Peripheral proinsulin expression controls low-avidity proinsulin-reactive CD8 T Cells in type 1 diabetes

Low-avidity autoreactive CD8 T cells (CTLs) escape from thymic negative selection, and peripheral tolerance mechanisms are essential for their regulation. We report the role of proinsulin (PI) expression on the development and activation of insulin-specific CTLs in the NOD mouse model of type 1 diabetes. We studied insulin B-chain–specific CTL from different T-cell receptor transgenic mice (G9Cα−/−) expressing normal PI1 and PI2 or altered PI expression levels. In the absence of PI2 (Ins2−/−), CTL in pancreatic lymph nodes (PLNs) were more activated, and male G9Cα−/− mice developed T1D. Furthermore, when the insulin-specific CTLs developed in transgenic mice lacking their specific PI epitope, the CTLs demonstrated increased cytotoxicity and proliferation in vitro and in vivo in the PLNs after adoptive transfer into NOD recipients. Dendritic cell–stimulated proliferation of insulin-specific T cells was reduced in the presence of lymph node stromal cells (LNSCs) from NOD mice but not from mice lacking the PI epitope. Our study shows that LNSCs regulate CTL activation and suggests that exposure to PI in the periphery is very important in maintenance of tolerance of autoreactive T cells. This is relevant for human type 1 diabetes and has implications for the use of antigen-specific therapy in tolerance induction

Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials

Cardiometabolic risk in a population of older adults with multiple co-morbidities in rural south africa: the HAALSI (Health and Aging in Africa: longitudinal studies of INDEPTH communities) study

Background: A consequence of the widespread uptake of anti-retroviral therapy (ART) is that the older South African population will experience an increase in life expectancy, increasing their risk for cardiometabolic diseases (CMD), and its risk factors. The long-term interactions between HIV infection, treatment, and CMD remain to be elucidated in the African population. The HAALSI cohort was established to investigate the impact of these interactions on CMD morbidity and mortality among middle-aged and older adults. Methods: We recruited randomly selected adults aged 40 or older residing in the rural Agincourt sub-district in Mpumalanga Province. In-person interviews were conducted to collect baseline household and socioeconomic data, self-reported health, anthropometric measures, blood pressure, high-sensitivity C-reactive protein (hsCRP), HbA1c, HIV-status, and point-of-care glucose and lipid levels. Results: Five thousand fifty nine persons (46.4% male) were enrolled with a mean age of 61.7 ± 13.06 years. Waist-to-hip ratio was high for men and women (0.92 ± 0.08 vs. 0.89 ± 0.08), with 70% of women and 44% of men being overweight or obese. Blood pressure was similar for men and women with a combined hypertension prevalence of 58.4% and statistically significant increases were observed with increasing age. High total cholesterol prevalence in women was twice that observed for men (8.5 vs. 4.1%). The prevalence of self-reported CMD conditions was higher among women, except for myocardial infarction, and women had a statistically significantly higher prevalence of angina (10.82 vs. 6.97%) using Rose Criteria. The HIV− persons were significantly more likely to have hypertension, diabetes, or be overweight or obese than HIV+ persons. Approximately 56% of the cohort had at least 2 measured or self-reported clinical co-morbidities, with HIV+ persons having a consistently lower prevalence of co-morbidities compared to those without HIV. Absolute 10-year risk cardiovascular risk scores ranged from 7.7–9.7% for women and from 12.5–15.3% for men, depending on the risk score equations used. Conclusions: This cohort has high CMD risk based on both traditional risk factors and novel markers like hsCRP. Longitudinal follow-up of the cohort will allow us to determine the long-term impact of increased lifespan in a population with both high HIV infection and CMD risk

Interim 2017/18 influenza seasonal vaccine effectiveness: Combined results from five European studies

Between September 2017 and February 2018, influenza A(H1N1)pdm09, A(H3N2) and B viruses (mainly B/Yamagata, not included in 2017/18 trivalent vaccines) co-circulated in Europe. Interim results from five European studies indicate that, in all age groups, 2017/18 influenza vaccine effectiveness was 25 to 52% against any influenza, 55 to 68% against influenza A(H1N1)pdm09, -42 to 7% against influenza A(H3N2) and 36 to 54% against influenza B. 2017/18 influenza vaccine should be promoted where influenza still circulates

End of season influenza vaccine effectiveness in adults and children in the United Kingdom in 2017/18

Background: In the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV). Aim: To estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue. Methods: This observational study employed the test-negative case–control approach to estimate aVE in primary care. The population-based seroprevalence survey used residual age-stratified samples. Results: Influenza viruses A(H3N2) (particularly subgroup 3C.2a2) and B (mainly B/Yamagata/16/88-lineage, similar to the quadrivalent vaccine B-virus component but mismatched to TIV) dominated. All-age aVE was 15% (95% confidence interval (CI): −6.3 to 32) against all influenza; −16.4% (95% CI: −59.3 to 14.9) against A(H3N2); 24.7% (95% CI: 1.1 to 42.7) against B and 66.3% (95% CI: 33.4 to 82.9) against A(H1N1)pdm09. For 2–17 year olds, LAIV4 aVE was 26.9% (95% CI: −32.6 to 59.7) against all influenza; −75.5% (95% CI: −289.6 to 21) against A(H3N2); 60.8% (95% CI: 8.2 to 83.3) against B and 90.3% (95% CI: 16.4 to 98.9) against A(H1N1)pdm09. For ≥ 18 year olds, TIV aVE against influenza B was 1.9% (95% CI: −63.6 to 41.2). The 2017 seroprevalence of antibody recognising tissue-grown A(H3N2) virus was significantly lower than that recognising egg-grown virus in all groups except 15–24 year olds. Conclusions: Overall aVE was low driven by no effectiveness against A(H3N2) possibly related to vaccine virus egg-adaption and a new A(H3N2) subgroup emergence. The TIV was not effective against influenza B. LAIV4 against influenza B and A(H1N1)pdm09 was effective