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

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La enfermedad neumoc&#243;cica invasiva &#40;ENI&#41; es un importante problema de salud p&#250;blica a escala mundial con una elevada morbilidad y mortalidad que causa un espectro amplio de enfermedades&#44; desde otitis media hasta sepsis y meningitis<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">1</span></a>&#46; La ENI se define como el aislamiento o detecci&#243;n de DNA o de ant&#237;geno de <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> en un lugar habitualmente est&#233;ril &#40;sangre&#44; l&#237;quido cefalorraqu&#237;deo&#44; l&#237;quido pleural&#44; l&#237;quido peritoneal&#44; l&#237;quido articular&#44; entre otros&#41;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Seg&#250;n la composici&#243;n de la c&#225;psula de polisac&#225;ridos&#44; se han identificado m&#225;s de 100 serotipos de <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#46; La circulaci&#243;n de estos serotipos y&#44; por lo tanto&#44; la epidemiolog&#237;a de la ENI ha cambiado en los &#250;ltimos a&#241;os de manera simult&#225;nea a la introducci&#243;n de las vacunas antineumoc&#243;cica conjugadas<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">3</span></a>&#46; La vacuna antineumoc&#243;cica heptavalente &#40;vacuna Pn7&#41;&#44; que contiene los serotipos 4&#44; 6B&#44; 9V&#44; 14&#44; 18C&#44; 19F y 23F&#44; se comercializ&#243; en el a&#241;o 2001 en Catalu&#241;a&#46; As&#237; mismo&#44; la vacuna antineumoc&#243;cica conjugada decavalente &#40;vacuna Pn10&#41;&#44; que incluye los serotipos de la Pn7 m&#225;s los serotipos 1&#44; 5 y 7F&#44; se comercializ&#243; en 2009&#46; La vacuna antineumoc&#243;cica conjugada 13-valente &#40;vacuna Pn13&#41;&#44; que incluye los serotipos de la Pn10 m&#225;s los serotipos 3&#44; 6A y 19A&#44; sustituy&#243; a la vacuna Pn7 en 2010<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Despu&#233;s de la introducci&#243;n de las vacunas Pn7&#44; Pn10 y Pn13&#44; la incidencia global de la ENI disminuy&#243; un 26&#37; durante los a&#241;os 2010-2014 respecto de los a&#241;os 2006-2009 en Catalu&#241;a&#46; La mayor reducci&#243;n se ha observado en ni&#241;os de 2&#8211;4 a&#241;os &#40;45&#37;&#41;&#46; La incidencia de los serotipos incluidos en la Pn13 se ha reducido en todos los grupos de edad&#44; desde un 52&#37; en ni&#241;os de 2&#8211;4 a&#241;os hasta un 35&#37; en adultos &#8805; 65 a&#241;os&#46; Por otro lado&#44; la incidencia de los serotipos no incluidos en la Pn13<span class="elsevierStyleHsp" style=""></span>ha aumentado en un 13&#37; en el grupo de &#8805; 65 a&#241;os<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">El efecto indirecto de la inmunizaci&#243;n de los ni&#241;os sobre las personas de 65 a&#241;os y m&#225;s se ha reflejado en la disminuci&#243;n de la incidencia en este grupo de edad&#44; que ha sido del 19&#37; durante el per&#237;odo 2014-2016<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">6</span></a>&#46; Esta disminuci&#243;n es debida a la reducci&#243;n de los serotipos incluidos en la Pn13&#44; acompa&#241;ada&#44; sin embargo&#44; de un aumento de los serotipos no Pn13&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">En Catalu&#241;a&#44; hasta julio de 2016&#44; ninguna de las vacunas conjugadas se hab&#237;a incluido en el calendario de vacunaciones sistem&#225;ticas y &#250;nicamente los ni&#241;os con factores de riesgo ten&#237;an indicaci&#243;n de vacunaci&#243;n&#46; No obstante&#44; las vacunas conjugadas neumoc&#243;cicas hab&#237;an sido recomendadas por los pediatras y se administraban seg&#250;n las pautas de la ficha t&#233;cnica&#46; A partir de 2016&#44; la vacuna Pn13 se incluy&#243; en el calendario sistem&#225;tico y se administra a los 2&#44; 4 y 11 meses de edad&#44; siguiendo las pautas acordadas por el Consejo Interterritorial del Sistema Nacional de Salud&#46; Tambi&#233;n se administra en poblaci&#243;n adulta si pertenece a un grupo de riesgo&#46; Desde el a&#241;o 1999 se recomienda la administraci&#243;n de la vacuna antineumoc&#243;cica 23-valente &#40;vacuna Pn23&#41; a todas las personas a partir de los 65 a&#241;os&#44; as&#237; como a los grupos de riesgo<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">7&#44;8</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">El objetivo de este estudio es describir la epidemiolog&#237;a de la ENI y la evoluci&#243;n de los serotipos circulantes en los diferentes grupos de edad y analizar el impacto de la vacuna Pn13 sobre la incidencia de la ENI durante los a&#241;os 2017-2018 con respecto a los a&#241;os 2014-2015 de los casos declarados al Sistema de Notificaci&#243;n Microbiol&#243;gico de Catalu&#241;a &#40;SNMC&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Definici&#243;n de caso</span><p id="par0035" class="elsevierStylePara elsevierViewall">Un caso de ENI se defini&#243; como un paciente con aislamiento&#44; detecci&#243;n de DNA o ant&#237;geno de <span class="elsevierStyleItalic">S&#46; pneumoniae</span> en un sitio normalmente est&#233;ril &#40;sangre&#44; l&#237;quido cefalorraqu&#237;deo o l&#237;quido pleural&#44; entre otros&#41; junto con manifestaciones cl&#237;nicas compatibles&#44; siendo neumon&#237;a&#44; meningitis y sepsis las m&#225;s frecuentes&#46; S&#243;lo se incluy&#243; un episodio de ENI por paciente&#44; excepto en los casos en que entre las muestras cl&#237;nicas hubieran pasado &#62;<span class="elsevierStyleHsp" style=""></span>30 d&#237;as o los serotipos identificados fueran diferentes&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Sistema de vigilancia de la ENI</span><p id="par0040" class="elsevierStylePara elsevierViewall">Se revisaron las notificaciones de casos confirmados de la ENI efectuadas por los laboratorios que participan en el SNMC de la Agencia de Salud P&#250;blica de Catalu&#241;a&#46; El SNMC est&#225; constituido por el conjunto de los laboratorios de microbiolog&#237;a de los centros sanitarios hospitalarios y extrahospitalarios de car&#225;cter p&#250;blico y privado de Catalu&#241;a&#46; Estos centros &#40;55 hospitales p&#250;blicos&#44; 1 hospital privado y 3 centros extrahospitalarios&#41; representan el 92&#44;8&#37; de las camas de agudos de los hospitales p&#250;blicos de la Red Hospitalaria de Utilizaci&#243;n P&#250;blica<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">9</span></a>&#46; Desde el a&#241;o 2016&#44; el SNMC es un sistema de vigilancia de declaraci&#243;n obligatoria por parte de la red de laboratorios a la Agencia de Salud P&#250;blica de Catalu&#241;a<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">10</span></a> y&#44; por tanto&#44; la ENI es una enfermedad de notificaci&#243;n obligatoria&#46; Los casos confirmados son reportados individualmente&#44; de forma diaria o semanal&#44; incluyendo las variables&#58; sexo&#44; edad&#44; presentaci&#243;n cl&#237;nica y m&#233;todo de diagn&#243;stico&#46; Durante el per&#237;odo de estudio&#44; en el contexto del proyecto europeo de vigilancia de la ENI en el que participa Catalu&#241;a junto con 15 regiones de 11 pa&#237;ses&#44; se ha efectuado una vigilancia reforzada y proactiva de la enfermedad&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Los aislamientos se env&#237;an al Laboratorio de Soporte de Salud P&#250;blica de Catalu&#241;a &#40;H&#46; Universitario Sant Joan de D&#233;u&#41; y al Centro Nacional de Microbiolog&#237;a-Instituto de Salud Carlos III &#40;CNM-ISCIII&#41; &#40;Madrid&#44; Espa&#241;a&#41; para su serotipado y estudio de sensibilidad antibi&#243;tica&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">M&#233;todos microbiol&#243;gicos</span><p id="par0050" class="elsevierStylePara elsevierViewall">Las cepas han sido serotipadas mediante la reacci&#243;n de Quellung o dot-blot<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">11</span></a>&#46; Cuando esto no ha sido posible&#44; los serotipos se han identificado mediante la t&#233;cnica de reacci&#243;n en cadena de la polimerasa &#40;PCR&#41; que permite la detecci&#243;n de 40 serotipos&#47;serogrupos<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">12</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">An&#225;lisis estad&#237;stico</span><p id="par0055" class="elsevierStylePara elsevierViewall">Se ha realizado un estudio retrospectivo de las notificaciones de casos confirmados de la ENI durante los a&#241;os 2014-2018&#46; Las variables estudiadas han sido el sexo&#44; la edad &#40;grupos de edad&#58; &#60;<span class="elsevierStyleHsp" style=""></span>5 a&#241;os&#44; 5-19 a&#241;os&#44; 20-64 a&#241;os y &#8805; 65 a&#241;os&#41;&#44; la fecha de diagn&#243;stico&#44; la presentaci&#243;n cl&#237;nica&#44; la muestra cl&#237;nica&#44; la t&#233;cnica microbiol&#243;gica y el serotipo&#46; El serotipo se ha analizado tambi&#233;n teniendo en cuenta su inclusi&#243;n o no en las vacunas conjugadas antineumoc&#243;cicas &#40;Pn7&#44; Pn10&#44; Pn13 y no Pn13&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Las tasas de incidencia se han calculado seg&#250;n los datos demogr&#225;ficos del Instituto de Estad&#237;stica de Catalu&#241;a para los grupos de edad estudiados&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">El estudio de impacto se ha realizado mediante el c&#225;lculo del riesgo relativo &#40;RR&#41; con los intervalos de confianza &#40;IC&#41; al 95&#37;&#44; asumiendo la distribuci&#243;n de Poisson&#44; y comparando el per&#237;odo 2017-2018 con el de 2014-2015&#46; La cobertura vacunal estimada de los a&#241;os 2014-2015<span class="elsevierStyleHsp" style=""></span>ha sido de un 64&#37;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">13</span></a> mientras que la cobertura de los a&#241;os 2017 y 2018&#44; con programa de inmunizaci&#243;n universal&#44; ha sido de 81&#44;8 y 92&#44;5&#37;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">14&#44;15</span></a>&#44; respectivamente&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Se ha analizado el impacto mediante la f&#243;rmula &#40;1-RR&#41; &#42;100&#46; No se ha tenido en cuenta el a&#241;o 2016 ya que la administraci&#243;n sistem&#225;tica de la vacuna Pn13 en los ni&#241;os se inici&#243; en julio de este a&#241;o&#46; Los valores de p&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 se consideraron estad&#237;sticamente significativos&#46; El an&#225;lisis se llev&#243; a cabo mediante el Statistical Package for Social Sciences &#40;SPSS&#44; versi&#243;n 18&#46;0&#59; SPSS&#44; Chicago&#44; Illinois&#44; USA&#41;&#174; y el R software &#40;R&#44; version 4&#46;0&#46;1&#59; R Core Team&#44; Vienna&#44; Austria&#41;&#174;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Los datos analizados en este manuscrito han sido parcialmente presentados en Epidemiolog&#237;a de la enfermedad neumoc&#243;cica invasiva en Catalu&#241;a&#46; Informe 2017-2018<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">16</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Resultados</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Evoluci&#243;n de las tasas de incidencia y de las manifestaciones cl&#237;nicas</span><p id="par0080" class="elsevierStylePara elsevierViewall">Durante el per&#237;odo 2014-2018 se notificaron 4&#46;764 casos de ENI&#44; lo que ha representado una tasa de incidencia &#40;TI&#41; de 12&#44;6 casos por 100&#46;000 personas&#47;a&#241;o&#46; Las incidencias m&#225;s elevadas se han presentado en adultos &#8805; 65 a&#241;os &#40;33&#44;6 casos por 100&#46;000 personas&#47;a&#241;o&#41; y en ni&#241;os &#60;<span class="elsevierStyleHsp" style=""></span>5 a&#241;os &#40;27&#44;5 casos por 100&#46;000 personas&#47;a&#241;o&#41;&#46; El n&#250;mero de ENI en hombres ha sido de 2&#46;824 casos &#40;59&#44;3&#37;&#41;&#46; En 4&#46;580 casos &#40;96&#44;1&#37;&#41; el diagn&#243;stico se ha realizado por cultivo&#44; en 145 casos &#40;3&#44;1&#37;&#41; por PCR y en 39 casos &#40;0&#44;8&#37;&#41;&#44; por detecci&#243;n de ant&#237;geno&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Durante los a&#241;os 2017 y 2018&#44; se ha observado un incremento en la TI global respecto la de 2014-2015 del 15&#37; &#40;RR&#58; 1&#44;15&#59; IC 95&#37;&#58; 1&#44;08-1&#44;23&#59; p &#60; 0&#44;001&#41;&#46; El aumento de la incidencia ha sido significativo en los grupos de 20 a 64 a&#241;os &#40;18&#37;&#41; y en &#8805; 65 a&#241;os &#40;18&#37;&#41;&#44; mientras que en los otros grupos de edad la incidencia se ha mantenido estable &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Durante el per&#237;odo analizado&#44; la mayor&#237;a de casos han presentado neumon&#237;a &#40;78&#44;6&#37;&#59; 3&#46;746&#47;4&#46;764&#41;&#44; seguida de las meningitis &#40;8&#44;7&#37;&#59; 413&#47;4&#46;764&#41; y las bacteriemias sin foco &#40;8&#44;6&#37;&#59; 409&#47;4&#46;764&#41;&#46; Las otras manifestaciones cl&#237;nicas &#40;4&#44;1&#37;&#59; 196&#47;4&#46;764&#41; han sido peritonitis&#44; artritis&#44; colecistitis&#44; endocarditis&#44; celulitis&#44; pancreatitis&#44; renal&#44; espondilodiscitis lumbar&#44; endoftalmitis&#44; pi&#243;metra&#44; miositis&#44; oclusi&#243;n intestinal y cerebral&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">La incidencia global de la neumon&#237;a mostr&#243; un incremento significativo del 19&#37; &#40;RR&#58; 1&#44;19&#59; IC 95&#37;&#58; 1&#44;11-1&#44;28&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; principalmente en el grupo de 20 a 64 a&#241;os &#40;23&#37;&#41; y en &#8805; 65 a&#241;os &#40;20&#37;&#41;&#44; mientras que en los otros grupos de edad la incidencia se mantuvo estable&#46; No se observaron cambios en las dem&#225;s manifestaciones cl&#237;nicas&#44; con excepci&#243;n de las bacteriemias sin foco que presentaron una disminuci&#243;n del 32&#37; &#40;RR&#58; 0&#44;68&#59; IC 95&#37;&#58; 0&#44;46-0&#44;99&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;045&#41; en el grupo de 20-64 a&#241;os &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Cambios en la distribuci&#243;n de los serotipos</span><p id="par0100" class="elsevierStylePara elsevierViewall">Durante los a&#241;os 2014-2018&#44; se ha identificado el serotipo en el 86&#44;0&#37; de los casos diagnosticados &#40;4&#46;086&#47;4&#46;764&#41; detectando 57 serotipos diferentes&#46; Los serotipos m&#225;s frecuentes fueron&#58; 8&#44; 3&#44; 12F&#44; 14&#44; 22F&#44; 24F y 19A&#44; representando el 50&#44;9&#37; de los casos&#46; La distribuci&#243;n de los serotipos identificados durante este per&#237;odo se muestra en la <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Al analizar los serotipos causantes de ENI por grupos de edad&#44; se ha observado que en los ni&#241;os &#60;<span class="elsevierStyleHsp" style=""></span>5 a&#241;os los serotipos incluidos en las vacunas Pn7&#44; Pn10 y Pn13 han representado el 16&#44;7&#37;&#44; 20&#44;8&#37; y 37&#44;3&#37;&#44; respectivamente&#46; Los serotipos m&#225;s frecuentes han sido el 24F &#40;12&#44;9&#37;&#41;&#44; el 3 &#40;12&#44;0&#37;&#41; y el 14 &#40;9&#44;9&#37;&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">En el grupo de edad de 5 a 19 a&#241;os&#44; los serotipos incluidos en las vacunas Pn7&#44; Pn10 y Pn13 representaron el 17&#44;4&#37;&#44; 46&#44;2&#37; y 58&#44;3&#37;&#44; respectivamente&#46; Los serotipos 1 &#40;25&#44;6&#37;&#41;&#44; 8 &#40;13&#44;5&#37;&#41; y 3 &#40;10&#44;5&#37;&#41; fueron los m&#225;s frecuentes&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">En los casos de 20 a 64 a&#241;os&#44; los serotipos incluidos en las vacunas Pn7&#44; Pn10 y Pn13 han representado el 12&#44;2&#37;&#44; 18&#44;5&#37; y 34&#44;3&#37;&#44; respectivamente&#46; Los serotipos m&#225;s frecuentes han sido el 8 &#40;17&#44;7&#37;&#41;&#44; el 12F &#40;11&#44;1&#37;&#41; y el 3 &#40;10&#44;9&#37;&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">En el grupo de edad de &#8805;65&#44; los serotipos incluidos en las vacunas Pn7&#44; Pn10 y Pn13 han representado el 13&#44;0&#37;&#44; 15&#44;4&#37; y 32&#44;6&#37;&#44; respectivamente&#46; Los serotipos m&#225;s frecuentes han sido el 3 &#40;11&#44;8&#37;&#41; y el 8 &#40;9&#44;5&#37;&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Entre 2017-2018 vs&#46; 2014-2015 se ha observado una disminuci&#243;n del 23&#37;&#44; 43&#37;&#44; 25&#37; y 4&#37; en los serotipos incluidos en las vacunas Pn7&#44; Pn10&#44; Pn13 y Pn23&#44; respectivamente&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Los serotipos incluidos en la vacuna Pn7 han disminuido la tasa de incidencia en los menores de 5 a&#241;os en un 51&#37;&#44; principalmente por el descenso del serotipo 14 &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a> y <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>&#41;&#46; La incidencia de los serotipos incluidos en la vacuna Pn10&#44; especialmente los serotipos 1 y 7F&#44; se ha reducido en todos los grupos de edad &#40;entre un 23&#37; y un 61&#37;&#41; durante los a&#241;os 2017-2018 respecto los a&#241;os 2014-2015&#44; a diferencia de los serotipos incluidos en la vacuna Pn13 que&#44; excepto en los menores de 5 a&#241;os&#44; en los que han disminuido un 36&#37; &#40;RR&#58; 0&#44;64&#59; IC 95&#37;&#58; 0&#44;44-0&#44;92&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;014&#41;&#44; han permanecido estables a causa de las altas incidencias observadas en los serotipos 3 y 19A durante los dos periodos&#46; Al analizar el conjunto de la poblaci&#243;n&#44; la disminuci&#243;n de serotipos Pn13 fue de un 15&#37;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">El serotipo 3 no ha presentado cambios en su incidencia respecto el 2014-2015 y ha sido el serotipo con mayor incidencia en &#60;<span class="elsevierStyleHsp" style=""></span>5 a&#241;os y en &#8805; 65 a&#241;os durante los a&#241;os 2017-2018&#46; En los grupos de edad de 5-19 a&#241;os y 20-64 a&#241;os&#44; el serotipo 3 ha estado en tercer y segundo lugar de frecuencia&#44; respectivamente&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Por otra parte&#44; se ha observado un aumento de los serotipos no incluidos en la vacuna Pn13 &#40;no Pn13&#41; del 31&#37; &#40;RR&#58; 1&#44;31&#59; IC 95&#37;&#58; 1&#44;20-1&#44;43&#59; p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; principalmente en adultos de 20-64 a&#241;os &#40;35&#37;&#41; y &#8805; 65 a&#241;os &#40;27&#37;&#41;&#46; De estos serotipos&#44; el serotipo 8 ha aumentado su incidencia en todos los grupos de edad y ha sido especialmente significativo en los<span class="elsevierStyleHsp" style=""></span>&#62;5 a&#241;os &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discusi&#243;n</span><p id="par0145" class="elsevierStylePara elsevierViewall">Este estudio nos ha permitido conocer el impacto&#44; a partir de sus efectos directos e indirectos&#44; que tiene sobre la ENI la introducci&#243;n de la vacuna Pn13 en el calendario de vacunaci&#243;n sistem&#225;tica en Catalu&#241;a&#46; Esta comunidad aut&#243;noma es una regi&#243;n cuya cobertura estimada era intermedia en los a&#241;os previos al inicio del programa de inmunizaci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">16&#8211;18</span></a> y que ha aumentado con su inclusi&#243;n en el calendario&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">La tasa de incidencia global de la ENI durante los a&#241;os 2017-2018 aument&#243; un 15&#37; respecto al periodo 2014-2015 debido al incremento de la incidencia en los grupos de 20 a 64 a&#241;os &#40;18&#37;&#41; y &#8805; 65 a&#241;os &#40;18&#37;&#41;&#46; Este aumento&#44; que tambi&#233;n se ha observado en otras comunidades aut&#243;nomas&#44; puede deberse a un aumento de los serotipos no vacunales<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">19</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">En ni&#241;os menores de 5 a&#241;os se ha observado una disminuci&#243;n en la incidencia de los serotipos incluidos en la vacuna Pn7 del 51&#37;&#44; debida principalmente al descenso del serotipo 14&#46; Este serotipo&#44; que se manten&#237;a como el m&#225;s frecuente en todos los grupos de edad durante el periodo 2010-2014<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">5</span></a>&#44; ha disminuido dr&#225;sticamente su presencia despu&#233;s de la introducci&#243;n de la vacuna en el calendario sistem&#225;tico&#46; Nuestros datos son similares a los observados en otros pa&#237;ses con programas de vacunaci&#243;n sistem&#225;tica con las vacunas Pn10 y Pn13&#46; En Italia&#44; Camilli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">20</span></a>&#44; observaron una disminuci&#243;n en los serotipos incluidos en la vacuna Pn7&#44; incluso la desaparici&#243;n de algunos de estos serotipos&#44; con excepci&#243;n del serotipo 14 que a pesar de la disminuci&#243;n se manten&#237;a todav&#237;a entre los cuatro m&#225;s frecuentes&#46; En Austria&#44; los resultados de Richter et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">21</span></a>&#44; mostraron que la mayor reducci&#243;n se produjo en el serotipo 14&#44; seguido de los serotipos 6B&#44; 18C y 19F&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">La incidencia de los serotipos incluidos en la vacuna Pn10 ha disminuido significativamente en todos los grupos de edad por la reducci&#243;n de la incidencia de los serotipos 1 y 7F&#46; Resultados similares se observaron en Alemania<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">22</span></a> e Inglaterra y Gales<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">23</span></a>&#44; donde estos serotipos&#44; que hab&#237;an sufrido un crecimiento debido a la introducci&#243;n de la vacuna Pn7&#44; disminuyeron con la vacuna Pn13&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">El estudio del comportamiento de los serotipos incluidos en la vacuna Pn13 ha mostrado que su incidencia ha disminuido en los ni&#241;os menores de 5 a&#241;os&#44; mientras que ha permanecido estable en el resto de grupos debido al serotipo 3 que mantiene altas incidencias en todos los grupos de edad&#46; Este serotipo&#44; frente al cual la vacuna Pn13 presenta una baja efectividad&#44; est&#225; asociado con un alto porcentaje de los fallos vacunales que se producen en ni&#241;os que han completado la pauta vacunal<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">24&#44;25</span></a>&#46; Estos resultados tambi&#233;n lo han observado otros autores&#44; tanto al analizar el impacto de la vacuna Pn13 en los primeros a&#241;os de su introducci&#243;n o per&#237;odo temprano<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">26&#44;27</span></a>&#44; como en los a&#241;os posteriores o per&#237;odo tard&#237;o<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">22&#44;23</span></a>&#46; Otros estudios&#44; centrados en poblaci&#243;n pedi&#225;trica<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">20&#44;24&#44;28</span></a> o en poblaci&#243;n adulta<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">29</span></a>&#44; tambi&#233;n han observado que el serotipo 3 se mantiene sin cambios&#46; Waight et al&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">30</span></a>&#44; sin embargo&#44; han encontrado una reducci&#243;n significativa de este serotipo en ni&#241;os y adultos&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Los resultados observados en los serotipos incluidos en la vacuna no Pn13 han mostrado un aumento de la incidencia en los adultos de 20 a&#241;os y m&#225;s&#44; principalmente por el aumento de la incidencia del serotipo 8&#46; Otros autores tambi&#233;n han reportado un aumento en estos serotipos&#44; siendo variable seg&#250;n el per&#237;odo que se haya considerado en el estudio y si la poblaci&#243;n objetivo han sido ni&#241;os<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">20</span></a>&#44; adultos<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">23</span></a> o ambos<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">30&#44;31</span></a>&#46; Por otro lado&#44; los nuevos serotipos que han comenzado a reemplazar a los vacunales han sido diferentes seg&#250;n el pa&#237;s y el grupo de edad&#46; En ni&#241;os&#44; los serotipos 24F y 12F<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">5&#44;20&#44;32</span></a> son los de mayor incidencia en Catalu&#241;a&#44; Italia e Israel&#44; mientras que en adultos lo son el 8&#44; 12F y 9N en Inglaterra y Gales<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">23</span></a>&#46; Sin embargo&#44; en Alemania los serotipos 15A y 23B son los emergentes en todos los grupos de edad<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">33</span></a>&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Con respecto a las manifestaciones cl&#237;nicas&#44; s&#243;lo la neumon&#237;a ha mostrado un incremento significativo en la incidencia global y en los mayores de 20 a&#241;os&#46; Sin embargo&#44; se ha detectado una disminuci&#243;n de las bacteriemias sin foco en el grupo de 20 a 64 a&#241;os&#46; En pa&#237;ses donde se ha analizado el impacto de las vacunas conjugadas sobre la entidad cl&#237;nica&#44; se han centrado principalmente en los cambios producidos en la meningitis en los menores de 5 a&#241;os<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">20&#44;34</span></a>&#44; con resultados que han indicado su disminuci&#243;n&#46; Otros autores que han estudiados el comportamiento de la neumon&#237;a y de otras manifestaciones cl&#237;nicas&#44; con aislamiento en sangre&#44; tambi&#233;n han encontrado que estas disminuyen despu&#233;s de la introducci&#243;n de las vacunas conjugadas<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">35</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">El presente estudio tiene algunas limitaciones&#46; Primero&#44; la falta de informaci&#243;n de serotipo en algunos casos&#44; el porcentaje de datos faltantes var&#237;a entre el 11&#37; y el 17&#37; en el periodo analizado&#46; Segundo&#44; la declaraci&#243;n de la ENI pas&#243; a ser obligatoria en 2016&#44; motivo por el cual pudo existir una subnotificaci&#243;n de casos durante los a&#241;os previos al periodo 2017-2018&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Una fortaleza de nuestro estudio es la robustez de la fuente de datos ya que se recogen del SNMC&#44; que incluye el 92&#44;8&#37; de las camas de agudos de hospitales p&#250;blicos&#46; Otra fortaleza es la participaci&#243;n de Catalu&#241;a en el proyecto europeo de la red de vigilancia activa de la ENI&#44; <span class="elsevierStyleItalic">SpID-NET</span><a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">36</span></a>&#44; junto con otras quince regiones europeas&#44; hecho que ha ayudado a mejorar sustancialmente la vigilancia de la ENI en nuestra regi&#243;n&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusiones</span><p id="par0190" class="elsevierStylePara elsevierViewall">La introducci&#243;n de la vacuna Pn13 en el calendario pedi&#225;trico de vacunaciones sistem&#225;ticas en Catalu&#241;a indica que el impacto que produce es beneficioso tanto en la poblaci&#243;n vacunada como en la poblaci&#243;n adulta&#46; Sin embargo&#44; junto a la disminuci&#243;n en la incidencia de los serotipos incluidos en la vacuna Pn13 se observa un incremento en los serotipos no incluidos en esta vacuna que podr&#237;an comprometer sus beneficios&#46; Por este motivo es necesario llevar a cabo una vigilancia epidemiol&#243;gica precisa y continuada de la ENI para detectar en forma r&#225;pida cambios en la incidencia de la enfermedad y de los serotipos circulantes&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Financiaci&#243;n</span><p id="par0195" class="elsevierStylePara elsevierViewall">Este estudio fue parcialmente financiado por SpIDnet &#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; red financiada por el Centro Europeo para la Prevenci&#243;n y Control de Enfermedades &#40;ECDC 2015&#47;031&#41;&#59; la Agencia Catalana de Gesti&#243;n de Ayudas a la Investigaci&#243;n Universitaria &#40;2017&#47;SGR 1342 y 2017&#47;SGR 0742&#41;&#59; el Centro de Investigaci&#243;n Biom&#233;dica en Red de Epidemiolog&#237;a y Salud P&#250;blica &#40;CIBERESP CB06&#47;02&#47;0076 and CB15&#47;00067&#41; y el Centro de Investigaci&#243;n Biom&#233;dica en Red de Enfermedades Respiratorias &#40;CIBERES CB06 &#47;06&#47;0037&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0225" class="elsevierStylePara elsevierViewall">CMA ha recibido subvenciones y honorarios personales de Pfizer&#44; Qiagen y BioMerieux y subvenciones de Genomica SAU&#46; Todos los dem&#225;s autores declaran no tener conflictos de intereses&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Los autores declaran que no tener conflicto de intereses econ&#243;micos o relaciones personales que pudieran influir en este art&#237;culo&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Los autores declaran los siguientes intereses econ&#243;micos&#47;relaciones personales que pueden considerarse como posible conflicto de intereses&#58;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Carmen Mu&#241;oz-Almagro ha recibido subvenciones y honorarios personales de Pfizer&#44; Qiagen y BioMerieux y subvenciones de Genomica SAU&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" 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 2017-2018 con respecto de 2014-2015&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todo</span><p id="spar0010" 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="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La incidencia global de ENI &#40;2014-2018&#41; fue de 12&#44;6 casos por 100&#46;000 personas&#47;a&#241;o&#46; Comparando 2017-2018 vs&#46; 2014-2015&#44; la incidencia de ENI causada por serotipos incluidos en la vacuna Pn13 disminuy&#243; en ni&#241;os &#60;<span class="elsevierStyleHsp" style=""></span>5 a&#241;os un 46&#37;&#44; mientras que en el resto de grupos de edad permaneci&#243; estable&#46; El serotipo 3&#44; a pesar de 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 20-64 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="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" 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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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" 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 2017-2018 compared to the years 2014-2015&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Method</span><p id="spar0030" 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="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The global incidence of IPD &#40;2014-2018&#41; was 12&#44;6 cases per 100&#44;000 persons&#47;year&#46; Comparing 2017-2018 vs 2014-2015&#44; the incidence of IPD caused by the serotypes included in the PCV13 vaccine has decreased in children &#60;<span class="elsevierStyleHsp" style=""></span>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 20-64 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="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" 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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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Evoluci&#243;n de los serotipos causantes de la enfermedad neumoc&#243;cica invasiva por a&#241;os&#46; Catalu&#241;a&#44; 2014-2018&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#42;En tres casos el serotipo se identific&#243; solo a nivel de grupo&#58; un 19F&#47;B&#47;C&#44; un 7F&#47;A y un 9V&#47;A&#46;</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">&#42;&#42;11B&#44; 11F&#44; 15B&#47;C&#44; 15C&#44; 17F&#44; 18A&#44; 21&#44; 24B&#44; 25F&#44; 27&#44; 28A&#44; 29&#44; 34&#44; 35A&#44; 35C&#44; 35F&#44; 37&#44; 38&#44; 39 y otros serotipos no vacunales&#46; Tambi&#233;n se han incluido en este grupo los serotipos identificados a nivel de grupo 6A&#47;B&#44; 6A&#47;C&#47;D&#44; 7<span class="elsevierStyleHsp" style=""></span>B&#44; 7<span class="elsevierStyleHsp" style=""></span>C&#44; 9<span class="elsevierStyleHsp" style=""></span>V&#47;A&#46;</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Pn7&#58; serotipos incluidos en la vacuna antineumoc&#243;cica conjugada heptavalente&#59; Pn10&#58; serotipos incluidos en la vacuna antineumoc&#243;cica conjugada decavalente&#59; Pn13&#58; serotipos incluidos en la vacuna antineumoc&#243;cica conjugada 13-valente&#59; Pn23&#58; serotipos incluidos en la vacuna antineumoc&#243;cica 23-valente &#40;el serotipo 6A no est&#225; incluido en la vacuna Pn23&#41;&#46;</p>"
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          "es" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Distribuci&#243;n de los serotipos causantes de la enfermedad neumoc&#243;cica invasiva seg&#250;n grupo de edad y periodo&#46; Catalu&#241;a&#44; 2014-2015 y 2017-2018&#46;</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">&#42;&#42;11B&#44; 11F&#44; 15B&#47;C&#44; 15C&#44; 17F&#44; 18A&#44; 21&#44; 24B&#44; 25F&#44; 27&#44; 28A&#44; 29&#44; 34&#44; 35A&#44; 35C&#44; 35F&#44; 37&#44; 38&#44; 39 y otros serotipos no vacunales&#46; Tambi&#233;n se han incluido en este grupo los serotipos identificados a nivel de grupo 6A&#47;B&#44; 6A&#47;C&#47;D&#44; 7B&#44; 7C&#44; 9V&#47;A&#46;</p> <p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Pn13&#58; serotipos incluidos en la vacuna antineumoc&#243;cica conjugada 13-valente&#59; no Pn13&#58; serotipos no incluidos en la vacuna antineumoc&#243;cica 13-valente&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Grupo de edad&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
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                  \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
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                  \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
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                  \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">2014-2015</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">2017-2018</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">RR &#40;IC 95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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">Valor p&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">&nbsp;\t\t\t\t\t\t\n
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                  \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">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="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" 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\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</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="left" 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="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2017-2018 vs&#46; 2014-2015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" 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;<span class="elsevierStyleHsp" style=""></span>5 a&#241;os&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&#44;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&#44;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
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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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#44;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&#44;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&#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">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&#44;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&#44;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">0&#44;99 &#40;0&#44;82-1&#44;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">0&#44;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">5-19 a&#241;os&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
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                  \t\t\t\t">2&#44;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&#44;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&#44;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&#44;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&#44;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&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t" scope="col">Manifestaci&#243;n cl&#237;nica&nbsp;\t\t\t\t\t\t\n
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                  \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">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2017-2018 vs&#46; 2014-2015&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="" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="17" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Neumon&#237;a</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;<span class="elsevierStyleHsp" style=""></span>5a&#241;os&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&#44;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&#44;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&#44;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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;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">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">17&#44;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">123&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&#44;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">118&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&#44;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&#44;04 &#40;0&#44;80-1&#44;35&#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">0&#44;798&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>5-19 a&#241;os&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;9&nbsp;\t\t\t\t\t\t\n
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                  \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&nbsp;\t\t\t\t\t\t\n
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                  \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&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \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&nbsp;\t\t\t\t\t\t\n
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                  \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&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \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">21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;8&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;7&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
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                  \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&#44;7&nbsp;\t\t\t\t\t\t\n
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                  \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">0&#44;79 &#40;0&#44;51-1&#44;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
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                  \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>20-64 a&#241;os&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">273&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">257&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">308&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">319&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#44;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">510&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">627&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6&#44;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;23 &#40;1&#44;10-1&#44;39&#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
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805; 65 a&#241;os&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">317&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">23&#44;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
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                  \t\t\t\t">372&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " colspan="17" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Otras formas cl&#237;nicas</span><a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;&#42;</a></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2844788.png"
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          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Tasa de incidencia por 100&#46;000 personas&#47;a&#241;o&#46;</p>"
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            1 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "&#42;&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Peritonitis &#40;24 casos&#41;&#59; artritis &#40;23 casos&#41;&#59; colecistitis &#40;7 casos&#41;&#59; endocarditis &#40;6 casos&#41;&#59; celulitis &#40;4 casos&#41;&#59; pancreatitis &#40;4 casos&#41;&#59; renal &#40;3 casos&#41;&#59; espondilodiscitis lumbar &#40;2 casos&#41;&#59; endoftalmitis &#40;1 caso&#41;&#59; pi&#243;metra &#40;1 caso&#41;&#59; miositis &#40;1 caso&#41;&#59; oclusi&#243;n intestinal &#40;1 caso&#41; y cerebral &#40;1 caso&#41;&#46;</p>"
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          "es" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Impacto de la vacuna antineumoc&#243;cica conjugada 13-valente en la incidencia de la enfermedad neumoc&#243;cica invasiva seg&#250;n manifestaci&#243;n cl&#237;nica y grupos de edad&#46; Catalu&#241;a&#44; 2014-2018</p>"
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          "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">N&#46;&#176;&#58; n&#250;mero de casos&#44; Pn7&#58; serotipos incluidos en la vacuna antineumoc&#243;cica conjugada heptavalente&#59; Pn10&#58; serotipos incluidos en la vacuna antineumoc&#243;cica conjugada decavalente&#59; Pn13&#58; serotipos incluidos en la vacuna antineumoc&#243;cica conjugada 13-valente</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-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Grupo de edad&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">2014-2015</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">2017-2018</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">RR<a class="elsevierStyleCrossRef" href="#tblfn0025">&#42;&#42;</a> &#40;IC 95&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Valor p&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="" 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><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">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tasa<a class="elsevierStyleCrossRef" href="#tblfn0020">&#42;</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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2017-2018 vs&#46; 2014-2015&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="" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="17" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">5 a&#241;os</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&#44;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&#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">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&#44;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&#44;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&#44;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&#44;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">0&#44;64 &#40;0&#44;44-0&#44;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">0&#44;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&#44;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&#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">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&#44;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&#44;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&#44;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&#44;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">0&#44;49 &#40;0&#44;26-0&#44;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">0&#44;016&nbsp;\t\t\t\t\t\t\n
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