Two antigenically distinct lineages of influenza B viruses have circulated globally since 1985. However, licensed trivalent seasonal influenza vaccines contain antigens from only a single influenza B virus and thus provide limited immunity against circulating influenza B strains of the lineage not present in the vaccine. In recent years, predictions about which B lineage will predominate in an upcoming influenza season have been no better than chance alone, correct in only 5 of the 10 seasons from 2001 to 2011. Consequently, seasonal influenza vaccines could be improved by inclusion of influenza B strains of both lineages. The resulting quadrivalent influenza vaccines would allow influenza vaccination campaigns to respond more effectively to current global influenza epidemiology. Manufacturing capacity for seasonal influenza vaccines has increased sufficiently to supply quadrivalent influenza vaccines, and methods to identify the influenza B strains to include in such vaccines are in place. Multiple manufacturers have initiated clinical studies of quadrivalent influenza vaccines. Data from those studies, taken together with epidemiologic data regarding the burden of disease caused by influenza B infections, will determine the safety, effectiveness, and benefit of utilizing quadrivalent vaccines for the prevention of seasonal influenza disease.
Introduction: Thymic stromal lymphopoietin (TSLP), an epithelial cytokine (alarmin), is a central regulator of the immune response to inhaled environmental insults such as allergens, viruses and pollutants, initiating a cascade of downstream inflammation. There is compelling evidence that TSLP plays a major role in the pathology of asthma, and therapies that aim to block its activity are in development.
Areas covered:We review studies conducted in humans and human cells, largely published in PubMed January 2010-October 2019, that investigated the innate and adaptive immune mechanisms of TSLP in asthma relevant to type 2-driven (eosinophilic/allergic) inflammation and non-type 2-driven (noneosinophilic/non-allergic) inflammation, and the role of TSLP as a mediator between immune cells and structural cells in the airway. Clinical data from studies evaluating TSLP blockade are also discussed. Expert opinion: The position of TSLP at the top of the inflammatory cascade makes it a promising therapeutic target in asthma. Systemic anti-TSLP monoclonal antibody therapy with tezepelumab has yielded positive results in clinical trials to date, reducing exacerbations and biomarkers of inflammation in patients across the spectrum of inflammatory endotypes. Inhaled anti-TSLP is an alternative route currently under evaluation. The long-term safety and efficacy of TSLP blockade need to be evaluated.
In the United States, two types of vaccines are recommended for the prevention of influenza: an intranasal live attenuated influenza vaccine (LAIV) for eligible individuals aged 2–49 years and unadjuvanted injectable trivalent inactivated vaccines (TIV) for eligible individuals aged ≥6 months. Several recent studies have compared the efficacy of the 2 vaccines in children and adults. In children 6 months to 18 years of age, each of the four comparative studies of LAIV and TIV demonstrated that LAIV was more protective. In individuals 17–49 years of age, most comparative studies have demonstrated that LAIV and TIV were similarly efficacious or that TIV was more efficacious. However, LAIV was shown to be more protective than TIV in new military recruits of all ages, and placebo-controlled studies in adults in 1997–1998 suggested that LAIV was more protective against the mismatched A/H3N2 strain. The relative efficacy of LAIV and TIV among young adults may vary depending on the specific population and the antigenic match between the vaccines and circulating strains. In adults 60 years of age and older, limited data suggest that the two vaccines are similarly effective. In children and adults, studies also suggest that the relative efficacy of LAIV versus TIV may increase when measured against more severe illness. Additional research comparing LAIV and TIV is needed in adults and would also be valuable in older children and adolescents. Studies should examine the role of pre-existing immunity as well as vaccine impact on influenza illness of varying severity.
BackgroundInfluenza illness in children causes significant clinical and economic burden. Although some European countries have adopted influenza immunisation policies for healthy children, the debate about paediatric influenza vaccination in most countries of the European Union is ongoing. Our aim was to summarise influenza burden (in terms of health outcomes and economic burden) in children in Western Europe via a systematic literature review.MethodsWe conducted a systematic literature search of PubMed, EMBASE, and the Cochrane Library (1970-April 2011) and extracted data on influenza burden in children (defined as aged ≤ 18 years) from 50 publications (13 reporting laboratory-confirmed influenza; 37 reporting influenza-like illness).ResultsChildren with laboratory-confirmed influenza experienced hospitalisations (0.3%-20%), medical visits (1.7-2.8 visits per case), antibiotic prescriptions (7%-55%), and antipyretic or other medications for symptomatic relief (76%-99%); young children and those with severe illness had the highest rates of health care use. Influenza in children also led to absenteeism from day care, school, or work for the children, their siblings, and their parents. Average (mean or median) length of absence from school or day care associated with confirmed influenza ranged from 2.8 to 12.0 days for the children, from 1.3 to 6.0 days for their siblings, and from 1.3 to 6.3 days for their parents. Influenza negatively affected health-related quality of life in children with asthma, including symptoms and activities; this negative effect was smaller in vaccinated children than in non-vaccinated children.ConclusionsInfluenza burden in children is substantial and has a significant direct impact on the ill children and an indirect impact on their siblings and parents. The identified evidence regarding the burden of influenza may help inform both influenza antiviral use in children and paediatric immunisation policies in European countries.
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