, we observed that the two strains differed in their ability to activate the TLR4-induced MyD88-independent pathway, but not the MyD88-dependent pathway. This idea was further supported by experiments where either of the two pathways was inhibited and IL-8 secretion was measured. These data therefore provide molecular insight into activation of the inflammatory response by N. meningitidis, which is one of the key events in the pathogenesis of meningococcal disease.
Publisher: BMJ
Date: 12-1997
DOI: 10.1136/STI.73.6.493
Abstract: To investigate, by use of the Amplicor PCR in a routine setting, the recovery rate of Chlamydia trachomatis in ano-rectal and pharyngeal swab s les obtained from males and females attending an STD clinic in relation to sexual practices, symptoms, and signs. Data regarding sexual practices, and symptoms and signs related to the rectum and pharynx, were obtained from 196 females and 208 males, including 31 homosexuals and eight bisexuals. Swab s les were obtained from the urethra, rectum, and pharynx from all the patients. An additional endocervical swab s le was obtained from the females. All s les were analysed by the Amplicor PCR (Roche). Rudolph Bergh's Hospital, a clinic for sexually transmitted diseases situated in the centre of Copenhagen, Denmark. The overall prevalence of urogenital C trachomatis infection was 9.2% (37/404). The specificity of the Amplicor PCR was 100% for both ano-rectal and pharyngeal swab s les. In females three (13%) of the 23 infections were detected only by testing an ano-rectal or throat swab s le. In homosexual males two (67%) of three infections were detected only by the anorectal swab s le. Ano-rectal intercourse without use of condom was reported by 44% of females and by 52% of homosexual males. Fellatio without condom use was reported by 91% of females, and 80% of heterosexual males practised cunnilingus. Pharyngeal infection, however, occurred only in females, and the presence of pharyngeal symptoms or signs seemed predictive for pharyngeal C trachomatis infection, for which the time of incubation or colonisation exceeded 3 months. The presence of ano-rectal signs or symptoms was not predictive for an ano-rectal C trachomatis infection. The Amplicor PCR can be used on ano-rectal and pharyngeal swab s les. Ano-rectal swab s les should be obtained in females and homosexual males at high risk of being infected. Pharyngeal s les should be taken in females at high risk of being infected, especially when pharyngeal signs or symptoms are present.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2021
Publisher: Mary Ann Liebert Inc
Date: 05-2017
Abstract: Human immunodeficiency virus (HIV) infection is a stressful disease, and depression is the most common form of psychologic distress experienced by those infected. The aim of this study was to further develop and validate a mind-body intervention to improve coping self-efficacy strategies and increase mental health. Feasibility study, a randomized trial. Participants were assigned into two blocks (female/male) and simple randomization in a 1:1 ratio was performed within each block to one of two arms (1) intervention group, (2) control group who received usual care. Setting/Location and Subjects: The authors enrolled 30 HIV-infected in iduals (10 women and 20 men) who had psychologic challenges and were motivated for working with personal development at the Department of Infectious Diseases at Aarhus University Hospital, Denmark. The intervention was a group intervention facilitated by an educated coach. The framework was a 3-day residential course plus two single-day/8-h follow-up events. The intervention was based primarily on a Native American philosophy of life and its understanding of how changes affect human beings and create imbalance. Primary outcomes were change in risk of depression and level of coping self-efficacy. Secondary outcomes were change in levels of stress and personal growth. Significant improvement between the intervention group and control group was seen in risk of depression and personal growth mean values from baseline to 6-month follow-up. Significant improvements were shown within the intervention group in mean values of risk of depression, coping self-efficacy, stress, and personal growth. There were no significant improvements within the control group. The authors suggest that interventions designed to increase resilience through enhancing coping self-efficacy be used in conjunction with HIV medication to make this approach and especially the "whole-person" commitment a fully integrated aspect of HIV care.
Publisher: BMJ
Date: 02-05-2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2005
DOI: 10.1097/01.OLQ.0000154512.86651.07
Abstract: Recent studies have shown that women with Chlamydia trachomatis-positive test results worry about their future fertility. The goal of this study was to give women infected with C. trachomatis a fertility prognosis by analyzing ectopic pregnancies and birth rates An historical follow-up study in a cohort of 22,264 women tested for the infection was conducted. Cox regression analysis with time-dependent covariates showed that women with at least 1 C. trachomatis-positive test result had a lower incidence rate of ectopic pregnancy than women with negative test results only (adjusted hazard ratio, 0.55 95% confidence interval [CI], 0.31-0.96). We found comparable birth rates in the 2 groups (adjusted hazard ratio, 0.92 95% CI, 0.84-1.00). Counseling of women with a C. trachomatis-positive test result should emphasize the benefit of detection and treatment of the infection in terms of future morbidity.
Publisher: BMJ
Date: 31-01-1998
Publisher: Springer Science and Business Media LLC
Date: 08-07-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2020
Publisher: Oxford University Press (OUP)
Date: 08-2001
DOI: 10.1046/J.0007-1323.2001.01845.X
Abstract: Macrolide treatment has been reported to lower the risk of recurrent ischaemic heart disease. The influence of macrolides on the expansion rate of abdominal aortic aneurysms (AAAs) remains unknown. The aim was to investigate the effect of roxithromycin on the expansion rate of small AAAs. A total of 92 subjects with a small AAA were recruited from two populations. One population consisted of 6339 men aged 65–73 years who were offered a hospital-based mass screening programme for AAA. From this population 66 subjects were recruited. The remaining 26 men were recruited from among 49 subjects diagnosed at interval screening for an initial aortic diameter between 25 and 29 mm. Subjects were randomized to receive either oral roxithromycin 300 mg once daily for 28 days or matching placebo, and followed for a mean of 1·5 years. The mean annual expansion rate of AAAs was reduced by 43 per cent in the intervention group (1·56 mm per year), compared with 2·75 mm per year following placebo (P = 0·02). Multiple linear regression analysis showed that roxithromycin treatment and initial AAA size were significantly related to AAA expansion when adjusted for smoking, diastolic blood pressure and immunoglobulin A level of 20 enzyme immunounits or more. Logistic regression analysis confirmed a significant difference in expansion rates above 2 mm annually between the intervention and placebo groups: odds ratio = 0·09 (95 per cent confidence interval 0·01–0·75). In comparison to placebo, roxithromycin 300 mg daily for 4 weeks reduced the expansion rate of AAAs.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Wiley
Date: 19-05-2014
DOI: 10.1111/HIV.12162
Abstract: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-11-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-03-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-06-2015
Publisher: Elsevier BV
Date: 03-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-11-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-08-2018
Publisher: Springer Science and Business Media LLC
Date: 11-03-2015
Publisher: Bentham Science Publishers Ltd.
Date: 03-2003
Abstract: Seroepidemiological studies have shown an association between Chlamydia pneumoniae and atherosclerosis, the risk of acute myocardial infarction and abdominal aortic aneurysms (AAA). Several studies have detected C. pneumoniae in atherosclerotic lesions from coronary and carotid arteries, in AAA, and in sclerotic aortic valves. However, culturing of C. pneumoniae is difficult and has seldomly succeeded from atherosclerotic lesions. Thus, the pathogenicity is unknown, and the significance of detecting the organism is unresolved. Nevertheless, in a large observational study comparing the risk of cardiovascular events among recipients of macrolide versus pencillins, macrolide treatment reduced the risk of such events after relevant adjustment. Furthermore, in two out of three minor randomized clinical trials were patients with ischaemic heart disease were randomized into antibiotic treated and placebo groups, a significant reduction in serious end-points were noticed in patients receiving macrolide. Similarly, two other minor randomized trials showed that macrolide treatment inhibited growth of small AAA. Macrolide therapy thus seems potential to improve the outcome of severe ischaemic heart disease, and growth of AAA. If true, it not known whether this is transient because of macrolide's non-specific anti-inflammatory effect or latent infection, or permanent because of eradicating C. pneumoniae organisms. In order to clarify this, large and long term randomized trials are needed, as well as diagnostic methods that can differentiate between in iduals who are or are not infected with C. pneumoniae. The latter are needed in order to clarify the impact of the presence of C. pneumoniae and to avoid overconsumption of antimicrobials, which can result in serious ecological problems.
Publisher: MDPI AG
Date: 15-11-2021
DOI: 10.3390/JCM10225298
Abstract: Follow-up studies of COVID-19 survivors have been performed to characterize persistence of long-term symptoms, but data are scarce on one year of follow-up. This study provides data from 48 weeks of follow-up after discharge. All patients discharged from the Department of Infectious Diseases at Aarhus University Hospital, Denmark between 1 March and 1 July 2020 were followed for 48 weeks. In total, 45 of 66 eligible patients were interviewed after 48 weeks. The median age was 57 (IQR 51–70) years, the majority were female (53%) and Caucasian (87%). Median BMI was 28.1 (IQR 24.8–32.6) kg/m2. One or more comorbidities were registered among 62% of the patients. In total, 39 out of 45 (87%) interviewed patients reported persistence of at least one symptom 48 weeks after hospitalization with COVID-19. Most frequently reported symptoms were fatigue, dyspnea, and concentration difficulties. This study provides new long-term data following COVID-19, contributing to the accumulating data of COVID-19 sequelae. Many patients suffer long-term sequelae and further research is urgently needed to gain further knowledge of the duration and therapeutic options.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2010
Publisher: Informa UK Limited
Date: 13-05-2013
DOI: 10.3109/00365513.2013.783229
Abstract: Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. As a pilot experiment we extracted RNA from blood s les before, and 6 weeks after, vaccination to analyze the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analyzed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. We found very few transcripts to alter systematically. Those that did mainly belonged to the Interferon (IFN) signalling pathway. We scrutinized this pathway as well as the Interleukin (IL) pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. The transcriptome changes following DTP booster vaccination were subtle, but although the material was small, it was possible to identify sub groups that deviate from each other, mainly in the IFN response.
Publisher: Elsevier BV
Date: 03-2022
Publisher: CSIRO Publishing
Date: 2007
DOI: 10.1071/SH06052
Abstract: Background: There has been increasing concern that HIV-infected in iduals may be more at risk for cardiovascular events in the highly-active antiretroviral therapy (HAART) era. This study examined the risk of thromboembolic events in HIV-infected and non-infected in iduals and the effect of macrolide prophylaxis on those outcomes. Methods: A subcohort analysis was undertaken using data collected in the Multicenter AIDS Cohort Study to examine the relative risk of vascular events (myocardial infarction, unstable angina and ischaemic stroke). Cox proportional hazard model using age as the time scale with time varying cofactors obtained at each semi-annual visit were used to assess the independent effect of macrolide use. Results: Controlling for other significant effects including race and smoking, HIV-infection was not independently associated with vascular events. Increased risk was observed among those who used HAART (relative hazard 1.09, 95% confidence intervals 1.00–1.19 in multivariate model), antihypertensive treatment (1.81 [1.26–2.60]), lipid-lowering medication (1.65 [1.12–2.42]), and antibiotics (1.72 [1.25–2.36]). The protective association of macrolide use for a vascular event in the HAART era was also significant (0.10 [0.01–0.75]). Conclusions: Traditional risk factors are important in the pathogenesis of vascular events in HIV-infected in iduals. Macrolide antibiotics may have a protective effect in the HIV-infected in iduals in the HAART era.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Public Library of Science (PLoS)
Date: 30-07-2012
Publisher: Public Library of Science (PLoS)
Date: 13-03-2014
Publisher: International Union Against Tuberculosis and Lung Disease
Date: 11-2014
Publisher: Oxford University Press (OUP)
Date: 15-01-2002
DOI: 10.1086/338268
Abstract: The effect of 2 population-based outreach screening strategies that used in-home s ling was compared with usual care practices for Chlamydia trachomatis infection. All 30,439 persons 21-23 years old in Aarhus County, Denmark, were ided randomly into 3 groups: group 1 (n=4500) had a home s ling kit mailed directly to their centrally registered home address group 2 (n=4500) had a reply card mailed to their home address with which a home s ling kit could be ordered and group 3 (n=21,439) had access to usual care. For women in groups 1 and 2, the relative risks of being tested were 4.1 (95% confidence interval [CI], 3.8-4.4) and 3.5 (95% CI, 3.2-3.9), respectively, compared with usual care. The corresponding figures for men were 19.1 (95% CI, 16.0-22.8) and 11.8 (95% CI, 9.8-14.2), respectively. Both screening strategies were highly effective, but men benefited the most from having the home s ling kit provided directly.
Publisher: Informa UK Limited
Date: 20-12-2017
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 07-2002
Abstract: antibodies against Chlamydia pneumoniae have been associated with atherosclerosis and with expansion of abdominal aortic aneurysms (AAA). C. pneumoniae has been demonstrated in coronary arteries, AAA and the carotid arteries by use of polymerase chain reactions (PCR), immunohistochemical procedures and electron microscopy. However, the correlation between demonstrating C. pneumoniae DNA or antigen in tissue from plaque material or aneurysms and the antibody titres in serum is controversial. The specificity of immunohistochemical procedures is unknown. The aim of this study was to assess the possibility of potential non-specific findings for methods based on immunostaining. twenty patients undergoing infrarenal AAA repair were studied. Full AAA thickness tissue was collected from the anterior wall of the aneurysm. Analysis was performed using polyacrylamide gelelectrophoresis, immunoblotting and mass spectrometric protein identification. C. pneumoniae antigen was not demonstrated in any of the AAA s les, whereas a major cross-reacting protein was present in all AAA s les. The protein was identified as the human haemoglobin beta chain. we were not able to find C. pneumoniae antigens reacting with an anti C. pneumoniae major outer membrane protein (MOMP). Direct detection of C. pneumoniae by immunohistostaining procedures should be interpreted with caution due to potential crossreaction with non chlamydial proteins.
Publisher: Informa UK Limited
Date: 1994
DOI: 10.3109/00365529409092469
Abstract: The presence of sphincter of Oddi (SO) slow waves has been noted in earlier studies on the effect of cholecystokinin (CCK) on the SO, but a more thorough description of changes in SO slow-wave and pressure activity induced by CCK is needed. The SO and duodenum in anaesthetized rabbits were prepared with perfused catheters and bipolar electrodes. Increasing, successive doses of CCK (1/32 to 1/1 Ivy Dog Units (IDU)/kg) were administered intravenously every 15th min. The digitized recordings were scored on a computer in control and stimulatory CCK sequences. CCK had a significantly stimulatory effect on SO and duodenum when estimated as area below pressure peaks (p < 0.001), but quantitatively, this effect did not differ in the two organs (p = 0.59). CCK significantly decreased SO slow-wave frequency (p < 0.05), whereas a similar trend in duodenal slow-wave frequency failed to reach statistical significance. Most pressure peaks recorded from the SO were associated with only one slow wave ('simple peak'), but the incidence of broad, irregular peaks belonging to more than one slow wave ('complex peaks') was significantly higher in CCK sequences (p < 0.02). Spectral analysis of SO pressure and slow-wave activity confirmed the dominating one-to-one relation between SO slow-wave and pressure peaks up to 1/4 IDU/kg, but also showed the disturbance caused by the increasing number of complex peaks generated by doses of at least 1/2 IDU/kg. CCK increases SO and duodenal activity equally. Up to a CCK dose of 1/4 IDU/kg the SO slow-wave regulatory mechanism is undisturbed, but higher doses lead to a fall in slow-wave frequency and qualitative changes in the relation between SO pressure and slow-wave activity.
Publisher: EMBO
Date: 17-02-2023
Abstract: The complement system which is part of the innate immune response against invading pathogens represents a powerful mechanism for killing of infected cells. Utilizing direct complement recruitment for complement‐mediated elimination of HIV‐1‐infected cells is underexplored. We developed a novel therapeutic modality to direct complement activity to the surface of HIV‐1‐infected cells. This bispecific complement engager (BiCE) is comprised of a nanobody recruiting the complement‐initiating protein C1q, and single‐chain variable fragments of broadly neutralizing antibodies (bNAbs) targeting the HIV‐1 envelope (Env) protein. Here, we show that two anti‐HIV BiCEs targeting the V3 loop and the CD4 binding site, respectively, increase C3 deposition and mediate complement‐dependent cytotoxicity (CDC) of HIV‐1 Env‐expressing Raji cells. Furthermore, anti‐HIV BiCEs trigger complement activation on primary CD4 T cells infected with laboratory‐adapted HIV‐1 strain and facilitates elimination of HIV‐1‐infected cells over time. In summary, we present a novel approach to direct complement deposition to the surface of HIV‐1‐infected cells leading to complement‐mediated killing of these cells.
Publisher: Mary Ann Liebert Inc
Date: 2015
Publisher: Informa UK Limited
Date: 10-2018
DOI: 10.2147/CEOR.S175835
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.CLIM.2015.11.003
Abstract: Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disease, leading to recurrent bacterial airway infections and often also autoimmune complications. To shed light on the regulatory lymphocytes from these patients, we analyzed the levels of regulatory B (pro-B10) cell and regulatory T (Treg) cell subpopulations in PBMCs from twenty-six patients diagnosed with CVID using multi-color flowcytometry. Pro-B10 cells were induced by 48h in vitro stimulation prior to analysis. Suppressor function was measured on a subset of patients with splenomegaly and autoimmune complications. The levels of regulatory B and T cells were correlated to clinical manifestations, including autoimmunity, splenomegaly and CVID EUROclass subgroups. We demonstrate a significant association between elevated levels of pro-B10 cells, decreased levels of Tregs and autoimmune phenomena in CVID patients. The finding of marked abnormalities in regulatory lymphocyte populations contribute to our understanding of the pathogenesis of CVID and potentially be valuable in the clinical management and treatment of patients.
Publisher: Public Library of Science (PLoS)
Date: 24-06-2011
Publisher: American Society for Microbiology
Date: 08-2000
DOI: 10.1128/JCM.38.8.3068-3071.2000
Abstract: A method for Chlamydia trachomatis restriction fragment length polymorphism (RFLP) analysis and complete sequencing of omp1 was developed for use on s les collected at home, and results were compared. Genotyping by sequencing was superior to RFLP analysis. The omp1 gene in 31 clinical strains harbored few mutations compared to the same gene in ATCC reference strains. Follow-up s les obtained during a 24-week period from 31 patients showed recurrence with the same genotype in five cases and a new genotype in one case.
Publisher: Springer Science and Business Media LLC
Date: 05-07-2007
Abstract: We investigated the role of DC-SIGN (CD209), long pentraxin 3 (PTX3) and vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) in susceptibility to pulmonary tuberculosis (TB) in 321 TB cases and 347 healthy controls from Guinea-Bissau. Five additional, functionally relevant SNPs within toll-like receptors (TLRs) 2, 4 and 9 were typed but found, when polymorphic, not to affect host vulnerability to pulmonary TB. We did not replicate an association between SNPs in the DC-SIGN promoter and TB. However, we found that two polymorphisms, one in DC-SIGN and one in VDR, were associated in a nonadditive model with disease risk when analyzed in combination with ethnicity (P=0.03 for DC-SIGN and P=0.003 for VDR). In addition, PTX3 haplotype frequencies significantly differed in cases compared to controls and a protective effect was found in association with a specific haplotype (OR 0.78, 95% CI 0.63-0.98). Our findings support previous data showing that VDR SNPs modulate the risk for TB in West Africans and suggest that variation within DC-SIGN and PTX3 also affect the disease outcome.
Publisher: Oxford University Press (OUP)
Date: 06-1998
Abstract: Patients with urogenital Chlamydia trachomatis infection are frequently seen in general practice. It is, therefore, important to assess GPs' management of these patients in order to ensure adequate control of the disease. We aimed to evaluate the GPs' routines in diagnosis, medical treatment, follow-up and contact tracing according to knowledge/attitude (criteria) and actual performance. The study comprised the 388 GPs in the County of Aarhus. Two questionnaires were used. The first questionnaire was mailed to each of 252 GPs who had attended a patient with urogenital C. trachomatis infection 4 weeks previously. Each GP was asked about his/her actual performance for that particular patient. In order to elucidate the GPs' criteria, the second questionnaire was mailed to each of the 388 GPs in the County of Aarhus, asking about their usual intended routines (criteria) for managing urogenital C. trachomatis infections. The questionnaires covered the same topics. Great variations among the GPs' management of urogenital C. trachomatis infection according to s ling-site, medical treatment, follow-up and contact tracing were found. Furthermore, a discrepancy between criteria and actual performance for obtaining an urethral swab-s le in women and for contact tracing of previous partners were demonstrated. The GPs stated that they had intended to obtain more urethral swab-s les and do more contact tracing than they actually did. We conclude that increasing the collection of urethral s les from women combined with greater emphasis on contact tracing procedures might limit the prevalence of the infection. In order to achieve this, continuous medical education and auditing procedures on urogenital chlamydial infections may be helpful.
Publisher: Peertechz Publications Private Limited
Date: 18-08-2014
Publisher: Wiley
Date: 29-08-2018
DOI: 10.1111/TMI.13136
Abstract: To estimate the magnitude of mortality and loss to follow-up and describe predictors of mortality among HIV-infected children in Guinea-Bissau. Retrospective follow-up study among HIV-infected children under 15 years of age at the largest HIV-clinic in Guinea-Bissau from 2006-2016. A multivariate Cox proportional hazards model was used to identify predictors of mortality. Of 525 children were included in the analysis: 371 (70.7%) with HIV-1, 17 (3.2%) with HIV-2, 25 (4.8%) with HIV-1/2, and 112 (21.3%) with HIV of unknown type. At diagnosis, the median age was 3.5 years, 44.7% met the WHO criteria for severe immunodeficiency by age based on CD4 cell count, and 59.4% were underweight. The median follow-up time was 6 months. Despite the availability of antiretroviral treatment, the mortality rate was 10.4 deaths per 100 person-years of follow-up. Within the first year of follow-up, 11.0% died, 3.1% were transferred and 38.8% were lost to follow-up, leaving 47.1% in follow-up. Severe immunodeficiency (adjusted hazard ratio (aHR) = 2.52, 95% CI: 1.22-5.21) and underweight (aHR = 3.14, 95% CI: 1.40-7.02) were independent predictors of mortality. This study reveals a high rate of early mortality and loss to follow-up among HIV-infected children in Guinea-Bissau. Initiatives to improve patient retention are urgently needed.
Publisher: Wiley
Date: 2014
Publisher: Wiley
Date: 09-2023
DOI: 10.1002/JMV.29089
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2006
DOI: 10.1097/01.OLQ.0000200609.77577.3F
Abstract: To estimate the incremental effects and costs of a home s ling screening approach for Chlamydia trachomatis over the current in-office screening practice in Denmark. To assess the effect of a new screening strategy. A dynamic Monte Carlo model estimated prevalence and incidence over 10 years for a home s ling screening program and the current in-office screening. Subsequently, the incremental number of major outcomes averted (MOA) and the related direct and indirect costs were estimated. Infection prevalence after 10 years was 1.0% with a home s ling program and 4.2% with the current in-office screening practice. The total costs per MOA reached 3186 US dollars during the first year of the home s ling strategy, but in year 4, the accumulated indirect costs offset the direct costs, and the program henceforth saved society costs. Home s ling should be considered a relevant alternative to the current practice of in-office screening.
Publisher: BMJ
Date: 08-1999
DOI: 10.1136/STI.75.4.228
Abstract: To assess the impact of the menstrual cycle on the diagnostic performance of various assays for detection of Chlamydia trachomatis in home obtained and mailed vaginal flush and urine specimens. A ligase chain reaction assay (LCR Abbott Laboratories), a transcription mediated lification assay (TMA Gen-Probe), and an enzyme lified immunoassay (PCE Dako Diagnostics) were evaluated for their validity in detecting C trachomatis in vaginal flush, first void urine, and midstream urine specimens obtained by female high school students at home and mailed directly to the diagnostic laboratory. C trachomatis was detected in 45 of 889 females (5.1%). The vaginal flush material was positive by TMA and LCR in 84% and 82% of the chlamydia positive females, respectively. First void urine was positive by TMA in 73% and by LCR in 49% of the cases. Midstream urine was positive by TMA and LCR in 69% and 42% of the females, respectively. On a pool of first void and midstream urine, PCE detected 49% of the chlamydia positive females. The overall prevalence of C trachomatis increased with increasing time after the last menstrual bleeding. In urine s les, but not vaginal flush specimens, obtained 3 weeks after the last menstrual bleeding, the sensitivities of TMA, LCR, and PCE decreased markedly suggesting that inhibitors to the assays are excreted in the urine but not in vaginal secretions at this time. Vaginal flush s les are superior to urines for detection of chlamydia infections in females. In screening of young asymptomatic females, s les should be obtained in the latter part of the menstrual cycle.
Publisher: Public Library of Science (PLoS)
Date: 27-02-2013
Publisher: Oxford University Press (OUP)
Date: 26-05-2006
DOI: 10.1189/JLB.1105626
Abstract: Toll-like receptors (TLRs) are pattern recognition receptors (PRR) that recognize molecular structures on pathogens and activate host defenses. Although much is known about specific bacterial components that activate TLRs, few studies have addressed the question of which TLRs are involved in immune activation by live bacteria. Here, we demonstrate that live Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, the three principal causes of bacterial meningitis, use distinct sets of TLRs to trigger the inflammatory response. Using human embryonic kidney 293 cell lines, each overexpressing one type of TLR, we found that S. pneumoniae triggered activation of the transcription factor nuclear factor-κB and expression of interleukin-8, only in cells expressing TLR2 or -9. The same response was evoked by H. influenzae in cells expressing TLR2 or -4 and by N. meningitidis in cells expressing TLR2, -4, or -9. It is interesting that the ability of S. pneumoniae and N. meningitidis to activate TLR9 was severely attenuated when bacteria had been heat-inactivated prior to stimulation of the cells. In human peripheral blood mononuclear cells, we blocked TLR2, -4, or -9 and confirmed the essential role of these TLRs and also identified differential functions of TLRs in activation of the inflammatory response. Collectively, we here demonstrate that S. pneumoniae, H. influenzae, and N. meningitidis each activate several TLRs in species-specific patterns and show that infection with live pathogens may lead to activation of PRR not targeted by inactivated bacteria.
Publisher: Informa UK Limited
Date: 08-2012
DOI: 10.4161/HV.20707
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1080/00365540110080494
Abstract: This study evaluates the use of dedicated telephone hotlines to provide advice to young in iduals who were offered the chance to be tested for Chlamydia trachomatis by means of home-obtained s les that were mailed directly to a testing laboratory. In a school-based screening study, a population-based screening study and a partner-tracing study we established hotlines and registered the calls. The target groups for the 3 studies comprised 8,909, 9,000 and 4,622 in iduals and 0.1% (8/8,909), 0.7% (66/9,000) and 2.7% (124/4,622) of the populations, respectively took the opportunity to call anonymously to receive advice. The number of calls per opening hour of the hotlines varied between 0.2 (8 calls/40 opening hours) and 0.4 (124 calls/300 opening hours). Major reasons for calling the hotlines included requests for more information about chlamydial infections, questions relating to the study and emotional concerns (e.g. problems relating to partner tracing, adultery or anxiety concerning infertility). Although only a small fraction of the target populations used the hotlines we conclude that there is a need for advice and counseling in connection with strategies involving home-obtained s les for C. trachomatis testing. The optimal setting for this, however, remains to be determined.
Publisher: Wiley
Date: 19-07-2013
DOI: 10.1111/HIV.12068
Publisher: CSIRO Publishing
Date: 2014
DOI: 10.1071/SH14015
Abstract: Background Men and women with HIV infection are at increased risk of developing cancers associated with human papillomavirus (HPV). The two licensed prophylactic HPV vaccines protect against de novo infection with HPV-16 and HPV-18, which cause the majority of HPV-associated cancers. Currently, no vaccine efficacy data are available for persons with HIV infection. Nevertheless, some countries have implemented specific HPV vaccination recommendations for HIV-positive populations. To specifically recommend prophylactic HPV vaccination in people with HIV, the vaccines must be safe and immunogenic in immunosuppressed people at a high risk of HPV infection. This review aims to summarise the current knowledge from published HPV vaccine trials in HIV-infected populations, to compile scheduled and ongoing HPV vaccine trials with HIV-positive study populations and to extrapolate the relevant knowledge about HPV vaccine efficacy in HIV-negative populations to an HIV context. Methods: The databases PubMed, Scopus and ClinicalTrials.gov were searched for peer-reviewed articles and scheduled or ongoing clinical HPV vaccine trials enrolling HIV-positive persons. Results: Current data indicate that prophylactic HPV vaccines are safe and immunogenic in different HIV-positive populations (children, female adolescents, adults). Increased immunogenicity has been reported in persons on antiretroviral therapy compared with antiretroviral-naïve persons, whereas no clear association has been found between CD4+ cell count at immunisation and vaccine response. Several scheduled and ongoing HPV vaccine trials aim to determine vaccine efficacy against disease endpoints in HIV-infected study populations. Conclusion: Prophylactic HPV vaccination appears safe, immunogenic and, by extrapolation, likely to reduce HPV-associated cancer development among persons with HIV infection.
Publisher: Public Library of Science (PLoS)
Date: 04-03-2014
Publisher: Public Library of Science (PLoS)
Date: 03-01-2014
Publisher: American College of Physicians
Date: 06-2021
DOI: 10.7326/M20-5226
Publisher: Springer Science and Business Media LLC
Date: 2002
Abstract: Chlamydia pneumoniae infection has been detected by serological methods, but PCR is gaining more interest. A number of different PCR assays have been developed and some are used in combination with serology for diagnosis. Real-time PCR could be an attractive new PCR method therefore it must be evaluated and compared to conventional PCR methods. We compared the performance of a newly developed real-time PCR with a conventional PCR method for detection of C. pneumoniae. The PCR methods were tested on reference s les containing C. pneumoniae DNA and on 136 nasopharyngeal s les from patients with chronic cough. We found the same detection limit for the two methods and clinical performance was equal for the real-time PCR and for the conventional PCR method, although only three s les tested positive. To investigate whether the low prevalence of C. pneumoniae among patients with chronic cough was caused by suboptimal PCR efficiency in the s les, PCR efficiency was determined based on the real-time PCR. Seventeen of twenty randomly selected clinical s les had similar PCR efficiency to s les containing pure genomic C. pneumoniae DNA. These results indicate that the performance of real-time PCR is comparable to that of conventional PCR, but this needs to be confirmed further. Real-time PCR can be used to investigate the PCR efficiency which gives a rough estimate of how well the real-time PCR assay work in a specific s le type. Suboptimal PCR efficiency of PCR is not a likely explanation for the low positivity rate of C. pneumoniae in patients with chronic cough.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-05-2021
Publisher: Oxford University Press (OUP)
Date: 15-11-2008
DOI: 10.1086/592692
Abstract: Human immunodeficiency virus (HIV)-infected in iduals with high CD4(+) cell counts may have increased susceptibility to other infections. We compared incidence rates of pneumonia among in iduals with and without HIV infection and explored risk factors for pneumonia in the HIV-infected population. This was an observational cohort study conducted during 1995-2007. Each member of a Danish population-based nationwide cohort of HIV-infected in iduals was matched with up to 99 control in iduals from the general population. Data on age, mortality, emigration, and hospital discharge diagnoses from 1977 onward were obtained from nationwide administrative databases. In iduals without previous hospitalization for pneumonia were observed from the date of HIV diagnosis until the first hospitalization to treat pneumonia (excluding pneumonia attributable to Pneumocystis jiroveci). Risk factors were assessed by Poisson regression. The study included 3516 persons with HIV infection and 328,738 persons without HIV infection, which provided 23,677 person-years and 2,944,760 person-years of observation, respectively. Incidence rates of pneumonia in HIV-infected in iduals decreased from 50.6 hospitalizations per 1000 person-years (95% confidence interval [CI], 42.9-59.7 hospitalizations per 1000 person-years) during 1995-1996 to 19.7 hospitalizations per 1000 person-years (95% CI, 16.2-23.8 hospitalizations per 1000 person-years) during 2005-2007. Compared with control in iduals, incidence rate ratios were 34.6 (95% CI, 28.4-41.8) during 1995-1996 6.3 (95% CI, 5.1-7.7) during 2005-2007 and 5.9 (95% CI, 4.2-7.6) during 2005-2007 for the subgroup with a CD4(+) cell count >500 cells/microL. Injection drug use, low current CD4(+) cell count, nadir CD4(+) cell count, increasing age, and no current receipt of highly active antiretroviral therapy increased the risk of pneumonia. The risk of pneumonia in persons with HIV infection has decreased substantially since the introduction of highly active antiretroviral therapy, but HIV infection remains a strong risk factor for the need for hospitalization to treat pneumonia, even in persons with high CD4(+) cell counts.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Public Library of Science (PLoS)
Date: 15-02-2013
Publisher: Elsevier BV
Date: 04-1999
Abstract: Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that causes acute upper and lower respiratory infections. Its distribution is worldwide. Seroepidemiological studies have shown an association between C. pneumoniae and atherosclerosis, and the risk of acute myocardial infarction. Several studies had detected C. pneumoniae in atherosclerotic lesions from coronary and carotid arteries, in abdominal aortic aneurysms (AAA), and in sclerotic aortic valves. One study consistently succeeded in culturing C. pneumoniae from an atherosclerotic lesion, indicating the presence of viable organisms. However, the pathogenicity is unknown, and the significance of detecting the organism is unresolved. In two minor controlled clinical trials, patients with ischaemic heart disease were randomised into antibiotic-treated and placebo groups. Both trials showed a significant reduction in serious endpoints in patients receiving macrolide. Macrolide therapy thus seems to improve the outcome of severe ischaemic heart disease. It is not known whether this is caused by eradicating C. pneumoniae organisms, or by the macrolide's non-specific anti-inflammatory effect. Since both C. pneumoniae and inflammation are found in the AAA wall, it may be considered that macrolide would also improve the outcome of AAA and other diseases related to vascular surgery. In order to confirm this, randomised trials with macrolide therapy are needed, as well as diagnostic methods that can differentiate between in iduals who are or are not infected with C. pneumoniae. The latter are needed in order to clarify the impact of the presence of C. pneumoniae and to avoid indiscriminate use of antimicrobials.
Publisher: Springer Science and Business Media LLC
Date: 25-03-2014
Publisher: Informa UK Limited
Date: 18-08-2014
DOI: 10.3109/00365548.2014.936492
Abstract: Data on occurrence and risk factors for pneumocystis pneumonia (PCP) in patients with end-stage renal disease (ESRD) are sparse. This was a nationwide population-based study assessing occurrence and risk factors for PCP among patients with ESRD and population controls over a 21-year period (1/1 1990 to 31/12 2010). Using Danish registry data, first-time diagnoses of PCP were identified. We identified 13 296 adult patients with ESRD and 244 255 controls, yielding 63 560 and 2 223 660 person-years of follow-up (PYFU), respectively. Fifty-eight first-time diagnoses of PCP were recorded in the ESRD group. Forty-six episodes occurred among renal transplant recipients (RTx) and 12 among haemodialysis patients (HD), yielding incidence rates of 181 (136-242) and 43.1 (24.5-75.9) per 100 000 PYFU. Compared to population controls, we found incidence rate-ratios of 125.9 (78.4-204) among RTx and 29.9 (14.1-59.7) among HD patients. Risk factors for PCP in RTx were age 50-65 years, age > 65 years, diabetes, polycystic kidney disease and hypertensive kidney disease/nephrosclerosis with an IRR of 2.22 (1.14-4.31), 3.12 (1.35-7.21), 3.44 (1.16-10.2), 4.25 (1.55-11.7) and 3.87 (1.49-10.0), respectively, and more than 36 months of dialysis before transplantation with an IRR of 1.99 (1.03-3.84). Among RTx the risk of PCP was highest during the first 6 months post-transplantation and increased from the beginning (IR1990-94 = 111 (46.3-267) per 100 000 PYFU) towards the end of the study period (IR2005-10 = 299 (203-439)). The PCP risk is substantial in RTx within the first 6 months of transplantation, emphasizing the potential benefit of prophylactic treatment in the early post-transplant period. Importantly, we identified subgroups within the RTx group that require more attention.
Publisher: SAGE Publications
Date: 04-03-2008
Abstract: High-sensitivity C-reactive protein is associated with increased risk of cardiovascular events. Consequently, the predictive value of this protein in patients with symptomatic peripheral arterial disease was examined. In all, 452 patients with symptomatic peripheral arterial disease had high-sensitivity C-reactive protein measured at baseline (mean follow-up = 2.1 ± 1.4 years). Events were defined as primary (death, utation, or peripheral revascularization) or secondary (lower limb thrombosis, myocardial infarction, or stroke).The level of high-sensitivity C-reactive protein was significantly higher among those dying ( P = .04), those who needed utation ( P = .01), and those developing an overall secondary endpoint ( P = .02). By receiver-operating characteristic curve analysis, the optimal cutoff point was constantly approximately 10 to 20 mg/L with a sensitivity and specificity of 56% to 63% and 54% to 56%, respectively. Baseline levels of high-sensitivity C-reactive protein are associated with future arterial events in symptomatic peripheral arterial disease patients but cannot stand alone as a predictive tool.
Publisher: BMJ
Date: 20-11-2010
Abstract: DNA lification assays are increasingly being used to facilitate the testing of asymptomatic in iduals for urogenital Chlamydia trachomatis. The long-term clinical benefit in terms of avoided infertility and ectopic pregnancy is unknown. In 1997, 15,459 women and 14,980 men aged 21-23 years were living in Aarhus County, Denmark. A random s le of 4000 women and 5000 men was contacted by mail and offered the opportunity to be tested for C trachomatis by means of a s le obtained at home and mailed directly to the laboratory. The remaining 11,459 women and 9980 men received usual care and constituted the control population. All men and women were subsequently followed for 9 years by the use of Danish health registers. Data were collected on pelvic inflammatory disease (PID), ectopic pregnancy (EP), infertility diagnoses, in-vitro fertilisation (IVF) treatment and births in women, and on epididymitis in men. The intervention and control groups were compared using Cox regression analyses and the intention-to-screen principle. Among women, no differences were found between the intervention group and the control group: HR (95% CI) for PID 1.12 (0.70 to 1.79) EP 0.97 (0.63 to 1.51) infertility 0.87 (0.71 to 1.07) IVF treatment 0.88 (0.62 to 1.26) and births 1.02 (0.95 to 1.10). In men, the HR for epididymitis was 1.25 (0.70 to 2.24). A population-based offer to be tested for urogenital C trachomatis infection by the use of non-invasive s les and DNA lification did not reduce the long-term risk of reproductive complications in women or of epididymitis in men.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2021
Publisher: Elsevier BV
Date: 07-2014
Publisher: American Society for Microbiology
Date: 11-2010
DOI: 10.1128/JVI.01106-10
Abstract: Innate recognition of viruses is mediated by pattern recognition receptors (PRRs) triggering expression of antiviral interferons (IFNs) and proinflammatory cytokines. In mice, Toll-like receptor 2 (TLR2) and TLR9 as well as intracellular nucleotide-sensing pathways have been shown to recognize herpes simplex virus (HSV). Here, we describe how human primary macrophages recognize early HSV infection via intracellular pathways. A number of inflammatory cytokines, IFNs, and IFN-stimulated genes were upregulated after HSV infection. We show that early recognition of HSV and induction of IFNs and inflammatory cytokines are independent of TLR2 and TLR9, since inhibition of TLR2 using TLR2 neutralizing antibodies did not affect virus-induced responses and the macrophages were unresponsive to TLR9 stimulation. Instead, HSV recognition involves intracellular recognition systems, since induction of tumor necrosis factor alpha (TNF-α) and IFNs was dependent on virus entry and replication. Importantly, expression of IFNs was strongly inhibited by small interfering RNA (siRNA) knockdown of MAVS, but this MAVS-dependent IFN induction occurred independently of the recently discovered polymerase III (Pol III)/RIG-I DNA sensing system. In contrast, induction of TNF-α was largely independent of MAVS, suggesting that induction of inflammatory cytokines during HSV infection proceeds via a novel pathway. Transfection with ODN2006, a broad inhibitor of intracellular nucleotide recognition, revealed that nucleotide-sensing systems are employed to induce both IFNs and TNF-α. Finally, using siRNA knockdown, we found that MDA5, but not RIG-I, was the primary mediator of HSV recognition. Thus, innate recognition of HSV by human primary macrophages occurs via two distinct intracellular nucleotide-sensing pathways responsible for induction of IFNs and inflammatory cytokine expression, respectively.
Publisher: Elsevier BV
Date: 11-1993
Abstract: In a 5-year period, 254 patients with community-acquired pneumonia were attended to. Transtracheal aspiration (TTA) could be performed on 119 patients, blood cultures were performed on 201 patients, and 74 patients underwent serologic examinations. By use of these procedures, an etiologic diagnosis was established in 93 cases. Streptococcus pneumoniae was the most common pathogen as it was found in 35 cases. Eleven of these 35 patients (31.4 percent) had pneumococcemia, and the mortality in this group was 27.3 percent. None of the patients with pneumococcal pneumonia and negative blood culture died. Haemophilus influenzae was the only isolated pathogen from transtracheal aspirated sputum in 16 cases and accounted for 17.5 percent of pneumonias in previous healthy in iduals under 50 years of age. Mycoplasma pneumonia infections, Legionella pneumophila infections, and Chlamydia infections were found in ten, eight, and three cases, respectively. The overall agreement between microscopy and culture of respiratory secretions obtained by TTA was 58.8 percent, and microscopy can be a guide when choosing the initial antibiotic treatment. No statistically significant difference in the rate of isolating bacteria among patients treated with antibiotics prior to TTA and patients not previously treated with antibiotics was seen. When contraindications were respected, we found TTA to be a safe procedure.
Publisher: Oxford University Press (OUP)
Date: 03-10-2020
DOI: 10.1093/CID/CIAA1471
Abstract: The objective of this study was to perform a seroprevalence survey on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among Danish healthcare workers to identify high-risk groups. All healthcare workers and administrative personnel at the 7 hospitals, prehospital services, and specialist practitioner clinics in the Central Denmark Region were invited to be tested by a commercial SARS-CoV-2 total antibody enzyme-linked immunosorbent assay (Wantai Biological Pharmacy Enterprise Co, Ltd, Beijing, China). A total of 25 950 participants were invited. Of these, 17 971 had s les available for SARS-CoV-2 antibody testing. After adjustment for assay sensitivity and specificity, the overall seroprevalence was 3.4% (95% confidence interval [CI], 2.5%–3.8%). The seroprevalence was higher in the western part of the region than in the eastern part (11.9% vs 1.2% difference: 10.7 percentage points [95% CI, 9.5–12.2]). In the high-prevalence area, the emergency departments had the highest seroprevalence (29.7%), whereas departments without patients or with limited patient contact had the lowest seroprevalence (2.2%). Among the total 668 seropositive participants, 433 (64.8%) had previously been tested for SARS-CoV-2 RNA, and 50.0% had a positive reverse-transcription polymerase chain reaction (PCR) result. We found large differences in the prevalence of SARS-CoV-2 antibodies in staff working in the healthcare sector within a small geographical area of Denmark. Half of all seropositive staff had been tested positive by PCR prior to this survey. This study raises awareness of precautions that should be taken to avoid in-hospital transmission. Regular testing of healthcare workers for SARS-CoV-2 should be considered to identify areas with increased transmission.
Publisher: Elsevier BV
Date: 08-2021
Publisher: American Society for Microbiology
Date: 09-2014
DOI: 10.1128/IAI.02221-14
Publisher: Oxford University Press (OUP)
Date: 04-02-2013
Publisher: BMJ
Date: 12-1997
DOI: 10.1136/STI.73.6.448
Abstract: To asses changes in sexual behaviour and use of contraceptive methods in Danish adolescents from the period before the advent of AIDS up to the present. Comparative study comparing data obtained from two identical cross sectional surveys Grenaa Gymnasium, Denmark. 626 high school students in 1982 and 499 high school students in 1996. An anonymous standardised self administered questionnaire handed out to high school students at Grenaa Gymnasium in spring 1982. In spring 1996 an identical questionnaire was handed out to every high school student at the same gymnasium. Age at first sexual intercourse, contraceptive use, and reasons for choice of contraceptive strategy. Today more males had experienced the first sexual intercourse before their 16th birthday (p = 0.047) compared with 1982, the reverse held for females (p = 0.003). From 1982 to 1996 condom use increased in males with no regular partner (p = 0.009). In females with no regular partner, there was during the same period an increase in considering the condom a personal contraceptive method (p = 0.017). In 1982 and 1996 protection from sexually transmitted diseases was given as reason for the choice of contraceptive strategy by 21% and 72% of males with no regular partner (p < 0.001), and by 7% and 32% of males with a regular partner (p < 0.001). The corresponding figures for females in 1982 and 1996 were 10% and 71% (p < 0.001) for those with no regular partner and 4% and 21% (p < 0.001) for those with a regular partner. Condom use has increased among adolescents with no regular partner brought up under the widespread awareness of AIDS, and the reason for this is to be protected from sexually transmitted diseases. A future decline in the incidence of various sexually transmitted diseases may be expected, and information on safe sexual practices should be continued.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-02-2014
Publisher: American College of Physicians
Date: 02-09-2008
DOI: 10.7326/0003-4819-149-5-200809020-00003
Abstract: Episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. To determine whether reinitiating continuous antiretroviral therapy in patients who received episodic treatment reduces excess risk for opportunistic disease or death. Randomized, controlled trial. Sites in 33 countries. 5472 HIV-infected in iduals with CD4(+) cell counts greater than 0.350 x 10(9) cells/L enrolled from January 2002 to January 2006. Episodic or continuous antiretroviral therapy initially, followed by continuous therapy in participants previously assigned to episodic treatment. Opportunistic disease or death was the primary outcome. Eighteen months after the recommendation to reinitiate continuous therapy, mean CD4+ cell counts were 0.152 x 10(9) cells/L (95% CI, 0.136 to 0.167 x 10(9) cells/L) less in participants previously assigned to episodic treatment (P < 0.001). The proportion of follow-up time spent with CD4+ cell counts of 0.500 x 10(9) cells/L or more and HIV RNA levels of 400 copies/mL or less was 29% for participants initially assigned to episodic therapy and 66% for those assigned to continuous therapy. Participants who reinitiated continuous therapy experienced rapid suppression of HIV RNA levels (89.7% with HIV RNA levels < or =400 copies/mL after 6 months), but CD4+ cell counts after 6 months remained 0.140 x 10(9) cells/L below baseline. The hazard ratio (episodic versus continuous treatment) for opportunistic disease or death decreased after the recommendation to reinitiate continuous therapy (from 2.5 [CI, 1.8 to 3.5] to 1.4 [CI, 1.0 to 2.0] P = 0.033 for difference). The residual excess risk was attributable to failure to reinitiate therapy by some participants and slow recovery of CD4+ cell counts for those who reinitiated therapy. Follow-up was too short to assess the full effect of switching from episodic to continuous antiretroviral therapy. Reinitiating continuous antiretroviral therapy in patients previously assigned to episodic treatment reduced excess risk for opportunistic disease or death, but excess risk remained. Episodic antiretroviral therapy, as used in the SMART study, should be avoided.
Publisher: Public Library of Science (PLoS)
Date: 18-07-2023
DOI: 10.1371/JOURNAL.PONE.0287671
Abstract: We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy. Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log 10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus . Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rif icin (n = 18) or vancomycin + rif icin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration. All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log 10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated. Vancomycin and rif icin treatment were superior to monotherapy with vancomycin, as it lead to a marked decrease in median bacterial load on the grafts (3.50 vs. 6.56 log 10 CFU/mL, p = 0.0016). The addition of tPA to vancomycin and rif icin combination treatment did not show a further decrease in bacterial load (4.078 vs. 3.50 log 10 CFU/mL, p = 0.26). The cure rate was 16% in the vancomycin + rif icin group vs. 37.5% cure rate in the vancomycin + rif icin + tPA group. Whilst interesting, this trend was not significant at our s le size (p = 0.24). We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rif icin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.
Publisher: Informa UK Limited
Date: 1993
DOI: 10.3109/00365549309008489
Abstract: Reactivation of Toxoplasma gondii can lead to a life-threatening intracerebral infection in immunocompromised HIV-positive patients. Due to the current diagnostic limitations for establishing an exact diagnosis of cerebral toxoplasmosis, a nested PCR system was developed for direct detection of T. gondii in cerebrospinal fluid. A storage temperature for s les of -20 degrees C and s le preparation using Proteinase K appeared to be critical for obtaining a high sensitivity of PCR. A total of 56 s les from 38 HIV-positive patients and 12 HIV-negative patients with symptoms or signs of neurological disease were evaluated by PCR. 5 of the 38 HIV-positive patients were diagnosed as having cerebral toxoplasmosis and PCR was positive in s les from all 5 patients. In the remaining 33, PCR was positive in one case and negative in 32. An exact etiological diagnosis other than cerebral toxoplasmosis was established in 5 patients. PCR performed on cerebrospinal fluid s les seems to be a fast, sensitive, specific and valuable tool for establishing the diagnosis of cerebral toxoplasmosis among HIV-positive patients at the time of presentation of symptoms or signs of neurological disease.
Publisher: Public Library of Science (PLoS)
Date: 20-09-2023
Publisher: Informa UK Limited
Date: 17-09-2013
DOI: 10.3109/00365548.2013.826876
Abstract: The TBscore, based on simple signs and symptoms, was introduced to predict unsuccessful outcome in tuberculosis patients on treatment. A recent inter-observer variation study showed profound variation in some variables. Further, some variables depend on a physician assessing them, making the score less applicable. The aim of the present study was to simplify the TBscore. Inter-observer variation assessment and exploratory factor analysis were combined to develop a simplified score, the TBscore II. To validate TBscore II we assessed the association between start score and failure (i.e. death or treatment failure), responsiveness using Cohen's effect size, and the relationship between severity class at treatment start and a decrease < 25% in score from the start until the end of the second treatment month and subsequent mortality. We analyzed data from 1070 Guinean (2003-2012) and 432 Ethiopian (2007-2012) pulmonary tuberculosis patients. For the refined score, items with less than substantial agreement (κ ≤ 0.6) and/or not associated with the underlying constructs were excluded. Items kept were: cough, dyspnea, chest pain, anemia, body mass index (BMI) < 18 kg/m(2), BMI < 16 kg/m(2), mid upper arm circumference (MUAC) < 220 mm, and MUAC < 200 mm. The effect sizes for the change between the start of treatment and the 2-month follow-up were 0.51 in Guinea-Bissau and 0.68 in Ethiopia, and for the change between the start of treatment and the end of treatment were 0.68 in Guinea-Bissau and 0.74 in Ethiopia. Severity class placement at treatment start predicted failure (p < 0.001 Guinea-Bissau, p = 0.208 Ethiopia). Inability to decrease at least 25% in score was associated with a higher failure rate during the remaining 4 months of treatment (p = 0.063 Guinea-Bissau, p = 0.008 Ethiopia). The TBscore II could be a useful monitoring tool, aiding triage at the beginning of treatment and during treatment.
Publisher: Oxford University Press (OUP)
Date: 09-06-2014
DOI: 10.1111/CEI.12317
Abstract: The innate immune system has been recognized to play a role in the pathogenesis of HIV infection, both by stimulating protective activities and through a contribution to chronic immune activation, the development of immunodeficiency and progression to AIDS. A role for DNA sensors in HIV recognition has been suggested recently, and the aim of the present study was to describe the influence of HIV infection on expression and function of intracellular DNA sensing. Here we demonstrate impaired expression of interferon-stimulated genes in responses to DNA in peripheral blood monuclear cells from HIV-positive in iduals, irrespective of whether patients receive anti-retroviral treatment. Furthermore, we show that expression levels of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic guanosine monophosphate-adenosine monophosphate synthase were increased in treatment-naive patients, and for IFI16 expression was correlated with high viral load and low CD4 cell count. Finally, our data demonstrate a correlation between IFI16 and CD38 expression, a marker of immune activation, in CD4+ central and effector memory T cells, which may indicate that IFI16-mediated DNA sensing and signalling contributes to chronic immune activation. Altogether, the present study demonstrates abnormal expression and function of cytosolic DNA sensors in HIV patients, which may have implications for control of opportunistic infections, chronic immune activation and T cell death.
Publisher: Elsevier BV
Date: 08-2022
Publisher: International Union Against Tuberculosis and Lung Disease
Date: 03-2014
Abstract: The Bandim Health Project study area in Bissau, Guinea-Bissau. To assess the potential usefulness of predictors (elsewhere applied) and clinical scores (TBscore and TBscore II) based on signs and symptoms typical of tuberculosis (TB) in case finding. Observational prospective cohort study of patients with signs and symptoms suggestive of pulmonary TB (PTB) from 2010 to 2012. We included 1089 PTB suspects with a mean age of 34 years (95%CI 33-35) human immunodeficiency virus (HIV) prevalence was 15.1%. PTB was diagnosed in 107 suspects (76.4% sputum smear-positive, 25.2% HIV-infected). Cough > 2 weeks had the highest diagnostic ability (area under the receiver operating characteristic curve [AUC] 0.66, 95%CI 0.62-0.71), while TBscore 2 weeks as a trigger for smear microscopy missed 32.1% of smear-positive PTB cases. Case finding could be improved by screening symptomatic adults for cough and/or weight loss using TBscore II as the trigger for smear microscopy. To suspect PTB only in patients with cough > 2 weeks (non-HIV-infected) or with current cough, fever, weight loss or night sweats (HIV-infected) was not effective in patients whose HIV status was unknown at first visit.
Publisher: American College of Physicians
Date: 07-06-2005
DOI: 10.7326/0003-4819-142-11-200506070-00010
Abstract: Testing of urine s les is noninvasive and could overcome several barriers to screening for chlamydial and gonococcal infections, but most test s les are obtained directly from the cervix or urethra. To systematically review studies that assessed the sensitivity and specificity of nucleic acid lification tests for Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens and to compare test characteristics according to type of assay, site of s le collection, presence of symptoms, disease prevalence, and characteristics of the reference standard. Relevant studies in all languages were identified by searching the MEDLINE database (January 1991 to December 2004) and by hand-searching the references of identified articles and relevant journals. Studies were selected that evaluated 1 of 3 commercially available nucleic acid lification tests, included data from tests of both a urine s le and a traditional s le (obtained from the cervix or urethra), and used an appropriate reference standard. From 29 eligible studies, 2 investigators independently abstracted data on s le characteristics, reference standard, sensitivity, and specificity. Articles were assessed qualitatively and quantitatively. Summary estimates for men and women were calculated separately for chlamydial and gonococcal infections and were stratified by assay and presence of symptoms. The pooled study specificities of each of the 3 assays exceeded 97% when urine s les were tested, for both chlamydial infection and gonorrhea and in both men and women. The pooled study sensitivities for the polymerase chain reaction, transcription-mediated lification, and strand displacement lification assays, respectively, were 83.3%, 92.5%, and 79.9% for chlamydial infections in women 84.0%, 87.7%, and 93.1% for chlamydial infections in men and 55.6%, 91.3%, and 84.9% for gonococcal infections in women. The pooled specificity of polymerase chain reaction to gonococcal infections in men was 90.4%. In subgroup analyses, the sensitivity did not vary according to the prevalence of infection or the presence of symptoms but did vary according to the reference standard used. Few published studies present data on the transcription-mediated lification or strand displacement lification assays, and few studies report data from asymptomatic patients or low-prevalence groups. Results of nucleic acid lification tests for C. trachomatis on urine s les are nearly identical to those obtained on s les collected directly from the cervix or urethra. Although all 3 assays can also be used to test for N. gonorrhoeae, the sensitivity of the polymerase chain reaction assay in women is too low to recommend its routine use to test for gonorrhea in urine specimens.
Publisher: Oxford University Press (OUP)
Date: 29-01-2021
DOI: 10.1093/OFID/OFAB042
Abstract: Although persistent symptoms after coronavirus disease 2019 (COVID-19) are emerging as a major complication to the infection, data on the ersity and duration of symptoms are needed. Patients aged ≥18 years with a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 who were hospitalized at the Department of Infectious Diseases, Aarhus University Hospital, Denmark, in the period from March 11 to May 15 were offered follow-up after hospitalization. On admission, a comprehensive symptom and medical history was collected, including demographic characteristics, duration of symptoms, comorbidities, and concomitant medications. At discharge, patients were offered follow-up consultations—either by telephone or at an in-person visit—at 6 and 12 weeks at our post-COVID-19 outpatient clinic to assess whether symptoms present at admission had resolved. During the inclusion period, 71 patients were admitted with COVID-19. Of these, 10 patients died, 3 were transferred to another region, 4 declined to participate, and 5 were lost to follow-up before the 12-week evaluation. Thus, 49 patients were included. Overall, 96% reported 1 or more persisting symptoms at 12-week follow-up. The main symptoms were fatigue, dyspnea, cough, chemosensory dysfunction, and headache. A wide range of persistent symptoms in patients recovering from COVID-19 were present 12 weeks after hospitalization, calling for larger descriptive studies and interdisciplinary research collaborations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-05-2014
Abstract: In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease ( CVD ) events. People with HIV have elevated levels of interleukin‐6 ( IL ‐6), high‐sensitivity C‐reactive protein (hs CRP ), and D‐dimer HIV ‐induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD . Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD . Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios ( OR s) (fatal versus nonfatal CVD ) (95% confidence intervals [ CIs ]) associated with a doubling of IL ‐6, D‐dimer, hs CRP , and a 1‐unit increase in an IL ‐6 and D‐dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD , 23 died during follow‐up. Hazard ratios (95% CI ) for all‐cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL ‐6, D‐dimer, hs CRP , and the IL ‐6 and D‐dimer score. Higher IL ‐6 and D‐dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD event. URL: www.clinicaltrial.gov Unique identifier: SMART: NCT00027352, ESPRIT: NCT00004978, SILCAAT: NCT00013611.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-10-2018
Publisher: American Society for Microbiology
Date: 15-07-2013
DOI: 10.1128/JVI.00240-13
Abstract: Influenza virus defective interfering (DI) particles are naturally occurring noninfectious virions typically generated during in vitro serial passages in cell culture of the virus at a high multiplicity of infection. DI particles are recognized for the role they play in inhibiting viral replication and for the impact they have on the production of infectious virions. To date, influenza virus DI particles have been reported primarily as a phenomenon of cell culture and in experimentally infected embryonated chicken eggs. They have also been isolated from a respiratory infection of chickens. Using a sequencing approach, we characterize several subgenomic viral RNAs from human nasopharyngeal specimens infected with the influenza A(H1N1)pdm09 virus. The distribution of these in vivo -derived DI-like RNAs was similar to that of in vitro DIs, with the majority of the defective RNAs generated from the PB2 (segment 1) of the polymerase complex, followed by PB1 and PA. The lengths of the in vivo -derived DI-like segments also are similar to those of known in vitro DIs, and the in vivo -derived DI-like segments share internal deletions of the same segments. The presence of identical DI-like RNAs in patients linked by direct contact is compatible with transmission between them. The functional role of DI-like RNAs in natural infections remains to be established.
Publisher: Wiley
Date: 06-05-2019
DOI: 10.1111/IMM.13061
Publisher: Public Library of Science (PLoS)
Date: 05-03-2012
Publisher: Elsevier BV
Date: 06-2021
Publisher: Informa UK Limited
Date: 2004
DOI: 10.1080/00365540310017500
Abstract: Meningococcal disease (MD) remains an important health problem. Crowding has been suggested to be a risk factor for MD in children, but the evidence is relatively sparse. We performed a nationwide nested case-control study comprising 1222 children with MD and 24,549 population controls. We identified MD cases younger than 6 y in the Danish National Hospital Discharge Registry from 1980 to 1999, and obtained information on household density as a measure of crowding, per capita income and other potential confounders through The Danish Civil Registration System and social registries. The risk of MD associated with household density was estimated by conditional logistic regression for children less than 1 y of age (infants) and children aged 1 to 5 y, respectively. The risk of MD increased with increasing household density. In both age groups, the crude OR was 1.8 (95% confidence interval [CI]: 1.4-2.3) at a density of less than 20 m2 per person compared with the reference of more than 50 m2 per person. The adjusted OR for MD was 1.5 (95% CI: 1.1-1.9) for infants, and 1.5 (95% CI: 1.1-2.0) for children older than 1 y. Household density appears to be a risk factor of MD in preschool children.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.IJID.2012.10.001
Abstract: A primary dose of the European Union (EU)-licensed meningococcal A, C, W-135, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) was immunogenic and well-tolerated in subjects aged 15-19 years. This study assessed antibody persistence at 3.5 years after vaccination with a MenACWY-TT or a tetravalent ACWY polysaccharide vaccine (MenPS, control). In the original study, participants were randomized to receive a single dose of MenACWY-TT or MenPS. Serum bactericidal activity using rabbit serum as exogenous complement source was evaluated up to 42 months post-vaccination. At 42 months post-vaccination with MenACWY-TT (n = 19) or MenPS (n = 17), all subjects in each group had serum bactericidal activity titers ≥1:8 against all serogroups, except for two subjects in the MenPS group against serogroup C. Geometric mean antibody titers were higher than pre-vaccination levels at all post-vaccination time-points in both groups, and were significantly higher in the MenACWY-TT group versus the MenPS group for serogroup W-135 at month 42 (exploratory analysis). These results indicate that seroprotection following primary vaccination with MenACWY-TT extends more than 3 years. Ongoing persistence data are required to understand the duration of protection following vaccination and to guide decisions on the need for future booster doses.
Publisher: BMJ
Date: 12-2022
DOI: 10.1136/BMJOPEN-2022-069065
Abstract: The ENFORCE cohort is a national Danish prospective cohort of adults who received a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as part of the Danish National SARS-CoV-2 vaccination programme. It was designed to investigate the long-term effectiveness, safety and durability of SARS-CoV-2 vaccines used in Denmark. A total of 6943 adults scheduled to receive a SARS-CoV-2 vaccine in the Danish COVID-19 vaccination programme were enrolled in the study prior to their first vaccination. Participants will be followed for a total of 2 years with five predetermined follow-up visits and additional visits in relation to any booster vaccination. Serology measurements are performed after each study visit. T-cell immunity is evaluated at each study visit for a subgroup of 699 participants. Safety information is collected from participants at visits following each vaccination. Data on hospital admissions, diagnoses, deaths and SARS-CoV-2 PCR results are collected from national registries throughout the study period. The median age of participants was 64 years (IQR 53–75), 56.6% were women and 23% were in iduals with an increased risk of a serious course of COVID-19. A total of 340 (4.9%) participants tested positive for SARS-CoV-2 spike IgG at baseline. Results have been published on risk factors for humoral hyporesponsiveness and non-durable response to SARS-CoV-2 vaccination, the risk of breakthrough infections at different levels of SARS-CoV-2 spike IgG by viral variant and on the antibody neutralising capacity against different SARS-CoV-2 variants following primary and booster vaccinations. The ENFORCE cohort will continuously generate studies investigating immunological response, effectiveness, safety and durability of the SARS-CoV-2 vaccines. NCT04760132 .
Publisher: American Medical Association (AMA)
Date: 12-07-2016
Abstract: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. Risk of within-couple HIV transmission to the HIV-negative partner. Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48] 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000. Although 11 HIV-negative partners became HIV-positive (10 MSM 1 heterosexual 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.
Publisher: Wiley
Date: 1998
DOI: 10.1111/J.1699-0463.1998.TB01354.X
Abstract: A commercially available kit, Amplicor®, was compared with a locally developed nested reverse‐transcriptase (RT) PCR for qualitative detection of HCV‐RNA. Sixty‐one serum s les from sixty‐one patients with liver disease, and 60 s les from 60 hemophiliacs without symptoms, but known to have been heavily exposed to hepatitis C virus, were investigated. There was a high degree of concordance between the two diagnostic tests (97%), the Amplicor® kit being slightly more sensitive than the in‐house PCR, when evaluated using serial dilutions of s les showing discrepant results. The relationship between viremia and abnormal ALT levels was studied in the two groups of patients. Among those with chronic liver disease, 8.3% of patients with viremia had normal ALT levels, whereas transaminases were normal in 20% of hemophiliacs with viremia. This points to ALT as being a poor marker of ongoing viral replication.
Publisher: Informa UK Limited
Date: 08-11-2016
DOI: 10.1080/23744235.2016.1248483
Abstract: Bacterial infections are common complications in kidney transplant recipients (KTRs). Little is known about incidence rates of bacteremia and fungemia (BAF) in KTRs. In this population-based cohort study, we used medical and administrative registries to identify episodes of BAF among KTRs in the Central Denmark and North Denmark Regions during 1995-2010. KTRs were followed from the date of their first transplantation to the earliest of BAF, graft loss, death, emigration or 31 December 2010. We calculated incidence rates of first BAF episode overall and stratified by time from transplantation. Potential risk factors were assessed using Cox regression analysis. The Kaplan-Meier analysis was used to estimate 30- and 90-day mortality. Among 612 KTRs, we identified 138 first episodes of bacteremia during 2397 person-years of follow-up (PYFU). The overall incidence rate (IR) was 5.8 BAF episodes per 100 PYFU (95% confidence interval [CI]: 4.9-6.8). The incidence rate declined from 84.0 per 100 PYFU (95% CI: 61.6-114.5) during post-transplant day 0-30 to 2.3 per 100 PYFU (95% CI: 1.7-3.0) from post-transplant day 365 and onwards. Hospital-onset BAF comprised 39% of the episodes of BAF. The most frequently isolated microorganisms were Escherichia coli and Klebsiella species causing 49 (35.5%) and 29 (21.0%) episodes of BAF, respectively. The 30-day mortality was 2.1% (95% CI: 0.7-6.6). While the risk of BAF in KTRs was high, thirty-day mortality was low. After the first post-transplant year, the IR of bacteremia was substantially lower than in the immediate post-transplant period.
Publisher: Oxford University Press (OUP)
Date: 21-12-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-02-2005
DOI: 10.1097/01.TP.0000149839.87843.64
Abstract: Bronchiolitis obliterans syndrome (BOS) is a common late complication in lung transplant recipients (LTR). Chlamydia pneumoniae (C. pneumoniae) is a common but difficult to diagnose respiratory pathogen with a propensity to latency. We studied the impact of C. pneumoniae on BOS development using donor-recipient serology obtained before transplantation in a cohort of 76 LTR. BOS was present in 29.9% patients (mean follow-up 866 days). High donor C. pneumoniae immunoglobulin (Ig)G titers were associated with BOS in the recipient (area under the curve [AUC] 0.71, 95% confidence interval [CI] 0.52-0.91, P=0.027), whereas high recipient titers were inversely associated with BOS (AUC 0.27, 95% CI 0.11-0.44, P=0.018). The risk of developing BOS was 75.0% in the case of a primary seromismatch for C. pneumoniae (D+/R-), whereas a reverse mismatch had a risk of 4.6% (likelihood ratio 9.8, P=0.02). In a multivariate model that included human leukocyte antigen matching, acute rejection and cytomegalovirus pneumonitis, C. pneumoniae IgG donor 32 or greater and C. pneumoniae IgG recipient 32 or greater remained positive and negative independent risk factors, respectively, for BOS in LTR. In the freedom from BOS analysis, BOS occurred more frequently and earlier in C. pneumoniae seropositive donors, and the reverse was true in seronegative recipients. C. pneumoniae serology in donor and recipient is associated with the development of BOS in LTR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2019
Publisher: Informa UK Limited
Date: 2006
DOI: 10.1080/00365540500372861
Abstract: Rapid aetiological diagnosis of bacterial meningitis is crucial for the early targeting of antimicrobial and adjuvant therapy. Broad-range polymerase chain reaction (PCR) targeting the 16S rRNA gene allows aetiological diagnosis of bacterial meningitis when applied to cerebrospinal fluid (CSF). We assessed the additional diagnostic effect of applying a novel broad-range real time PCR and subsequent DNA sequencing to culture, microscopy, and broad-range conventional PCR on CSF in patients with suspected bacterial meningitis. Broad-range conventional PCR and broad-range real time PCR with subsequent DNA sequencing were applied to 206 CSF specimens collected consecutively from 203 patients aged 6 d to 86 y. Patients' charts were reviewed for clinical information. 17 pathogens were identified by PCR and DNA sequencing or culture. Three specimens were negative by culture but positive by broad-range real time PCR. Three specimens were positive by culture but negative by broad-range real time PCR. Compared with culture, the sensitivity of broad-range real time PCR was 86%, and the specificity 98%. Conventional PCR resulted in a sensitivity of 64% and specificity of 98%. Broad-range real time PCR was generally comparable to culture of CSF and may be a useful supplement, particularly when antimicrobial therapy has been administered. Broad-range real time PCR was more sensitive than broad-range conventional PCR and microscopy.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 09-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-05-2004
DOI: 10.1161/01.CIR.0000127772.58427.7E
Abstract: Background— Chlamydia pneumoniae ( Cp ) has been demonstrated in arteries and abdominal aortic aneurysms (AAAs). However, the validity of the methods used is questioned, and antibiotic treatment trials have thus far shown disappointing results. Nevertheless, antibodies against the Cp outer membrane proteins (OMPs) have been associated with progression of atherosclerosis and AAAs. The aim of this study was to detect Cp OMPs in the wall of AAA patients by use of purified serum antibodies directed against Cp OMP and to assess potential cross-reacting proteins in AAA walls. Methods and Results— Seventeen patients undergoing infrarenal AAA repair were studied. Full AAA thickness tissue was collected from the anterior wall of the aneurysm. Anti-OMP was extracted from seropositive AAA patients by use of an ELISA kit (Labsystems). Analysis was performed by use of 2D polyacrylamide gel electrophoresis, immunoblotting, and mass spectrometric protein identification. OMP antigens were not detected in 16 of 17 AAA walls. However, 3 major AAA proteins cross-reacted with anti-OMP. The proteins were all identified as heavy chains of human immunoglobulin. Conclusions— We could not find evidence of Cp OMP in 16 of 17 AAA walls, but instead, all s les showed a strong cross-reaction between Cp OMP antibodies and human immunoglobulin. This might indicate that AAA is an autoimmune disease, perhaps triggered by an initial Cp infection.
Publisher: Public Library of Science (PLoS)
Date: 22-07-2010
Publisher: Informa UK Limited
Date: 1988
DOI: 10.3109/00365528809090193
Abstract: An animal experimental model featuring simultaneous recordings of electromyography and pressure from the sphincter of Oddi (SO) and duodenum is demonstrated. On the basis of data from 10 rabbits, pressure recordings from the SO were shown to have phasic activity with an average basic pressure peak interval of 2.6 to 3.5 sec. Histographic analysis of SO pressure recordings showed a multimodal appearance, suggesting that the activity is paced. A substantial amount of overlap between SO and duodenal contractions was observed. As many as 30% of the pressure peaks recorded from the SO could not be assigned to a spike complex in the corresponding EMG tracings. It is suggested that combined recordings of EMG and pressure activity are needed to characterize fully the motility of the SO and duodenum.
Publisher: Springer Science and Business Media LLC
Date: 2003
Publisher: Oxford University Press (OUP)
Date: 15-04-2008
DOI: 10.1086/529523
Abstract: Background and methodsThe SMART study compared 2 strategies for using antiretroviral therapy—drug conservation (DC) and viral suppression (VS)—in 5472 human immunodeficiency virus (HIV)–infected patients with CD4+ cell counts & cells/μL. Rates and predictors of opportunistic disease or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported ResultsDuring a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count & cells/μL (for DC vs. VS, 31% vs. 8%) and with a latest HIV RNA level & copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow-up with a CD4+ cell count & cells/μL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the rates were higher in DC versus VS patients (2.3 vs. 1.0/100 person-years RR, 2.3 [95% confidence interval, 1.5–3.4]) for periods with the latest CD4+ cell count ⩾350 cells/μL—an increase explained by the higher HIV RNA levels in the DC group ConclusionsThe higher risk of OD/death in DC patients was associated with (1) spending more follow-up time with relative immunodeficiency and (2) living longer with uncontrolled HIV replication even at higher CD4+ cell counts. Ongoing HIV replication at a given CD4+ cell count places patients at an excess risk of OD/death Trial registrationClinicalTrials.gov identifier: NCT00027352
Publisher: Wiley
Date: 23-06-2022
DOI: 10.1111/ENE.15435
Abstract: Among post‐COVID‐19 symptoms, fatigue is reported as one of the most common, even after mild acute infection, and as the cause of fatigue, myopathy diagnosed by electromyography has been proposed in previous reports. This study aimed to explore the histopathological changes in patients with post‐COVID‐19 fatigue. Sixteen patients (mean age = 46 years) with post‐COVID‐19 complaints of fatigue, myalgia, or weakness persisting for up to 14 months were included. In all patients, quantitative electromyography and muscle biopsies analyzed with light and electron microscopy were taken. Muscle weakness was present in 50% and myopathic electromyography in 75%, and in all patients there were histological changes. Muscle fiber atrophy was found in 38%, and 56% showed indications of fiber regeneration. Mitochondrial changes, comprising loss of cytochrome c oxidase activity, subsarcollemmal accumulation, and/or abnormal cristae, were present in 62%. Inflammation was found in 62%, seen as T lymphocytes and/or muscle fiber human leukocyte antigen ABC expression. In 75%, capillaries were affected, involving basal lamina and cells. In two patients, uncommon amounts of basal lamina were found, not only surrounding muscle fibers but also around nerves and capillaries. The wide variety of histological changes in this study suggests that skeletal muscles may be a major target of SARS‐CoV‐2, causing muscular post‐COVID‐19 symptoms. The mitochondrial changes, inflammation, and capillary injury in muscle biopsies can cause fatigue in part due to reduced energy supply. Because most patients had mild–moderate acute affection, the new variants that might cause less severe acute disease could still have the ability to cause long‐term myopathy.
Publisher: American Society for Microbiology
Date: 28-02-2018
Abstract: The effect of treatment with histone deacetylase inhibitors on the immune system in HIV-infected in iduals is not clear. Analysis of results from a clinical trial in which 15 HIV-infected in iduals received 12 doses of panobinostat identified a significant impact on both T cell activation status and regulatory T cell suppressive marker expression and a reduced level of monocytic responsiveness to inflammatory stimuli. These changes were substantiated by global gene expression analysis. Collectively, the results suggest that panobinostat has multiple effects on innate and adaptive immune responses. Importantly, all the effects were transient, and further panobinostat treatment did not cause persistent long-term changes in gene expression patterns in HIV-infected in iduals.
Publisher: Public Library of Science (PLoS)
Date: 26-04-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-11-2013
DOI: 10.1097/01.AIDS.0000432457.91228.F3
Abstract: To consider associations between the latest/nadir CD4 cell count, and time spent with CD4 cell count less than 200 cells/μl (duration of immune depression), and myocardial infarction (MI), coronary heart disease (CHD), stroke, or cardiovascular disease (CVD) (CHD or stroke) in 33 301 HIV-positive in iduals. Longitudinal cohort study. Analyses were undertaken using Poisson regression. To investigate whether analyses of stroke were robust to the type of endpoint, we additionally included stroke-like events and rejected strokes into the stroke endpoint. Participants experienced 716 MI, 1056 CHD, 303 stroke, and 1284 CVD events. Whereas there was no evidence of a higher MI/CHD risk in those with lower latest/nadir CD4 cell counts after adjustment [current CD4 <100 cells/μl: relative rate (95% confidence interval) 0.96 (0.62-1.50) for MI, 0.89 (0.30-2.36) for CHD nadir CD4 <100 cells/μl: 1.36 (0.57-3.23) for MI, 0.98 (0.45-2.16) for CHD], stroke and CVD rates were higher in those with a latest CD4 cell count less than 100 cells/μl [2.26 (1.29-3.94) and 1.14 (0.84-1.56), respectively]. All events occurred less frequently in those who had not experienced immune depression, although evidence for a linear association with duration of immune depression was weak. The association between stroke risk and the latest CD4 cell count strengthened as stroke-like and rejected strokes were included conversely, associations with established stroke risk factors weakened. We do not find strong evidence that HIV-positive in iduals with a low CD4 cell count are more likely to experience MI/CHD. Although strokes appear to occur more commonly at low CD4 cell counts, this may be partly explained by misclassification or other biases.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.IJID.2013.12.008
Abstract: Having effective ways to cope helps HIV-infected in iduals maintain good psychological and physical well-being. This study investigated the relationship between coping self-efficacy levels, as determined by the Coping Self-Efficacy Scale (CSE), HIV status disclosure, and depression in a Danish cohort. In 2008, the CSE was administered to 304 HIV-infected in iduals to measure their confidence in their ability to cope with HIV infection. HIV status disclosure was assessed on a three-point scale: living openly with the disease, partly openly, or secretly. The Beck Depression Inventory (BDI) was used to assess depression prevalence and severity. The CSE score was significantly related to depression (Spearman's rho = -0.71 the test of H0: BDI and coping, probability >t=0.0001). There was a significant relationship between higher CSE scores and living openly with HIV. The risk of depression was four times higher in HIV-infected in iduals who did not disclose their HIV status (i.e. who lived 'secretly' odds ratio = 4.1) than in in iduals who lived openly. Those with low CSE scores were more likely to report living secretly with HIV and to be depressed. Disclosing HIV may constitute a social stressor, and a lack of coping self-efficacy may increase the likelihood of non-disclosure and depression. Interventions that enhance self-efficacy may help in managing the demands of daily life with HIV, increase disclosure, and reduce depression.
Publisher: Elsevier BV
Date: 11-1996
DOI: 10.1016/S0163-4453(96)92225-2
Abstract: Relative bradycardia in infectious diseases is a poorly defined term. No exact and useful definition exists and the underlying mechanisms are unknown. Despite this, the term is often used in the literature and in clinical practice both as a clinical sign for an in idual patient and as a characteristic feature of certain specific diseases. In this study a definition of relative bradycardia as a clinical sign in an in idual patient and a definition of relative bradycardia as a characteristic feature of a specific disease were established based on a reference population comprising 673 patients with various infectious diseases. Relative bradycardia as a clinical sign in an in idual patient held no predictive value regarding the likely type of infection. Relative bradycardia as a characteristic feature of specific disease was found for typhoid fever (P = 0.003), Legionnaire's disease (P = 0.005), and pneumonia caused by Chlamydia sp. (P = 0.0005), but not for mycoplasma pneumonia. It was not found for other pulmonary infections, infections caused by other Salmonella sp., other extracellular Gram-negative infections, or viral infections. Thus, relative bradycardia as a clinical sign has no predictive value for obtaining a tentative diagnosis, but relative bradycardia as a feature of specific disease is seen in typhoid fever, Legionnaire's disease, and pneumonia caused by Chlamydia sp. It seems that relative bradycardia as a feature of specific disease only occurs in diseases caused by organisms that are both Gram-negative and intracellular.
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JINF.2013.03.006
Abstract: In iduals with immunodeficiencies are at increased risk of central nervous system (CNS) infections. Data are limited on the risk of CNS infections in patients with end-stage renal disease (ESRD). We conducted a population-based, nationwide cohort study among ESRD patients from 1990 to 2009. Data on ESRD patients was obtained from the Danish Nephrology Registry database. Each ESRD patient was matched with up to 19 population controls. Using the National Hospital Registry we identified hospital admissions with CNS infection as primary discharge diagnosis. The study included 13,374 ESRD patients and 245,397 population controls, providing 67,012 person-years and 2,237,237 person-years of observation, respectively. The overall incidence rate (IR) of first-time hospitalisation for CNS infection was 149 per 100,000 person-years (95%-confidence interval [CI], 123-181) among ESRD patients. The IR of CNS infection was comparable among dialysis and transplant patients. Compared to population controls, the incidence rate-ratio of first CNS infection was 5.58 (95%-CI, 4.47-6.91) for ESRD patients in general. The 30-day mortality following hospitalisation for CNS infections was 21% (95%-CI, 14-30) among ESRD patients and 13% (95%-CI, 10-16) among population controls. ESRD patients have considerable excess risk and mortality from CNS infections, which is of great clinical and public health concern.
Publisher: American Society for Microbiology
Date: 14-02-2023
DOI: 10.1128/SPECTRUM.04174-22
Abstract: Identifying at-risk groups and evaluating preventive interventions in at-risk groups is imperative for the ongoing pandemic as well as for the control of future epidemics. Although DCS staff have a much higher risk of being infected within their own household than at their workplace, most are fearful of being infected with COVID-19 or bringing COVID-19 to work.
Publisher: Springer Science and Business Media LLC
Date: 09-04-2015
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.VACCINE.2016.01.044
Abstract: Neisseria meningitidis serogroup B (MnB) is an important cause of invasive meningococcal disease (IMD). A MnB vaccine (bivalent rLP2086, Trumenba(®)) consisting of 2 factor H binding protein variants received accelerated approval in the United States for the prevention of IMD caused by MnB in in iduals 10-25 years of age. This randomized, active-controlled, observer-blind study further assessed the safety and tolerability of bivalent rLP2086. Eligible subjects ≥ 10 to < 26 years were randomized (2:1) to receive bivalent rLP2086 at months 0, 2, and 6, or hepatitis A virus vaccine (HAV, Havrix(®)) at months 0 and 6, and saline at month 2. The primary endpoints were serious adverse events (SAEs) throughout the study and medically-attended adverse events (MAEs) within 30 days after vaccination. Additional safety assessments included SAEs at other study intervals and adverse events (AEs) during the vaccination phase. Of 5712 subjects randomized, 84.6% (n = 3219) of bivalent rLP2086 recipients and 87.2% (n = 1663) of HAV/saline recipients completed the study. Throughout the study, SAEs were reported for 1.6% and 2.5% of bivalent rLP2086 and HAV/saline recipients, respectively. SAEs related to either vaccine were rare. MAEs occurred in 7.0% and 6.1% of subjects after vaccination 1 5.5% and 6.1% after vaccination 2 and 5.3% and 5.5% after vaccination 3 in the bivalent rLP2086 and HAV/saline groups, respectively. A greater proportion of subjects reported AEs during the vaccination phase after bivalent rLP2086 compared with HAV/saline recipients however, when reactogenicity events were excluded, the proportion between groups was similar. This safety study, the largest randomized, active-controlled trial evaluating a recombinant MnB vaccine, demonstrated that bivalent rLP2086 is safe and tolerable in healthy in iduals ≥ 10 to < 26 years of age.
Publisher: Oxford University Press (OUP)
Date: 09-03-2017
DOI: 10.1093/CID/CIX201
Publisher: Oxford University Press (OUP)
Date: 11-1999
DOI: 10.1086/313448
Abstract: To evaluate Bordetella pertussis as a cause of persistent cough in adults, we examined 201 patients who had a cough for 2-12 weeks and no pulmonary disease. We obtained the following at presentation: medical history, chest radiograph, respiratory function measurement, nasopharyngeal aspirate for polymerase chain reaction (PCR), nasopharyngeal swab specimen for culture, and a blood s le (acute serum). Four weeks later a second blood s le (convalescent serum) was obtained. Control sera were obtained from 164 age-matched healthy blood donors with no history of cough during the previous 12 weeks. Four patients were B. pertussis culture-positive 11 (including the culture-positive patients) were B. pertussis PCR-positive and 33, including 10 of the 11 PCR-positive patients, had serological evidence of recent B. pertussis infection. Pertussis-positive and -negative patients could not be discriminated by a history of cough. We conclude that B. pertussis infection is a common cause of persistent cough in adults. This is of concern, because these patients may be B. pertussis reservoirs from which transmission may occur to infants, in whom the disease can be devastating.
Publisher: Rockefeller University Press
Date: 27-07-2015
DOI: 10.1084/JEM.20142274
Abstract: Herpes simplex encephalitis (HSE) in children has previously been linked to defects in type I interferon (IFN) production downstream of Toll-like receptor 3. Here, we describe a novel genetic etiology of HSE by identifying a heterozygous loss-of-function mutation in the IFN regulatory factor 3 (IRF3) gene, leading to autosomal dominant (AD) IRF3 deficiency by haploinsufficiency, in an adolescent female patient with HSE. IRF3 is activated by most pattern recognition receptors recognizing viral infections and plays an essential role in induction of type I IFN. The identified IRF3 R285Q amino acid substitution results in impaired IFN responses to HSV-1 infection and particularly impairs signaling through the TLR3–TRIF pathway. In addition, the R285Q mutant of IRF3 fails to become phosphorylated at S386 and undergo dimerization, and thus has impaired ability to activate transcription. Finally, transduction with WT IRF3 rescues the ability of patient fibroblasts to express IFN in response to HSV-1 infection. The identification of IRF3 deficiency in HSE provides the first description of a defect in an IFN-regulating transcription factor conferring increased susceptibility to a viral infection in the CNS in humans.
Publisher: Frontiers Media SA
Date: 10-2021
DOI: 10.3389/FVIRO.2021.736395
Abstract: A cure for human immunodeficiency virus (HIV-1) is restricted by the continued presence of a latent reservoir of memory CD4 + T cells with proviruses integrated into their DNA despite suppressive antiretroviral therapy (ART). A predominant strategy currently pursued in HIV-1 cure-related research is the “kick and kill” approach, where latency reversal agents (LRAs) are used to reactivate transcription from integrated proviruses. The premise of this approach is that “kicking” latent virus out of hiding allows the host immune system to recognize and kill infected cells. Clinical trials investigating the efficacy of LRAs, such as romidepsin, have shown that these interventions do induce transient spikes in viral RNA in HIV-1-infected in iduals. However, since these trials failed to significantly reduce viral reservoir size or significantly delay time to viral rebound during analytical treatment interruptions, it is questioned how much each in idual latent provirus is actually “kicked” to produce viral transcripts and/or proteins by the LRA. Here, we developed sensitive and specific digital droplet PCR-based assays with single-provirus level resolution. Combining these assays allowed us to interrogate the level of viral RNA transcripts from single proviruses in in iduals on suppressive ART with or without concomitant romidepsin treatment. Small numbers of proviruses in peripheral blood memory CD4 + T cells were triggered to become marginally transcriptionally active upon romidepsin treatment. These novel assays can be applied retrospectively and prospectively in HIV-1 cure-related clinical trials to gain crucial insights into LRA efficacy at the single provirus level.
Publisher: BMJ
Date: 10-11-2006
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.AHJ.2016.08.012
Abstract: Chronic hemodialysis is a risk factor for invasive bacterial infections. We conducted a nationwide study of risk and mortality of infective endocarditis (IE) among patients undergoing chronic hemodialysis. In this observational cohort study, patients with end-stage renal disease who initiated hemodialysis in Denmark during 1990 to 2010 were matched on age, gender, and municipality with up to 19 population controls. We extracted information on first admissions with IE, comorbidity, and arteriovenous fistula surgery from medical administrative databases. Incidence rates (IRs) of IE were compared between patients undergoing hemodialysis and population controls using Poisson regression. Risk factors for IE were assessed by Cox regression. IE was diagnosed in 150 of 9392 patients undergoing hemodialysis (IR: 6.83 per 1000 person-years, 95% confidence interval [CI] 5.82-8.01) and 250 of 176,369 population controls (IR: 0.18 per 1000 person-years, 95% CI 0.16-0.20) yielding an incidence rate-ratio of 38.1 (95% CI 31.2-46.7). Among patients undergoing hemodialysis, absence of arteriovenous fistula surgery was associated with increased risk of IE (hazard ratio [HR] = 1.57 95% CI 1.09-2.27) after adjusting for age, sex, valvular disease, diabetes and period of first hemodialysis. Age ≥70 years was associated with a lower risk of IE (HR = 0.59 95% CI 0.37-0.93). The 90-day all-cause mortality following diagnose of IE was 27% (95% CI 20-35) for patients undergoing hemodialysis and 23% (95% CI 18-29) for controls. Patients undergoing hemodialysis have markedly elevated risk of IE compared to the general population. Future challenges will be to develop strategies to prevent IE, to reduce IE-related morbidity and mortality in this vulnerable population.
Publisher: Springer Science and Business Media LLC
Date: 2005
DOI: 10.1007/S10654-004-4341-5
Abstract: Chlamydia pneumoniae has been linked with increased risk of cardiovascular disease, but data on stroke are sparse. We examined whether seropositivity to Chlamydia pneumoniae was associated with the risk of ischemic stroke in a nested case-control study. Data on Chlamydia pneumoniae serology, lifestyle factors, and medical history were obtained at baseline. Verified cases (n = 254) were compared with gender- and age-matched controls (n = 254). Positive IgA (> or = 1:16) or IgG (> or = 1:64) titers were associated with an increased risk of acute ischemic stroke, i.e. adjusted odds ratios (ORs) were 1.54 (95% confidence interval, CI: 0.96-2.47) and 1.28 (95% CI: 0.83-1.95). The adjusted OR was 1.77 (95% CI: 1.04-3.00) when both titers were elevated. The highest point estimates were seen for ischemic stroke due to large-artery atherosclerosis, adjusted OR: 6.32 (95% CI: 0.76-52.61) (IgG (> or = 1:64)). No clear associations were found for other types of ischemic stroke. The strength of the association varied depending on gender and the chosen cut-off values for the antibody titers. These results partly support the hypothesis that serologic evidence of Chlamydia pneumoniae infection may be associated with an increased risk of ischemic stroke. However, the risk may differ according to gender, subtype of ischemic stroke, and cut-off value of antibody titers.
Publisher: Springer Science and Business Media LLC
Date: 08-2011
Abstract: This study evaluates the immunogenicity of the HIV envelope protein (env) in mice presented either attached to γ-retroviral virus-like-particles (VLPs), associated with cell-derived microsomes or as solubilized recombinant protein (gp160). The magnitude and polyfunctionality of the cellular immune response was enhanced when delivering HIV env in the VLP or microsome form compared to recombinant gp160. Humoral responses measured by antibody titres were comparable across the groups and low levels of antibody neutralization were observed. Lastly, we identified stronger IgG2a class switching in the two particle-delivered antigen vaccinations modalities compared to recombinant gp160.
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1080/00365540110080854
Abstract: Plasma levels of tumour necrosis factor (TNF)-alpha levels increase with age. High levels are associated with dementia and atherosclerosis in centenarians. Chlamydia pneumoniae induces the production of proinflammatory cytokines and has been related to the pathogeneses of Alzheimer's disease and cardiovascular diseases. The purpose of this study was to test the hypothesis that circulating levels of TNF-alpha represent a link between C. pneumoniae, high prevalences of dementia and cardiovascular diseases in 126 Danish centenarians. IgA antibody titres against C. pneumoniae were linearly correlated with high plasma levels of TNF-alpha in centenarians. However, both parameters were also correlated with total IgA in the blood and the association between C. pneumoniae IgA and TNF-alpha was not significant when total IgA was included in a multiple linear regression model. Accordingly, the association between C. pneumoniae-specific IgA and TNF-alpha may reflect immune activation rather than a specific antibody response. No associations were found between antibodies to C. pneumoniae and dementia or cardiovascular diseases. Although TNF-alpha is likely to be involved in the pathogenesis of atherosclerosis and dementia, the present study does not support the hypothesis that TNF-alpha represents a link between chronic C. pneumoniae infection and these disorders.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-03-2016
Publisher: Oxford University Press (OUP)
Date: 08-05-2023
DOI: 10.1093/OFID/OFAD248
Abstract: Side effects to SARS-CoV-2 vaccines are a key concern contributing to vaccine hesitancy, but more in iduals may be encouraged if they were known to lead to a stronger immune response. Adult participants were included from the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE), who completed a questionnaire to assess systemic reactions following SARS-CoV-2 vaccination (BTN162b2, mRNA-1273, ChAdOx1) and had SARS-CoV-2 spike IgG levels measured at baseline and post-vaccine. A symptom score was developed to measure severity of systemic adverse reactions (+1 for each moderate, +2 for each severe). Post-vaccination SARS-CoV-2 spike IgG levels were compared between participants with different scores using multivariable linear regression. A total of 6528 participants were included (56.3% females, median age 64 years [IQR 54-75]). After first vaccination, no association was found between symptom score and post-vaccine dose spike IgG level (p-value=0.575). Following second vaccination, significantly higher spike IgG levels were observed according to higher symptom score (p& .001) adjusted geometric mean ratios (95% CIs) were 1.16 (1.04-1.30), 1.24 (1.09-1.41), 1.25 (1.06-1.46), and 1.21 (1.08-1.35), for scores of 2, 3, 4, ≥5, respectively, compared to a score of 0. After adjustment for pre-vaccine dose spike IgG, this association was attenuated. An association was found between more severe adverse reactions and stronger antibody response after the second vaccination but not the first, likely attributed to higher levels of pre-existing immunity gained from response to first vaccination. Regardless of side effects, most people experienced an effective immune response following vaccination.
Publisher: Elsevier BV
Date: 2002
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-07-2014
Publisher: Public Library of Science (PLoS)
Date: 17-09-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2019
Publisher: Oxford University Press (OUP)
Date: 08-05-2018
DOI: 10.1093/CID/CIY088
Publisher: American Chemical Society (ACS)
Date: 23-02-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2007
Publisher: American Society for Microbiology
Date: 07-2015
DOI: 10.1128/AAC.00574-15
Abstract: Adjunct therapy with the histone deacetylase inhibitor (HDACi) romidepsin increases plasma viremia in HIV patients on combination antiretroviral therapy (cART). However, a potential concern is that reversing HIV latency with an HDACi may reactivate the virus in anatomical compartments with suboptimal cART concentrations, leading to de novo infection of susceptible cells in these sites. We tested physiologically relevant romidepsin concentrations known to reactivate latent HIV in order to definitively address this concern. We found that romidepsin significantly inhibited HIV infection in peripheral blood mononuclear cells and CD4 + T cells but not in monocyte-derived macrophages. In addition, romidepsin impaired HIV spreading in CD4 + T cell cultures. When we evaluated the impact of romidepsin on quantitative viral outgrowth assays with primary resting CD4 + T cells, we found that resting CD4 + T cells exposed to romidepsin exhibited reduced proliferation and viability. This significantly lowered assay sensitivity when measuring the efficacy of romidepsin as an HIV latency reversal agent. Altogether, our data indicate that romidepsin-based HIV eradication strategies are unlikely to reseed a latent T cell reservoir, even under suboptimal cART conditions, because romidepsin profoundly restricts de novo HIV infections.
Publisher: Elsevier BV
Date: 06-2096
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-07-2015
Publisher: Frontiers Media SA
Date: 05-07-2022
DOI: 10.3389/FCIMB.2022.919097
Abstract: Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll -like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo , in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p& .0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected in iduals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo , in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment.
Publisher: Springer Science and Business Media LLC
Date: 05-06-2014
DOI: 10.1038/GENE.2014.28
Publisher: BMJ
Date: 10-2003
DOI: 10.1136/STI.79.5.358
Abstract: To compare the effectiveness of "home s ling" with that of "office s ling" for testing partners to men and women infected with Chlamydia trachomatis. A randomised controlled effectiveness trial took place in the general community in Denmark. 1300 index women and 526 index men (>/=18 years) with a positive test result for C trachomatis were identified. Of these, 414 index women and 148 index men gave implied consent. Index patients were randomly assigned to provide their partner(s) through the past 12 months with either (1) a kit by which partner(s) could be tested by home s ling, or (2) a kit by which partner(s) could only be tested by seeing a healthcare professional (office s ling). The mainoutcome measure was the proportion of index patients who had at least one partner tested for C trachomatis. The proportion of index women with at least one partner tested was higher in the home s ling group (0.26) than in the office group (0.12) (difference 0.14 95% CI 0.10 to 0.19 p<0.0001) and so it was for index men (0.15 v 0.03 difference 0.12 95% CI 0.07 to 0.16 p<0.0001). Also the proportion of index women for whom at least one partner was identified as infected was higher in the home s ling group compared with the office group (0.11 v 0.07, p=0.01). The corresponding figures for index men were 0.06 v 0.01, p=0.02. The effectiveness of partner testing is higher when partners of C trachomatis infected patients are offered home s ling than when they are offered office s ling.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-07-2015
Publisher: Wiley
Date: 29-04-2015
DOI: 10.1111/LIV.12848
Abstract: In the last decade, several outbreaks of sexually acquired acute hepatitis C (HCV) infection have been described in HIV-positive men who have sex with men (MSM). The aims of this study were to determine whether there has been an increase in the number of acute HCV infections in different parts of Europe. HCV seroconversion was defined as an HCV-antibody test change from negative to positive within the observation period in EuroSIDA. Binomial regression was performed to determine factors associated with being tested for HCV and HCV seroconversion. A total of 223 HCV seroconversions were observed from 16,188 tests [1.38% (95%CI 1.20-1.56)] among 5736 patients between 2002 and 2013. Overall the odds of acquiring HCV infection increased by 4% per year (OR 1.04 [95%CI 0.99-1.09] P = 0.10). Overall 63.2% (141/223) of all seroconversions were seen among MSM. Similar patterns were observed across all European regions (P = 0.69, test for interaction) and HIV transmission risks groups (P = 0.69, test for interaction). In multivariate analysis, North, South and East Europe had higher odds of HCV seroconversion compared with Western Europe [OR 1.90 (1.28-2.81), 1.55 (0.99-2.45) and 1.86 (1.21-2.84) P = 0.0014, P = 0.058 and P = 0.0044 respectively]. Within EuroSIDA a significant increase in HCV seroconversions can be observed after accounting for increased levels of testing for HCV in recent years. This highlights the need for increased HCV prevention efforts among HIV-positive persons in Europe.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-11-2011
Publisher: Massachusetts Medical Society
Date: 14-12-2017
Publisher: Springer Science and Business Media LLC
Date: 11-09-2023
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.VACCINE.2018.11.073
Abstract: The period of heightened risk of invasive meningococcal disease in adolescence extends for >10 years. This study aimed to evaluate persistence of the immune response to the serogroup B meningococcal (MenB) vaccine MenB-FHbp (Trumenba This was an open-label extension study of a phase 2 randomized MenB-FHbp study (primary study). This interim analysis includes data through 1 month after booster vaccination. In the primary study, adolescents 11-18 years of age were randomized using an interactive voice or web-based response system to receive 120 μg MenB-FHbp under 0-, 1-, 6-month 0-, 2-, 6-month 0-, 6-month 0-, 2-month or 0-, 4-month schedules (termed study groups for the current analysis). For the primary study, participants were blinded to their vaccine study group allocation, but investigators and the study sponsor were unblinded. Immune responses in subjects from the primary study were evaluated through 48 months after primary vaccination (persistence stage 17 sites in Czech Republic, Denmark, Germany, and Sweden). Safety and immunogenicity of a booster dose given at 48 months after primary vaccination (booster stage 14 sites in Czech Republic, Denmark, and Sweden) were also assessed. Immune responses were evaluated in serum bactericidal assays with human complement (hSBAs) using four MenB test strains representative of disease-causing MenB strains in the United States and Europe and expressing factor H binding proteins (FHbps) heterologous to the vaccine antigens. The primary immunogenicity endpoints were the proportions of subjects with hSBA titers greater than or equal to the assays' lower limit of quantitation (LLOQ 1:8 or 1:16 depending on strain) at 12, 18, 24, 36, and 48 months after primary vaccination (persistence stage) and 1 and 48 months after the primary vaccination series and 1 month after receipt of the booster dose (booster stage). Safety evaluations during the booster stage included local reactions and systemic events by severity, antipyretic use, adverse events (AEs), immediate AEs, serious AEs (SAEs), medically attended AEs (MAEs), newly diagnosed chronic medical conditions (NDCMCs), and missed days of school and work because of AEs. The modified intent-to-treat (mITT) population was used for immunogenicity evaluations in the persistence stage. The booster stage immunogenicity evaluations used the evaluable immunogenicity population analyses were also performed in the mITT population. For the persistence stage, safety evaluations included subjects with at least one blood draw, whereas for the booster stage, they included subjects who received the booster dose and had available safety data. This trial is registered at ClinicalTrials.gov number NCT01543087. A total of 465 subjects were enrolled in the persistence stage, and 271 subjects were enrolled in the booster stage. Sera for the extension phase of this interim analysis were collected from September 7, 2012 to December 7, 2015. One month after primary vaccination, 73.8-100.0% of subjects depending on study group responded with hSBA titers ≥LLOQ. Response rates declined during the 12 months after last primary vaccination and then remained stable through 48 months, with 18.0-61.3% of subjects depending on study group having hSBA titers ≥LLOQ at this time point. One month after receipt of the booster dose, 91.9-100.0% of subjects depending on study group had hSBA titers ≥LLOQ against the four primary strains in idually and 91.8-98.2% had hSBA titers ≥LLOQ against all four strains combined (composite response). Geometric mean titers were higher after booster vaccination than at 1 month after primary vaccination. Immune responses were generally similar across study groups, regardless of whether a two- or three-dose primary series was received. None of the AEs (2.2-6.9% of subjects depending on study group) or NDCMCs (1.8-5.0%) that were reported during the persistence stage were considered related to the investigational product. Local reactions and systemic events were reported by 84.4-93.8% and 68.8-76.6% of subjects depending on study group, respectively, in the booster stage these were generally similar across study groups, transient, and less frequent than after any primary vaccination. Additionally, there was no general progressive worsening in severity of reactogenicity events (ie, potentiation ≤3 subjects per group), and reactogenicity events did not lead to any study withdrawals. No NDCMCs or immediate AEs were reported during the booster stage. AEs were reported by 3.7-12.5% of subjects depending on study group during the booster stage. The two possibly related AEs included a mild worsening of psoriasis and a severe influenza-like illness that resolved in 10 days. Immune responses declined after the primary vaccination series however, a substantially greater number of subjects retained protective responses at 48 months after primary vaccination compared with subjects having protective responses before vaccination. Persistence trends were similar across all 5 study groups regardless of whether a two- or three-dose primary schedule was received. Furthermore, a booster dose given 48 months after primary vaccination was safe, well-tolerated, and elicited robust immune responses indicative of immunologic memory these responses were similar between two- and three-dose primary schedule study groups. Use of a booster dose may help further extend protection against MenB disease in adolescents. Pfizer Inc.
Publisher: Wiley
Date: 1998
DOI: 10.1111/J.1699-0463.1998.TB01387.X
Abstract: Endocervical s ling for microbiological and pathological screening is laborious and expensive due to different s ling devices and techniques. The purpose of this study was to examine if the routine procedure could be simplified by using a cytobrush for concurrent cytology and s ling for Chlamydia trachomatis detection using the PCR method or cell culture. As a s ling device control we used a conventional rayon swab. Results : Culture: Out of 873 paired endocervical specimens, C. trachomatis was isolated in 68 swab specimens and in 65 cytobrush specimens (overall detection rate 8.4%). The cytobrush proved less suitable than the swab for the isolation of C. trachomatis as 31.5% of the cytobrush s les showed cytotoxicity to the cultured cells vs 0.9% of the swab s les. PCR: In a random s le of 427 paired endocervical specimens, C. trachomatis was detected in 45 pairs without any difference between the two s ling devices. The sensitivity of PCR was 93.8% vs 89.6% and 87.5% in cultured swab and cultured cytobrush specimens, respectively. The cytobrush can therefore be recommended as a cervical s ling device if a PCR assay is used for the detection of C. trachomatis , but not if the cell culture method is used, due to high cytotoxicity. Furthermore, the same cytobrush may be used for cervical cytological s ling and thereafter placed in transport medium for subsequent C. trachomatis detection if the PCR technique is used.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/120605
Abstract: Intestinal CD4 + T cell depletion is rapid and profound during early HIV-1 infection. This leads to a compromised mucosal barrier that prompts chronic systemic inflammation. The preferential loss of intestinal T helper 17 (Th17) cells in HIV-1 disease is a driver of the damage within the mucosal barrier and of disease progression. Thus, understanding the effects of new therapeutic strategies in the intestines has high priority. Histone deacetylase (HDAC) inhibitors (e.g., panobinostat) are actively under investigation as potential latency reversing agents in HIV eradication studies. These drugs have broad effects that go beyond reactivating virus, including modulation of immune pathways. We examined colonic biopsies from ART suppressed HIV-1 infected in iduals (clinicaltrials.gov: NCT01680094 ) for the effects of panobinostat on intestinal T cell activation and on inflammatory cytokine production. We compared biopsy s les that were collected before and during oral panobinostat treatment and observed that panobinostat had a clear biological impact in this anatomical compartment. Specifically, we observed a decrease in CD69 + intestinal lamina propria T cell frequency and increased IL-17A mRNA expression in the intestinal epithelium. These results suggest that panobinostat therapy may influence the restoration of mucosal barrier function in these patients.
Publisher: Oxford University Press (OUP)
Date: 02-07-2019
DOI: 10.1093/CID/CIZ601
Abstract: Hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers but its impact on clinical endpoints among treated HIV/HCV coinfected persons is unclear. HIV-positive persons from EuroSIDA with known HCV status after January 2001 were classified into strata based on time-updated HCV-RNA measurements and HCV treatment: HCV antibody negative, spontaneously resolved HCV, chronic untreated HCV, cured HCV (HCV-RNA-negative), HCV treatment failures (HCV-RNA-positive). Poisson regression compared incidence rates between HCV groups for end-stage liver disease (ESLD including hepatocellular carcinoma [HCC]), non-AIDS defining malignancy (NADM excluding HCC) and cardiovascular disease (CVD). 16618 persons were included (median follow-up 8.3 (interquartile range 3.1–13.7) years). There were 887 CVD, 902 NADM and 436 ESLD events crude incidence rates/1000 person-years follow-up (95% confidence interval [CI]) were 6.4 (6.0–6.9) CVD, 6.5 (6.1–6.9) NADM and 3.1 (2.8–3.4) ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the five groups. HCV-negative in iduals (adjusted incidence rate ratio [aIRR] 0.22 95% CI 0.14–0.34) and those with spontaneous clearance (aIRR 0.61 95% CI 0.36–1.02) had reduced rates of ESLD compared to cured in iduals. Persons with chronic untreated HCV infection (aIRR 1.47 95% CI 1.02–2.13) or treatment failure (aIRR 1.80 95% CI 1.22–2.66) had significantly raised rates of ESLD compared to those cured. Incidence of NADM or CVD was independent of HCV group whereas those cured had a substantially lower incidence of ESLD, underlining the importance of successful HCV treatment for reducing ESLD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-04-2015
Publisher: Springer Science and Business Media LLC
Date: 27-06-2022
DOI: 10.1186/S12889-022-13642-7
Abstract: People experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with “Severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark. In November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay. We included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9–59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1–55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p = 0.87) and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, p 0.001). When combining all participants who reported sex work or were recruited at designated safe havens, we found a significantly increased risk of seropositivity compared to other participants (OR 2.23, 95%CI 1.06–4.43, p = 0.02). Seropositive and seronegative participants reported a similar presence of at least one SARS-CoV-2 associated symptom (49% and 54%, respectively). The prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. These results could be taken into consideration when deciding in which phase PEH are eligible for a vaccine, as part of the Danish national SARS-CoV-2 vaccination program rollout. TrygFonden and HelseFonden.
Publisher: Springer Science and Business Media LLC
Date: 07-08-2015
Publisher: American Society for Microbiology
Date: 21-12-2022
DOI: 10.1128/SPECTRUM.02537-22
Abstract: This cohort study included questionnaire data as well as anti-nucleocapsid antibody analysis, allowing us to determine whether participants were seropositive due to vaccination or natural infection. The study emphasizes the importance of early confirmation of COVID-19, as antibodies recede with time, and it indicates an overlap between long COVID symptoms and symptoms possibly of another origin.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2015
Publisher: European Respiratory Society (ERS)
Date: 1999
DOI: 10.1034/J.1399-3003.1999.13A32.X
Abstract: Pneumonia is one of the most frequent complications in acquired immunodeficiency syndrome-patients with Pneumocystis carinii as the leading cause. The true prevalence of atypical agents such as Chlamydia pneumoniae, C. trachomatis, Legionella pneumophila and Mycoplasma pneumoniae in this population of patients is unknown as the currently used method for diagnosing these agents is measurement of antibody levels. However, this method is of limited value in human immunodeficiency virus (HIV)-positive patients who may have a compromised antibody response. To evaluate the prevalence of Chlamydia spp., Legionella spp. and M. pneumoniae in HIV-infected patients with pulmonary disease, this retrospective study has applied inhibitor-controlled polymerase chain reaction analyses on 103 bronchoalveolar lavage (BAL) fluids representing 103 episodes of pneumonia in 83 HIV-positive patients. L. pneumophila was detected in 1% of the BAL fluids and M. pneumoniae was found as a coexisting pathogen in 2% of the s les. Chlamydia spp. could not be detected in any of the BAL fluids. By culture and staining methods 106 other microorganisms were detected with P. carinii and Streptococcus pneumoniae as the most frequently occurring. Pneumonia due to Chlamydia pneumoniae, Legionella pneumophila or Mycoplasma pneumoniae seems to be rare in Danish human immunodeficiency virus-infected patients, but might be considered as a possible cause in cases of treatment failure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-09-2018
Publisher: American Society for Microbiology
Date: 15-10-2015
DOI: 10.1128/JVI.01484-15
Abstract: The pharmaceutical reactivation of dormant HIV-1 proviruses by histone deacetylase inhibitors (HDACi) represents a possible strategy to reduce the reservoir of HIV-1-infected cells in in iduals treated with suppressive combination antiretroviral therapy (cART). However, the effects of such latency-reversing agents on the viral reservoir size are likely to be influenced by host immune responses. Here, we analyzed the immune factors associated with changes in proviral HIV-1 DNA levels during treatment with the potent HDACi panobinostat in a human clinical trial involving 15 cART-treated HIV-1-infected patients. We observed that the magnitude, breadth, and cytokine secretion profile of HIV-1-specific CD8 T cell responses were unrelated to changes in HIV-1 DNA levels in CD4 T cells during panobinostat treatment. In contrast, the proportions of CD3 − CD56 + total NK cells and CD16 + CD56 dim NK cells were inversely correlated with HIV-1 DNA levels throughout the study, and changes in HIV-1 DNA levels during panobinostat treatment were negatively associated with the corresponding changes in CD69 + NK cells. Decreasing levels of HIV-1 DNA during latency-reversing treatment were also related to the proportions of plasmacytoid dendritic cells, to distinct expression patterns of interferon-stimulated genes, and to the expression of the IL28B CC genotype. Together, these data suggest that innate immune activity can critically modulate the effects of latency-reversing agents on the viral reservoir and may represent a target for future immunotherapeutic interventions in HIV-1 eradication studies. IMPORTANCE Currently available antiretroviral drugs are highly effective in suppressing HIV-1 replication, but the virus persists, despite treatment, in a latent form that does not actively express HIV-1 gene products. One approach to eliminate these cells, colloquially termed the “shock-and-kill” strategy, focuses on the use of latency-reversing agents that induce active viral gene expression in latently infected cells, followed by immune-mediated killing. Panobinostat, a histone deacetylase inhibitor, demonstrated potent activities in reversing HIV-1 latency in a recent pilot clinical trial and reduced HIV-1 DNA levels in a subset of patients. Interestingly, we found that innate immune factors, such as natural killer cells, plasmacytoid dendritic cells, and the expression patterns of interferon-stimulated genes, were most closely linked to a decline in the HIV-1 DNA level during treatment with panobinostat. These data suggest that innate immune activity may play an important role in reducing the residual reservoir of HIV-1-infected cells.
Publisher: Informa UK Limited
Date: 21-05-2015
Publisher: Springer Science and Business Media LLC
Date: 08-09-2016
DOI: 10.1038/NCOMMS12731
Abstract: The ‘shock and kill’ approach to cure human immunodeficiency virus (HIV) includes transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with targeted immunotherapy to purge infected cells. The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected in iduals on antiretroviral therapy induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4 + T cells. However, it is important to discern whether the increases in CA-US HIV-1 RNA are due to limited or broad activation of HIV-1 proviruses. Here we use single-genome sequencing to find that the RNA transcripts observed following LRA administration are genetically erse, indicating activation of transcription from an extensive range of proviruses. Defective sequences are more frequently found in CA HIV-1 RNA than in HIV-1 DNA, which has implications for developing an accurate measure of HIV-1 reservoir size. Our findings provide insights into the effects of panobinostat and vorinostat as LRAs for latent HIV-1.
Publisher: Informa UK Limited
Date: 04-2013
DOI: 10.4161/HV.23202
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.IJID.2013.01.024
Abstract: Reproductive patterns among HIV patients in Denmark have not previously been described. We aimed to uncover the fertility wishes among Danish HIV-infected persons. A cross-sectional questionnaire survey was done at six outpatient HIV clinics in Denmark. A total of 409 (56%) HIV patients returned the questionnaire 323 had completed the questionnaire, although they had not all responded to all of the questions. Among HIV-infected in iduals, 49% (137/280) had their own biological children. Fifteen percent (43/280) desired (additional) children and 15% (43/280) were undecided. Female gender, birth outside Europe, young age, completed high school education, heterosexuality, present partner, and non-disclosure were associated with a desire for children in the univariate analysis. In the multivariate analysis only young age, heterosexual orientation, and non-disclosure were significant. Thirty-seven percent (93/250) felt that HIV infection was a hindrance to having more children. The most common reasons indicated were fear of HIV transmission to the child (24%, 59/244) and to the partner (16%, 40/244). Many HIV-infected patients have children and a substantial proportion of HIV-infected patients desire (additional) children, although there is a high degree of fear of HIV transmission to their partner or child. This highlights the need for care providers to improve the services provided to HIV-infected patients who desire to have children.
Publisher: Informa UK Limited
Date: 19-02-2014
DOI: 10.4161/HV.27925
Publisher: Informa UK Limited
Date: 11-2018
DOI: 10.2147/IDR.S176384
Publisher: Springer Science and Business Media LLC
Date: 23-03-2004
Publisher: Springer Science and Business Media LLC
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 08-11-2019
DOI: 10.1007/S10461-019-02717-Z
Abstract: As partner notification (PN) has shown effective in increasing the number of partners of HIV infected patients being tested we aimed to evaluate the feasibility of implementing PN in the West-African country Guinea-Bissau. Patients enrolled were offered the choice of three different PN methods. Acceptance, successful referrals and HIV status of partners were evaluated. Of 697 patients offered PN, 495 (71.0%) accepted and listed 547 partners. At end of follow-up 118 (21.5%) partners had been tested of which 44 (37.3%) were HIV infected. HIV infected partners had a higher median CD4 count at diagnosis compared with index patients 401 cells/mm
Publisher: Oxford University Press (OUP)
Date: 03-2017
Publisher: Informa UK Limited
Date: 2004
DOI: 10.1080/00365540310017618
Abstract: Overall morbidity and mortality rates in childhood are reported to be higher in males than females. As respiratory tract infections constitute the leading cause of childhood hospitalization, we examined the gender difference in rates of hospitalization due to respiratory tract infections in Danish youth (under age 25). We studied a total of 64,049 hospitalizations for otitis media, pneumonia, influenza, and other acute respiratory tract infections from 1995 to 1999, with calculation of hospitalization rates by age and gender. The male-female hospitalization rate ratio (HRR) for admission due to a respiratory tract infection decreased from 1.45 (95% confidence interval (CI) 1.42-1.48) in the age group 0 - < 5 y, to 1.62 (95% CI 1.55-1.70) in the age group 5 - < 10 y, 1.13 (95% CI 1.04-1.22) in the age group 10 - < 15 y, 0.83 (95% CI 0.76-0.90) in the age group 15 - < 20 y, and 0.87 (95% CI 0.80-0.95) in the age group 20 - < 25 y. In young children, boys were hospitalized more often than girls, but the reverse applied in children and adolescents 15-25 y of age. The study generates the hypothesis that gender plays a role in the susceptibility for respiratory infections in early childhood.
Publisher: Springer Science and Business Media LLC
Date: 08-1993
DOI: 10.1007/BF01973655
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.JINF.2017.09.004
Abstract: The REDUC clinical study Part B investigated Vacc-4x/rhuGM-CSF therapeutic vaccination prior to HIV latency reversal using romidepsin. The main finding was a statistically significant reduction from baseline in viral reservoir measurements. Here we evaluated HIV-specific functional T-cell responses following Vacc-4x/rhuGM-CSF immunotherapy in relation to virological outcomes on the HIV reservoir. This study, conducted in Aarhus, Denmark, enrolled participants (n = 20) with CD4>500 cells/mm The frequency of participants with CD8+ T-cell proliferation assay positivity was 8/16 (50%) at baseline, 11/15 (73%) post-vaccination, 6/14 (43%) during romidepsin, and 9/15 (60%)post-romidepsin. Participants with CD8+ T-cell proliferation assay positivity post-vaccination showed reductions in total HIV DNA post-vaccination (p = 0.006 q = 0.183), post-latency reversal (p = 0.005 q = 0.183), and CA-RNA reductions post-vaccination (p = 0.015 q = 0.254). Participants (40%) were defined as proliferation 'Responders' having ≥2-fold increase in assay positivity post-baseline. Robust ELISpot baseline responses were found in 87.5% participants. No significant changes were observed in the proportion of polyfunctional CD8+ T-cells to HIV In this 'shock and kill' approach supported by therapeutic vaccination, CD8+ T-cell proliferation represents a valuable means to monitor functional immune responses as part of the path towards functional HIV cure.
Publisher: Elsevier BV
Date: 10-2023
Location: Denmark
Start Date: 2013
End Date: 2014
Funder: amfAR, The Foundation for AIDS Research
View Funded ActivityStart Date: 2013
End Date: 2016
Funder: The Danish Council for Strategic Research
View Funded ActivityStart Date: 2012
End Date: 2014
Funder: Pfizer
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Pfizer
View Funded ActivityStart Date: 2014
End Date: 2015
Funder: Pfizer
View Funded ActivityStart Date: 2018
End Date: 2009
Funder: Novo Nordisk Foundation
View Funded ActivityStart Date: 2018
End Date: 2009
Funder: The Danish Rhaumatism Association
View Funded ActivityStart Date: 2016
End Date: 2009
Funder: amfAR, The Foundation for AIDS Research
View Funded ActivityStart Date: 2017
End Date: 2009
Funder: Gilead Sciences
View Funded ActivityStart Date: 2012
End Date: 2014
Funder: Pfizer
View Funded ActivityStart Date: 2011
End Date: 2012
Funder: Danish Eye Research Foundation
View Funded Activity