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Special article
Universal childhood influenza vaccination in Spain: Has the time come?
Vacunación antigripal universal en la infancia en España: ¿ha llegado la hora?
Josep Marès Bermúdez
Servicio de Pediatría, Institut Pediàtric Marès-Riera, Blanes (Girona), Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0005" class="elsevierStylePara elsevierViewall">Has the epidemiology of influenza&#44; its severity in the paediatric age group&#44; its impact and its age distribution changed recently&#63; Or&#44; perhaps&#44; do we now have new vaccines with much greater effectiveness and better safety profiles than the vaccines we had a few years ago&#63; No&#44; the answer is categorically no&#46;</p><p id="p0010" class="elsevierStylePara elsevierViewall">So why the recent debate&#44; in our environment&#44; about the need to vaccinate or not to vaccinate children against influenza&#63; Perhaps the experience with COVID-19 and its prevention with vaccines&#44; the possibility of co-infection by both viruses&#44; influenza and SARS-CoV-2&#44; or of overlapping or alternating outbreaks of both viruses has generated greater concern about influenza and its prevention&#63; No&#44; in my opinion&#44; it is not the compelling reason to rethink the issue either&#44; although it may have helped to re-arouse approaches that have been only timidly addressed for many years&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">The old debate on routine influenza vaccination in childhood in Spain has been repeatedly addressed in the last 10 years by different scientific societies&#44; expert vaccinologists&#44; opinion leaders&#44; and health authorities&#44; among others&#46; However&#44; in my opinion few have had the will to analyse it in depth or with conviction&#44; and with scientific arguments&#46; Assessment has been timid&#44; tiptoeing around it and lacking the courage to take any steps forward&#46; This has turned paediatric influenza vaccination into an unquestionable unresolved issue&#46; The Spanish Association of Paediatrics &#40;AEP for initials in Spanish&#41; recommended systematic flu vaccination between the ages of 6 months and 5 years for the first time last season 2021-221&#44; although with irregular involvement on the part of health professionals&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">With this article I propose a serious&#44; evidence-based&#44; courageous and committed reflection on whether or not we should vaccinate our children against influenza&#46;</p><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Childhood influenza</span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Is influenza in childhood so relevant that we should consider its prevention&#63;</span><p id="p0025" class="elsevierStylePara elsevierViewall">Influenza continues to be an underestimated and underdiagnosed disease in children&#44; with the perception still widely held&#44; both by healthcare workers and the general population&#44; that it has little impact in terms of morbidity in children&#46; How will they become aware of the need to prevent it with vaccines&#63;</p><p id="p0030" class="elsevierStylePara elsevierViewall">Children suffer the highest seasonal influenza attack rates of any age group each year&#44; and in certain seasons&#44; this can be as high as 45&#37; overall&#46; As many as 35&#37; of pre-school children&#44; 30&#37; of school children and in some years up to 50&#37; of nursery school children are infected by the influenza virus&#46;<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> In general&#44; viral infections&#44; colds&#44; pharyngitis&#44; otitis&#44; bronchitis&#44; pneumonia&#44; etc&#46; are diagnosed&#44; but the etiological diagnosis of origin &#8211; influenza - remains hidden&#46;<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0035" class="elsevierStylePara elsevierViewall">We can affirm that <span class="elsevierStyleItalic">Influenza is the immunopreventable infectious disease with the highest incidence in children&#46;</span><a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a></p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Is influenza in childhood serious and does it cause hospitalisations&#63;</span><p id="p0040" class="elsevierStylePara elsevierViewall">It has been shown that children under 2 years of age are the age group with the highest rate of hospitalisation due to influenza&#44; in some seasons&#44; similar to and even higher than those over 64 years of age&#46;<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a><a class="elsevierStyleCrossRef" href="#f0010">Fig&#46; 2</a> shows the cumulative hospitalisation rates of confirmed severe cases of influenza in different age ranges in Spain&#44; from the 2013-2014 to the 2019-2020 season&#44; where the similarity of these rates can be seen comparing children under 5 and over 64 years of age&#46; Specifically&#44; in the 2019-2020 season&#44; a total of 27&#44;657 people were hospitalised&#44; of which 10&#37; of the serious hospitalised cases were under 5 years of age&#44; with a hospitalisation rate of 52 cases per 100&#44;000 inhabitants&#44; higher than that of those over 64 years of age &#40;40 cases per 100&#44;000 inhabitants&#41;&#46; Moreover&#44; a highly relevant fact remains&#58; unlike in adults&#44; where most hospitalisations were linked to people with underlying diseases &#40;risk groups&#41;&#44; in children up to 70&#37; of hospitalisations were healthy children&#46;<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> &#40;See <a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>&#46;&#41;</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0045" class="elsevierStylePara elsevierViewall">The rate of complications caused by influenza in healthy children is not negligible either&#46; The main complications are bacterial infections of the respiratory tract&#44; especially pneumonia and acute otitis media&#44; and usually occur early in the convalescent phase&#46; In community studies including paediatric patients of all ages&#44; an overall incidence of superinfection is observed in approximately 10&#37; of cases&#46; Acute otitis media is especially common in &#60; 2 years&#44; and may occur in up to 25&#37; of confirmed influenza cases&#46; Pneumonia is mostly caused by bacterial superinfection&#44; usually pneumococcal&#46;<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a></p><p id="p0050" class="elsevierStylePara elsevierViewall">Fortunately&#44; influenza does not cause more mortality in children under 2 years of age&#44; except in the under 6 months age group&#44; with the estimated mortality from influenza in childhood being less than 1 case per 100&#44;000 people per year for seasonal influenza&#44; similar in all paediatric age ranges&#46;<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a></p></span></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Do children play a role in the transmission of influenza to their home environment and the community&#63;</span><p id="p0055" class="elsevierStylePara elsevierViewall">The onset of the influenza epidemic outbreak in children precedes the adult outbreak by a few days &#40;up to 1-2 weeks&#41;&#44; with children playing a major role in the spread of the disease and transmission to other children in their school environment&#44; to their families and to the rest of the population&#46; At the beginning of the epidemic wave&#44; more than 60&#37; of those affected are under 14 years of age&#44; while at the end of the epidemic wave&#44; they represent less than 40&#37;&#46;<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a></p><p id="p0060" class="elsevierStylePara elsevierViewall">In influenza&#44; unlike what we have learned with COVID-19&#44; children of all age groups have the highest rates of infection and play a crucial role in transmitting the disease to healthy people in their environment&#44; as well as to those in at-risk groups&#44; with greater complications and mortality&#44; both in the home and in the community&#46;<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">Prevention in childhood <span class="elsevierStyleItalic">can reduce the impact of influenza in the community&#46;</span><a class="elsevierStyleCrossRefs" href="#bb0060"><span class="elsevierStyleSup">12&#8211;14</span></a></p><p id="p0070" class="elsevierStylePara elsevierViewall">If influenza is the most common immunopreventable infectious disease in the paediatric age group&#44; it causes high rates of hospitalisation in childhood&#44; mostly in people without risk factors&#44; with high consumption of health resources&#44; and its prevention in healthy children can reduce the overall impact of influenza in the community&#46; <span class="elsevierStyleItalic">Should its prevention in childhood not be a priority from a public health perspective&#63;</span></p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Influenza vaccination in children</span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Are there data on the effectiveness of routine influenza vaccination in childhood and its impact&#63;</span><p id="p0075" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">Cochrane Collaboration</span> regularly conducts systematic reviews of the most scientifically rigorous publications assessing the efficacy and effectiveness of currently available influenza vaccines&#46; In their latest meta-analysis&#44; published in 2018&#44; specifically evaluating the impact of influenza vaccines in the paediatric age group&#44; compared to non-vaccination&#44; they corroborate that both inactivated and attenuated intranasal vaccines produce a significant reduction in the incidence of influenza infection in healthy girls and boys under 16 years of age &#40;RR &#46;36 &#91;95&#37; CI&#58; &#46;28&#44; &#46;48&#93; and &#46;22 &#91;95&#37; CI&#58; &#46;11&#44; &#46;41&#93;&#44; respectively&#41;&#44; and a significant reduction in influenza-like illness &#40;ILI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a></p><p id="p0080" class="elsevierStylePara elsevierViewall">In a pilot study conducted in the UK in the 2014-2015 influenza season&#44; with school vaccination using intranasal tetravalent attenuated vaccine in children aged 4-11 years&#44; with an average coverage of 56&#37;&#44; a comparison of regions with and without vaccination showed a 94&#37; reduction in primary care visits for influenza syndrome&#44; a 74&#37; reduction in emergency department visits for respiratory illness and a 93&#37; reduction in hospitalisations for influenza confirmed by PCR in school children vaccinated&#46; At the community level&#44; a 59&#37; reduction in adult consultations for influenza syndrome was observed in regions with school vaccination&#44; confirming the population impact of childhood vaccination&#46;<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> Effectiveness data for the 2021-2022 season in the UK&#44; a country with routine childhood vaccination for 8 years now&#44; have already been reported and the interim results are more than encouraging&#58; for girls and boys aged 1-17 years&#44; the overall vaccine effectiveness was 73&#37; &#40;95&#37; CI 53-84&#37;&#41; and specifically with the intranasal attenuated vaccine in the age range 2-17 years was 72&#37; &#40;95&#37; CI 50-85&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a></p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Are influenza vaccines safe&#63;</span><p id="p0085" class="elsevierStylePara elsevierViewall">This is an indispensable premise before establishing any vaccination strategy&#46; We currently have a wealth of information that corroborates the adequate benefit-risk profile of both inactivated and attenuated influenza vaccines&#44; not only because of the clinical trials conducted throughout their clinical development&#44; but also thanks to the worldwide pharmacovigilance systems&#44; following the use of these vaccines in real life&#44; with data endorsed by the World Health Organisation&#39;s Committee on Vaccine Safety after millions of doses have been administered&#46; The adverse reactions observed are mild&#44; self-limiting and well tolerated&#46; Influenza vaccines are not associated with an increase in acute respiratory infections after administration&#44; there is no increase in febrile convulsions&#44; no increase in autoimmune diseases or mortality&#44; and cases of Guillain Barr&#233; syndrome associated with vaccination occur at an extremely low incidence rate&#44; clearly lower than cases associated with natural influenza virus infection&#46;<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a></p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Why vacinate boys and girls agains influenza&#63;</span><p id="p0090" class="elsevierStylePara elsevierViewall">The objective of a systematic influenza vaccination programme in the paediatric age group is none other than to contribute very significantly to reducing the impact of influenza disease on the health of the entire population&#44; based on&#58;</p><p id="p0095" class="elsevierStylePara elsevierViewall">- Providing direct protection to those vaccinated by reducing the large number of cases of influenza in children&#58;<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a> influenza is the most common immunopreventable infectious disease in the paediatric age group&#44; with highly significant&#44; but underestimated&#44; morbidity&#46;</p><p id="p0100" class="elsevierStylePara elsevierViewall">- Providing indirect protection by reducing the transmission of influenza from child to child&#44; from children to adults&#44; from children to people in at-risk groups of any age&#44; and avoiding secondary cases of influenza in their home&#44; school or community environment&#46;<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a></p><p id="p0105" class="elsevierStylePara elsevierViewall">- Reducing the transmission of influenza in the community&#46;<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a><ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="li0005"><span class="elsevierStyleLabel">&#8226;</span><p id="p0110" class="elsevierStylePara elsevierViewall">Preventing severe influenza cases and influenza-related deaths&#59; specifically&#44; in people in at-risk groups&#58; pregnant women&#44; adults over 60 years of age&#44; and people with underlying illnesses&#46;</p></li></ul></p><p id="p0115" class="elsevierStylePara elsevierViewall">- Significant reduction in influenza-related illnesses that generate a high consumption of health and social resources&#58;<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a></p><p id="p0120" class="elsevierStylePara elsevierViewall">o Medical consultations&#44; treatment&#44; complementary tests&#46;&#46;&#46;</p><p id="p0125" class="elsevierStylePara elsevierViewall">o Hospitalisations&#44; admissions to the ICU&#46;&#46;&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">o Absenteeism from work and school&#44; family and social costs&#44; deaths&#46;&#46;&#46;</p><p id="p0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Influenza vaccination is the most effective strategy to prevent influenza virus infection</span>&#46;<span class="elsevierStyleSup">3&#44;4&#44;6&#44;18&#44;20</span> Vaccination campaigns aimed exclusively at people considered to be at-risk groups or essential personnel for the community have globally failed worldwide to achieve optimal coverages or even close to the targets set by the WHO or by the health authorities of each country or region&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> The multiple strategies to promote vaccination in these groups&#44; despite encouraging results in some subgroups&#44; fail globally year after year&#44; calling into question the main objective of the campaign&#58; to reduce severe forms&#44; hospitalisations and deaths from influenza&#46;<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> A further element to be taken into consideration is the lack of impact of these selective vaccination campaigns on the generation of herd immunity at the community level&#46; These realities&#44; together with the benefits of systematic vaccination at paediatric ages&#44; have led some countries in our environment&#44; such as the United Kingdom and Finland&#44; following in the footsteps of Canada&#44; the USA and some Latin American countries&#44; to include universal influenza vaccination in the different age ranges in girls and boys&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a></p><p id="p0140" class="elsevierStylePara elsevierViewall">The time has come to include systematic influenza vaccination in childhood in Spain&#44; and to deal with our unfinished business with society&#46; The debate is no longer about whether or not to vaccinate girls and boys&#46; This has already been resolved&#46; The consensus effort of our scientific societies&#44; vaccine experts&#44; advisory committees&#44; the Vaccination Programme and Registry Committee&#44; and our health authorities with responsibilities in Public Health&#44; should be aimed at determining the age ranges to be vaccinated and the type of influenza vaccines we should use&#46;</p></span></span></span>"
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