Assessment of two complementary influenza surveillance systems : Sentinel primary care influenza-like illness versus severe hospitalized laboratory-confirmed influenza using the moving epidemic method

Monitoring seasonal influenza epidemics is the corner stone to epidemiological surveillance of acute respiratory virus infections worldwide. This work aims to compare two sentinel surveillance systems within the Daily Acute Respiratory Infection Information System of Catalonia (PIDIRAC), the primary care ILI and Influenza confirmed samples from primary care (PIDIRAC-ILI and PIDIRAC-FLU) and the severe hospitalized laboratory confirmed influenza system (SHLCI), in regard to how they behave in the forecasting of epidemic onset and severity allowing for healthcare preparedness. Epidemiological study carried out during seven influenza seasons (2010-2017) in Catalonia, with data from influenza sentinel surveillance of primary care physicians reporting ILI along with laboratory confirmation of influenza from systematic sampling of ILI cases and 12 hospitals that provided data on severe hospitalized cases with laboratory-confirmed influenza (SHLCI-FLU). Epidemic thresholds for ILI and SHLCI-FLU (overall) as well as influenza A (SHLCI-FLUA) and influenza B (SHLCI-FLUB) incidence rates were assessed by the Moving Epidemics Method. Epidemic thresholds for primary care sentinel surveillance influenza-like illness (PIDIRAC-ILI) incidence rates ranged from 83.65 to 503.92 per 100.000 h. Paired incidence rate curves for SHLCI-FLU/PIDIRAC-ILI and SHLCI-FLUA/PIDIRAC-FLUA showed best correlation index' (0.805 and 0.724 respectively). Assessing delay in reaching epidemic level, PIDIRAC-ILI source forecasts an average of 1.6 weeks before the rest of sources paired. Differences are higher when SHLCI cases are paired to PIDIRAC-ILI and PIDIRAC-FLUB although statistical significance was observed only for SHLCI-FLU/PIDIRAC-ILI (p-value Wilcoxon test = 0.039). The combined ILI and confirmed influenza from primary care along with the severe hospitalized laboratory confirmed influenza data from PIDIRAC sentinel surveillance system provides timely and accurate syndromic and virological surveillance of influenza from the community level to hospitalization of severe cases

Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration

INTRODUCTION: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach. METHODS AND ANALYSIS: Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients' immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo. ETHICS AND DISSEMINATION: Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations. TRIAL REGISTRATION NUMBERS: NCT02618902 and NCT02903537; EudraCT numbers: 2015-002975-16 and 2015-003541-26

Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration

Introductio: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach. Methods and analysis: Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients’ immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo. Ethics and dissemination: Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations

Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration

Introductio: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach. Methods and analysis: Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients’ immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo. Ethics and dissemination: Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations