Review article
Two B or not two B, that is the question. Statements in favor of the quadrivalent influenza vaccine
Incluir los dos linajes B o no incluirlos, esa es la cuestión. Declaraciones a favor de la vacuna cuadrivalente frente a la gripe
M. Van Ranst
Rega Institute, Laboratory of Clinical and Epidemiological Virology, Herestraat 49 – PO box 1040, 3000 Leuven, Belgium
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Talebi Bezmin Abadi, A.T.B. Abadi, A.A. Farahani, M. Darvishi" "autores" => array:4 [ 0 => array:2 [ "nombre" => "H." "apellidos" => "Talebi Bezmin Abadi" ] 1 => array:2 [ "nombre" => "A.T.B." "apellidos" => "Abadi" ] 2 => array:2 [ "nombre" => "A.A." "apellidos" => "Farahani" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Darvishi" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2445146021000066?idApp=UINPBA00004N" "url" => "/24451460/0000002200000001/v1_202102160833/S2445146021000066/v1_202102160833/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2445146021000042" "issn" => "24451460" "doi" => "10.1016/j.vacune.2021.01.004" "estado" => "S300" "fechaPublicacion" => "2021-01-01" "aid" => "172" "copyright" => "Elsevier España, S.L.U." 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Ghaemi, S-E. Tabtabaeizadeh" "autores" => array:2 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Ghaemi" ] 1 => array:2 [ "nombre" => "S-E." "apellidos" => "Tabtabaeizadeh" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2445146021000042?idApp=UINPBA00004N" "url" => "/24451460/0000002200000001/v1_202102160833/S2445146021000042/v1_202102160833/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Two B or not two B, that is the question. Statements in favor of the quadrivalent influenza vaccine" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "47" "paginaFinal" => "51" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "M. Van Ranst" "autores" => array:1 [ 0 => array:3 [ "nombre" => "M." "apellidos" => "Van Ranst" "email" => array:1 [ 0 => "marc.vanranst@uz.kuleuven.ac.be" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Rega Institute, Laboratory of Clinical and Epidemiological Virology, Herestraat 49 – PO box 1040, 3000 Leuven, Belgium" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Incluir los dos linajes B o no incluirlos, esa es la cuestión. Declaraciones a favor de la vacuna cuadrivalente frente a la gripe" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Seasonal influenza is an infectious disease that imposes a significant burden on society and healthcare services annually and is thought to affect more than 1 billion people globally each year. Although it is typically a mild disease, it can occur in a severe form in certain population groups, requiring hospital admission or even causing death. Up to 650<span class="elsevierStyleHsp" style=""></span>000 people are estimated to die each year due to the respiratory complications associated with influenza.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> Additionally, direct and indirect costs associated with influenza incur a significant burden, globally.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">There are four types of influenza viruses that cause seasonal influenza: A, B, C and D. However, over the last 30 years, the type A (subtypes H1N1 and H3N2) and B viruses (Victoria and Yamagata lineages) have been mainly responsible for the outbreaks and epidemics in humans, while C and D have barely been present.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">3</span></a> During the influenza season, the A and B viruses often appear simultaneously, although the largest global burden of disease is associated with the type A viruses (≈75%).<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">4</span></a> Furthermore, the type A H1N1 strain was the one responsible for the 2009 influenza pandemic, which is why society often considers it as mainly responsible for the disease. B virus also causes serious clinical symptoms and presents a global prevalence of 25% that should not be disregarded. This prevalence varies considerably throughout the seasons, becoming the predominant virus in some periods.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Given that the influenza type A virus has reservoirs in the animal kingdom and can cause zoonosis, eradicating influenza is not a feasible process. The most effective way of preventing the disease and its complications is by vaccination. Today, there are essentially two pharmacological presentations for the flu vaccine: the inactivated influenza vaccine, which is the main one and is administered at any age by intramuscular injection, and the attenuated influenza vaccine, which is applied intranasally and is generally used in the pediatric population. There are also other less common forms of administration that could mean a qualitative leap for patients in the future. This is the case of the intradermal vaccine using individual patches that can be self-administered,<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> or the sublingual vaccine.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In February each year, the World Health Organization (WHO) issues its recommendations for the composition of the influenza vaccines for the following season for the northern hemisphere. These recommendations are based on epidemiological data obtained at world level in the previous period, and forecasts on which viruses could be the most common in the next season. The virus formulation is sent to the vaccine manufacturers, who propagate the viruses to generate sufficient doses for the population. Today, influenza viruses continue to be grown mainly in fertilized chicken eggs, although cell culture for virus growth is also permitted. If there are no setbacks, the manufacturing process takes around 5–6 months, to which must be added the time needed to perform quality controls. Thus, vaccination campaigns can never be started before October. This is, consequently, a race against the clock every year.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The influenza vaccine is not 100% effective, with efficacy varying between 40% and 70% according to the season and geographical area, among other factors.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a> In order to increase this effectiveness, improved influenza vaccines have been under development for some time. These vaccines seek to induce a better immunogenic response than conventional vaccines by changing the composition, dose or route of administration.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> One of the solutions could be the inclusion of adjuvants, substances that increase the immune response and accelerate the effect of the vaccine. New experimental adjuvants are currently being tested in clinical trials.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> Other measures for the generation of potentially improved vaccines are the addition of a higher antigen content (high-dose) or the intradermal administration route.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> These vaccines could be particularly beneficial for populations with a weakened immune system, such as immunosuppressed or elderly people. However, the main problem with current vaccines is not their lack of immunogenicity, but the speed with which the viruses evolve with respect to the antigens included in them, so that, even if the improved vaccines manage to improve the effectiveness, they would not resolve the real problem.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Another of the measures that the WHO implemented since the 2013–2014 season was to increase the valence of the vaccines. Since then, in addition to the trivalent vaccine, which includes the two virus A subtypes and one of the two B lineages, a quadrivalent vaccine is also manufactured that includes both type B virus lineages (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). It is still, however, a lesser-used vaccine.’</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Type B influenza. Why should we give it greater consideration?</span><p id="par0035" class="elsevierStylePara elsevierViewall">The influenza type B virus is generally a great unknown for most of the population. Seasonal influenza is associated more with the type A virus due to its higher prevalence and its prominence in the 2009 pandemic crisis.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> However, the type B virus causes more than 20% of influenza cases.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">5,6</span></a> In fact, a recent epidemiological study in Spain put the percentage of influenza cases caused by the B virus between 2007 and 2017 at 27.2%.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The prevalence of influenza B is highly variable, depending on the geographical location and season. In Europe, the percentage of influenza caused by the B virus between 2001 and 2011 was 1.0% during the 2003–2004 season, while in the 2005–2006 season, it was the prevalent virus and was found in 59.8% of patients.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> These data do not correspond with the prevalence data for the virus in other countries during the same period. In the United States, for example, the percentage of influenza in the 2005–2006 season was considerably lower (20.3%). Similarly, it was found that the mean proportion of influenza type B varied from 17.8% in the southern hemisphere to 24.3% in countries in the intertropical belt.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Although influenza B infection affects all age groups, its incidence is significantly higher in school-age children (5–14 years old).<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a> A recent study conducted in France found that the median age of patients infected with influenza A in the period between 2003 and 2013 was 14 years old, while for influenza B, this was 10 years old (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01).<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">15</span></a> Similar findings have also been reported in Spain and Brazil.<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">16,17</span></a> Specifically, Victoria B type strain seems to predominantly affect the young population while adults are more affected by the Yamagata strain.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The type B virus is equally as pathogenic as the type A and produces similar clinical symptoms.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">18,19</span></a> The number of admissions to the intensive care unit (ICU) due to influenza type B is comparable to the number of hospitalizations observed for the A virus, in both adult and pediatric patients.<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">20,21</span></a> In fact, in one of the studies conducted in children under the age of 16 in Canada, the only significant difference observed between hospital admissions with influenza A or B was the higher presence of myalgias in patients with influenza type B.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> Moreover, the frequency of the B virus is usually high in epidemic seasons, which corroborates its virulence.<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">22,23</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Mortality data also highlight the importance of influenza type B. Although all age groups are affected by both types of influenza, the higher presence of influenza B in young patients means that a high number of pediatric deaths due to this virus has been observed, with an average of 34% of pediatric deaths between 2001 and 2011 (excluding the 2009 pandemic) caused by the B virus.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> A recent study published by Martínez et al. in 2019 demonstrated also an increased risk of mortality (OR 9.02; 95% CI 3.05–26.69) due to influenza type B virus in immunosuppressed patients.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Since the 1980s, there has been a genetic and antigenic divergence that has led to the existence of two different type B lineages: Victoria and Yamagata. Both strains cocirculate around the world, although they present some differences. At the genetic level, Victoria is more similar to virus A subtype H3N2, while Yamagata is more similar to H1N1.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">25</span></a> Victoria is a more active lineage, with a higher effective reproduction number than Yamagata. Additionally, the age range that they affect is also slightly different, and Victoria usually affects younger people than Yamagata.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">17,25</span></a> Thus, in a study conducted in Spain in which the age distribution of the type B virus lineages was monitored during the 2017–2018 season and compared with the 2015–2016 season, it was observed that Yamagata seems to have special predilection for the adult population while Victoria affects young patients more.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a> Previous studies in other countries have shown the same pattern.<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">26–28</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The presence of one or other influenza B lineage each season is unpredictable. In some seasons, such as during 2005–2006, Victoria predominated, while in others the most prevalent was Yamagata, as happened in 2007–2008 and 2017–2018.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> There does not appear to be any pattern that might allow the predominant lineage to be predicted. This means than on many occasions there is no match with the trivalent vaccine of the season, with the consequent associated healthcare problems. In addition, the antigenic difference between the two lineages is such that immunization against a strain of one of the lineages does not confer a sufficient cross-response against the other.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">9,19,29–31</span></a> Thus, the success of the trivalent vaccine with respect to influenza B is practically a matter of luck.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">The need for a quadrivalent vaccine</span><p id="par0070" class="elsevierStylePara elsevierViewall">The predictions made by the WHO each year on the viruses that are going to be more active in the next season are usually 50% correct on average.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a> However, there are seasons in which there is greater mismatch, which reduces the protection conferred by the vaccine, thereby increasing epidemic crises and giving rise to a public health problem.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In the 2015–2016 season, there was a seasonal influenza epidemic. During the summer of 2015, a significant increase in influenza B was observed in the southern hemisphere. Specifically, there was an unexpected increase in the Victoria lineage, which rose from being positive in 10% of influenza B cases in 2014, to 32% in 2015.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a> These data suggested that influenza virus B lineage could also be the prevalent virus in the northern hemisphere for that season. However, the trivalent vaccine generated contained the influenza B/Yamagata lineage, which had been the predominant virus in previous years. The forecasts were met and approximately 49% of all influenza cases in Europe were caused by the B/Victoria virus.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> Thus, the population vaccinated with the trivalent formulation was not protected for the circulating influenza type B virus, which resulted in an increase in the total number of people affected by influenza and its complications, with 8500 hospitalizations.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> Similarly, during season 2017–2018 in Europe, the B strain that was included in the trivalent vaccine (Victoria) did not match the circulating B strain (Yamagata), and an excess number of influenza cases occurred.<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">35,36</span></a> In Spain, a recent study confirmed combined dominance/codominance of influenza B and mismatch with the vaccine lineage in more than 25% of the epidemics that occurred between 2007 and 2017.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Thus, given that prediction of the predominant type B lineage is often unsuccessful, and considering that, in any case, both lineages usually coexist every season, the quadrivalent vaccine offers a clear benefit with respect to the trivalent vaccine at biological level. By including another antigen, the spectrum of action of the vaccine is broadened, and it should provide additional coverage for those vaccinated, if the immunogenic superiority observed in numerous clinical trials translates,<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">37–39</span></a> as expected, into better protection of vaccinated people. Due to the unpredictability of influenza types and subtypes that are going to circulate, clinical trials to demonstrate superior efficacy of quadrivalent vs trivalent vaccines would require such sample size that make it unfeasible. Also, inclusion of an additional antigen would limit the emergence of cases due to mismatch between the circulating influenza viruses and the vaccine strains.</p><p id="par0085" class="elsevierStylePara elsevierViewall">In that case, why is the use of the quadrivalent vaccine not promoted more? Although the WHO has been including it in its recommendations for more than five years, its use has still not been actively encouraged. One of the reasons is that, at present, the production levels for this vaccine are low in comparison with the trivalent vaccine, and there is little vaccine on the market. If its immediate use were promoted, it would generate a vaccine demand that could not be covered, as well as an excess of trivalent vaccine that would mean a huge financial loss. We are at a point in which both vaccines coexist, and this will remain so until the quadrivalent vaccine gains more supporters and the necessary changes are made at production level. This is a procedure that may take time, but that will surely arrive.</p><p id="par0090" class="elsevierStylePara elsevierViewall">In summary, there is conclusive evidence to support the need to promote the use of quadrivalent vaccines for seasonal influenza (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The world population will benefit from greater protection against the infection, which will have a positive impact not only at global health level, but also at the socioeconomic level.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Funding</span><p id="par0095" class="elsevierStylePara elsevierViewall">Medical Writing support was provided by <span class="elsevierStyleGrantSponsor" id="gs1">Medical Statistics Consulting (MSC)</span> and funded by <span class="elsevierStyleGrantSponsor" id="gs2">Sanofi</span>.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflicts of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">Dr. Van Ranst reports receiving payments for consultancies and lecture fees during the conduct of the study from GSK, Sanofi, Merck, Crucell and Novartis.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1465661" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1334862" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1465662" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1334863" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Type B influenza. Why should we give it greater consideration?" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "The need for a quadrivalent vaccine" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 9 => array:2 [ "identificador" => "xack513129" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-02-03" "fechaAceptado" => "2020-07-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1334862" "palabras" => array:5 [ 0 => "Influenza" 1 => "Quadrivalent vaccine" 2 => "Tetravalent vaccine" 3 => "Influenza B" 4 => "Seasonal influenza" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1334863" "palabras" => array:5 [ 0 => "Gripe" 1 => "Vacuna cuadrivalente" 2 => "Vacuna tetravalente" 3 => "Gripe B" 4 => "Gripe estacional" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Each year, over 1 billion people worldwide are affected by the influenza virus. Vaccination is the most effective method of protection against this disease. Although the WHO has included a quadrivalent influenza vaccine formulation in its official recommendations since 2013–2014, it is not yet widely used. The impact of influenza B viruses is underestimated. Nevertheless, they are responsible for 20–25% of influenza infections worldwide, causing similar clinical symptoms to influenza A that particularly affect the pediatric population. There is no way to predict which B virus lineage will be more prevalent each season. Consequently, the trivalent vaccine composition often fails to include the most prevalent B lineage in that season, and the vaccinated population is therefore not well protected against type B influenza. The quadrivalent influenza vaccine protects against four strains of influenza virus and will represent an opportunity to reduce the influenza burden.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cada año, más de 1.000 millones de personas a nivel mundial se ven afectadas por la gripe estacional. La manera más efectiva de prevenirla es mediante la vacunación anual. Desde la temporada 2013-2014, la OMS incluye en sus recomendaciones una formulación de vacuna cuadrivalente (que incluye los dos subtipos de virus tipo A y ambos linajes de virus B) e indica el linaje de virus B que se debe incluir en la vacuna trivalente. Sin embargo, el uso de la vacuna cuadrivalente en España sigue siendo minoritario. El efecto patogénico del virus tipo B de la gripe se ha subestimado durante mucho tiempo. No obstante, es responsable de entre un 20 y un 25% de los casos de gripe global, con un cuadro clínico similar al que produce el virus tipo A y afectando especialmente a la población pediátrica. La presencia de uno u otro linaje de gripe B es imprevisible cada temporada, lo que provoca que a menudo el linaje de la cepa incluida en la vacuna trivalente no concuerde con el del virus B más prevalente, dejando a la población vacunada expuesta a los efectos de la gripe B. El uso de la vacuna cuadrivalente de forma habitual supondría una medida efectiva para ampliar el espectro de la vacuna y asegurar la protección de más personas contra la gripe estacional.</p></span>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Name of product \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Manufacturer \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vaccine type \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Administration route \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age recommended \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluarix Tetra<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GlaxoSmithKline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inactivated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intramuscular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From 6 months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Flucelvax Tetra \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Seqirus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inactivated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intramuscular \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From 9 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fluenz Tetra \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AstraZeneca \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Live attenuated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intranasal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From 24 months to 17 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Influvac Tetra \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mylan Products Ltd. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inactivated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intramuscular/subcutaneous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From 3 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vaxigrip Tetra<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sanofi Pasteur \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inactivated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intramuscular/subcutaneous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From 6 months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Xanaflu Tetra Influenza vaccine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mylan Products Ltd./(Marketing Authorization Holder) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inactivated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Intramuscular/deeply subcutaneous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From 3years \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2521647.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Available in Spain for the 2019–2020 season.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Overview of available quadrivalent influenza vaccines in the EU/EEA for the 2019/20 season.<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a></p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Influenza B is present in all seasons and is responsible for more than 20% of global influenza cases on average. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Depending on the circulating B lineage, some population groups are affected more than others. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Both influenza B lineages, Victoria and Yamagata, often cocirculate. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• The predominant B lineage each season cannot be predicted. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• There is no optimal cross-protection between the type B virus strains due to the significant antigenic mismatch between the lineages. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• The mismatch between the composition of the trivalent vaccine and the circulating B virus lineage reduces protection against influenza in vaccinated people. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• World epidemiological data support the use of the quadrivalent vaccine versus the trivalent formulation. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2521648.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Key points for the promotion of the quadrivalent vaccine.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0205" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization (WHO). 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