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Original article
Impact of the 13-valent conjugate pneumococcal vaccine on the incidence of invasive pneumococcal disease in Catalonia: Retrospective study, 2014–2015 vs. 2017–2018
Impacto de la vacuna antineumocócica conjugada 13-valente en la incidencia de la enfermedad neumocócica invasiva en Cataluña: Estudio retrospectivo, 2014−2015 vs. 2017−2018
S. Bronera,
Corresponding author
sonia.broner@gencat.cat

Corresponding author.
, C. Izquierdoa, M.M. Noguerasa, S. Hernándeza, C. Muñoz-Almagrob,c,d, R. Pallarése,f, M. Janéa,b, P. Ciruelaa,b, Grupo de Trabajo de Vigilancia de la Enfermedad Neumocócica Invasiva en Cataluña
a Agència de Salut Pública de Catalunya, Generalitat de Catalunya, Barcelona, Spain
b Hospital Universitari Sant Joan de Déu, Barcelona, Spain
c Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain
d CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
e Hospital Universitari Bellvitge, Universitat de Barcelona, Barcelona, Spain
f CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Invasive pneumococcal disease &#40;IPD&#41; is a major public health problem worldwide with a high rate of morbidity and mortality&#46; It causes a broad spectrum of diseases&#44; from otitis media to sepsis and meningitis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and is defined as the isolation or detection of the DNA or antigen of <span class="elsevierStyleItalic">Streptococcus pneumonia</span> in a normally sterile place &#40;including blood&#44; brain stem fluid&#44; pleural fluid&#44; peritoneal fluid&#44; and joint fluid&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Depending on the polysaccharide capsule composition&#44; over 100 serotypes of <span class="elsevierStyleItalic">S&#46; pneumonia</span> have been identified&#46; The circulation of these serotypes and therefore&#44; the epidemiology of the IPD has changed during the last few years&#44; simultaneously with the introduction of pneumococcal conjugatevaccines&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The heptavalent pneumococcal vaccine &#40;Pn7 vaccine&#41;&#44; which contains serotypes 4&#44; 6B&#44; 9V&#44; 14&#44; 18C&#44; 19F and 23F&#44; was marketed in the year 2001 in Catalonia&#46; Also&#44; the decavalent pneumococcal conjugate vaccine &#40;vaccine 10&#41;&#44; which includes the Pn7 serotypes plus serotypes 1&#44; 5 and 7F&#44; was marketed in 2009&#46; The 13-valent pneumococcal conjugate vaccine &#40;Pn13 vaccine&#41;&#44; which includes Pn10 serotypes plus serotypes 3&#44; 6A and 19A&#44; replaced the Pn7 vaccine in 2010&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">After the introduction of vaccines Pn7&#44; Pn10 and Pn13&#44; the global rate of IPD in Catalonia dropped by 26&#37; from 2010 to 2014 compared with years 2006&#8722;2009&#46; The highest reduction was observed in children aged 2&#8211;4 years &#40;45&#37;&#41;&#46; The rate of serotypes included in Pn13 dropped in all age groups&#44; from 52&#37; in children aged 2&#8211;4 years to 35&#37; in adults &#8805;65 years&#46; Furthermore&#44; the rate of serotypes not included in Pn13 rose by 13&#37; in the group &#8805;65 years&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The indirect effect of immunisation of children on people aged 65 and over is reflected in the drop of the rate in this age group&#44; which was 19&#37; during the 2014&#8211;2016 period&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> This drop was due to the reduction of serotypes included in the Pn13&#44; but accompanied by an increase in non Pn13 serotypes&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In Catalonia up until July 2016&#44; none of the conjugate vaccines had been included in the routine vaccination schedule and only children with risk factors were recommended to have it&#46; However&#44; the pneumococcal conjugate vaccines had been recommended by paediatricians were administered in keeping with technical file guidelines&#46; From 2016 onwards&#44; the Pn13 vaccine was included in the technical file and was administered to children of 2&#44; 4 and 11 months&#44; in keeping with the guidelines agreed by the Interterritorial Council of the National Health System&#46; It was also administered within the adult population when an individual formed part of a risk group&#46; Since 1999 the administration of the 23-valent pneumococcal vaccine &#40;Pn23 vaccine&#41; has been recommended to all people from 65 years of age&#44; and to those in risk groups&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The aim of this study was to describe the epidemiology of the IPD and the evolution of circulating serotypes in different age groups and to analyse the impact of the Pn13 vaccine on the incidence of IPD during the years 2017&#8722;2018 compared to the years 2014&#8722;2015 of the cases reported to the Microbiological notification system of Catalonia &#40;SNMC for its initials in Spanish&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Case definition</span><p id="par0035" class="elsevierStylePara elsevierViewall">A case of IPD was defined as a patient with isolation&#44; detection of <span class="elsevierStyleItalic">S&#46; Pneumonia</span> DNA or antigen in a normally sterile site &#40;blood&#44; cerebrospinal fluid or pleural fluid&#44; among others&#41;&#44; together with compatible clinical manifestations&#44; with pneumonia&#44; meningitis and sepsis being the most common&#46; This included one episode of IPD per patient&#44; except in cases where &#62;30 days had elapsed between clinical samples or the serotypes identified were different&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">IPD monitoring system</span><p id="par0040" class="elsevierStylePara elsevierViewall">Notifications of confirmed cases of IPD made by the laboratories which participated in the SNMCof the Public Health Agency of Catalonia were made&#46; The SNMC comprises all the microbiology laboratories of the public and private hospital and out-of-hospital health centres of Catalonia&#46; These centres &#40;55 public hospitals&#44; 1 private hospital and 3 out-of-hospital health centres&#41; represents 92&#46;8&#37; of acute care beds in public hospitals of the Public Hospital Network&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Since 2016&#44; the SNMC has been a mandatory reporting monitoring system by the laboratory network of the Public health Agency of Catalonia<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and IPD is therefore a mandatory reporting disease&#46; Confirmed cases are reported individually&#44; on a daily or weekly basis&#44; including the variables&#58; sex&#44; age&#44; clinical presentation and diagnostic method&#46; During the study period&#44; in the context of the IPD European monitoring Project&#44; in which Catalonia participated together with 15 regions of 11 countries&#44; reinforced and proactive surveillance of the disease took place&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The isolates were sent to the Public Health Support Laboratory of Catalonia &#40;Sant Joan de D&#233;u university hospital&#41; and the National Microbiology Centre-Carlos III Institute of Health &#40;CNM-ISCIII&#41; &#40;Madrid&#44; Spain&#41;&#44; for their serotype and antibiotic sensitivity study&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Microbiological methods</span><p id="par0050" class="elsevierStylePara elsevierViewall">The strains were serotyped using the Quellung or dot-blot reaction&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> When this was not possible&#44; serotypes were identified using the polymerase chain reaction technique &#40;PCR&#41; which allows the detection of 40 serotypes&#47;serogroups&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">A retrospective study was conducted on notifications of confirmed cases of IPD during the years 2014&#8211;2018&#46; The variables studied were sex&#44; age &#40;age groups&#58; &#60;5 years&#44; 5&#8722;19 years&#44; 20&#8722;64 years and &#8805;65 years&#41;&#44; date of diagnosis&#44; clinical presentation&#44; clinical specimen&#44; microbiological technique and serotype&#46; Serotype was also analysed in terms of inclusion or non-inclusion in pneumococcal conjugate vaccines &#40;Pn7&#44; Pn10&#44; Pn13 and non Pn13&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Incidence rates were calculated according to demographic data from the Statistics Institute of Catalonia for the age groups studied&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The impact study was conducted using the relative risk &#40;RR&#41; calculation with confidence intervals &#40;CI&#41; of 95&#37;&#44; assuming the Poisson distribution and comparing the period 2017&#8722;2018 to that of 2014&#8722;2015&#46; Vaccination coverage was estimated for 2014&#8722;2015 to be 64&#37;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> whilst cover for 2017 and 2018&#44; with the universal immunisation programme was 81&#46;8&#37; and 92&#46;5&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> respectively&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Impact was analysed using the &#40;1-RR&#41; &#42;100 formula&#46; The year 2016 was not considered because routine administration of the Pn13 vaccine in children began in July of that year&#46; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;05 values were considered statistically significant&#46; Analysis was performed using the Statistical Package for Social Sciences &#40;SPSS 19&#46;0&#41;&#174;and the R 3&#46;2&#46;0 &#40;R Development Core Team 2015&#41;&#174;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The data analysed in this manuscript were partially presented in the 2017&#8722;2018 invasive pneumococcal disease report &#40;<a href="https://canalsalut.gencat.cat/web/.content/_Professionals/Vigilancia_epidemiologica/documents/arxius/malaltia-pneumoccocica-invasiva-informe-2017-2018_final-es.pdf">https&#58;&#47;&#47;canalsalut&#46;gencat&#46;cat&#47;web&#47;&#46;content&#47;&#95;Professionals&#47;Vigilancia&#95;epidemiologica&#47;documents&#47;arxius&#47;malaltia-pneumoccocica-invasiva-informe-2017-2018&#95;final-es&#46;pdf</a>&#41;&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Evolution of the incidence rates and of clinical symptoms</span><p id="par0080" class="elsevierStylePara elsevierViewall">During the 2014&#8211;2018 period 4764 IPD cases were reported&#44; which represents an incidence rate &#40;IR&#41; of 12&#46;6 cases per 100&#44;000 people&#47;year&#46; The highest incidences were presented in adults aged 65 or over &#40;33&#46;6 cases per 100&#46;000 peoples&#47;year&#41; and in children &#60;5 years &#40;27&#46;5 cases per 100&#44;000 people&#47;year&#41;&#46; The number of IPD cases in men was 2824 cases &#40;59&#46;3&#37;&#41;&#46; In 4580 cases &#40;96&#46;1&#37;&#41; the diagnosis was made by culture&#44; in 145 cases &#40;3&#46;1&#37;&#41; from PCR and in 39 cases &#40;&#46;8&#37;&#41;&#44; by antigen detection&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">During the years 2017 and 2018&#44; a global IR increase of 15&#37; was observed compared to 2014&#8722;2015 &#40;RR&#58; 1&#46;15&#59; 95&#37; CI&#58; 1&#46;08&#8722;1&#46;23&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41;&#46; The increase of the rate was significant in the groups of 20&#8211;64 years &#40;18&#37;&#41; and in &#8805;65 years &#40;18&#37;&#41;&#44; whilst in the other age groups the rate remained stable &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">During the analysed period&#44; most cases presented with pneumonia &#40;78&#46;6&#37;&#59; 3746&#47;4764&#41;&#44; followed by meningitis &#40;8&#46;7&#37;&#59; 413&#47;4764&#41; and unfocused bacteraemias &#40;8&#46;6&#37;&#59; 409&#47;4764&#41;&#46; The other clinical symptoms &#40;4&#46;1&#37;&#59; 196&#47;4764&#41; were peritonitis&#44; arthritis&#44; cholecystitis&#44; endocarditis&#44; cellulitis&#44; pancreatitis&#44; renal&#44; lumbar spondylodiscitis&#44; endophthalmitis&#44; pyometra&#44; myositis&#44; intestinal and cerebral occlusion&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Global incidence of pneumonia showed a significant increase of 19&#37; &#40;RR&#58; 1&#46;19&#59; 95&#37; CI&#58; 1&#46;11&#8211;1&#44;28&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41;&#44; mainly in the group aged 20&#8211;64 years &#40;23&#37;&#41; and in &#8805;65 years &#40;20&#37;&#41;&#44; whilst in the other age groups the incidence remained stable&#46; No changes were observed in the other clinical symptoms&#44; with the exception of unfocused bacteraemia which presented a drop of 32&#37; &#40;RR&#58; &#46;68&#59; 95&#37; CI&#58; &#46;46&#8722;&#46;99&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;045&#41; in the group aged 20&#8722;64 years &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Changes in serotype distributions</span><p id="par0100" class="elsevierStylePara elsevierViewall">During the years 2014&#8211;2018&#44; the serotype in 86&#46;0&#37; cases diagnosed was identified &#40;4086&#47;4764&#41; with 57 different serotypes being detected&#46; The most frequent serotypes were&#58; 8&#44; 3&#44; 12F&#44; 14&#44; 22F&#44; 24F and 19A&#44; representing 50&#46;9&#37; of cases&#46; The distribution of the serotypes identified during this period is contained in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">When analysing the serotypes causing IPD by age group&#44; it was observed that in children &#60;5 years the serotypes included in the Pn7&#44; Pn10 and Pn13 vaccines accounted for 16&#46;7&#37;&#44; 20&#46;8&#37; and 37&#46;3&#37;&#44; respectively&#46; The most frequent serotypes were 24F &#40;12&#46;9&#37;&#41;&#44; 3 &#40;12&#46;0&#37;&#41; and 14 &#40;9&#46;9&#37;&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In the age group from 5 to 19 years&#44; the serotypes included in the Pn7&#44; Pn10 and Pn13 vaccines accounted for 17&#46;4&#37;&#44; 46&#46;2&#37; and 58&#46;3&#37;&#44; respectively&#46; Serotypes 1 &#40;25&#46;6&#37;&#41;&#44; 8 &#40;13&#46;5&#37;&#41; and 3 &#40;10&#46;5&#37;&#41; were the most frequent&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In the cases from 20 to 64 years&#44; the serotypes included in the Pn7&#44; Pn10 and Pn13 vaccines accounted for 12&#46;2&#37;&#44; 18&#46;5&#37; and 34&#46;3&#37;&#44; respectively&#46; Serotypes 8 &#40;17&#46;7&#37;&#41;&#44; 12F &#40;11&#46;1&#37;&#41; and 3 &#40;10&#46;9&#37;&#41; were the most frequent&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In the age group de &#8805;65&#44; the serotypes included in the Pn7&#44; Pn10 and Pn13 vaccines accounted for 13&#46;0&#37;&#44; 15&#46;4&#37; and 32&#46;6&#37;&#44; respectively&#46; Serotypes 3 &#40;11&#46;8&#37;&#41; and 8 &#40;9&#46;5&#37;&#41; were the most frequent&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Between 2017&#8722;2018 vs&#46; 2014&#8722;2015 a drop of 23&#37;&#44; 43&#37;&#44; 25&#37; and 4&#37; in the serotypes included in the Pn7&#44; Pn10&#44; Pn13 and Pn23 vaccines&#44; respectively was observed&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The serotypes included in the Pn7 vaccine decreased the incidence rate in children under 5 years of age by 51&#37;&#44; mainly due to the decrease of serotype 14 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The incidence of serotypes included in the Pn10 vaccine&#44; especially serotypes 1 and 7F&#44; decreased in all age groups &#40;between 23&#37; and 61&#37;&#41; during the years 2017&#8722;2018 compared to the years 2014&#8722;2015&#44; unlike serotypes included in the Pn13 vaccine&#44; which&#44; except in children under 5 years of age&#44; decreased by 36&#37; &#40;RR&#58; &#46;64&#59; 95&#37; CI&#58; &#46;44&#8722;&#46;92&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;014&#41;&#44; remained stable due to the high incidences observed in serotypes 3 and 19A during the two periods&#46; When analysing the whole population&#44; the decrease in Pn13 serotypes was 15&#37;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">Serotype 3 showed no change in incidence compared to 2014&#8722;2015 and was the serotype with the highest incidence in &#60;5 years and &#8805;65 years during 2017&#8722;2018&#46; In the age groups 5&#8722;19 years and 20&#8722;64 years&#44; serotype 3 was in third and second place in frequency&#44; respectively&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">However&#44; an increase in serotypes not included in the Pn13 vaccine &#40;non-Pn13&#41; of 31&#37; &#40;RR&#58; 1&#46;31&#59; 95&#37; CI&#58; 1&#46;20&#8722;1&#46;43&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41; was observed&#44; mainly in adults aged 20&#8722;64 years &#40;35&#37;&#41; and &#8805;65 years &#40;27&#37;&#41;&#46; Of these serotypes&#44; serotype 8 increased its incidence in all age groups and was especially significant in &#62;5 years &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;05&#41;&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0145" class="elsevierStylePara elsevierViewall">This study has allowed us to determine the impact on IPD&#44; in terms of direct and indirect effects&#44; of the introduction of the Pn13 vaccine in the routine vaccination schedule in Catalonia&#46; This autonomous community is a region whose estimated coverage was intermediate in the years prior to the start of the immunisation programme<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;18</span></a> and which has increased with its inclusion in the routine vaccination schedule&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The global incidence rate of IPD during the years 2017&#8722;2018 increased by 15&#37; compared with the 2014&#8722;2015 period&#44; due to the increase of incidence in the groups from 20 to 64 years &#40;18&#37;&#41; and &#8805;65 years &#40;18&#37;&#41;&#46; This increase&#44; which was also observed in other autonomous communities&#44; could be due to a rise in the non-vaccine serotypes&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">In children under 5 years of age&#44; a 51&#37; decrease in the incidence of the serotypes included in the Pn7 vaccine was observed&#44; mainly due to the decrease in serotype 14&#46; This serotype&#44; which remained the most frequent in all age groups during the period 2010&#8211;2014&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> drastically decreased its presence after the introduction of the vaccine in the routine schedule&#46; Our data are similar to those observed in other countries with routine vaccination programmes with Pn10 and Pn13 vaccines&#46; In Italy&#44; Camilli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> observed a decrease in the serotypes included in the Pn7 vaccine&#44; and even the disappearance of some of these serotypes&#44; with the exception of serotype 14 which&#44; despite the decrease&#44; was still among the four most frequent serotypes&#46; In Austria&#44; the results of Richter et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> showed that the largest reduction occurred in serotype 14&#44; followed by serotypes 14 and 14 and 14&#44; followed by serotypes 6B&#44; 18C and 19F&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The incidence of serotypes included in the Pn10 vaccine decreased significantly in all age groups due to a reduction in the incidence of serotypes 1 and 7F&#46; Similar results were observed in Germany&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> England and Wales&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> where these serotypes&#44; which had experienced an increase due to the introduction of the Pn7 vaccine&#44; decreased with the Pn13 vaccine&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The study of the behaviour of the serotypes included in the Pn13 vaccine has shown that their incidence has decreased in children under 5 years of age&#44; while it has remained stable in the rest of the groups due to serotype 3&#44; which maintains high incidences in all age groups&#46; This serotype&#44; against which the Pn13 vaccine has a low effectiveness&#44; is associated with a high percentage of vaccine failures that occur in children who have completed the vaccination schedule l&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a> These results have also been observed by other authors&#44; both when analysing the impact of the Pn13 vaccine in the first years of its introduction or early period&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> and in the later years or late period&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> Other studies which focused on the paediatric population<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;24&#44;28</span></a> or in the adult population&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> have also observed that serotype 3 remained stable with no changes&#46; However&#44; Waight et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> found a significant reduction in this serotype in children and adults&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The results observed for the serotypes included in the non-Pn13 vaccine have shown an increase in incidence in adults aged 20 years and older&#44; mainly due to an increase in the incidence of serotype 8&#46; Other authors have also reported an increase in these serotypes&#44; which varies according to the period considered in the study and whether the target population was children&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> adults<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> or both&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a> On the other hand&#44; the new serotypes that have started to replace the vaccine serotypes have been different depending on the country and Age group&#46; In children&#44; serotypes 24F and 12F<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;20&#44;32</span></a> are the most prevalent in Catalonia&#44; Italy and Israel&#44; while in adults serotypes 8&#44; 12F and 9N are the most prevalent in England and Wales&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> In Germany&#44; however&#44; serotypes 15A and 23B are the emerging serotypes in all age groups&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">With regard to clinical symptoms&#44; only pneumonia showed a significant increase in overall incidence and in those over 20 years of age&#46; However&#44; a decrease in unfocused bacteraemia was detected in the 20&#8722;64 years age group&#46; In countries where the impact of conjugate vaccines on the clinical entity was analysed&#44; the main focus has been on the changes produced in meningitis in children under 5 years of age&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;34</span></a> with results indicating a decrease&#46; Other authors who have studied the behaviour of pneumonia and other clinical manifestations&#44; with isolation in blood&#44; have also found that these decrease after the introduction of conjugate vaccines&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">This study has some limitations&#46; First&#44; the lack of serotype information in some cases&#44; the percentage of missing data varies between 11&#37; and 17&#37; in the period analysed&#46; Second&#44; IPD reporting became mandatory in 2016&#44; which may have led to underreporting of cases during the years prior to the 2017&#8722;2018 period&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">A strength of our study is the robustness of the data source as it is collected from the SNMC&#44; which includes 92&#46;8&#37; of acute care beds in public hospitals&#46; Another strength is the participation of Catalonia in the European project of the IPD active surveillance network&#44; <span class="elsevierStyleItalic">SpID-NET</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> together with fifteen other European regions&#44; which has helped to substantially improve the surveillance of IPD in this region&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0190" class="elsevierStylePara elsevierViewall">The introduction of the Pn13 vaccine in the paediatric routine vaccination schedule in Catalonia indicates that the impact it produces is beneficial both in the vaccinated population and in the adult population&#46; However&#44; together with the decrease in the incidence of serotypes included in the Pn13 vaccine&#44; an increase in serotypes not included in this vaccine has been observed&#44; which could compromise its benefits&#46; For this reason&#44; it is necessary to carry out accurate and continuous epidemiological surveillance of IPD in order to rapidly detect changes in the incidence of the disease and circulating serotypes&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Financing</span><p id="par0195" class="elsevierStylePara elsevierViewall">This study was partially financed by <span class="elsevierStyleGrantSponsor" id="gs0005">SpIDnet</span> &#40;<span class="elsevierStyleItalic">Assessing the impact of vaccination with the conjugate vaccines on the epidemiology of invasive pneumococcal disease in Europe</span>&#41;&#44; a network financed by the <span class="elsevierStyleGrantSponsor" id="gs0010">European Centre for Disease Prevention and Control</span> &#40;ECDC <span class="elsevierStyleGrantNumber" refid="gs0010">2015&#47;031</span>&#41;&#59; the <span class="elsevierStyleGrantSponsor" id="gs0015">Catalan Agency for the Management of University Research Grants</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0015">2017&#47;SGR 1342</span> and <span class="elsevierStyleGrantNumber" refid="gs0015">2017&#47;SGR 0742</span>&#41;&#59; the <span class="elsevierStyleGrantSponsor" id="gs0020">Centre for Biomedical Research Network on Epidemiology and Public Health</span> &#40;CIBERESP <span class="elsevierStyleGrantNumber" refid="gs0020">CB06&#47;02&#47;0076</span> and <span class="elsevierStyleGrantNumber" refid="gs0020">CB15&#47;00067</span>&#41; and the <span class="elsevierStyleGrantSponsor" id="gs0025">Centre for Biomedical Research Network on Respiratory Diseases</span> &#40;CIBERES <span class="elsevierStyleGrantNumber" refid="gs0025">CB06 &#47;06&#47;0037</span>&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">CMA has received grants and personal fees from Pfizer&#44; Qiagen and BioMerieux and grants from Genomica SAU&#46; All other authors have no conflicts of interest to declare&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The authors declare the following financial interests&#47;personal relationships which may be considered as potential competing interests&#58;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Carmen Mu&#241;oz-Almagro has received grants and personal fees from Pfizer&#44; Qiagen and BioMerieux and grants from Genomica SAU&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Invasive pneumococcal disease &#40;IPD&#41; is a major public health problem worldwide with high morbidity and mortality that causes a wide spectrum of diseases&#44; from otitis media to sepsis and meningitis&#46; In Catalonia&#44; the universal immunization program with the 13-valent conjugated pneumococcal vaccine &#40;Pn13 vaccine&#41; began in 2016&#46; The objective of this study was to analyse the impact of the 13-valent pneumococcal conjugate vaccine &#40;PCV13 vaccine&#41; on the incidence of IPD during the years 2017&#8722;2018 compared to the years 2014&#8722;2015&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Retrospective study of IPD cases notified by reporting laboratories to the Microbiological Reporting System of Catalonia &#40;MRSC&#41; from 2014 to 2018&#46; Incidence rates &#40;IR&#41; and relative risk &#40;RR&#41; were calculated&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">The global incidence of IPD &#40;2014&#8211;2018&#41; was 12&#44;6 cases per 100&#44;000 persons&#47;year&#46; Comparing 2017&#8722;2018 vs 2014&#8722;2015&#44; the incidence of IPD caused by the serotypes included in the PCV13 vaccine has decreased in children &#60;5 years by 46&#37; while it has remained stable in the rest of the groups&#46; Serotype 3&#44; despite being included in the PCV13 vaccine&#44; remained a high incidence&#46; In contrast&#44; the incidence of IPD caused by non PCV13 serotypes increased in adults aged 20&#8722;64 years &#40;35&#37;&#41; and &#8805;65 years &#40;27&#37;&#41;&#44; mainly due to the increase of serotype 8&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">PCV13 introduction is beneficial for both&#44; vaccinated and non-vaccinated people &#40;due to herd immunity&#41;&#46; However&#44; a precise and continuous epidemiological surveillance of IPD must be carried out to detect changes in the incidence of the disease and circulating serotypes&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">La enfermedad neumoc&#243;cica invasiva &#40;ENI&#41; es un importante problema de salud p&#250;blica a escala mundial con elevada morbilidad y mortalidad que causa un espectro amplio de enfermedades&#44; desde otitis media hasta sepsis y meningitis&#46; En Catalu&#241;a&#44; el programa de inmunizaci&#243;n universal con la vacuna antineumoc&#243;cica conjugada 13-valente &#40;vacuna Pn13&#41; se inici&#243; en 2016&#46; El objetivo de este estudio fue analizar el impacto de la vacuna Pn13 sobre la incidencia de ENI durante 2017&#8722;2018 respecto de 2014&#8722;2015&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de casos de ENI notificados por laboratorios participantes al sistema de notificaci&#243;n microbiol&#243;gica de Catalu&#241;a del 2014 al 2018&#46; Se calcularon las tasas de incidencia &#40;TI&#41; y riesgo relativo &#40;RR&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">La incidencia global de ENI &#40;2014&#8211;2018&#41; fue de 12&#44;6 casos por 100&#44;000 personas&#47;a&#241;o&#46; Comparando 2017&#8722;2018 vs 2014&#8722;2015&#44; la incidencia de ENI causada por serotipos incluidos en la vacuna Pn13 disminuy&#243; en ni&#241;os &#60;5 a&#241;os un 46&#37; mientras que en el resto de grupos de edad permaneci&#243; estable&#46; El serotipo 3&#44; pesar a estar incluido en la vacuna Pn13&#44; mantuvo una incidencia elevada&#46; Por el contrario&#44; la incidencia de ENI por serotipos no vacunales aument&#243; en adultos de 20&#8722;64 a&#241;os &#40;35&#37;&#41; y de &#8805;65 a&#241;os &#40;27&#37;&#41;&#44; principalmente debido al aumento del serotipo 8&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">La introducci&#243;n de la vacuna Pn13 es beneficiosa tanto para la poblaci&#243;n vacunada como la no vacunada &#40;por efecto indirecto o inmunidad de grupo&#41;&#46; Debe llevarse a cabo una vigilancia epidemiol&#243;gica precisa y continuada de la ENI para detectar cambios en la incidencia de la enfermedad y los serotipos circulantes&#46;</p></span>"
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2017&#8722;2018 vs&#46; 2014&#8722;2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">117&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">214&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">196&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;99 &#40;&#46;82&#8722;1&#46;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;998&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8722;19 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;90 &#40;&#46;62&#8722;1&#46;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;611&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#8722;64 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">318&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">348&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">329&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">391&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">391&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">666&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">782&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;18 &#40;1&#46;06&#8722;1&#46;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;65 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">388&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">449&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">448&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">496&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">534&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">837&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1030&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;18 &#40;1&#46;07&#8722;1&#46;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">829&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">951&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">917&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1056&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1780&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2067&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;15 &#40;1&#46;08&#8722;1&#46;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">N&#46;&#176;&#58; number of cases&#59; RR&#58; relative risk&#46;</p>"
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            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Clinical symptom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2014</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2015</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2016</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2017</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2018</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2014&#8722;2015</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2017&#8722;2018</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">RR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">P</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2017&#8722;2018 vs&#46; 2014&#8722;2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="17" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Pneumonia</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#46;84 &#40;&#46;61&#8722;1&#46;15&#41;&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Peritonitis &#40;24 cases&#41;&#59; arthritis &#40;23 cases&#41;&#59; cholecystitis &#40;7 cases&#41;&#59; endocarditis &#40;6 cases&#41;&#59; celullitis &#40;4 cases&#41;&#59; pancreatitis &#40;4 cases&#41;&#59; renal &#40;3 cases&#41;&#59; lumbar spondylodiscitis &#40;2 cases&#41;&#59; endophthalmitis &#40;1 case&#41;&#59; pyometra &#40;1 case&#41;&#59; myositis &#40;1 case&#41;&#59; intestinal occlusion &#40;1 case&#41; and cerebral occlusion &#40;1 case&#41;&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Age group&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2014</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2015</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2016</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2014&#8722;2015</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2017&#8722;2018</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">RR<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#46;&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rate <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2017&#8722;18 vs&#46; 2014&#8722;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="17" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">&#60;5 years</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pn13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;64 &#40;&#46;44&#8211;&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pn7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;49 &#40;&#46;26&#8722;&#46;88&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pn10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;39 &#40;&#46;22&#8722;&#46;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>no Pn13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">14&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">14&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">18&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  "referenciaCompleta" => "World Health Organization&#46; Pneumococcal conjugatevaccines&#46; WHO position paper&#46; Vol&#46; 8&#44; 2019&#44; 94&#44; 85-104&#46;"
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                    0 => array:2 [
                      "titulo" => "Estimates of the global&#44; regional&#44; and national morbidity&#44; mortality&#44; and aetiologies of lower respiratory infections in 195 countries&#44; 1990&#8211;2016&#58; a systematic analysis for the Global Burden of Disease Study 2016"
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                      "doi" => "10.1016/S1473-3099(18)30310-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Infect Dis&#46;"
                        "fecha" => "2018"
                        "volumen" => "18"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30243584"
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                            0 => "M&#46; Tin Tin Htar"
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Article information
ISSN: 24451460
Original language: English
DOI:10.1016/j.vacune.2022.01.001
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