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      Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden

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          Summary

          Influenza illness is caused by influenza A and influenza B strains. Although influenza A viruses are perceived to carry greater risk because they account for the majority of influenza cases in most seasons and have been responsible for influenza pandemics, influenza B viruses also impose a substantial public health burden, particularly among children and at-risk subjects.

          Furthermore, since the 2001-2002 influenza season, both influenza B lineages, B/Victoria-like viruses and B/Yamagata-like viruses have co-circulated in Europe.

          The conventional trivalent influenza vaccines have shown a limited ability to induce effective protection when major or minor mismatches between the influenza B vaccine component and circulating strains occur. For this reason, the inclusion of a second B strain in influenza vaccines may help to overcome the well-known difficulties of predicting the circulating B lineage and choosing the influenza B vaccine component.

          Two quadrivalent influenza vaccines, a live-attenuated quadrivalent influenza vaccine (Q/LAIV) and a split inactivated quadrivalent influenza vaccine (I/QIV), were first licensed in the US in 2012. Since their introduction, models simulating the inclusion of QIV in influenza immunization programs have demonstrated the substantial health benefits, in terms of reducing the number of influenza cases, their complications and mortality.

          In the near future, evaluations from simulation models should be confirmed by effectiveness studies in the field, and more costeffectiveness analyses should be conducted in order to verify the expected benefits.

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          Most cited references33

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          Global Role and Burden of Influenza in Pediatric Respiratory Hospitalizations, 1982–2012: A Systematic Analysis

          Background The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide. Methods and Findings We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (<6 mo, <1 y, <2 y, <5 y, 5–17 y, and <18 y). We applied this proportion to global estimates of acute lower respiratory infection hospitalizations among children aged <1 y and <5 y, to obtain the number and per capita rate of influenza-associated hospitalizations by geographic region and socio-economic status. Influenza was associated with 10% (95% CI 8%–11%) of respiratory hospitalizations in children <18 y worldwide, ranging from 5% (95% CI 3%–7%) among children <6 mo to 16% (95% CI 14%–20%) among children 5–17 y. On average, we estimated that influenza results in approximately 374,000 (95% CI 264,000 to 539,000) hospitalizations in children <1 y—of which 228,000 (95% CI 150,000 to 344,000) occur in children <6 mo—and 870,000 (95% CI 610,000 to 1,237,000) hospitalizations in children <5 y annually. Influenza-associated hospitalization rates were more than three times higher in developing countries than in industrialized countries (150/100,000 children/year versus 48/100,000). However, differences in hospitalization practices between settings are an important limitation in interpreting these findings. Conclusions Influenza is an important contributor to respiratory hospitalizations among young children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could reduce this burden and protect infants <6 mo.
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            The rationale for quadrivalent influenza vaccines

            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.
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              Cocirculation of two distinct evolutionary lineages of influenza type B virus since 1983.

              During 1988-1989 two highly distinct antigenic variants of influenza type B were recognized in hemagglutination-inhibition tests with postinfection ferret serum. These viruses were antigenically related to either B/Victoria/2/87, the most recent reference strain, or B/Yamagata/16/88, a variant that was isolated in Japan in May 1988. All influenza B viruses isolated in the United States during an epidemic in the winter of 1988-1989 were antigenically related to B/Victoria/2/87. However, in several countries in Asia, both B/Victoria/2/87-like viruses and B/Yamagata/16/88-like viruses were isolated. Sequence analysis of the hemagglutinin (HA) genes of several influenza B isolates from 1987 to 1988 indicated that the HA1 domains of the B/Yamagata/16/88-like viruses and B/VI/87-like viruses isolated in 1988 differed by 27 amino acids. Evolutionary relationships based on this sequence data indicated that the B/Yamagata/16/88-like viruses were more closely related to epidemic viruses from 1983 (B/USSR/100/83-like viruses) than to more recent reference strains such as B/Victoria/2/87. All other Asian strains, as well as selected isolates from the United States in 1988, were confirmed by sequence analysis as being genetically related to B/Victoria/2/87. These data provide clear evidence that two parallel evolutionary pathways of influenza type B have existed since at least 1983 and that viruses from each of the separate lineages were isolated from cases of influenza B in 1988. This finding is similar to earlier observations for type A H1N1 and H3N2 influenza viruses.
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                Author and article information

                Journal
                J Prev Med Hyg
                J Prev Med Hyg
                Pacini
                Journal of Preventive Medicine and Hygiene
                Pacini Editore SRL
                1121-2233
                2421-4248
                March 2016
                : 57
                : 1
                : E28-E33
                Affiliations
                [1 ]Department of Health Sciences, University of Genoa, Genoa, Italy;
                [2 ]IRCCS AOU S. Martino, IST Genoa, Italy
                Author notes
                Ilaria Barberis, Department of Health Sciences, University of Genoa, via A. Pastore 1, 16132 Genoa, Italy - Tel. +39 010 3538123 - Fax +39 010 505618 E-mail: ilaria.barberis@ 123456fastwebnet.it
                Article
                Pacini
                4910440
                27346937
                bfdb28c3-5f3e-49fa-a180-90c2665ef53c
                © Copyright by Pacini Editore SRL, Pisa, Italy

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License, which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way. For details, please refer to http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 13 February 2016
                : 29 February 2016
                Categories
                Research Article

                quadrivalent influenza vaccine,safety,immunogenicity,cost-effectiveness

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