Consensus position document on the child with an allergic reaction after vaccination or an allergy to vaccine components

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Echeverría Zudaire, L. Ortigosa del Castillo, E. Alonso Lebrero, F.J. Álvarez García, N. Cortés Álvarez, N. García Sánchez, A. Martorell Aragonés" "autores" => array:8 [ 0 => array:4 [ "nombre" => "L." "apellidos" => "Echeverría Zudaire" "email" => array:1 [ 0 => "lecheverria3@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Ortigosa del Castillo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Alonso Lebrero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "F.J." "apellidos" => "Álvarez García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "N." "apellidos" => "Cortés Álvarez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "N." "apellidos" => "García Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] 6 => array:3 [ "nombre" => "A." "apellidos" => "Martorell Aragonés" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0035" ] ] ] 7 => array:1 [ "colaborador" => "en representación de la Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica (SEICAP) y el Comité Asesor de Vacunas de la Asociación Española de Pediatría (CAV-AEP)" ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Unidad de Alergia y Neumología Pediátrica, Servicio de Pediatría, Hospital Universitario Severo Ochoa, Leganés, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital Universitario Ntra. Sra. de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Alergia, Hospital Materno-Infantil Gregorio Marañón, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Centro de Salud de Llanera, Asturias, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Unidad de Alergia Infantil, Hospital Universitario Mútua Terrassa, Terrassa, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Centro de Salud “Delicias Sur”, Zaragoza, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Unidad de Alergología, Hospital General Universitario, Valencia, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Documento de consenso sobre la actitud ante un niño con una reacción alérgica tras la vacunación o alergia a componentes vacunales" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2131 "Ancho" => 1567 "Tamanyo" => 149041 ] ] "descripcion" => array:1 [ "en" => "Algorithm for the identification of an allergy reaction to vaccines (modified from Kelso et al.<a class="elsevierStyleCrossRef" href="#bib0235">7</a>)." ] ] ] "textoCompleto" => "Explanation and seriousness of the issueThe aim of vaccination programmes is to protect the vaccinated child and prevent the recipient from having the disease against which he or she was vaccinated. The goal is to vaccinate the greatest possible number of susceptible individuals to produce a collective protective environment for the entire population.If a child is labelled as having had an allergic reaction to a vaccine (ARV), subsequent vaccinations will probably be suspended and that child will join the pool of individuals susceptible to the diseases against which he or she has stopped being vaccinated. Therefore, diagnosing the ARV accurately and confirming whether there is a direct relationship between the allergic reaction and the administration of the vaccine are of the essence.The approach to a child with suspected ARV should start by determining whether the signs and symptoms presented by the child were directly related to the administration of the vaccine, managing the allergic reaction, and then assessing whether the adverse event was a reaction against the vaccine antigen itself or to any of the vaccine components, as this will determine the administration of future doses of the vaccine in question or similar vaccines.<a class="elsevierStyleCrossRef" href="#bib0205">1</a>There is a wide variety of ARV. They are usually mild, local reactions, and exceptionally severe anaphylactic reactions that may even be fatal.<a class="elsevierStyleCrossRef" href="#bib0210">2</a>Vaccine composition: antigens, preservatives and adjuvantsVaccines do not only contain the antigen responsible for stimulating the immune response in the vaccinated individual, but may also contain additional constituents (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Epidemiological data. Incidence of allergic reactions after vaccinationAllergic reactions to vaccines are rare and usually have no causal relationship with immunisation. Estimates of true immediate hypersensibility reactions to vaccines range from 1 in 50000 doses for the DTP vaccine to 0.5–1 reaction per million doses for other vaccines.<a class="elsevierStyleCrossRef" href="#bib0205">1</a> The Brighton Anaphylaxis Working Group estimates that the number of true severe anaphylactic reactions to vaccines ranges between 0.5 and 1 in 100000 doses.<a class="elsevierStyleCrossRef" href="#bib0215">3</a> The number of reported deaths due to anaphylaxis secondary to vaccination is approximately 1 in 50 million doses.<a class="elsevierStyleCrossRef" href="#bib0220">4</a>There are few published data for Spain, with reported incidences ranging between 0.59% and 1.27% of reactions suspected to be associated with vaccination in the first visits to a paediatric allergy unit.<a class="elsevierStyleCrossRef" href="#bib0210">2</a>Among the allergic reactions attributed to residual proteins, the most common are those related to egg in vaccines grown in both chicken embryo fibroblasts and fertilised chicken eggs.It is convenient to complete a questionnaire before vaccination<a class="elsevierStyleCrossRef" href="#bib0225">5</a> asking the parents of the child that is to be vaccinated about the presence of certain circumstances that may lead to consider the vaccination to be contraindicated either temporarily or permanently, or to take specific precautions (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>What is an allergic reaction? Types of allergic reactions to vaccinesAn allergic reaction is defined as an adverse response produced by an immune mechanism. It can include a wide range of symptoms affecting the skin and the respiratory and cardiovascular systems. Anaphylaxis can be confirmed by determination of serum tryptase levels.Allergy is much less frequent than other types of adverse reactions. In many instances, the ARV is not confirmed and the patient may continue the course of vaccination with the same preparation.<a class="elsevierStyleCrossRef" href="#bib0230">6</a>Reactions are classified, depending on their reach, into local or systemic and, depending on the time elapsed since the administration of the vaccine and the development of symptoms, into immediate or delayed. This criterion helps to distinguish IgE-mediated reactions from those that do not involve IgE.<a class="elsevierStyleCrossRef" href="#bib0205">1</a>Immediate reactionsThey start within an hour from vaccination (from a few minutes to 4h). They may include a wide range of symptoms affecting the skin, the respiratory system and the cardiovascular system.Delayed reactionsThey start hours or days after vaccination and there is a very low probability that they are mediated by IgE. They are not usually caused by an immune mechanism and should not be diagnosed as allergies to vaccines. They are self-limiting processes that do not contraindicate future doses of the same vaccine.Differential diagnosis of allergic reactions during and after vaccine administrationA previous diagnosis of ARV is important for two reasons: firstly, individuals that experienced an IgE-mediated reaction, and especially anaphylaxis, could experience new severe reactions after vaccination; and secondly, overdiagnosis of ARV could increase the number of children that do not complete vaccination, which carries an individual and collective loss of protection against vaccine-preventable diseases.The algorithm for the approach to diagnosis can be seen in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.<a class="elsevierStyleCrossRef" href="#bib0235">7</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Delayed reactions are nonspecific, and serum IgE and skin tests are usually not helpful; although these reactions cause discomfort, they are not life-threatening.<a class="elsevierStyleCrossRef" href="#bib0240">8</a>Vaccine components that may cause allergic reactionsThe components of vaccines marketed in Spain that may be involved in AVR can be found in the online manual of vaccines of the AEP (<a href="http://vacunasaep.org/documentos/manual/anx-ii">http://vacunasaep.org/documentos/manual/anx-ii</a><a class="elsevierStyleCrossRef" href="#bib0245">9</a>). None of the vaccines currently marketed in Spain contains thiomersal.Vaccination of children with a history of possible allergic reaction after administration of a vaccine. Action guidelineAn accurate diagnosis of VAR is based in the medical history and in vitro and in vivo allergy testing.<a class="elsevierStyleCrossRef" href="#bib0250">10</a>The diagnostic algorithm is presented in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>The medical records will help determine whether the hypersensibility reaction experienced by the child was immediate or delayed.<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•If an IgE-mediated immediate reaction is suspected, allergy testing should be done, especially if additional doses of the vaccine are required and to avoid the risk of cross-reactivity with components of other vaccines or foods.<a class="elsevierStyleCrossRef" href="#bib0250">10</a></li><li class="elsevierStyleListItem" id="lsti0010">•If a non-immediate reaction is suspected, the vaccine can be given in the usual manner in most cases.<a class="elsevierStyleCrossRef" href="#bib0240">8</a></li></ul>The determination of IgG antibodies against the immunising agent can be useful if the patient has received fewer than the recommended number of doses in order to assess the level of immunity. If a patient has protective levels of antibody, subsequent doses could be withheld, although the duration of immunity might be shorter.<a class="elsevierStyleCrossRef" href="#bib0235">7</a> These levels have been determined for some vaccines (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>If additional doses are required or the level of protective antibodies cannot be determined, allergy testing should be done for the intact vaccine or for specific components if an allergy to those components is suspected.<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">•If test results are negative, administration of a full-strength dose of vaccine will be considered, keeping the patient under observation for 30min.</li><li class="elsevierStyleListItem" id="lsti0020">•If test results are positive, administration in graded doses will be considered if a vaccine preparation without the component to which the patient is allergic is not available.<a class="elsevierStyleCrossRef" href="#bib0250">10</a></li></ul>Medical historyAnamnesis<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0025">•Detailed history of the adverse reaction: patient age, date of reaction, brand of the administered vaccine, lot number, latent period, symptoms, urgent medical care, treatment received, duration of reaction.</li><li class="elsevierStyleListItem" id="lsti0030">•Vaccine composition.</li><li class="elsevierStyleListItem" id="lsti0035">•Simultaneous exposure to other allergens: medications, foods, latex, etc.</li><li class="elsevierStyleListItem" id="lsti0040">•Previous or subsequence tolerance to other vaccines.</li><li class="elsevierStyleListItem" id="lsti0045">•Tolerance to vaccine components.</li></ul>Allergy workup (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>)Allergy workup and revaccination for immediate and delayed hypersensibilityImmediate hypersensibilitySkin tests with the intact vaccineSkin tests (STs) start with a full-strength skin prick, and if the result is negative an intradermal (ID) test with a 1:100 dilution in normal saline is performed.<a class="elsevierStyleCrossRef" href="#bib0255">11</a><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>In cases of severe anaphylactic reaction, testing should start with a 1:10 concentration skin prick and a 1:1000 dilution for the ID test.The sensitivity and specificity of vaccine STs for confirming or ruling out allergy to a vaccine or its components have not been established, but if the ST results are negative it is very improbable that the patient has IgE antibodies against the vaccine or its components.If more than one year has elapsed since the IgE-mediated reaction, there may be low levels of circulating IgE and the ST results may be negative, so administration of the vaccine may not cause a reaction, although if the patient is sensitised it can trigger a booster response and a reaction may occur when the vaccine is administered after a long period of time.<a class="elsevierStyleCrossRef" href="#bib0260">12</a>Investigation of sensitivity to vaccine componentsIf the result of the ST with the intact vaccine is positive, the patient will be tested for sensitivity to vaccine components to try to prevent reactions to other vaccines that have the same components.The available tests for vaccine components are:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0050">a.Tetanus toxoid: determination of specific IgE serum levels (sensitive, but with low specificity).</li><li class="elsevierStyleListItem" id="lsti0055">b.Egg: ST and determination of specific IgE serum levels for egg white and ovalbumin.</li><li class="elsevierStyleListItem" id="lsti0060">c.Cow's milk: ST with extracted cow's milk proteins: bovine alpha-lactalbumin, beta-lactoglobulin, casein and serum albumin; specific IgE antibody assay for the same proteins.</li><li class="elsevierStyleListItem" id="lsti0065">d.Gelatin: nonstandardised ST using commercial gelatin powder (5g of gelatin dissolved in 5mL of normal saline)<a class="elsevierStyleCrossRef" href="#bib0265">13</a>; specific IgE antibody assays.</li><li class="elsevierStyleListItem" id="lsti0070">e.Latex: latex ST and specific IgE antibody assay.</li></ul>Delayed hypersensitivitySensitivity testing for vaccine components.Patients with a history of eczematous reaction to a vaccine containing phenoxyethanol or formaldehyde:a. Patch test with standardised concentrationPatients that have had an eczematous reaction or persistent injection-site nodules with an aluminium-containing vaccine:<a class="elsevierStyleCrossRef" href="#bib0265">13</a>a. Patch test with:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0075">i.Metallic aluminium using an empty Finn Chamber.</li><li class="elsevierStyleListItem" id="lsti0080">ii.Aluminium chloride hexahydrate 2% in glycerine placed in a plastic chamber.</li></ul>Revaccination of patients with immediate hypersensitivity reactions<a class="elsevierStyleCrossRefs" href="#bib0240">8,10,13</a>If vaccine or vaccine component allergy test results are negative, the vaccine can be administered in a single dose keeping the patient under observation for a minimum of 30min afterward. If there is a history of severe reaction, the vaccine will be administered in two doses: a first dose with a 1:10 dilution of vaccine followed 30min later by the rest of the full dose, keeping the patient under observation for at least another 30min. There are no published cases of patients with negative vaccine ST results that had a severe anaphylactic reaction following revaccination.If the ST or specific IgE assay results are positive in a patient with a history of IgE-mediated reaction to one of the components of the vaccine, a preparation that does not contain that component will be used whenever possible. If it is not available and the administration of the suspect vaccine or another vaccine containing the suspect component is necessary, the vaccine will be administered in graded doses in a hospital setting, following the protocol shown in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>If the allergy workup is inconclusive and the reaction occurred after the simultaneous administration of several vaccines, revaccination must be performed administering each of the vaccines on a different day.Revaccination of patients with delayed allergic reactions<a class="elsevierStyleCrossRefs" href="#bib0270">14,15</a>Revaccination must be considered on the basis of its necessity and the nature and severity of previous adverse reactions. If the vaccine is administered, the patient must stay under observation for 30min.If several vaccines had been administered simultaneously, revaccination must be carried out by administering each of the vaccines on a different day, starting with the vaccine suspected to be the least risky.It has been demonstrated that STs are not useful in predicting the development of delayed reactions in subsequent administrations of the vaccine.In patients that had persistent injection-site nodules after administration of a vaccine containing aluminium salts and with positive patch-test results, vaccines that do not contain these salts should be used whenever possible. If the child is sensitive to aluminium salts and needs a dose of a vaccine that contains them, it is recommended that the vaccine be administered with a deep intramuscular injection to minimise the local reaction.Vaccination of children with suspected or confirmed allergies to vaccine components. Action guidelineWhen vaccination is considered in a child, he or she may be allergic to one or more of the residual proteins from the manufacturing process or to any other product used in its preparation. There is no evidence that children with atopy are at greater risk of having allergic reactions following vaccination, and they should receive all the recommended vaccinations.<a class="elsevierStyleCrossRefs" href="#bib0280">16,17</a>Children with allergy to egg proteinsEgg allergy is the leading food allergy in children,<a class="elsevierStyleCrossRef" href="#bib0290">18</a> with an estimated prevalence of 2.5% in the first 2 years of life.<a class="elsevierStyleCrossRef" href="#bib0295">19</a> The measles-mumps-rubella (MMR) vaccine is growth in chicken embryo fibroblasts, while the influenza vaccine and the yellow fever vaccine are cultured in fertilised eggs that may contain greater amounts of egg proteins. Other vaccines that contain egg proteins are the hepatitis A vaccine Epaxal® and the vaccine against Central European encephalitis. One of the vaccines against rabies marketed in Spain is not cultured in chick embryo cells, but in human diploid cells.Measles mumps rubella vaccineIt does not contain egg proteins capable of triggering an allergic reaction, and therefore all children with egg allergies, including those who have anaphylactic reactions, should be given this vaccine in the setting where they are routinely vaccinated.<a class="elsevierStyleCrossRef" href="#bib0300">20</a> Children that have had a reaction to a previous dose of MMR vaccine should be assessed by an allergist or paediatric allergist. These reactions are triggered by other vaccine components.Influenza vaccineAdministration of the influenza vaccine is recommended in children older than 6 months in certain at-risk groups.<a class="elsevierStyleCrossRef" href="#bib0305">21</a> If egg has yet to be introduced in the child's diet and it is suspected that the child may be allergic, the child should be evaluated by a paediatric allergist prior to vaccination.The influenza vaccine may contain traces of ovalbumin,<a class="elsevierStyleCrossRef" href="#bib0310">22</a> and since it does not undergo heat treatment during manufacturing, heat-labile egg proteins remain intact and may trigger reactions even in children that tolerate cooked eggs.In cases of anaphylaxis following vaccination against influenza, no additional doses will be administered (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>In cases of egg allergy without severe anaphylaxis, it is safe to administer an influenza vaccine with less than 0.6–1μg of ovalbumin per dose,<a class="elsevierStyleCrossRef" href="#bib0315">23</a> so the vaccine can be administered in the usual setting<a class="elsevierStyleCrossRefs" href="#bib0320">24,25</a> in a single dose, and prior skin testing is unnecessary.<a class="elsevierStyleCrossRef" href="#bib0330">26</a> It has been demonstrated that immunisation against influenza with vaccines with a low content of ovalbumin without dividing the dose is safe in patients with egg allergy with severe anaphylactic reactions, and vaccines with a high ovalbumin content have even been used without complications in children with anaphylactic reactions to egg in the diet.<a class="elsevierStyleCrossRefs" href="#bib0335">27–29</a>Yellow fever vaccineIt is cultured in chicken embryos, so it may contain significant amounts of egg proteins.<a class="elsevierStyleCrossRef" href="#bib0350">30</a> If administration of the vaccine is necessary, children with egg allergies should be evaluated by an allergist or paediatric allergist. If test results are negative, the patient can be vaccinated in the usual manner, and if they are positive and vaccination is absolutely necessary, the vaccine must be administered in graded doses in a hospital setting.<a class="elsevierStyleCrossRefs" href="#bib0355">31,32</a>Children with cow's milk allergyThe presence of milk derivatives in vaccines is very rare. The summaries of product characteristics of the vaccines marketed in Spain do not mention the potential presence of cow's milk proteins, although inadvertent contamination with proteins from the culture medium may occur. Lactose may be added as an excipient to some vaccines, but these are still free of cow's milk proteins. From a practical standpoint, it is safe to vaccinate a child that has a cow's milk allergy.Children with allergies to antibiotics, gelatin, fungi, yeasts and aluminiumNeomycin and other antibioticsAminoglycosides (gentamicin, kanamycin), polymyxin, chlortetracycline and neomycin are added to vaccines to avoid bacterial contamination during the manufacturing process.Neomycin can cause systemic allergic reactions that contraindicate the administration of vaccines containing it.<a class="elsevierStyleCrossRef" href="#bib0365">33</a> It can also cause local reactions, such as contact dermatitis, that require much greater amounts of neomycin than those usually contained in vaccines, and that do not contraindicate vaccination.<a class="elsevierStyleCrossRef" href="#bib0370">34</a>There have been no reports of reactions to any of the other antibiotics triggered by vaccination.<a class="elsevierStyleCrossRefs" href="#bib0375">35,36</a>GelatinGelatin is an animal protein obtained from the connective tissue in cows and pigs. It is used as a stabiliser in live-attenuated virus vaccines.<a class="elsevierStyleCrossRef" href="#bib0235">7</a> If the patient is allergic to gelatin, a vaccine skin prick test should be performed prior to vaccination. If the result is positive and no other preparation is available that does not contain gelatin, the vaccine will be administered in graded doses, and if the result is negative the vaccine will be given in the usual manner.<a class="elsevierStyleCrossRef" href="#bib0265">13</a>Fungi and yeastsThe hepatitis B vaccine and one of the human papillomavirus vaccines are manufactured by harvesting the antigens from cell cultures of recombinant Saccharomyces cerevisiae strains. The amount of yeast contained in a vaccine can be of up to 5mgpermL in the hepatitis B vaccine and is smaller in the human papillomavirus vaccine.<a class="elsevierStyleCrossRef" href="#bib0235">7</a> If there is suspicion of a yeast allergy in the patient, a skin prick test and a specific IgE assay need to be performed. If the results are negative, vaccination can be done in the usual manner. If the results are positive and vaccination is absolutely necessary, the vaccine should be administered in graded doses.<a class="elsevierStyleCrossRef" href="#bib0280">16</a>AluminiumAluminium is used as an adjuvant to enhance the immune response.<a class="elsevierStyleCrossRef" href="#bib0385">37</a> The reaction usually triggered by aluminium consists of painful itching nodules at the site of injection that do not contraindicate vaccination.<a class="elsevierStyleCrossRef" href="#bib0390">38</a> There are very few references to generalised eczema in the literature,<a class="elsevierStyleCrossRef" href="#bib0395">39</a> so there is no scientific evidence to justify not recommending vaccination in children with a sensitivity to aluminium diagnosed by patch testing.<a class="elsevierStyleCrossRef" href="#bib0400">40</a>Children with a latex allergyChildren with a confirmed allergy to latex should be vaccinated in a latex-free environment. Most of the products currently used are synthetic (butyl, chlorobutyl, styrene-butadiene or halobutyl rubber), although a few have a type I elastomeric closure with 10% of latex.If the symptoms reported by the child consist solely of contact allergy to latex, the patient can be vaccinated in the usual manner.<a class="elsevierStyleCrossRef" href="#bib0250">10</a> If the previous reaction was anaphylactic, administration of the vaccine in a latex-free environment must be guaranteed.Conflict of interestsThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres535723" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec556007" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres535724" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec556006" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Explanation and seriousness of the issue" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Vaccine composition: antigens, preservatives and adjuvants" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Epidemiological data. Incidence of allergic reactions after vaccination" ] 2 => array:3 [ "identificador" => "sec0020" "titulo" => "What is an allergic reaction? Types of allergic reactions to vaccines" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Immediate reactions" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Delayed reactions" ] ] ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Differential diagnosis of allergic reactions during and after vaccine administration" ] 4 => array:2 [ "identificador" => "sec0040" "titulo" => "Vaccine components that may cause allergic reactions" ] ] ] 5 => array:3 [ "identificador" => "sec0045" "titulo" => "Vaccination of children with a history of possible allergic reaction after administration of a vaccine. Action guideline" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0050" "titulo" => "Medical history" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Anamnesis" ] ] ] ] ] 6 => array:3 [ "identificador" => "sec0060" "titulo" => "Allergy workup (Table 4)" "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0065" "titulo" => "Allergy workup and revaccination for immediate and delayed hypersensibility" "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0070" "titulo" => "Immediate hypersensibility" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Skin tests with the intact vaccine" ] ] ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Investigation of sensitivity to vaccine components" ] 2 => array:2 [ "identificador" => "sec0085" "titulo" => "Delayed hypersensitivity" ] ] ] 1 => array:2 [ "identificador" => "sec0090" "titulo" => "Revaccination of patients with immediate hypersensitivity reactions" ] 2 => array:2 [ "identificador" => "sec0095" "titulo" => "Revaccination of patients with delayed allergic reactions" ] ] ] 7 => array:3 [ "identificador" => "sec0100" "titulo" => "Vaccination of children with suspected or confirmed allergies to vaccine components. Action guideline" "secciones" => array:4 [ 0 => array:3 [ "identificador" => "sec0105" "titulo" => "Children with allergy to egg proteins" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0110" "titulo" => "Measles mumps rubella vaccine" ] 1 => array:2 [ "identificador" => "sec0115" "titulo" => "Influenza vaccine" ] 2 => array:2 [ "identificador" => "sec0120" "titulo" => "Yellow fever vaccine" ] ] ] 1 => array:2 [ "identificador" => "sec0125" "titulo" => "Children with cow's milk allergy" ] 2 => array:3 [ "identificador" => "sec0130" "titulo" => "Children with allergies to antibiotics, gelatin, fungi, yeasts and aluminium" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0135" "titulo" => "Neomycin and other antibiotics" ] 1 => array:2 [ "identificador" => "sec0140" "titulo" => "Gelatin" ] 2 => array:2 [ "identificador" => "sec0145" "titulo" => "Fungi and yeasts" ] 3 => array:2 [ "identificador" => "sec0150" "titulo" => "Aluminium" ] ] ] 3 => array:2 [ "identificador" => "sec0155" "titulo" => "Children with a latex allergy" ] ] ] 8 => array:2 [ "identificador" => "sec0160" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-09-03" "fechaAceptado" => "2014-11-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec556007" "palabras" => array:4 [ 0 => "Vaccines allergy" 1 => "Immediate hypersensitivity due to vaccines allergy" 2 => "Delayed reactions" 3 => "Anaphylaxis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec556006" "palabras" => array:4 [ 0 => "Alergia a vacunas" 1 => "Hipersensibilidad inmediata por alergia a vacunas" 2 => "Reacciones retardadas" 3 => "Anafilaxia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Vaccinations are one of the main public health tools for the control of vaccine-preventable diseases. If a child is labelled to have had an allergic reaction to a vaccine, the next immunizations will probably be suspended in that child, with the risks involved in this decision. The rate of severe allergic reactions is very low, ranging between 0.5 and 1/100,000 doses. The causes of allergic reactions to vaccines, more than the vaccine itself, are often due to residual protein components in the manufacturing process, such as gelatin or egg, and rarely to yeast or latex. Most of vaccine reactions are mild, localised at the site of injection, but in some circumstances, severe anaphylactic reactions can occur. If an immediate-type allergic reaction is suspected when vaccinating, or a child allergic to some of the vaccine components has to be vaccinated, a correct diagnosis of the possible allergy has to be made. The usual components of each vaccine should be known, in order to determine if vaccination can be performed safely on the child." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Las vacunaciones constituyen una de las principales herramientas de salud pública para el control de las enfermedades inmunoprevenibles. Si un niño es etiquetado de haber presentado una reacción alérgica a una vacuna es probable que se suspendan las siguientes inmunizaciones, con los riesgos que ello conlleva. La tasa de reacciones alérgicas graves es muy baja, oscilando entre 0,5 y 1/100.000 dosis. Las proteínas causantes de las reacciones alérgicas, más que los propios antígenos vacunales, son frecuentemente componentes residuales del proceso de fabricación, como son la gelatina y el huevo, y más raramente las levaduras o el látex. La mayoría de las reacciones son leves y localizadas en el lugar de la inyección, aunque en algunos casos pueden producirse reacciones anafilácticas graves. Si se sospecha que se ha producido una reacción alérgica inmediata a la vacuna, o si debemos vacunar a un niño con alergia a alguno de sus componentes, se deberá realizar un correcto diagnóstico de la posible alergia y conocer los componentes habituales de cada vacuna con el fin de determinar si la vacunación puede continuarse de forma segura." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Echeverría Zudaire L, Ortigosa del Castillo L, Alonso Lebrero E, Álvarez García FJ, Cortés Álvarez N, García Sánchez N, et al. Documento de consenso sobre la actitud ante un niño con una reacción alérgica tras la vacunación o alergia a componentes vacunales. An Pediatr (Barc). 2015;83:63." ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2131 "Ancho" => 1567 "Tamanyo" => 149041 ] ] "descripcion" => array:1 [ "en" => "Algorithm for the identification of an allergy reaction to vaccines (modified from Kelso et al.<a class="elsevierStyleCrossRef" href="#bib0235">7</a>)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2414 "Ancho" => 2953 "Tamanyo" => 359450 ] ] "descripcion" => array:1 [ "en" => "Diagnostic algorithm for the management of a child with suspected allergic reaction to vaccination." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1962 "Ancho" => 2451 "Tamanyo" => 227320 ] ] "descripcion" => array:1 [ "en" => "Protocol of vaccination against influenza in children allergic to egg proteins." ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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" title="table-entry " align="left" valign="top">• Immunising antigen \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">• Suspending fluid: may contain proteins or other components from cultures \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">• Antibiotics: to prevent contamination \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">• Preservatives: extend the shelf-life \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">• Stabilisers: the most common is gelatin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">• Adjuvants: enhance the immunogenicity of antigens \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab861372.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Vaccine composition." ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "HPV4, tetravalent human papillomavirus; MMR, measles mumps rubella.Source: Adapted from Fernández Cuesta et al.<a class="elsevierStyleCrossRef" href="#bib0225">5</a>" "tablatextoimagen" => array:5 [ 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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Delay vaccination: \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Has the patient been ill in the past few days?</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Acute moderate or severe disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Until patient recovery or stabilisation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Fever>38.5°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Acute allergy or asthma episodes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Acute decompensated heart failure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Acute nephropathies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Measles \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 months after onset of rash \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Active tuberculosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 months after initiation of treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Progressive or unstable neurological disorder, or one predisposing to seizures, such as acute encephalitis, tuberous sclerosis or uncontrolled epilepsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Delay pertussis vaccination until neurological condition has stabilised \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab861366.png" ] ] 1 => 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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Contraindicated: \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Primary immunodeficiency, solid or blood tumours, long-term immunosuppression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MMR, varicella, rotavirus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HIV infection with severe immunodeficiency (CD4+ T-lymphocyte percentage <15% for age) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MMR, varicella, rotavirus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">History of intussusception or congenital gastrointestinal malformation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rotavirus \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab861368.png" ] ] 2 => 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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Precaution: \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Disease or treatment leading to coagulation abnormalities or thrombocytopaenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">For parenteral vaccines, use the subcutaneous route when allowed by the summary of product characteristics. If administration must be intramuscular, use 25G or 23G needles only, apply pressure to the injection site for 2min, do not massage injection site and watch for subsequent development of haematoma \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab861369.png" ] ] 3 => 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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Delay vaccination (from the time treatment ends) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Is the patient currently taking any medications or receiving any kind of treatment?</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Blood productsGamma globulinsMore time for very high doses of gamma globulin (consult) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3–6 months for MMR and varicella (depending on the preparation) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">High-dose systemic corticosteroids (≥2mg/kg or 20mg a day of prednisone or equivalent) for more than 2weeks or ≥1mg/kg for more than 1monthNo need to delay vaccination if corticosteroid therapy is short-term, nonsystemic, low-dose, given every other day or is a replacement therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1month for MMR and varicella \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Acyclovir, famciclovir, valacyclovir \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">One week for varicella \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">If female, is the patient pregnant or suspects that she is?</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">If pregnant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MMR and varicella are contraindicated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">If in the first trimester of gestation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Avoid all vaccines, except for the influenza vaccine (evaluate specific risk) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Has the patient received any other vaccines previously?</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">If patient has received any live attenuated vaccine shots (MMR, varicella, yellow fever) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Wait a minimum of 4 weeks before administering another live attenuated vaccine (MMR, varicella, yellow fever) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Does patient have a history of severe reaction to vaccines?</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Severe allergic reaction (anaphylaxis) following a previous dose of the vaccine or to a vaccine component \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The vaccine in question is contraindicated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Encephalopathy within 7 days from administration of the DTP/DTaP vaccine in the absence of any other identifiable cause \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pertussis vaccine contraindicated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">One of the following after DTP/DTaP vaccine:- Fever>40.5°C, hypotonic-hyporesponsive episode, inconsolable crying lasting ≥3h, within 48h of vaccination- Seizures within 3 days of vaccination \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Exercise caution with pertussis vaccine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Guillain-Barré syndrome in the 6 weeks following vaccination \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Exercise caution with vaccine in question \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Arthus reaction after a dose of vaccine containing tetanus toxoid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Delay any other doses of tetanus vaccine for at least 10 years \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab861373.png" ] ] 4 => 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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Contraindicated: \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Is the patient allergic to any of the vaccine components?</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Only in case of anaphylaxis (immediate and potentially serious reaction)</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Allergy to neomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hepatitis A (Havrix®), hepatitis A+B, hexavalent vaccines, influenza (Chiroflu®, Chiromas®, Dotaricin®, Inflexal V®, Intanza®, Mutagrip®, Vaxigrip®), pentavalent vaccines, injectable polio, rabies, MMR and varicella \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Allergy to streptomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hexavalent (Hexyon®), pentavalent (Pentavac®) and injectable polio \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Allergy to polymyxin B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Influenza (Inflexal V®), hepatitis A (Epaxal®), hexavalent, pentavalent and injectable polio \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Allergy to gentamicin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Influenza (Fluarix®, Fluenz®, Influvac®) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Allergy to kanamycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Influenza (Chiroflu®, Chiromax®, Dotaricin®) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Allergy to gelatin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Typhoid fever (Vivotif®), MMR (MMRVaxpro®) and varicella (Varivax®) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Allergy to baker's yeast \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hepatitis A+B, hepatitis B, hexavalent vaccine and HPV4 (Gardasil®) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Allergy to egg proteins \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Central European encephalitis, yellow fever, influenza, hepatitis A (Epaxal®) and rabies (Rabipur®). Egg allergy is not a contraindication to the MMR vaccine \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab861374.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Pre-vaccination questionnaire." ] ] 5 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "PRN, plaque reduction neutralisation; VNA, virus-neutralising antibodies.Source: Kelso et al.<a class="elsevierStyleCrossRef" href="#bib0265">13</a>" "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Vaccine \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Protective level of IgG antibody \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Diphtheria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥0.1IU/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Haemophilus influenzae b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥0.15μcg/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hepatitis A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥10mIU/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hepatitis B surface antibody \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥10mIU/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Measles \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥120 PRN titre \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Polio types 1, 2 and 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥1:8 neutralising antibody titre \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Rabies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥0.5IU VNA/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Rubella \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥10IU/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Tetanus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥0.1IU/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Yellow fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥0.7IU/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab861367.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Protection levels of antibodies to vaccine (IgG)." ] ] 6 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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" title="table-entry " align="left" valign="top">Skin allergy tests: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Intraepidermal puncture or “skin prick” testing \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Intradermal testing (ID) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Epicutaneous or patch testing (24). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Specific IgE antibody serology assays with the ImmunoCAP (RAST) method, considered positive for values above 0.35kU/L \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab861370.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Allergy workup of adverse reactions to vaccines." ] ] 7 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Recommendations of the American Academy of Paediatrics.<a class="elsevierStyleCrossRef" href="#bib0280">16</a>" "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" title="table-entry " align="left" valign="top">1st dose: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.05mL of 1:10 dilution in normal saline \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2nd dose: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.05mL full-strength \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3rd dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.10mL full-strength \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4th dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.15mL full-strength \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5th dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.20mL full-strength \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">6th dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5mL dose (for vaccines requiring a 1mL volume) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab861371.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Dose-escalating administration of the vaccine." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0205" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Allergic reactions to vaccines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.A. Wood" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/pai.12102" "Revista" => array:6 [ "tituloSerie" => "Pediatr Allergy Immunol" "fecha" => "2013" "volumen" => "24" "paginaInicial" => "521" "paginaFinal" => "526" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23902374" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0210" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reacciones adversas a vacunas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.L. Eseverri" 1 => "S. Ranea" 2 => "A. Marin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Allergol Immunopathol (Madr)" "fecha" => "2003" "volumen" => "31" "paginaInicial" => "125" "paginaFinal" => "138" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0215" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anaphylaxis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.U. Rüggeberg" 1 => "M.S. Gold" 2 => "J.M. Bayas" 3 => "M.D. Blum" 4 => "J. Bonhoeffer" 5 => "S. 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Consensus position document on the child with an allergic reaction after vaccination or an allergy to vaccine components

Documento de consenso sobre la actitud ante un niño con una reacción alérgica tras la vacunación o alergia a componentes vacunales

L. Echeverría Zudairea,

Corresponding author

lecheverria3@gmail.com

Corresponding author.

, L. Ortigosa del Castillob, E. Alonso Lebreroc, F.J. Álvarez Garcíad, N. Cortés Álvareze, N. García Sánchezf, A. Martorell Aragonésg, en representación de la Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica (SEICAP) y el Comité Asesor de Vacunas de la Asociación Española de Pediatría (CAV-AEP)

a Unidad de Alergia y Neumología Pediátrica, Servicio de Pediatría, Hospital Universitario Severo Ochoa, Leganés, Madrid, Spain

b Servicio de Pediatría, Hospital Universitario Ntra. Sra. de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain

c Servicio de Alergia, Hospital Materno-Infantil Gregorio Marañón, Madrid, Spain

d Centro de Salud de Llanera, Asturias, Spain

e Unidad de Alergia Infantil, Hospital Universitario Mútua Terrassa, Terrassa, Barcelona, Spain

f Centro de Salud “Delicias Sur”, Zaragoza, Spain

g Unidad de Alergología, Hospital General Universitario, Valencia, Spain

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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Algorithm for the identification of an allergy reaction to vaccines &#40;modified from Kelso et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a>&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Explanation and seriousness of the issue</span><p id="par0005" class="elsevierStylePara elsevierViewall">The aim of vaccination programmes is to protect the vaccinated child and prevent the recipient from having the disease against which he or she was vaccinated&#46; The goal is to vaccinate the greatest possible number of susceptible individuals to produce a collective protective environment for the entire population&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">If a child is labelled as having had an allergic reaction to a vaccine &#40;ARV&#41;&#44; subsequent vaccinations will probably be suspended and that child will join the pool of individuals susceptible to the diseases against which he or she has stopped being vaccinated&#46; Therefore&#44; diagnosing the ARV accurately and confirming whether there is a direct relationship between the allergic reaction and the administration of the vaccine are of the essence&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The approach to a child with suspected ARV should start by determining whether the signs and symptoms presented by the child were directly related to the administration of the vaccine&#44; managing the allergic reaction&#44; and then assessing whether the adverse event was a reaction against the vaccine antigen itself or to any of the vaccine components&#44; as this will determine the administration of future doses of the vaccine in question or similar vaccines&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">There is a wide variety of ARV&#46; They are usually mild&#44; local reactions&#44; and exceptionally severe anaphylactic reactions that may even be fatal&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a></p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Vaccine composition&#58; antigens&#44; preservatives and adjuvants</span><p id="par0025" class="elsevierStylePara elsevierViewall">Vaccines do not only contain the antigen responsible for stimulating the immune response in the vaccinated individual&#44; but may also contain additional constituents &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Epidemiological data&#46; Incidence of allergic reactions after vaccination</span><p id="par0030" class="elsevierStylePara elsevierViewall">Allergic reactions to vaccines are rare and usually have no causal relationship with immunisation&#46; Estimates of true immediate hypersensibility reactions to vaccines range from 1 in 50<span class="elsevierStyleHsp" style=""></span>000 doses for the DTP vaccine to 0&#46;5&#8211;1 reaction per million doses for other vaccines&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> The Brighton Anaphylaxis Working Group estimates that the number of true severe anaphylactic reactions to vaccines ranges between 0&#46;5 and 1 in 100<span class="elsevierStyleHsp" style=""></span>000 doses&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">3</span></a> The number of reported deaths due to anaphylaxis secondary to vaccination is approximately 1 in 50 million doses&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">There are few published data for Spain&#44; with reported incidences ranging between 0&#46;59&#37; and 1&#46;27&#37; of reactions suspected to be associated with vaccination in the first visits to a paediatric allergy unit&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Among the allergic reactions attributed to residual proteins&#44; the most common are those related to egg in vaccines grown in both chicken embryo fibroblasts and fertilised chicken eggs&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">It is convenient to complete a questionnaire before vaccination<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> asking the parents of the child that is to be vaccinated about the presence of certain circumstances that may lead to consider the vaccination to be contraindicated either temporarily or permanently&#44; or to take specific precautions &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">What is an allergic reaction&#63; Types of allergic reactions to vaccines</span><p id="par0050" class="elsevierStylePara elsevierViewall">An allergic reaction is defined as an adverse response produced by an immune mechanism&#46; It can include a wide range of symptoms affecting the skin and the respiratory and cardiovascular systems&#46; Anaphylaxis can be confirmed by determination of serum tryptase levels&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Allergy is much less frequent than other types of adverse reactions&#46; In many instances&#44; the ARV is not confirmed and the patient may continue the course of vaccination with the same preparation&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Reactions are classified&#44; depending on their reach&#44; into local or systemic and&#44; depending on the time elapsed since the administration of the vaccine and the development of symptoms&#44; into immediate or delayed&#46; This criterion helps to distinguish IgE-mediated reactions from those that do not involve IgE&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Immediate reactions</span><p id="par0065" class="elsevierStylePara elsevierViewall">They start within an hour from vaccination &#40;from a few minutes to 4<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; They may include a wide range of symptoms affecting the skin&#44; the respiratory system and the cardiovascular system&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Delayed reactions</span><p id="par0070" class="elsevierStylePara elsevierViewall">They start hours or days after vaccination and there is a very low probability that they are mediated by IgE&#46; They are not usually caused by an immune mechanism and should not be diagnosed as allergies to vaccines&#46; They are self-limiting processes that do not contraindicate future doses of the same vaccine&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Differential diagnosis of allergic reactions during and after vaccine administration</span><p id="par0075" class="elsevierStylePara elsevierViewall">A previous diagnosis of ARV is important for two reasons&#58; firstly&#44; individuals that experienced an IgE-mediated reaction&#44; and especially anaphylaxis&#44; could experience new severe reactions after vaccination&#59; and secondly&#44; overdiagnosis of ARV could increase the number of children that do not complete vaccination&#44; which carries an individual and collective loss of protection against vaccine-preventable diseases&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The algorithm for the approach to diagnosis can be seen in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Delayed reactions are nonspecific&#44; and serum IgE and skin tests are usually not helpful&#59; although these reactions cause discomfort&#44; they are not life-threatening&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Vaccine components that may cause allergic reactions</span><p id="par0090" class="elsevierStylePara elsevierViewall">The components of vaccines marketed in Spain that may be involved in AVR can be found in the online manual of vaccines of the AEP &#40;<a href="http://vacunasaep.org/documentos/manual/anx-ii">http&#58;&#47;&#47;vacunasaep&#46;org&#47;documentos&#47;manual&#47;anx-ii</a><a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">9</span></a>&#41;&#46; None of the vaccines currently marketed in Spain contains thiomersal&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Vaccination of children with a history of possible allergic reaction after administration of a vaccine&#46; Action guideline</span><p id="par0095" class="elsevierStylePara elsevierViewall">An accurate diagnosis of VAR is based in the medical history and <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo</span> allergy testing&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The diagnostic algorithm is presented in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The medical records will help determine whether the hypersensibility reaction experienced by the child was immediate or delayed&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0110" class="elsevierStylePara elsevierViewall">If an IgE-mediated immediate reaction is suspected&#44; allergy testing should be done&#44; especially if additional doses of the vaccine are required and to avoid the risk of cross-reactivity with components of other vaccines or foods&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0115" class="elsevierStylePara elsevierViewall">If a non-immediate reaction is suspected&#44; the vaccine can be given in the usual manner in most cases&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a></p></li></ul></p><p id="par0120" class="elsevierStylePara elsevierViewall">The determination of IgG antibodies against the immunising agent can be useful if the patient has received fewer than the recommended number of doses in order to assess the level of immunity&#46; If a patient has protective levels of antibody&#44; subsequent doses could be withheld&#44; although the duration of immunity might be shorter&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> These levels have been determined for some vaccines &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">If additional doses are required or the level of protective antibodies cannot be determined&#44; allergy testing should be done for the intact vaccine or for specific components if an allergy to those components is suspected&#46;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">If test results are negative&#44; administration of a full-strength dose of vaccine will be considered&#44; keeping the patient under observation for 30<span class="elsevierStyleHsp" style=""></span>min&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">If test results are positive&#44; administration in graded doses will be considered if a vaccine preparation without the component to which the patient is allergic is not available&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a></p></li></ul></p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Medical history</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Anamnesis</span><p id="par0140" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Detailed history of the adverse reaction&#58; patient age&#44; date of reaction&#44; brand of the administered vaccine&#44; lot number&#44; latent period&#44; symptoms&#44; urgent medical care&#44; treatment received&#44; duration of reaction&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Vaccine composition&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0155" class="elsevierStylePara elsevierViewall">Simultaneous exposure to other allergens&#58; medications&#44; foods&#44; latex&#44; <span class="elsevierStyleItalic">etc&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Previous or subsequence tolerance to other vaccines&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Tolerance to vaccine components&#46;</p></li></ul></p></span></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Allergy workup &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Allergy workup and revaccination for immediate and delayed hypersensibility</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Immediate hypersensibility</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Skin tests with the intact vaccine</span><p id="par0170" class="elsevierStylePara elsevierViewall">Skin tests &#40;STs&#41; start with a full-strength skin prick&#44; and if the result is negative an intradermal &#40;ID&#41; test with a 1&#58;100 dilution in normal saline is performed&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">In cases of severe anaphylactic reaction&#44; testing should start with a 1&#58;10 concentration skin prick and a 1&#58;1000 dilution for the ID test&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The sensitivity and specificity of vaccine STs for confirming or ruling out allergy to a vaccine or its components have not been established&#44; but if the ST results are negative it is very improbable that the patient has IgE antibodies against the vaccine or its components&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">If more than one year has elapsed since the IgE-mediated reaction&#44; there may be low levels of circulating IgE and the ST results may be negative&#44; so administration of the vaccine may not cause a reaction&#44; although if the patient is sensitised it can trigger a booster response and a reaction may occur when the vaccine is administered after a long period of time&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Investigation of sensitivity to vaccine components</span><p id="par0190" class="elsevierStylePara elsevierViewall">If the result of the ST with the intact vaccine is positive&#44; the patient will be tested for sensitivity to vaccine components to try to prevent reactions to other vaccines that have the same components&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The available tests for vaccine components are&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">a&#46;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Tetanus toxoid&#58; determination of specific IgE serum levels &#40;sensitive&#44; but with low specificity&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">b&#46;</span><p id="par0205" class="elsevierStylePara elsevierViewall">Egg&#58; ST and determination of specific IgE serum levels for egg white and ovalbumin&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">c&#46;</span><p id="par0210" class="elsevierStylePara elsevierViewall">Cow&#39;s milk&#58; ST with extracted cow&#39;s milk proteins&#58; bovine alpha-lactalbumin&#44; beta-lactoglobulin&#44; casein and serum albumin&#59; specific IgE antibody assay for the same proteins&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">d&#46;</span><p id="par0215" class="elsevierStylePara elsevierViewall">Gelatin&#58; nonstandardised ST using commercial gelatin powder &#40;5<span class="elsevierStyleHsp" style=""></span>g of gelatin dissolved in 5<span class="elsevierStyleHsp" style=""></span>mL of normal saline&#41;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a>&#59; specific IgE antibody assays&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">e&#46;</span><p id="par0220" class="elsevierStylePara elsevierViewall">Latex&#58; latex ST and specific IgE antibody assay&#46;</p></li></ul></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Delayed hypersensitivity</span><p id="par0225" class="elsevierStylePara elsevierViewall">Sensitivity testing for vaccine components&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Patients with a history of eczematous reaction to a vaccine containing phenoxyethanol or formaldehyde&#58;</p><p id="par0235" class="elsevierStylePara elsevierViewall">a&#46; Patch test with standardised concentration</p><p id="par0240" class="elsevierStylePara elsevierViewall">Patients that have had an eczematous reaction or persistent injection-site nodules with an aluminium-containing vaccine&#58;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a>a&#46; Patch test with&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">i&#46;</span><p id="par0245" class="elsevierStylePara elsevierViewall">Metallic aluminium using an empty Finn Chamber&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">ii&#46;</span><p id="par0250" class="elsevierStylePara elsevierViewall">Aluminium chloride hexahydrate 2&#37; in glycerine placed in a plastic chamber&#46;</p></li></ul></p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Revaccination of patients with immediate hypersensitivity reactions<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">8&#44;10&#44;13</span></a></span><p id="par0255" class="elsevierStylePara elsevierViewall">If vaccine or vaccine component allergy test results are negative&#44; the vaccine can be administered in a single dose keeping the patient under observation for a minimum of 30<span class="elsevierStyleHsp" style=""></span>min afterward&#46; If there is a history of severe reaction&#44; the vaccine will be administered in two doses&#58; a first dose with a 1&#58;10 dilution of vaccine followed 30<span class="elsevierStyleHsp" style=""></span>min later by the rest of the full dose&#44; keeping the patient under observation for at least another 30<span class="elsevierStyleHsp" style=""></span>min&#46; There are no published cases of patients with negative vaccine ST results that had a severe anaphylactic reaction following revaccination&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">If the ST or specific IgE assay results are positive in a patient with a history of IgE-mediated reaction to one of the components of the vaccine&#44; a preparation that does not contain that component will be used whenever possible&#46; If it is not available and the administration of the suspect vaccine or another vaccine containing the suspect component is necessary&#44; the vaccine will be administered in graded doses in a hospital setting&#44; following the protocol shown in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0265" class="elsevierStylePara elsevierViewall">If the allergy workup is inconclusive and the reaction occurred after the simultaneous administration of several vaccines&#44; revaccination must be performed administering each of the vaccines on a different day&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Revaccination of patients with delayed allergic reactions<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">14&#44;15</span></a></span><p id="par0270" class="elsevierStylePara elsevierViewall">Revaccination must be considered on the basis of its necessity and the nature and severity of previous adverse reactions&#46; If the vaccine is administered&#44; the patient must stay under observation for 30<span class="elsevierStyleHsp" style=""></span>min&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">If several vaccines had been administered simultaneously&#44; revaccination must be carried out by administering each of the vaccines on a different day&#44; starting with the vaccine suspected to be the least risky&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">It has been demonstrated that STs are not useful in predicting the development of delayed reactions in subsequent administrations of the vaccine&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">In patients that had persistent injection-site nodules after administration of a vaccine containing aluminium salts and with positive patch-test results&#44; vaccines that do not contain these salts should be used whenever possible&#46; If the child is sensitive to aluminium salts and needs a dose of a vaccine that contains them&#44; it is recommended that the vaccine be administered with a deep intramuscular injection to minimise the local reaction&#46;</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Vaccination of children with suspected or confirmed allergies to vaccine components&#46; Action guideline</span><p id="par0290" class="elsevierStylePara elsevierViewall">When vaccination is considered in a child&#44; he or she may be allergic to one or more of the residual proteins from the manufacturing process or to any other product used in its preparation&#46; There is no evidence that children with atopy are at greater risk of having allergic reactions following vaccination&#44; and they should receive all the recommended vaccinations&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">16&#44;17</span></a></p><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Children with allergy to egg proteins</span><p id="par0295" class="elsevierStylePara elsevierViewall">Egg allergy is the leading food allergy in children&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a> with an estimated prevalence of 2&#46;5&#37; in the first 2 years of life&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">19</span></a> The measles-mumps-rubella &#40;MMR&#41; vaccine is growth in chicken embryo fibroblasts&#44; while the influenza vaccine and the yellow fever vaccine are cultured in fertilised eggs that may contain greater amounts of egg proteins&#46; Other vaccines that contain egg proteins are the hepatitis A vaccine Epaxal<span class="elsevierStyleSup">&#174;</span> and the vaccine against Central European encephalitis&#46; One of the vaccines against rabies marketed in Spain is not cultured in chick embryo cells&#44; but in human diploid cells&#46;</p><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Measles mumps rubella vaccine</span><p id="par0300" class="elsevierStylePara elsevierViewall">It does not contain egg proteins capable of triggering an allergic reaction&#44; and therefore all children with egg allergies&#44; including those who have anaphylactic reactions&#44; should be given this vaccine in the setting where they are routinely vaccinated&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> Children that have had a reaction to a previous dose of MMR vaccine should be assessed by an allergist or paediatric allergist&#46; These reactions are triggered by other vaccine components&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Influenza vaccine</span><p id="par0305" class="elsevierStylePara elsevierViewall">Administration of the influenza vaccine is recommended in children older than 6 months in certain at-risk groups&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a> If egg has yet to be introduced in the child&#39;s diet and it is suspected that the child may be allergic&#44; the child should be evaluated by a paediatric allergist prior to vaccination&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">The influenza vaccine may contain traces of ovalbumin&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a> and since it does not undergo heat treatment during manufacturing&#44; heat-labile egg proteins remain intact and may trigger reactions even in children that tolerate cooked eggs&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">In cases of anaphylaxis following vaccination against influenza&#44; no additional doses will be administered &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0320" class="elsevierStylePara elsevierViewall">In cases of egg allergy without severe anaphylaxis&#44; it is safe to administer an influenza vaccine with less than 0&#46;6&#8211;1<span class="elsevierStyleHsp" style=""></span>&#956;g of ovalbumin per dose&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a> so the vaccine can be administered in the usual setting<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24&#44;25</span></a> in a single dose&#44; and prior skin testing is unnecessary&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> It has been demonstrated that immunisation against influenza with vaccines with a low content of ovalbumin without dividing the dose is safe in patients with egg allergy with severe anaphylactic reactions&#44; and vaccines with a high ovalbumin content have even been used without complications in children with anaphylactic reactions to egg in the diet&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">27&#8211;29</span></a></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Yellow fever vaccine</span><p id="par0325" class="elsevierStylePara elsevierViewall">It is cultured in chicken embryos&#44; so it may contain significant amounts of egg proteins&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a> If administration of the vaccine is necessary&#44; children with egg allergies should be evaluated by an allergist or paediatric allergist&#46; If test results are negative&#44; the patient can be vaccinated in the usual manner&#44; and if they are positive and vaccination is absolutely necessary&#44; the vaccine must be administered in graded doses in a hospital setting&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">31&#44;32</span></a></p></span></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Children with cow&#39;s milk allergy</span><p id="par0330" class="elsevierStylePara elsevierViewall">The presence of milk derivatives in vaccines is very rare&#46; The summaries of product characteristics of the vaccines marketed in Spain do not mention the potential presence of cow&#39;s milk proteins&#44; although inadvertent contamination with proteins from the culture medium may occur&#46; Lactose may be added as an excipient to some vaccines&#44; but these are still free of cow&#39;s milk proteins&#46; From a practical standpoint&#44; it is safe to vaccinate a child that has a cow&#39;s milk allergy&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Children with allergies to antibiotics&#44; gelatin&#44; fungi&#44; yeasts and aluminium</span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Neomycin and other antibiotics</span><p id="par0335" class="elsevierStylePara elsevierViewall">Aminoglycosides &#40;gentamicin&#44; kanamycin&#41;&#44; polymyxin&#44; chlortetracycline and neomycin are added to vaccines to avoid bacterial contamination during the manufacturing process&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Neomycin can cause systemic allergic reactions that contraindicate the administration of vaccines containing it&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a> It can also cause local reactions&#44; such as contact dermatitis&#44; that require much greater amounts of neomycin than those usually contained in vaccines&#44; and that do not contraindicate vaccination&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">There have been no reports of reactions to any of the other antibiotics triggered by vaccination&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">35&#44;36</span></a></p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Gelatin</span><p id="par0350" class="elsevierStylePara elsevierViewall">Gelatin is an animal protein obtained from the connective tissue in cows and pigs&#46; It is used as a stabiliser in live-attenuated virus vaccines&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> If the patient is allergic to gelatin&#44; a vaccine skin prick test should be performed prior to vaccination&#46; If the result is positive and no other preparation is available that does not contain gelatin&#44; the vaccine will be administered in graded doses&#44; and if the result is negative the vaccine will be given in the usual manner&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Fungi and yeasts</span><p id="par0355" class="elsevierStylePara elsevierViewall">The hepatitis B vaccine and one of the human papillomavirus vaccines are manufactured by harvesting the antigens from cell cultures of recombinant <span class="elsevierStyleItalic">Saccharomyces cerevisiae</span> strains&#46; The amount of yeast contained in a vaccine can be of up to 5<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>per<span class="elsevierStyleHsp" style=""></span>mL in the hepatitis B vaccine and is smaller in the human papillomavirus vaccine&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a> If there is suspicion of a yeast allergy in the patient&#44; a skin prick test and a specific IgE assay need to be performed&#46; If the results are negative&#44; vaccination can be done in the usual manner&#46; If the results are positive and vaccination is absolutely necessary&#44; the vaccine should be administered in graded doses&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Aluminium</span><p id="par0360" class="elsevierStylePara elsevierViewall">Aluminium is used as an adjuvant to enhance the immune response&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a> The reaction usually triggered by aluminium consists of painful itching nodules at the site of injection that do not contraindicate vaccination&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> There are very few references to generalised eczema in the literature&#44;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a> so there is no scientific evidence to justify not recommending vaccination in children with a sensitivity to aluminium diagnosed by patch testing&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a></p></span></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Children with a latex allergy</span><p id="par0365" class="elsevierStylePara elsevierViewall">Children with a confirmed allergy to latex should be vaccinated in a latex-free environment&#46; Most of the products currently used are synthetic &#40;butyl&#44; chlorobutyl&#44; styrene-butadiene or halobutyl rubber&#41;&#44; although a few have a type I elastomeric closure with 10&#37; of latex&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">If the symptoms reported by the child consist solely of contact allergy to latex&#44; the patient can be vaccinated in the usual manner&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">10</span></a> If the previous reaction was anaphylactic&#44; administration of the vaccine in a latex-free environment must be guaranteed&#46;</p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Conflict of interests</span><p id="par0375" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "Explanation and seriousness of the issue"
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              "titulo" => "Vaccine composition&#58; antigens&#44; preservatives and adjuvants"
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              "titulo" => "Epidemiological data&#46; Incidence of allergic reactions after vaccination"
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              "titulo" => "What is an allergic reaction&#63; Types of allergic reactions to vaccines"
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          "titulo" => "Allergy workup &#40;Table 4&#41;"
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              "titulo" => "Allergy workup and revaccination for immediate and delayed hypersensibility"
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                  "titulo" => "Immediate hypersensibility"
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                  "titulo" => "Investigation of sensitivity to vaccine components"
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              "titulo" => "Revaccination of patients with immediate hypersensitivity reactions"
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              "titulo" => "Revaccination of patients with delayed allergic reactions"
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          "titulo" => "Vaccination of children with suspected or confirmed allergies to vaccine components&#46; Action guideline"
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              "titulo" => "Children with allergy to egg proteins"
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                  "titulo" => "Measles mumps rubella vaccine"
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                  "identificador" => "sec0115"
                  "titulo" => "Influenza vaccine"
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                  "titulo" => "Yellow fever vaccine"
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              "titulo" => "Children with cow&#39;s milk allergy"
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              "titulo" => "Children with allergies to antibiotics&#44; gelatin&#44; fungi&#44; yeasts and aluminium"
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                  "identificador" => "sec0135"
                  "titulo" => "Neomycin and other antibiotics"
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                  "titulo" => "Gelatin"
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                  "titulo" => "Fungi and yeasts"
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                  "titulo" => "Aluminium"
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              "titulo" => "Children with a latex allergy"
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          "titulo" => "Conflict of interests"
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    "fechaRecibido" => "2014-09-03"
    "fechaAceptado" => "2014-11-08"
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Vaccines allergy"
            1 => "Immediate hypersensitivity due to vaccines allergy"
            2 => "Delayed reactions"
            3 => "Anaphylaxis"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:4 [
            0 => "Alergia a vacunas"
            1 => "Hipersensibilidad inmediata por alergia a vacunas"
            2 => "Reacciones retardadas"
            3 => "Anafilaxia"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Vaccinations are one of the main public health tools for the control of vaccine-preventable diseases&#46; If a child is labelled to have had an allergic reaction to a vaccine&#44; the next immunizations will probably be suspended in that child&#44; with the risks involved in this decision&#46; The rate of severe allergic reactions is very low&#44; ranging between 0&#46;5 and 1&#47;100&#44;000 doses&#46; The causes of allergic reactions to vaccines&#44; more than the vaccine itself&#44; are often due to residual protein components in the manufacturing process&#44; such as gelatin or egg&#44; and rarely to yeast or latex&#46; Most of vaccine reactions are mild&#44; localised at the site of injection&#44; but in some circumstances&#44; severe anaphylactic reactions can occur&#46; If an immediate-type allergic reaction is suspected when vaccinating&#44; or a child allergic to some of the vaccine components has to be vaccinated&#44; a correct diagnosis of the possible allergy has to be made&#46; The usual components of each vaccine should be known&#44; in order to determine if vaccination can be performed safely on the child&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Las vacunaciones constituyen una de las principales herramientas de salud p&#250;blica para el control de las enfermedades inmunoprevenibles&#46; Si un ni&#241;o es etiquetado de haber presentado una reacci&#243;n al&#233;rgica a una vacuna es probable que se suspendan las siguientes inmunizaciones&#44; con los riesgos que ello conlleva&#46; La tasa de reacciones al&#233;rgicas graves es muy baja&#44; oscilando entre 0&#44;5 y 1&#47;100&#46;000 dosis&#46; Las prote&#237;nas causantes de las reacciones al&#233;rgicas&#44; m&#225;s que los propios ant&#237;genos vacunales&#44; son frecuentemente componentes residuales del proceso de fabricaci&#243;n&#44; como son la gelatina y el huevo&#44; y m&#225;s raramente las levaduras o el l&#225;tex&#46; La mayor&#237;a de las reacciones son leves y localizadas en el lugar de la inyecci&#243;n&#44; aunque en algunos casos pueden producirse reacciones anafil&#225;cticas graves&#46; Si se sospecha que se ha producido una reacci&#243;n al&#233;rgica inmediata a la vacuna&#44; o si debemos vacunar a un ni&#241;o con alergia a alguno de sus componentes&#44; se deber&#225; realizar un correcto diagn&#243;stico de la posible alergia y conocer los componentes habituales de cada vacuna con el fin de determinar si la vacunaci&#243;n puede continuarse de forma segura&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Echeverr&#237;a Zudaire L&#44; Ortigosa del Castillo L&#44; Alonso Lebrero E&#44; &#193;lvarez Garc&#237;a FJ&#44; Cort&#233;s &#193;lvarez N&#44; Garc&#237;a S&#225;nchez N&#44; et al&#46; Documento de consenso sobre la actitud ante un ni&#241;o con una reacci&#243;n al&#233;rgica tras la vacunaci&#243;n o alergia a componentes vacunales&#46; An Pediatr &#40;Barc&#41;&#46; 2015&#59;83&#58;63&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Algorithm for the identification of an allergy reaction to vaccines &#40;modified from Kelso et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">7</span></a>&#41;&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Diagnostic algorithm for the management of a child with suspected allergic reaction to vaccination&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Immunising antigen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Suspending fluid&#58; may contain proteins or other components from cultures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Antibiotics&#58; to prevent contamination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Preservatives&#58; extend the shelf-life&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Stabilisers&#58; the most common is gelatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">&#8226; Adjuvants&#58; enhance the immunogenicity of antigens&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Vaccine composition&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">HPV4&#44; tetravalent human papillomavirus&#59; MMR&#44; measles mumps rubella&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; Adapted from Fern&#225;ndez Cuesta et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a></p>"
          "tablatextoimagen" => array:5 [
            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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Delay vaccination&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Has the patient been ill in the past few days&#63;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Acute moderate or severe disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Until patient recovery or stabilisation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fever<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>38&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute allergy or asthma episodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute decompensated heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute nephropathies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Measles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 months after onset of rash&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Active tuberculosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 months after initiation of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Progressive or unstable neurological disorder&#44; or one predisposing to seizures&#44; such as acute encephalitis&#44; tuberous sclerosis or uncontrolled epilepsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Delay pertussis vaccination until neurological condition has stabilised&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            1 => 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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Contraindicated&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Primary immunodeficiency&#44; solid or blood tumours&#44; long-term immunosuppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MMR&#44; varicella&#44; rotavirus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">HIV infection with severe immunodeficiency &#40;CD4&#43; T-lymphocyte percentage &#60;15&#37; for age&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MMR&#44; varicella&#44; rotavirus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">History of intussusception or congenital gastrointestinal malformation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rotavirus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                0 => "xTab861368.png"
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            2 => 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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Precaution&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Disease or treatment leading to coagulation abnormalities or thrombocytopaenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">For parenteral vaccines&#44; use the subcutaneous route when allowed by the summary of product characteristics&#46; If administration must be intramuscular&#44; use 25G or 23G needles only&#44; apply pressure to the injection site for 2<span class="elsevierStyleHsp" style=""></span>min&#44; do not massage injection site and watch for subsequent development of haematoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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            3 => 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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Delay vaccination &#40;from the time treatment ends&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Is the patient currently taking any medications or receiving any kind of treatment&#63;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Blood products<span class="elsevierStyleHsp" style=""></span>Gamma globulins<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">More time for very high doses of gamma globulin &#40;consult&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#8211;6 months for MMR and varicella &#40;depending on the preparation&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">High-dose systemic corticosteroids &#40;&#8805;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg or 20<span class="elsevierStyleHsp" style=""></span>mg a day of prednisone or equivalent&#41; for more than 2<span class="elsevierStyleHsp" style=""></span>weeks or &#8805;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg for more than 1<span class="elsevierStyleHsp" style=""></span>month<span class="elsevierStyleItalic">No need to delay vaccination if corticosteroid therapy is short-term&#44; nonsystemic&#44; low-dose&#44; given every other day or is a replacement therapy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>month for MMR and varicella&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Acyclovir&#44; famciclovir&#44; valacyclovir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">One week for varicella&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">If female&#44; is the patient pregnant or suspects that she is&#63;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">If pregnant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MMR and varicella are contraindicated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">If in the first trimester of gestation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Avoid all vaccines&#44; except for the influenza vaccine &#40;evaluate specific risk&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Has the patient received any other vaccines previously&#63;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">If patient has received any live attenuated vaccine shots &#40;MMR&#44; varicella&#44; yellow fever&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Wait a minimum of 4 weeks before administering another live attenuated vaccine &#40;MMR&#44; varicella&#44; yellow fever&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Does patient have a history of severe reaction to vaccines&#63;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Severe allergic reaction &#40;anaphylaxis&#41; following a previous dose of the vaccine or to a vaccine component&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The vaccine in question is contraindicated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Encephalopathy within 7 days from administration of the DTP&#47;DTaP vaccine in the absence of any other identifiable cause&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pertussis vaccine contraindicated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">One of the following after DTP&#47;DTaP vaccine&#58;- Fever<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>40&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; hypotonic-hyporesponsive episode&#44; inconsolable crying lasting &#8805;3<span class="elsevierStyleHsp" style=""></span>h&#44; within 48<span class="elsevierStyleHsp" style=""></span>h of vaccination- Seizures within 3 days of vaccination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Exercise caution with pertussis vaccine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Guillain-Barr&#233; syndrome in the 6 weeks following vaccination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Exercise caution with vaccine in question&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Arthus reaction after a dose of vaccine containing tetanus toxoid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Delay any other doses of tetanus vaccine for at least 10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            4 => 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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Contraindicated&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top">Is the patient allergic to any of the vaccine components&#63;</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Only in case of anaphylaxis &#40;immediate and potentially serious reaction&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Allergy to neomycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hepatitis A &#40;Havrix<span class="elsevierStyleSup">&#174;</span>&#41;&#44; hepatitis A<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>B&#44; hexavalent vaccines&#44; influenza &#40;Chiroflu<span class="elsevierStyleSup">&#174;</span>&#44; Chiromas<span class="elsevierStyleSup">&#174;</span>&#44; Dotaricin<span class="elsevierStyleSup">&#174;</span>&#44; Inflexal <span class="elsevierStyleSmallCaps">V</span><span class="elsevierStyleSup">&#174;</span>&#44; Intanza<span class="elsevierStyleSup">&#174;</span>&#44; Mutagrip<span class="elsevierStyleSup">&#174;</span>&#44; Vaxigrip<span class="elsevierStyleSup">&#174;</span>&#41;&#44; pentavalent vaccines&#44; injectable polio&#44; rabies&#44; MMR and varicella&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Allergy to streptomycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hexavalent &#40;Hexyon<span class="elsevierStyleSup">&#174;</span>&#41;&#44; pentavalent &#40;Pentavac<span class="elsevierStyleSup">&#174;</span>&#41; and injectable polio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Allergy to polymyxin B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Influenza &#40;Inflexal V<span class="elsevierStyleSup">&#174;</span>&#41;&#44; hepatitis A &#40;Epaxal<span class="elsevierStyleSup">&#174;</span>&#41;&#44; hexavalent&#44; pentavalent and injectable polio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Allergy to gentamicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Influenza &#40;Fluarix<span class="elsevierStyleSup">&#174;</span>&#44; Fluenz<span class="elsevierStyleSup">&#174;</span>&#44; Influvac<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Allergy to kanamycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Influenza &#40;Chiroflu<span class="elsevierStyleSup">&#174;</span>&#44; Chiromax<span class="elsevierStyleSup">&#174;</span>&#44; Dotaricin<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Allergy to gelatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Typhoid fever &#40;Vivotif<span class="elsevierStyleSup">&#174;</span>&#41;&#44; MMR &#40;MMRVaxpro<span class="elsevierStyleSup">&#174;</span>&#41; and varicella &#40;Varivax<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Allergy to baker&#39;s yeast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hepatitis A<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>B&#44; hepatitis B&#44; hexavalent vaccine and HPV4 &#40;Gardasil<span class="elsevierStyleSup">&#174;</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Allergy to egg proteins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Central European encephalitis&#44; yellow fever&#44; influenza&#44; hepatitis A &#40;Epaxal<span class="elsevierStyleSup">&#174;</span>&#41; and rabies &#40;Rabipur<span class="elsevierStyleSup">&#174;</span>&#41;&#46; Egg allergy is not a contraindication to the MMR vaccine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Pre-vaccination questionnaire&#46;</p>"
        ]
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">PRN&#44; plaque reduction neutralisation&#59; VNA&#44; virus-neutralising antibodies&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; Kelso et al&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a></p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Vaccine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Protective level of IgG antibody&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Diphtheria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;0&#46;1<span class="elsevierStyleHsp" style=""></span>IU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Haemophilus influenzae</span> b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;0&#46;15<span class="elsevierStyleHsp" style=""></span>&#956;cg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Hepatitis A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Hepatitis B surface antibody&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Measles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;120 PRN titre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Polio types 1&#44; 2 and 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;1&#58;8 neutralising antibody titre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Rabies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;0&#46;5<span class="elsevierStyleHsp" style=""></span>IU VNA&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Rubella&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;10<span class="elsevierStyleHsp" style=""></span>IU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Tetanus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;0&#46;1<span class="elsevierStyleHsp" style=""></span>IU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Yellow fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;0&#46;7<span class="elsevierStyleHsp" style=""></span>IU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Protection levels of antibodies to vaccine &#40;IgG&#41;&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Skin allergy tests&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Intraepidermal puncture or &#8220;skin prick&#8221; testing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Intradermal testing &#40;ID&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Epicutaneous or patch testing &#40;24&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Specific IgE antibody serology assays with the ImmunoCAP &#40;RAST&#41; method&#44; considered positive for values above 0&#46;35</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">kU&#47;L</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Recommendations of the American Academy of Paediatrics&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">16</span></a></p>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;05<span class="elsevierStyleHsp" style=""></span>mL full-strength&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3rd dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;10<span class="elsevierStyleHsp" style=""></span>mL full-strength&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">4th dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;15<span class="elsevierStyleHsp" style=""></span>mL full-strength&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">5th dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;20<span class="elsevierStyleHsp" style=""></span>mL full-strength&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">6th dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;5<span class="elsevierStyleHsp" style=""></span>mL dose &#40;for vaccines requiring a 1<span class="elsevierStyleHsp" style=""></span>mL volume&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Dose-escalating administration of the vaccine&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:40 [
            0 => array:3 [
              "identificador" => "bib0205"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Allergic reactions to vaccines"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;A&#46; Wood"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1111/pai.12102"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Allergy Immunol"
                        "fecha" => "2013"
                        "volumen" => "24"
                        "paginaInicial" => "521"
                        "paginaFinal" => "526"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23902374"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            1 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reacciones adversas a vacunas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;L&#46; Eseverri"
                            1 => "S&#46; Ranea"
                            2 => "A&#46; Marin"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Allergol Immunopathol &#40;Madr&#41;"
                        "fecha" => "2003"
                        "volumen" => "31"
                        "paginaInicial" => "125"
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            ]
            2 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anaphylaxis&#58; case definition and guidelines for data collection&#44; analysis&#44; and presentation of immunization safety data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "J&#46;U&#46; R&#252;ggeberg"
                            1 => "M&#46;S&#46; Gold"
                            2 => "J&#46;M&#46; Bayas"
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                            4 => "J&#46; Bonhoeffer"
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                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.vaccine.2007.02.064"
                      "Revista" => array:6 [
                        "tituloSerie" => "Vaccine"
                        "fecha" => "2007"
                        "volumen" => "25"
                        "paginaInicial" => "5675"
                        "paginaFinal" => "5684"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17448577"
                            "web" => "Medline"
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            3 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                            0 => "W&#46; Zhou"
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                    0 => array:1 [
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            4 => array:3 [
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                0 => array:1 [
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
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            ]
            5 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Micheletti"
                            1 => "D&#46; Peroni"
                            2 => "G&#46; Piacentini"
                            3 => "V&#46; SchweIg Er"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2222.2012.03985.x"
                      "Revista" => array:6 [
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            6 => array:3 [
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              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
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                      "Revista" => array:6 [
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            7 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "8"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;A&#46; Wood"
                            1 => "M&#46; Berger"
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                      "Revista" => array:6 [
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            8 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "F&#46; &#193;lvarez Garc&#237;a"
                          ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:4 [
                        "titulo" => "Vacunas en Pediatr&#237;a&#46; Manual de la AEP 2012&#46; Comit&#233; Asesor de Vacunas"
                        "paginaInicial" => "627"
                        "paginaFinal" => "635"
                        "serieFecha" => "2012"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0250"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/pai.12132"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Allergy Immunol"
                        "fecha" => "2014"
                        "volumen" => "25"
                        "paginaInicial" => "394"
                        "paginaFinal" => "403"
                        "link" => array:1 [
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                            "web" => "Medline"
                          ]
                        ]
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                    ]
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                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
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Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2015.06.005

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Year/Month	Html	Pdf	Total

2024 November	6	10	16
2024 October	73	39	112
2024 September	98	32	130
2024 August	111	65	176
2024 July	136	46	182
2024 June	118	36	154
2024 May	109	45	154
2024 April	81	36	117
2024 March	75	38	113
2024 February	82	36	118
2024 January	89	42	131
2023 December	89	21	110
2023 November	88	37	125
2023 October	60	48	108
2023 September	63	42	105
2023 August	51	29	80
2023 July	54	31	85
2023 June	69	27	96
2023 May	93	27	120
2023 April	65	31	96
2023 March	78	27	105
2023 February	69	22	91
2023 January	69	34	103
2022 December	68	33	101
2022 November	90	30	120
2022 October	117	70	187
2022 September	82	32	114
2022 August	102	46	148
2022 July	109	49	158
2022 June	93	56	149
2022 May	93	67	160
2022 April	76	45	121
2022 March	122	70	192
2022 February	89	38	127
2022 January	89	55	144
2021 December	101	47	148
2021 November	92	50	142
2021 October	145	56	201
2021 September	117	58	175
2021 August	101	52	153
2021 July	77	44	121
2021 June	85	40	125
2021 May	81	47	128
2021 April	180	81	261
2021 March	161	26	187
2021 February	89	26	115
2021 January	153	27	180
2020 December	285	35	320
2020 November	78	28	106
2020 October	144	19	163
2020 September	90	26	116
2020 August	122	20	142
2020 July	101	16	117
2020 June	130	26	156
2020 May	91	53	144
2020 April	66	37	103
2020 March	74	39	113
2020 February	76	18	94
2020 January	61	21	82
2019 December	76	28	104
2019 November	53	25	78
2019 October	185	23	208
2019 September	236	15	251
2019 August	258	30	288
2019 July	211	24	235
2019 June	236	25	261
2019 May	319	31	350
2019 April	277	26	303
2019 March	233	26	259
2019 February	188	36	224
2019 January	243	29	272
2018 December	229	35	264
2018 November	303	43	346
2018 October	439	38	477
2018 September	195	25	220
2018 August	6	0	6
2018 July	4	0	4
2018 June	6	0	6
2018 May	12	0	12
2018 April	73	0	73
2018 March	54	0	54
2018 February	39	0	39
2018 January	41	0	41
2017 December	36	0	36
2017 November	40	0	40
2017 October	48	0	48
2017 September	45	0	45
2017 August	45	0	45
2017 July	52	0	52
2017 June	73	25	98
2017 May	114	17	131
2017 April	108	28	136
2017 March	50	15	65
2017 February	124	16	140
2017 January	32	8	40
2016 December	45	7	52
2016 November	98	15	113
2016 October	119	13	132
2016 September	173	8	181
2016 August	101	16	117
2016 July	42	29	71

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