Global mortality associated with seasonal influenza epidemics: new burden estimates and predictors from the GLaMOR Project.

Background Until recently, the World Health Organization (WHO) estimated the annual mortality burden of influenza to be 250000 to 500000 all-cause deaths globally; however, a 2017 study indicated a substantially higher mortality burden, at 290000-650000 influenza-associated deaths from respiratory causes alone, and a 2019 study estimated 99000-200000 deaths from lower respiratory tract infections directly caused by influenza. Here we revisit global and regional estimates of influenza mortality burden and explore mortality trends over time and geography. Methods We compiled influenza-associated excess respiratory mortality estimates for 31 ountries representing 5 WHO regions during 2002-2011. From these we extrapolated the influenza burden for all 193 countries of the world using a multiple imputation approach. We then used mixed linear regression models to identify factors associated with high seasonal influenza mortality burden, including influenza types and subtypes, health care and socio-demographic development indicators, and baseline mortality levels. Results We estimated an average of 389 000 (uncertainty range 294000-518000) respiratory deaths were associated with influenza globally each year during the study period, corresponding to~2% of all annual respiratory deaths. Of these, 67% were among people 65 years and older. Global burden estimates were robust to the choice of countries included in the extrapolation model. For people <65 years, higher baseline respiratory mortality, lower level of access to health care and seasons dominated by the A(H1N1)pdm09 subtype were associated with higher influenza-associated mortality, while lower level of socio-demographic development and A(H3N2) dominance was associated with higher influenza mortality in adults ≥65 years. Conclusions Our global estimate of influenza-associated excess respiratory mortality is consistent with the 2017 estimate, despite a different modelling strategy, and the lower 2019 estimate which only captured deaths directly caused by influenza. Our finding that baseline respiratory mortality and access to health care are associated with influenza-related mortality in persons <65 years suggests that health care improvements in low and middle-income countries might substantially reduce seasonal influenza mortality. Our estimates add to the body of evidence on the variation in influenza burden over time and geography, and begin to address the relationship between influenza-associated mortality, health and development

Global seasonal influenza mortality estimates: a comparison of 3 different approaches.

Background Prior to updating global influenza-associated mortality estimates, the World Health Organization convened a consultation in July 2017 to understand differences in methodology and implications on results of three influenza mortality projects from the United States Centers for Disease Control and Prevention (CDC), the Netherlands Institute for Health Service Research (GLaMOR), and the Institute for Health Metrics and Evaluation (IHME). The expert panel reviewed estimates and discussed differences in data sources, analysis, and modeling assumptions. Method We performed a comparison analysis of the estimates. Influenza-associated respiratory death counts were comparable between CDC and GLaMOR; IHME estimate was considerably lower. Results The greatest country-specific influenza-associated mortality rate fold differences between CDC/IHME and between GLaMOR/IHME estimates were among countries in South-East Asia and Eastern Mediterranean region. The data envelope used for the calculation was one of the major differences (CDC and GLaMOR: all respiratory deaths; IHME: low respiratory infection deaths). With the assumption that there is only one cause of death for each death, IHME estimates a fraction of the full influenza-associated respiratory mortality that is measured by the other two groups. Wide variability of parameters was observed. Conclusion Continued coordination between groups could assist with better understanding of methodological differences and new approaches to estimating influenza deaths globally

Interpretation of molecular detection of avian influenza A virus in respiratory specimens collected from live bird market workers in Dhaka, Bangladesh: infection or contamination?

Objectives: Interpreting real-time reverse transcription-polymerase chain reaction (rRT-PCR) results for human avian influenza A virus (AIV) detection in contaminated settings like live bird markets (LBMs) without serology or viral culture poses a challenge. Methods: During February-March 2012 and November 2012-February 2013, we screened workers at nine LBMs in Dhaka, Bangladesh, to confirm molecular detections of AIV RNA in respiratory specimens with serology. We tested nasopharyngeal (NP) and throat swabs from workers with influenza-like illness (ILI) and NP, throat, and arm swabs from asymptomatic workers for influenza virus by rRT-PCR and sera for seroconversion and antibodies against HPAI A(H5N1) and A(H9N2) viruses. Results: Among 1273 ILI cases, 34 (2.6%) had A(H5), 56 (4%) had A(H9), and six (0.4%) had both A(H5) and A(H9) detected by rRT-PCR. Of 192 asymptomatic workers, A(H5) was detected in eight (4%) NP and 38 (20%) arm swabs. Of 28 ILI cases with A(H5) or A(H9) detected, none had evidence of seroconversion, but one (3.5%) and 12 (43%) were seropositive for A(H5) and A(H9), respectively. Conclusion: Detection of AIV RNA in respiratory specimens from symptomatic and asymptomatic LBM workers without evidence of seroconversion or virus isolation suggests environmental contamination, emphasizing caution in interpreting rRT-PCR results in high viral load settings

Measurement of the cosmic ray muon flux seasonal variation with the OPERA detector

The OPERA experiment discovered muon neutrino into tau neutrino oscillations in appearance mode, detecting tau leptons by means of nuclear emulsion films. The apparatus was also endowed with electronic detectors with tracking capability, such as scintillator strips and resistive plate chambers. Because of its location in the underground Gran Sasso laboratory, under 3800 m.w.e., the OPERA detector has also been used as an observatory for TeV muons produced by cosmic rays in the atmosphere. In this paper the measurement of the single muon flux modulation and its correlation with the seasonal cycle of atmospheric temperature is reported

The experimental facility for the Search for Hidden Particles at the CERN SPS

The Search for Hidden Particles (SHiP) Collaboration has shown that the CERN SPS accelerator with its 400 GeV/c proton beam offers a unique opportunity to explore the Hidden Sector [1-3]. The proposed experiment is an intensity frontier experiment which is capable of searching for hidden particles through both visible decays and through scattering signatures from recoil of electrons or nuclei. The high-intensity experimental facility developed by the SHiP Collaboration is based on a number of key features and developments which provide the possibility of probing a large part of the parameter space for a wide range of models with light long-lived super-weakly interacting particles with masses up to (10) GeV/c2 in an environment of extremely clean background conditions. This paper describes the proposal for the experimental facility together with the most important feasibility studies. The paper focuses on the challenging new ideas behind the beam extraction and beam delivery, the proton beam dump, and the suppression of beam-induced background