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Epidemiología molecular de la colonización nasofaríngea neumocócica en niños de Sevilla, tras la implementación del programa de vacunación con VNC13 en Andalucía (España)
Molecular epidemiology of pneumococcal carriage in children from Seville, following implementation of the PCV13 immunization program in Andalusia, Spain
Beatriz de Felipea, Marta Aboza-Garcíaa,b, Verónica González-Galánc, Ignacio Salamanca de la Cuevad, Juan Alfonso Martín-Quinteroe, Benito Amil-Pérezf, Cristóbal Coronel-Rodríguezg, María Ángeles Palacios-Soriah, María Isabel García Ruiz-Santaquiteriai, María José Torres-Sánchezj, Francisco Javier Morónk, Juan A. Cordero-Varelal, Pablo Obando-Pachecom,
Autor para correspondencia
pabobapac@gmail.com

Autor para correspondencia.
, Ignacio Obandoa,n
a Alteraciones Congénitas de la Inmunidad, Instituto de Biomedicina de Sevilla, Universidad de Sevilla/ Hospital Universitario Virgen del Rocío/CSIC, Sevilla, España
b Centro de Salud Polígono Norte, Sevilla, España
c Servicio de Microbiología, UCEIMP, Hospital Universitario Virgen del Rocío, Sevilla, España
d Instituto Hispalense de Pediatría, Sevilla, España
e Enfermería, Unidad de Estudios, Grupo Instituto Hispalense de Pediatría, Sevilla, España
f Servicio de Pediatría, Grupo Instituto Hispalense de Pediatría, Sevilla, España
g Centro de Salud Amante Laffón, Distrito de Atención Primaria Sevilla, Servicio Andaluz de Salud, Sevilla, España
h Centro de Salud Pino Montano, Sevilla, España
i Centro de Salud Mercedes Navarro, Sevilla, España
j Departamento de Microbiología, Facultad de Medicina, Universidad de Sevilla, Sevilla, España
k Unidad de Genómica, Instituto de Biomedicina de Sevilla, Universidad de Sevilla/Hospital Universitario Virgen del Rocío/CSIC, Sevilla, España
l Unidad de Bioinformática, Instituto de Biomedicina de Sevilla, Universidad de Sevilla/Hospital Universitario Virgen del Rocío/CSIC, Sevilla, España
m UGC de Pediatría, Hospital Universitario Virgen de Valme, Sevilla, España
n Sección de Infectología e Inmunopatologías Pediátricas, Hospital Universitario Virgen de Valme, Sevilla, España
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Comparaci&#243;n de la distribuci&#243;n de los serotipos neumoc&#243;cicos identificados en los periodos VNC13 y VNC7&#46;</p>"
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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="par0175" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Streptococcus pneumoniae</span> es un comensal habitual de la nasofaringe humana&#46; La colonizaci&#243;n neumoc&#243;cica es un proceso universal&#44; con una mayor prevalencia en los ni&#241;os peque&#241;os y se considera un requisito para el desarrollo de la enfermedad neumoc&#243;cica &#40;mucosal o invasiva&#41;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a>&#46; Esta tiene una gran relevancia en la enfermedad infecciosa en todo el mundo por su prevalencia y elevada carga de enfermedad<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Las vacunas neumoc&#243;cicas conjugadas &#40;VNC&#41; han reducido de forma significativa la incidencia de enfermedad neumoc&#243;cica invasiva &#40;ENI&#41; en la poblaci&#243;n inmunizada y tambi&#233;n&#44; aunque en menor escala&#44; entre personas no inmunizadas por &#171;efecto reba&#241;o&#187;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; No obstante&#44;&#160;su efectividad est&#225; limitada por la cobertura parcial de serotipos y puede disminuir con el tiempo por el denominado fen&#243;meno de reemplazamiento &#40;incremento en la incidencia de ENI por serotipos no vacunales &#91;SNV&#93; debido a su mayor presencia en colonizaci&#243;n nasofar&#237;ngea por la presi&#243;n inmune vacunal sobre los serotipos vacunales &#91;SV&#93;&#41;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a>&#46; La vigilancia activa de la epidemiolog&#237;a de la ENI tras la introducci&#243;n de las VNC es fundamental para analizar el impacto vacunal en la incidencia de ENI en todos los grupos etarios&#44; los cambios en la distribuci&#243;n de serotipos y la posible aparici&#243;n de enfermedad de remplazamiento&#46; Como complemento a la vigilancia epidemiol&#243;gica en la ENI&#44; los estudios transversales de portaci&#243;n nasofar&#237;ngea son de gran importancia para comprender los mecanismos subyacentes del &#171;efecto reba&#241;o&#187; y del reemplazamiento serot&#237;pico e informan sobre los cambios en prevalencia&#44; tasas de resistencia y potencial invasivo de los SNV reemplazantes en la nasofaringe&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">La vacunaci&#243;n sistem&#225;tica frente al neumococo con VNC tridecavalente &#40;VNC13&#41; se introdujo en diciembre de 2016 en el calendario de vacunaci&#243;n infantil de Andaluc&#237;a &#40;Espa&#241;a&#41;&#46; Diversas formulaciones de las VNC ya hab&#237;an estado disponibles &#40;7 y 10 valentes y VNC13 desde los a&#241;os 2001&#44; 2009 y 2010&#44; respectivamente&#41; en el mercado privado con tasas de vacunaci&#243;n antineumoc&#243;cica variables &#40;41-61&#37;&#41; entre la poblaci&#243;n pedi&#225;trica andaluza<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; Las coberturas vacunales de VNC13 en la poblaci&#243;n pedi&#225;trica de Andaluc&#237;a tras el inicio del programa de vacunaci&#243;n infantil tuvieron un rango del 97&#44;2&#37; en 2018 al 98&#44;2&#37; en 2020 &#40;Moreno D&#46; comunicaci&#243;n personal&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Nuestro grupo ha desarrollado 2<span class="elsevierStyleHsp" style=""></span>estudios paralelos de vigilancia epidemiol&#243;gica molecular de la ENI y de colonizaci&#243;n de la nasofaringe en poblaci&#243;n pedi&#225;trica andaluza para una mejor comprensi&#243;n de los beneficios del programa de vacunaci&#243;n sistem&#225;tica frente al neumococo y para monitorizar la evoluci&#243;n de los SNV&#46; El objetivo del presente trabajo fue describir la distribuci&#243;n de serotipos y genotipos y las tasas de resistencia antimicrobiana en los aislados neumoc&#243;cicos obtenidos de la nasofaringe de ni&#241;os sanos menores de 5 a&#241;os atendidos en diversos centros de salud de la ciudad de Sevilla tras la introducci&#243;n de la vacunaci&#243;n universal infantil con VNC13&#46; Adem&#225;s y como objetivo secundario se ha comparado esta informaci&#243;n con otra similar obtenida en los &#250;ltimos 30 meses de un estudio transversal de portaci&#243;n nasofar&#237;ngea desarrollado en el mismo &#225;mbito geogr&#225;fico en un periodo con vacunaci&#243;n parcial con VNC 7 valente &#40;VNC7&#41;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">7&#44;8</span></a>&#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">Dise&#241;o&#44; &#225;mbito y periodo de estudio</span><p id="par0025" class="elsevierStylePara elsevierViewall">Estudio descriptivo observacional transversal sobre la epidemiolog&#237;a de la colonizaci&#243;n nasofar&#237;ngea neumoc&#243;cica&#46; Se seleccion&#243; a 394 ni&#241;os sanos de edades comprendidas entre 6 meses y 5 a&#241;os atendidos en consulta de ni&#241;o sano o a demanda en 10 centros de atenci&#243;n primaria p&#250;blicos y privados de la ciudad de Sevilla seleccionados por criterios log&#237;sticos&#46; El estudio se extendi&#243; durante los periodos 1&#47;4&#47;2018-28&#47;2&#47;2020 y 1&#47;11&#47;2021-28&#47;2&#47;2022 &#40;periodo VNC13&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Procedimientos de toma de muestras y recogida de datos</span><p id="par0030" class="elsevierStylePara elsevierViewall">Se seleccion&#243; a los ni&#241;os participantes sin que hubiera criterios de aleatorizaci&#243;n previa&#46; Este estudio se ha realizado teniendo en cuenta la legislaci&#243;n vigente&#44; las normas &#233;ticas de la Declaraci&#243;n de Helsinki y las directrices de buenas pr&#225;cticas de laboratorio cl&#237;nico&#46; A los padres o tutores legales se les inform&#243; de forma verbal y por escrito de las caracter&#237;sticas del estudio y se les solicit&#243; la firma del consentimiento informado&#46; El estudio fue aprobado por el Comit&#233; &#201;tico del Hospital Universitario Virgen del Roc&#237;o de Sevilla &#40;c&#243;digo 2017&#47;176&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">De forma previa a la obtenci&#243;n de la muestra de la nasofaringe se recogi&#243; informaci&#243;n sobre los siguientes factores de riesgo potenciales de la colonizaci&#243;n neumoc&#243;cica&#58; edad&#44; g&#233;nero&#44; asistencia a guarder&#237;a&#44; utilizaci&#243;n de antibi&#243;ticos en los 2 meses previos y tipo de antibi&#243;tico utilizado&#44; estado de tabaquismo pasivo y estado vacunal frente al neumococo&#46; Las muestras de la nasofaringe las obtuvieron profesionales sanitarios previamente adiestrados en el procedimiento seg&#250;n una metodolog&#237;a descrita con anterioridad<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a>&#46; Las muestras se transportaron en un periodo<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>24 h al departamento de Microbiolog&#237;a del Hospital Universitario de Virgen del Roc&#237;o para su procesamiento microbiol&#243;gico convencional&#44; tras el cual se congelaron a &#8211;80<span class="elsevierStyleHsp" style=""></span>&#176;C hasta completar posteriormente los procedimientos de serotipaci&#243;n y genotipaci&#243;n&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Estudios microbiol&#243;gicos&#44; serotipaci&#243;n y genotipaci&#243;n</span><p id="par0040" class="elsevierStylePara elsevierViewall">Las muestras nasofar&#237;ngeas se sembraron en placas de agar sangre Columbia&#44; suplementadas con 5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml de gentamicina&#44; y las colonias &#945;-hemol&#237;ticas se identificaron como neumococos con base en su morfolog&#237;a&#44; susceptibilidad a la optoquina y solubilidad en bilis&#46; Para la serotipaci&#243;n y genotipaci&#243;n se procedi&#243; a la extracci&#243;n del ADN gen&#243;mico de las aislados neumoc&#243;cicos y su secuenciaci&#243;n completa en el Instituto de Biomedicina de Sevilla&#46; La determinaci&#243;n del serotipo capsular se realiz&#243; por deducci&#243;n bioinform&#225;tica a partir de las secuencias gen&#243;micas del locus capsular<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a>&#46; El grupo de SV incluy&#243; todos los serotipos cubiertos por la formulaci&#243;n de la VNC13 &#40;1&#44; 3&#44; 4&#44; 5&#44; 6A&#44; 6B&#44; 7F&#44; 9V&#44; 14&#44; 18C&#44; 19A&#44; 19F&#44; 23F&#41;&#46; Los serotipos restantes se consideraron SNV&#46; La genotipaci&#243;n se realiz&#243; por tipificaci&#243;n de secuencias multilocus seg&#250;n metodolog&#237;a est&#225;ndar<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a>&#46; Se defini&#243; un complejo clonal &#40;CC&#41; como un secuenciotipo &#40;ST&#41; que compart&#237;a al menos 5 de las 7 variantes al&#233;licas&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">La sensibilidad antimicrobiana a penicilina&#44; ampicilina&#44; cefotaxima y eritromicina se determin&#243; por E-test con utilizaci&#243;n de los puntos de corte recomendados por EUCAST en 2022 para la asignaci&#243;n de las categor&#237;as interpretativas &#40;<a href="https://www.eucast.org/clinical_breakpoints">https&#58;&#47;&#47;www&#46;eucast&#46;org&#47;clinical&#95;breakpoints</a>&#41;&#46; Dentro de la categor&#237;a de no sensibles se combinaron las cepas sensibles a altas dosis y resistentes&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Controles hist&#243;ricos VNC7</span><p id="par0050" class="elsevierStylePara elsevierViewall">Para comparar la distribuci&#243;n de serotipos y genotipos y las tasas de resistencias antibi&#243;ticas se utiliz&#243; una colecci&#243;n hist&#243;rica de 154 aislados neumoc&#243;cicos del periodo temporal VNC7 entre el 1&#47;01&#47;2006 y el 30&#47;06&#47;2008&#44; que se hab&#237;an comunicado de forma parcial &#40;periodo 1&#47;01&#47;2006 al 30&#47;06&#47;2006&#41; en la literatura<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">8</span></a>&#46; Estas cepas colonizantes fueron obtenidas en un estudio de portaci&#243;n nasofar&#237;ngea desarrollado en 4 centros de salud y 2 urgencias hospitalarias de Sevilla&#44; seg&#250;n la metodolog&#237;a descrita<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">7</span></a>&#46; En este periodo se evalu&#243; la sensibilidad antimicrobiana a la amoxicilina oral&#44; y no a la ampicilina&#44; como en el periodo VNC13&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">An&#225;lisis estad&#237;stico</span><p id="par0055" class="elsevierStylePara elsevierViewall">El procesamiento estad&#237;stico se realiz&#243; utilizando el paquete SSPS 26&#46;0&#46; Las variables categ&#243;ricas se compararon mediante la &#967;<span class="elsevierStyleSup">2</span> y el test exacto de Fisher&#44; seg&#250;n fuera apropiado&#46; Las variables con un valor <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;10 en el an&#225;lisis univariante de predictoras del estado de portador neumoc&#243;cico se introdujeron en un modelo de regresi&#243;n log&#237;stica binaria&#46; Se consider&#243; en una prueba significativa cuando el valor de <span class="elsevierStyleItalic">p</span> fue<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Resultados</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Caracter&#237;sticas demogr&#225;ficas</span><p id="par0060" class="elsevierStylePara elsevierViewall">Se identificaron 76 &#40;19&#37;&#41; cepas colonizantes nasofar&#237;ngeas de <span class="elsevierStyleItalic">S&#46; pneumoniae</span> en 397 ni&#241;os sanos durante el periodo VNC13 y se dispuso de una colecci&#243;n hist&#243;rica de 154 &#40;35&#37;&#41; aislados nasofar&#237;ngeos neumoc&#243;cicos obtenidos de 443 participantes &#40;89&#44; 20&#37; de ni&#241;os sanos y 354&#44; 80&#37; de ni&#241;os con infecciones leves respiratorias de v&#237;as altas&#41; durante el periodo VNC7&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">El periodo VNC13 comparado con el periodo VNC7 se asoci&#243; con menores tasas de colonizaci&#243;n &#40;19 vs&#46; 35&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#44; de utilizaci&#243;n de antibi&#243;ticos en los 2 meses previos &#40;21 vs&#46; 33&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0002&#41; y de h&#225;bito tab&#225;quico en alguno de los padres &#40;28 vs&#46; 53&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41; y con una mayor proporci&#243;n de ni&#241;os sanos &#40;100 vs&#46; 20&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41; e inmunizados con VNC &#40;96 vs&#46; 54&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; Por otra parte&#44; no hubo diferencias entre ambos periodos en las proporciones de ni&#241;os de menor edad &#40;6 meses-3 a&#241;os&#41; y con asistencia a guarder&#237;a o colegio&#46; Por &#250;ltimo&#44; el reclutamiento de participantes fue significativamente mayor en el segundo cuatrimestre en el estudio contempor&#225;neo que en el hist&#243;rico &#40;42 vs&#46; 10&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">En el an&#225;lisis univariante&#44; la colonizaci&#243;n neumoc&#243;cica en el global de los 2<span class="elsevierStyleHsp" style=""></span>periodos de estudio se asoci&#243; significativamente con edad<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3 a&#241;os&#44; presencia concomitante de infecci&#243;n respiratoria de v&#237;as altas &#40;ni&#241;os enfermos&#41; y reclutamiento en primer o tercer cuatrimestre &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; Estas variables continuaron asociadas de forma positiva con un mayor riesgo de colonizaci&#243;n en el an&#225;lisis multivariante&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Distribuci&#243;n de serotipos</span><p id="par0075" class="elsevierStylePara elsevierViewall">Se identificaron 27 y 32 serotipos individuales diferentes en el total de las 76 y 154 cepas de los periodo de estudios contempor&#225;neo e hist&#243;rico&#44; respectivamente&#46; La colonizaci&#243;n por SV&#44; incluidos en la VNC13&#44; disminuy&#243; de forma significativa entre los periodos VNC13 y VNC7 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44; 11&#37; frente a n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>58&#44; 38&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Durante el periodo del estudio m&#225;s reciente se identificaron solo los SV 19F &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#44; 8&#37;&#41;&#44; 3 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; 1&#37;&#41; y 6B &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; 1&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Estos hab&#237;an circulado en el periodo VNC7&#44; sin que se observaran diferencias significativas entre ambos periodos&#46; Los restantes SV presentes en el peri&#243;dico hist&#243;rico y erradicados en el periodo contempor&#225;neo incluyeron los serotipos&#58; 19A &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#44; 10&#37;&#41;&#44; 6A &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#44; 6&#37;&#41;&#44; 23F &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44; 4&#37;&#41;&#44; 9V &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; 2&#37;&#41;&#44; 7F &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 1&#37;&#41;&#44; 14 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 1&#37;&#41;&#44; 5 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; 1&#37;&#41; y 18C &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; 1&#37;&#41;&#46; La proporci&#243;n de aislados del serotipo 19A disminuy&#243; significativamente entre los 2<span class="elsevierStyleHsp" style=""></span>periodos de tiempo &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;003&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Por otra parte&#44; se identificaron en el periodo VNC 13 los siguientes SNV con prevalencia &#8805; 3&#37;&#58; 15B&#47;C &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#44; 14&#37;&#41;&#44; 11A &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44; 11&#37;&#41;&#44; 23A &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#44; 7&#37;&#41;&#44; 10A &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44; 5&#37;&#41;&#44; 16F &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44; 5&#37;&#41;&#44; 31 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44; 5&#37;&#41;&#44; no tipable &#40;NT&#41; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44; 5&#37;&#41;&#44; 23B &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; 4&#37;&#41;&#44; 21 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; 4&#37;&#41;&#44; 6C &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 3&#37;&#41;&#44; 15A &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 3&#37;&#41;&#44; 22F &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 3&#37;&#41;&#44; 34 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 3&#37;&#41;&#44; 35B &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 3&#37;&#41;&#44; 35F &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 3&#37;&#41; y 38 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; 3&#37;&#41;&#46; Otros SNV presentes durante el este periodo temporal se describen en la <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#46; Al comparar los periodos VNC13 y VNC7&#44; se observ&#243; un incremento significativo en las proporciones de los serotipos 11A y 31 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04 para ambos serotipos&#41; y no hubo cambios significativos en los restantes SNV&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Distribuci&#243;n de genotipos</span><p id="par0090" class="elsevierStylePara elsevierViewall">Se identificaron por tipificaci&#243;n de secuencias multilocus un total de 40 ST y 67 ST diferentes&#44; de un total de 76 y 152 aislamientos genotipados de los periodos VNC13 y VNC7&#44; respectivamente&#46; Los complejos clonales m&#225;s comunes en el periodo VNC13 fue CC156 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#44; 12&#37;&#41;&#44; seguido de CC42&#44; CC51 y CC97 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44; 5&#37;&#44; todos&#41;&#44; mientras que&#44; por otra parte&#44; ST1262 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#44; 11&#41;&#44; ST433&#44; ST1760 y ST2670 &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; 4&#37;&#44; todos&#41; fueron los secuenciotipos de mayores frecuencias en este mismo periodo &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46; El CC156 se asoci&#243; predominantemente en el periodo VNC13 con el secuenciotipo ST6521&#44; una variante gen&#233;tica del clon global Spain9V-ST156 expresada como serotipo 11A&#46; Este serotipo se asoci&#243; exclusivamente con el clon ST62 en el periodo hist&#243;rico y fue reemplazado por ST6521 en los a&#241;os m&#225;s recientes&#46; ST1262 se expres&#243; como serotipo 15B&#47;C y&#44; a diferencia de ST6521&#44; permaneci&#243; estable durante ambos periodos de estudio&#46; Otros genotipos identificados en los periodos hist&#243;rico y contempor&#225;neo se muestran en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a> y en la tabla del material adicional <a class="elsevierStyleCrossRef" href="#sec0085">Appendix B</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Tasas de resistencias antimicrobianas</span><p id="par0095" class="elsevierStylePara elsevierViewall">De las 76 cepas del periodo VNC13&#44; 20 &#40;16&#37;&#41; mostraron sensibilidad disminuida a la penicilina&#44; de las que 2 aislados &#40;3&#37;&#41; se clasificaron como resistentes a la penicilina&#46; Las tasas de sensibilidad disminuida y resistencia a los otros 2<span class="elsevierStyleHsp" style=""></span>antibi&#243;ticos &#946;-lact&#225;micos evaluados en ambos periodos fueron las siguientes&#58; ampicilina &#40;17&#37; y 16&#37;&#41; y cefotaxima &#40;7&#37; y 0&#37;&#41;&#59; 15 cepas &#40;20&#37;&#41; presentaron tambi&#233;n resistencia a la eritromicina&#46; Las tasas de resistencia antimicrobianas del periodo VNC7 no mostraron diferencias estad&#237;sticamente significativas comparadas con las del periodo VNC13 para la penicilina &#40;con sensibilidad disminuida a la penicilina 32 vs&#46; 26&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;34 y resistentes a la penicilina 0 vs&#46; 3&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;11&#41; y la cefotaxima &#40;sensibilidad disminuida 4 vs&#46; 7&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;37 y resistencia 0 vs&#46; 0&#37;&#41;&#44; pero fueron&#44; por el contrario&#44; significativamente m&#225;s elevadas para la eritromicina &#40;38 vs&#46; 20&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;006&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> se muestra la distribuci&#243;n en el periodo VNC13 de los serotipos con sensibilidad disminuida a los antibi&#243;ticos &#946;-lact&#225;micos y con resistencia a la eritromicina&#46; Los aislamientos con resistencias a la ampicilina en estos a&#241;os correspondieron de forma mayoritaria a las cepas del serotipo 11A &#40;clones ST6521 y gen&#233;ticamente relacionada ST14698&#41; &#40;8&#47;12&#44; 67&#37;&#41;&#44; mientras que&#44; por el contrario&#44; los 5 aislados del genotipo ST62 asociado al este serotipo en el periodo VNC7 mostraron sensibilidad plena a la amoxicilina oral &#40;CMI 0&#44;06 mg&#47;L&#41;&#46; Los restantes serotipos y genotipos con resistencias a la ampicilina en el periodo VNC13 se describen en la <a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discusi&#243;n</span><p id="par0105" class="elsevierStylePara elsevierViewall">El presente estudio&#44; realizado tras la introducci&#243;n de la vacunaci&#243;n sistem&#225;tica con VNC13 en el calendario de inmunizaci&#243;n infantil de Andaluc&#237;a&#44; constituye la primera comunicaci&#243;n nacional sobre la epidemiolog&#237;a molecular de la colonizaci&#243;n nasofar&#237;ngea neumoc&#243;cica en ni&#241;os sanos con coberturas plenas de vacunaci&#243;n con VNC13&#46; Se han publicado previamente diversos estudios de portaci&#243;n neumoc&#243;cica en ni&#241;os de diversas comunidades aut&#243;nomas de Espa&#241;a&#44; pero estos se desarrollaron en &#225;mbitos con vacunaci&#243;n privada y coberturas parciales y solo se evalu&#243; la distribuci&#243;n de genotipos en 2<span class="elsevierStyleHsp" style=""></span>estudios del periodo VNC7<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">8&#44;9&#44;12-15</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Las VNC ejercen un impacto profundo en la poblaci&#243;n neumoc&#243;cica de la nasofaringe&#46; Disminuyen de forma muy importante la circulaci&#243;n de los SV&#44; aunque sin llegar a su completa eliminaci&#243;n&#46; Esta reducci&#243;n se ve compensada por un incremento en la prevalencia de los SNV&#46; Como consecuencia&#44; se han descrito&#44; tras la introducci&#243;n de las VNC&#44; tasas de colonizaci&#243;n neumoc&#243;cica similares<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">16&#44;17</span></a> o inferiores<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">18&#44;19</span></a> a las de la &#233;poca prevacunal&#44; en funci&#243;n de que el grado de reemplazamiento de los SV por los SNV fuera total o parcial&#44; respectivamente&#46; Nosotros observamos en el periodo VNC13 tasas de colonizaci&#243;n inferiores a las registradas durante el periodo VNC7 &#40;19&#37; vs&#46; 35&#37;&#41;&#46; Esta diferencia podr&#237;a relacionarse con la distribuci&#243;n no balanceada entre ambas poblaciones de estudio de algunas de las caracter&#237;sticas demogr&#225;ficas&#44; como infecci&#243;n respiratoria de v&#237;as altas concomitante y reclutamiento en el primer o en el tercer cuatrimestres &#40;meses menos c&#225;lidos&#41;&#44; que fueron predictoras independientes por an&#225;lisis multivariante de la colonizaci&#243;n neumoc&#243;cica&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Como era previsible&#44; la colonizaci&#243;n por SV disminuy&#243; de forma muy marcada&#44; en un 79&#37;&#44; entre los per&#237;odos VNC13 y VNC7&#46; Se erradicaron 7 de los 10 SV circulantes durante el periodo hist&#243;rico&#44; incluyendo al serotipo 19A identificado en el 10&#37; de los aislados de este &#250;ltimo periodo&#44; mientras que por el contrario se observ&#243; &#250;nicamente una persistencia significativa &#40;8&#37;&#41; del serotipo 19F&#46; Por otra parte&#44; los serotipos 3 y 6B&#44; cuyas proporciones disminuyeron entre ambos periodos de tiempo&#44; aunque sin alcanzar la significaci&#243;n estad&#237;stica&#44; se detectaron de forma muy infrecuente &#40;1&#37;&#41; en el periodo VNC13&#46; Este hallazgo no es insospechado&#44; porque el serotipo 19F se incluye entre los SV detectados con mayor frecuencia en los estudios de colonizaci&#243;n realizados tras la introducci&#243;n de VNC13<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">12&#44;16&#44;20</span></a>&#46; El serotipo 19F fue gen&#233;ticamente diverso y asociado con multirresistencias antibi&#243;ticas&#46; Este serotipo tiene gran capacidad de formar biofilm y&#44; por tanto&#44; alta capacidad de evadir el sistema inmune&#44; lo que junto a las resistencias antibi&#243;ticas son factores que pueden haber contribuido a su circulaci&#243;n persistente<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">21&#44;22</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Hubo una distribuci&#243;n amplia de SNV en el per&#237;odo VNC13&#44; con identificaci&#243;n de 24 serotipos diferentes&#46; Los SNV dominantes incluyeron los serotipos 15B&#47;C&#44; 11A&#44; 23A&#44; 10A&#44; 16F&#44; 31&#44; NT&#44; 23B y 21&#44; que son SNV habituales en los estudios de colonizaci&#243;n del periodo VNC13&#44; aunque con algunas diferencias en el <span class="elsevierStyleItalic">ranking</span> de prevalencia entre los diversos &#225;mbitos geogr&#225;ficos<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">12&#44;16&#44;20&#44;23&#44;24</span></a>&#46; Estos serotipos se han asociado con bajo potencial invasivo &#40;OR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1 en la comparaci&#243;n de las prevalencias en ENI y portadores&#41; en el periodo VNC13&#44; excepto el serotipo 10A&#44; que present&#243; OR en rango de 1&#44;2-1&#44;7 en algunos estudios<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">17&#44;19&#44;25</span></a>&#46; La VNC 20 valente&#44; aprobada para prevenci&#243;n de neumon&#237;a y ENI en pacientes adultos y de probable pr&#243;xima comercializaci&#243;n en poblaci&#243;n pedi&#225;trica&#44; incluye en su formulaci&#243;n este &#250;ltimo serotipo y los serotipos 11A y 15B&#44; de elevada prevalencia en el presente estudio&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Las proporciones de los serotipos 11A y 31 aumentaron significativamente entre los periodos VNC13 y VNC7 por la expansi&#243;n de clones &#40;ST6521 y ST1766&#44; repectivamente&#41; no detectados en el estudio del periodo VNC7&#46; ST6521 surgi&#243; por recombinaci&#243;n entre los clones 11A-ST62 y NT-ST344 y el clon global Spain9V-ST156&#44; asociado con los serotipos 9V y 14<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a>&#46; La expansi&#243;n clonal de ST6521 es preocupante por sus caracter&#237;sticas fenot&#237;picas de resistencia a ampicilina&#47;amoxicilina&#44; mayor capacidad para producir biofilm y elevada capacidad de evadir la activaci&#243;n de la v&#237;a cl&#225;sica del complemento y la fagocitosis en comparaci&#243;n con ST838&#44; que tambi&#233;n procede de Spain9V-ST156<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a>&#46; En un contexto de presi&#243;n antibi&#243;tica e inmunidad vacunal&#44; estas propiedades pueden haber contribuido a su relevancia creciente en la etiolog&#237;a de la otitis media aguda en ni&#241;os y de las exacerbaciones agudas del EPOC en adultos en ciertas localizaciones geogr&#225;ficas de Espa&#241;a<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">28&#44;29</span></a>&#46; Adem&#225;s&#44; este serotipo se puede asociar con ENI en ni&#241;os y adultos por su elevada prevalencia en portadores y por su marcada letalidad&#58; es incluso m&#225;s letal que el serotipo 3<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">30&#44;31</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Las tasas de sensibilidad disminuida a penicilina y cefotaxima permanecieron estables y se observ&#243; una disminuci&#243;n significativa de las tasas de resistencia a eritromicina entre los periodos VNC13 y VNC7&#46; Aunque se erradicaron varios SV &#40;6<span class="elsevierStyleHsp" style=""></span>A&#44; 9V&#44; 19A y 23F&#41; asociados en grado variable con sensibilidad disminuida a los antibi&#243;ticos &#946;-lact&#225;micos en el periodo VNC7&#44; este efecto beneficioso se vio compensado por la aparici&#243;n y expansi&#243;n clonal de ST11A-ST6511&#46; Este es un patr&#243;n de evoluci&#243;n de las resistencias antimicrobianas descrito tras la introducci&#243;n de las VNC&#44; de forma que la disminuci&#243;n de las tasas de resistencia derivada de la erradicaci&#243;n de los SV tiende a amortiguarse con el tiempo por la adquisici&#243;n progresiva de determinantes de resistencia en los SNV<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">32&#44;33</span></a>&#46; Debe se&#241;alarse&#44; adem&#225;s&#44; que la pandemia por SARS-CoV-2<span class="elsevierStyleHsp" style=""></span>ha provocado un aumento en el porcentaje de cepas resistentes de neumococo&#46; Esto se aprecia de forma clara en el serotipo 11A&#44; que ha pasado de tener en Espa&#241;a una CMI90 a penicilina de 2&#160;ug&#47;ml en el periodo prepand&#233;mico &#40;2016-2019&#41; a una CMI90 a penicilina de 4&#160;ug&#47;ml en 2020&#44; que es un valor considerado como resistente<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">34</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Esta investigaci&#243;n tiene varias limitaciones&#46; En primer lugar&#44; como ya se ha mencionado&#44; las diferentes caracter&#237;sticas demogr&#225;ficas de las poblaciones de estudio de los periodos VNC7 y VNC13 son un factor de confusi&#243;n para el an&#225;lisis comparativo de las tasas de colonizaci&#243;n&#46; En segundo lugar&#44; la distribuci&#243;n de algunos serotipos puede diferir entre los ni&#241;os sanos y aquellos con infecci&#243;n respiratoria superior<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a>&#46; Por &#250;ltimo&#44; no se evaluaron las colonizaciones m&#250;ltiples por t&#233;cnicas moleculares&#44; ni tampoco se realiz&#243; preenriquecimiento en el cultivo&#44; lo que&#44; de haberse llevado a cabo&#44; podr&#237;a haber incrementado la capacidad de detecci&#243;n de los neumococos en la colonizaci&#243;n nasofar&#237;ngea&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; en los a&#241;os posteriores a la introducci&#243;n de VNC13 en el calendario de inmunizaci&#243;n pedi&#225;trica de Andaluc&#237;a&#44; se observ&#243; una circulaci&#243;n muy residual de los SV en colonizantes de la nasofaringe&#44; excepto para el serotipo 19F&#44; y la expansi&#243;n clonal entre los SNV de ST11A-ST6511&#44; con capacidad patog&#233;nica y asociada a sensibilidad disminuida a la penicilina y resistencia a ampicilina&#46; Ser&#237;a recomendable mantener la vigilancia epidemiol&#243;gica de la colonizaci&#243;n neumoc&#243;cica para monitorizar la evoluci&#243;n de los SNV y las tasas de resistencias antibi&#243;ticas&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Financiaci&#243;n</span><p id="par0150" class="elsevierStylePara elsevierViewall">Este trabajo se ha financiado con una ayuda al proyecto de investigaci&#243;n por parte de Pfizer a IO &#40;grant 5323485&#41;&#46; No existi&#243; ning&#250;n tipo de participaci&#243;n del promotor en el dise&#241;o del estudio&#44; la recolecci&#243;n&#44; el an&#225;lisis y la interpretaci&#243;n de los datos&#44; la redacci&#243;n del art&#237;culo ni en la decisi&#243;n de enviar el art&#237;culo para su publicaci&#243;n&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflictos de intereses</span><p id="par0155" class="elsevierStylePara elsevierViewall">IO recibi&#243; ayudas de Pfizer para inscripci&#243;n a congresos y para la realizaci&#243;n de este proyecto&#46; ISC ha recibido becas u honorarios como consultor&#47;asesor y ponente&#44; as&#237; como ayudas para la asistencia a congresos y cursos pr&#225;cticos de Pfizer&#44; GlaxoSmithKline&#44; Sanofi Pasteur&#44; MSD y AstraZeneca&#46; CC ha recibido ayudas para asistencia a congresos de Pfizer&#44; GlaxoSmithKline y MSD&#46; No hay conflictos de intereses en los otros autores&#46;</p></span></span>"
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              "titulo" => "Distribuci&#243;n de genotipos"
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    "fechaRecibido" => "2022-10-10"
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            0 => "<span class="elsevierStyleItalic">Streptococcus pneumoniae</span>"
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    "resumen" => array:2 [
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El programa de vacunaci&#243;n universal con la vacuna antineumoc&#243;cica conjugada 13-valente &#40;VNC13&#41; se implant&#243; en Andaluc&#237;a en diciembre de 2016&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio transversal de colonizaci&#243;n nasofar&#237;ngea por <span class="elsevierStyleItalic">Streptococcus pneumoniae</span>&#46; Se seleccion&#243; a 397 ni&#241;os sanos en centros de atenci&#243;n primaria de Sevilla durante los periodos 1&#47;4&#47;2018-28&#47;2&#47;2020 y 1&#47;11&#47;2021-28&#47;2&#47;2022 &#40;periodo VNC13&#41;&#46; Se utiliz&#243; una colecci&#243;n hist&#243;rica de un estudio de colonizaci&#243;n desarrollado en ni&#241;os sanos y con infecci&#243;n respiratoria superior entre el 1&#47;01&#47;2006 y el 30&#47;06&#47;2008 &#40;periodo VNC7&#41; para comparar las distribuciones de serotipos&#47;genotipos y las tasas de resistencias antibi&#243;ticas&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Un total de 76 &#40;19&#37;&#41; ni&#241;os estaban colonizados con <span class="elsevierStyleItalic">S&#46; pneumoniae</span> en el periodo VNC13 y se dispuso de 154 aislamientos del periodo VNC7&#46; La colonizaci&#243;n por serotipos incluidos en VNC13 disminuy&#243; significativamente entre los periodos VNC13 y VNC7 &#40;11 vs&#46; 38&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#59; los serotipos 19F &#40;8&#37;&#41;&#44; 3 &#40;1&#37;&#41; y 6B &#40;1&#37;&#41; fueron los &#250;nicos serotipos vacunales circulantes&#46; Los serotipos 15B&#47;C y 11A fueron los serotipos no VNC13 m&#225;s prevalentes durante el periodo VNC13 &#40;14&#37; y 11&#37;&#44; respectivamente&#41;&#59; este &#250;ltimo se increment&#243; de forma significativa entre periodos de tiempo &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#46; El serotipo 11A solo se asoci&#243; en el periodo VNC13 con variantes resistentes a la ampicilina del clon Spain9V-ST156 &#40;ST6521 y gen&#233;ticamente relacionado ST14698&#41;&#44; no detectados en el periodo anterior&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Hubo una circulaci&#243;n muy residual de los serotipos vacunales durante el periodo VNC13&#44; con excepci&#243;n del serotipo19F&#46; El serotipo 11A se increment&#243; de forma significativa entre los periodos VNC13 y VNC7 por expansi&#243;n clonal del genotipo resistente a la ampicilina ST6521&#46;</p></span>"
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          0 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Background</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The 13-valent pneumococcal conjugate vaccine &#40;PCV13&#41; universal vaccination program was introduced in December 2016 in Andalusia&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A cross-sectional study was conducted on the molecular epidemiology of pneumococcal nasopharyngeal colonization&#46; A total of 397 healthy children were recruited from primary healthcare centres in Seville for the periods 1&#47;4&#47;2018 to 28&#47;2&#47;2020 and 1&#47;11&#47;2021 to 28&#47;2&#47;2022 &#40;PCV13 period&#41;&#46; Data from a previous carriage study conducted among healthy and sick children from 1&#47;01&#47;2006 to 30&#47;06&#47;2008 &#40;PCV7 period&#41; were used for comparison of serotype&#47;genotype distributions and antibiotic resistance rates&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Overall&#44; 76 &#40;19&#37;&#41; children were colonized with <span class="elsevierStyleItalic">S&#46; pneumoniae</span> during the PCV13 period and there were information available from 154 isolates collected during the PCV7 period&#46; Colonization with PCV13 serotypes declined significantly in the PCV13 period compared with historical controls &#40;11 vs&#46; 38&#37;&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; being serotypes 19F &#40;8&#37;&#41;&#44; 3 &#40;1&#37;&#41; and 6B &#40;1&#37;&#41; the only circulating vaccine type<span class="elsevierStyleBold">s</span>&#46; Serotypes 15B&#47;C and 11A were the most frequently identified non-PCV13 serotypes during the PCV13 period &#40;14&#37; and 11&#37;&#44; respectively&#41;&#59; the later one increased significantly between time periods &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46; Serotype 11A was exclusively associated in the PCV13 period with ampicillin-resistant variants of the Spain9V-ST156 clone &#40;ST6521 and genetically related ST14698&#41;&#44; not detected in the preceding period&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">There was a residual circulation of vaccine types following PCV13 introduction&#44; apart from serotype 19F&#46; Serotype 11A increased between PCV13 and PCV7 periods due to emergence and clonal expansion of ampicillin-resistant genotype ST6521&#46;</p></span>"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Comparaci&#243;n de la distribuci&#243;n de los serotipos neumoc&#243;cicos identificados en los periodos VNC13 y VNC7&#46;</p>"
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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><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<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>397&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<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>443&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-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">Colonizados por <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&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">76 &#40;19&#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">154 &#40;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"><span class="elsevierStyleBold">0&#44;0001</span>&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">Edad 6 meses-<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3 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">254 &#40;64&#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">297 &#40;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;35&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">Ni&#241;os sanos<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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">397 &#40;100&#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">89 &#40;20&#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"><span class="elsevierStyleBold">0&#44;0001</span>&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">Utilizaci&#243;n previa de antibi&#243;ticos &#40;&#60; 2 meses&#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">83 &#40;21&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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">144 &#40;33&#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"><span class="elsevierStyleBold">0&#44;0002</span>&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">Inmunizados con VNC7&#47;VNC13<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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">381 &#40;96&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&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">237 &#40;54&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a>&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"><span class="elsevierStyleBold">0&#44;0001</span>&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">Asistencia a colegio o guarderia&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">267 &#40;66&#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">310 &#40;70&#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;40&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">Tabaquismo padres&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">109 &#40;28&#41;<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">f</span></a>&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">232 &#40;53&#41;<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">g</span></a>&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"><span class="elsevierStyleBold">0&#44;0001</span>&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">Periodo de toma de muestra&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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">1&#46;<span class="elsevierStyleSup">er</span> o 3&#46;<span class="elsevierStyleSup">er</span> cuatrimestres&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">229 &#40;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">400 &#40;90&#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"><span class="elsevierStyleBold">0&#44;0001</span>&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">2&#46;&#176; cuatrimestre&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">168 &#40;42&#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">43 &#40;10&#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"><span class="elsevierStyleBold">0&#44;0001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>438&#46;</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">En negrillas&#44; valores <span class="elsevierStyleItalic">p</span> estad&#237;sticamente significativos&#46;</p>"
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                  \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">Variable&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">An&#225;lisis univariante&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">Analisis multivariante</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"><span class="elsevierStyleItalic">p</span>&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">OR &#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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&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">Edad 6 meses-&#60;3 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"><span class="elsevierStyleBold">0&#44;01</span>&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;76 &#40;1&#44;16-2&#44;53&#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"><span class="elsevierStyleBold">0&#44;02</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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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
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \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 ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Inmunizados con VNC7&#47;VNC13<a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8230;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">CC&#47;ST&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;1&#41;&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">ST838&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\ttop\n
                  \t\t\t\t">9V&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">ST2944&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">ST6521&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3501072.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Complejos clonales y secuenciotipos con &#8805; 3 aislados en los periodos de estudio VNC13 o VNC7 y serotipos asociados</p>"
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      4 => array:8 [
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        "mostrarFloat" => true
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Proporci&#243;n de cepas con sensibilidad disminuida &#40;&#37; resistentes plenas&#42;&#41; a</span></th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eritromicina<a class="elsevierStyleCrossRef" href="#tblfn0050">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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Información del artículo
ISSN: 0213005X
Idioma original: Español
DOI:10.1016/j.eimc.2022.11.005
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