No abstract

Background Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middleincome countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.Methods We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and populationbased childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries.Findings In 2018, among children under 5 years globally, there were an estimated 109•5 million influenza virus episodes (uncertainty range [UR] 63•1-190•6), 10•1 million influenza-virus-associated ALRI cases (6•8-15•1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.Interpretation A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middleincome countries.Funding WHO; Bill & Melinda Gates Foundation.

We report the characterization of three novel flaviviruses isolated in Spain. Marisma Mosquito virus, a novel mosquito borne virus, was isolated from Ochlerotatus caspius mosquitoes; Spanish Ochlerotatus flavivirus and Spanish Culex flavivirus, two novel insect flaviviruses, were isolated from Oc. caspius and Culex pipiens, respectively. During this investigation, we designed a sensitive RT-nested polymerase chain reaction method that amplifies a 1019bp fragment of the flavivirus NS5 gene and could be directly used in clinical or environmental samples for flavivirus characterization and surveillance. Analysis of the sequence generated from that amplicon contains enough phylogenetic information for proper taxonomic studies. Moreover, the use of this tool allowed the detection of additional flavivirus DNA forms in Culex, Culiseta, and Ochlerotatus mosquitoes.

HRV-C infections were frequent in hospitalized children with respiratory diseases and were associated with asthma, recurrent wheezing, and bronchiolitis. No clinical differences were found with the HRV-A group: HRV-B group had clinical differences with both the other groups.

Influenza epidemics affect all age groups, although children, the elderly and those with underlying medical conditions are the most severely affected. Whereas co-morbidities are present in 50 % of fatal cases, 25-50 % of deaths are in apparently healthy individuals. This suggests underlying genetic determinants that govern infection severity. Although some viral factors that contribute to influenza disease are known, the role of host genetic factors remains undetermined. Data for small cohorts of influenza-infected patients are contradictory regarding the potential role of chemokine receptor 5 deficiency (CCR5-D32 mutation, a 32 bp deletion in the CCR5 gene) in the outcome of influenza virus infection. We tested 171 respiratory samples from influenza patients (2009 pandemic) for CCR5-D32 and evaluated its correlation with patient mortality. CCR5-D32 patients (17.4 %) showed a higher mortality rate than WT individuals (4.7 %; P50.021), which indicates that CCR5-D32 patients are at higher risk than the normal population of a fatal outcome in influenza infection. Influenza A viruses are a major source of acute respiratory infections and continue to be an important cause of acute illness and death worldwide. They cause annual epidemics and occasional pandemics with potentially fatal outcome. The mean global burden of seasonal influenza is more than 600 million cases, with 3 million cases of severe illness and almost 500 000 deaths per year worldwide (http://www. who.int/en/). A new H1N1 subtype influenza A virus emerged in 2009 [A(H1N1)pdm09], which was highly transmissible with relatively low virulence and caused the first pandemic of the 21st century (Neumann et al., 2009).Differences in disease severity can be due to pre-existing health conditions, predisposing host genetic factors, differences in the virulence of circulating viruses or a combination of these factors. The co-morbid conditions for A(H1N1)pdm09 include chronic metabolic disease, primarily diabetes mellitus and renal disease, chronic lung and cardiac disease, immunosuppressive conditions, neoplasms, obesity and pregnancy (Falagas et al., 2011; Louie et al., 2011;Singanayagam et al., 2011).Although co-morbidities are present in half of fatal cases, one-third of fatal cases have no co-morbid conditions (http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm), suggesting that host genetic variation accounts for the distinct disease severity of A(H1N1)pdm09 infection. Several potential genetic determinants associated with A(H1N1)pdm09 infection have been described, including TNF (Antonopoulou et al., 2012), IFN-inducible transmembrane (Everitt et al., 2012), killer-cell immunoglobulin-like receptor (Aranda-Romo et al., 2012), complement regulatory protein CD55 (Zhou et al., 2012) and Toll-like receptor 3 (Esposito et al., 2012). Data relating to the role of chemokine receptor 5 (CCR5) in severe A(H1N1)pdm09-infected patients are contradictory and have been debated (Keynan et al., 2010;Rodriguez et al., 2013;Sironi et al., 2014).CCR5 regulates various aspec...