Reduction in the incidence of invasive infections caused by encapsulated bacteria after the onset of the COVID-19 pandemic / Reducción de la incidencia de infecciones invasivas por bacterias capsuladas luego del inicio de la Pandemia por COVID-19

Abstract Interaction between severe acute respiratory coronavirus 2 (SARS-CoV-2) and IIEB remains under investigation. Objective: to compare IIEB incidence before and during COVID-19 pandemic, and assess incidence of coinfection with COVID-19 and case fatality. A cross-sectional study was performed on data from a centralized microbiology laboratory serving a network of healthcare centers comprising 713 pediatric and adult inpatient beds, expanded by 20% during the pandemic. Three periods were evaluated: (1) pre-pandemic: March 1, 2019-February 29, 2020; (2) pandemic year 1: March 1, 2020-February 28, 2021; (3) pandemic year 2: March 1, 2021-July 31, 2021. Descriptive statistical analysis was performed. 56502 samples (96% blood cultures) from 27224 patients were analyzed. Of these, 54 samples (from 54 patients) were positive for encapsulated bacteria. IIEB incidence was: 167.4, 32.6, and 50.4 per 100000 samples for periods 1, 2, and 3, respectively. Twelve IIEB episodes occurred during the pandemic period: 10 Streptococcus pneumoniae, and 2 Haemophilus influenzae, of which 7 were SARS-CoV-2/S. pneumoniae coinfections, with an incidence of 5.68 per 10000 COVID-19-related hospitalizations (0.056%). IIEB case fatality was 31%, 29%, and 60% for each period, respectively, 3/7 patients with coinfection died (43%). Case fatality for invasive pneumococcal disease (IPD) in patients without COVID-19, was 32.5%. Significant reduction in IIEB incidence was observed during the pandemic, coinciding with implementation of containment measures. The incidence of SARS-CoV-2/S. pneumoniae coinfection was low, with higher case fatality than IPD patients without COVID-19.

Resumen La interacción entre SARS-CoV-2 e infecciones invasivas por bacterias capsuladas (IIBC) continúa bajo estudio. Objetivos: comparar la incidencia de IIBC antes y durante la pandemia por COVID-19, evaluar la incidencia de coinfección con COVID-19 y la letalidad. Estudio transversal de registros de un laboratorio centralizado de Microbiología, que asiste a una red de centros asistenciales con 713 camas de internación para adultos y pediátricos, expandida 20% durante la pandemia. Tres periodos evaluados: 1) Pre-pandemia: 1-Marzo-2019 al 29-Febrero-2020; 2) Primer año de Pandemia: 1-Marzo-2020 al 28-Febrero-2021; 3) Pandemia 2021: 1-Marzo-2021 al 31-Julio-2021. Análisis estadístico descriptivo: Se analizaron 56.502 muestras (96% hemocultivos) correspondientes a 27.224 pacientes. De estas, 54 muestras (de 54 pacientes) fueron positivas para bacterias capsuladas. La incidencia de IIBC fue 167,4, 32,6 y 50,4 por cada 100.000 muestras para los periodos 1, 2 y 3, respectivamente. Doce IIBC ocurrieron durante la pandemia: 10 Streptococcus pneumoniae y dos Haemophilus influenzae, siete de ellos corresponden a coinfección SARS-CoV-2/S. pneumoniae, con una incidencia de 5,68 por cada 10.000 internaciones por COVID 19 (0,056%). La letalidad de las IIBC fue de 31, 29 y 60% para los tres periodos, respectivamente, 3/7 coinfectados fallecieron (43%). La letalidad por enfermedad neumocócica invasiva (ENI), sin COVID fue de 32,5%. Se evidenció una reducción significativa de la incidencia de IIBC luego del comienzo de la pandemia, coincidente con la implementación de las medidas sanitarias de contención de la pandemia. La incidencia de coinfección de SARS-CoV-2/S. pneumoniae fue baja y presentó mayor letalidad que las ENI sin COVID-19.

Reduction in the incidence of invasive infections caused by encapsulated bacteria after the onset of the COVID-19 pandemic.

Interaction between severe acute respiratory coronavirus 2 (SARS-CoV-2) and IIEB remains under investigation. Objective: to compare IIEB incidence before and during COVID-19 pandemic, and assess incidence of coinfection with COVID-19 and case fatality. A cross-sectional study was performed on data from a centralized microbiology laboratory serving a network of healthcare centers comprising 713 pediatric and adult inpatient beds, expanded by 20% during the pandemic. Three periods were evaluated: (1) pre-pandemic: March 1, 2019-February 29, 2020; (2) pandemic year 1: March 1, 2020-February 28, 2021; (3) pandemic year 2: March 1, 2021-July 31, 2021. Descriptive statistical analysis was performed. 56 502 samples (96% blood cultures) from 27224 patients were analyzed. Of these, 54 samples (from 54 patients) were positive for encapsulated bacteria. IIEB incidence was: 167.4, 32.6, and 50.4 per 100000 samples for periods 1, 2, and 3, respectively. Twelve IIEB episodes occurred during the pandemic period: 10 Streptococcus pneumoniae, and 2 Haemophilus influenzae, of which 7 were SARS-CoV-2/S. pneumoniae coinfections, with an incidence of 5.68 per 10000 COVID-19-related hospitalizations (0.056%). IIEB case fatality was 31%, 29%, and 60% for each period, respectively, 3/7 patients with coinfection died (43%). Case fatality for invasive pneumococcal disease (IPD) in patients without COVID-19, was 32.5%. Significant reduction in IIEB incidence was observed during the pandemic, coinciding with implementation of containment measures. The incidence of SARS-CoV-2/S. pneumoniae coinfection was low, with higher case fatality than IPD patients without COVID-19.

Características microbiológicas de la enfermedad neumocócica en niños menores de 5 años de Santiago de Cuba / Microbiologic characteristics of the pneumococcus disease in children under 5 years from Santiago de Cuba i: en

Introducción: La infección por Streptococcus pneumoniae constituye una causa importante de morbimortalidad en el mundo, sobre todo en niños menores de 5 años, en los que ocasiona de 1 a 2 millones de muertes anuales. Objetivo: Determinar la presencia de S. pneumoniae en muestras clínicas obtenidas en niños. Métodos: Se realizó un estudio descriptivo y transversal en niños menores de 5 años de edad con diagnóstico clínico de enfermedad neumocócica invasiva, asistidos en dos hospitales pediátricos de Santiago de Cuba durante el periodo 2014-2018. De las 1466 muestras clínicas tomadas y procesadas, en 131 fue aislado el agente patógeno; estas correspondieron a 59 pacientes con formas clínicas de la infección y 72 portadores. Para el procesamiento estadístico de la información se utilizaron las frecuencias absoluta y relativa como medidas de resumen. Resultados: En general, la positividad por S. pneumoniae fue de 8,9 %, con mayores frecuencias de aislamiento en las muestras de líquido cefalorraquídeo (81,8 %), líquido pleural (47,1 %) y exudado ótico (21,9 %), que asimismo coincidieron con los porcentajes más elevados de neumonía (61,0), otitis media aguda (23,7) y meningitis (15,3), como formas clínicas de la enfermedad neumocócica, que aquejó principalmente a niños de 1 año de edad, seguidos de los mayores de 2 años. De igual modo, se identificaron 9 serotipos de S. pneumoniae, con predominio del 19A (39,0 %), el 14 (25,4 %) y el 6A (11,9 %). En los pacientes que portaban la bacteria en la nasofaringe se identificaron 8 tipos serológicos, predominantemente el 19A y el 14. Por último, se halló una alta resistencia microbiana a la eritromicina y a la combinación trimetoprima-sulfametoxazol. Conclusiones: Los resultados de este estudio proporcionaron un referente científico antes de la introducción de la vacuna antineumocócica cubana, lo que permitirá evaluar su impacto en la incidencia de dicha enfermedad.

Introduction: The infection due to Streptococcus pneumoniae constitutes an important cause of morbimortality in the world, mainly in children under 5 years, that causes from 1 to 2 million annual deaths. Objective: To determine the presence of S. pneumoniae in clinical samples obtained in children. Methods: A descriptive and cross-sectional study was carried out in children under 5 years with clinical diagnosis of invasive pneumococcus disease, assisted in two children hospitals from Santiago de Cuba during the period 2014-2018. Of the 1466 clinical samples taken and processed, in 131 the pathogen agent was isolated; these corresponded to 59 patients with clinical forms of the infection and 72 carriers of the disease. For the statistical processing of the information the absolute and relative frequencies were used as summary measures. Results: In general the positivity for S. pneumoniae was of 8.9 %, with more isolation frequencies in the samples of cerebrospinal fluid (81.8 %), pleural fluid (47.1 %) and otic exudate (21.9 %) that also coincided with the highest percentages of pneumonia (61.0), acute otitis media (23.7) and meningitis (15.3), as clinical forms of the neumococcus disease that mainly affected 1 year children, followed by those over 2 years. In a same way, 9 serotypes of S. pneumoniae were identified, with prevalence of the 19A (39.0 %), and 14 (25.4 %) and the 6A (11.9 %). In the nasopharyngeal carriers 8 serotypes were identified, of which the 19A and 14 prevailed. Lastly, a high microbian resistance to erythromycin and the combination trimethoprim-sulfametoxazole was found. Conclusions: The results of this study provided a scientific referent before the introduction of the Cuban antipneumococcus vaccine that will allow to evaluate its impact in the incidence of this disease.

Análisis espacial y temporal de la enfermedad neumocócica invasora por serotipos resistentes a eritromicina / Spatial and temporal analysis of invasive pneumococcal disease due to erythromycinresistant serotypes

Objetivos: Estudiar la distribución espacio-temporal de los casos de enfermedad neumocócica invasora (ENI) por serotipos resistentes a eritromicina y su relación con el consumo comunitario de macrólidos y la cobertura vacunal infantil. Métodos: Se seleccionaron los casos de ENI en mayores de 59 años residentes en la Comunidad de Madrid (CM) notificados en el periodo de 2007 a 2016. Las variables estudiadas fueron obtenidas de los sistemas de información vacunal y de Prestación Farmacéutica. Se utilizó el punto de corte (concentración mínima inhibitoria de eritromicina > 0,5 mg/L) de la clasificación de EUCAST para definir los serotipos resistentes a eritromicina. Mediante JointPoint se estimaron las tendencias de las incidencias de casos por serotipos resistentes a eritromicina incluidos en la vacuna trecevalente (STVCN13) y no incluidos (STnoVCN13). La asociación de esas incidencias con el consumo comunitario de macrólidos y la cobertura vacunal se hizo mediante modelos de Poisson. Para la detección de clústeres espacio-temporales se utilizó el estadístico Satscan. Resultados: Se identificaron 1.936 casos, de ellos, se detectó que 427 serotipos eran resistentes a la eritromicina. La incidencia de todos los casos por serotipos resistentes fue descendente (AAPC: -5,40%). La incidencia de casos por STVCN13 resistentes a la eritromicina fue descendente con un porcentaje anual del cambio (APC: -13,8) y estuvo asociada inversamente a la cobertura vacunal infantil (IRR 0,641), mientras que la de casos por STnoVCN13 resistentes a eritromicina fue ascendente (APC: 4,5) y no se asoció con la cobertura. Se detectó un clúster por STnoVCN13 y ninguno por STVCN13 tras la inclusión de la trecevalente en el calendario vacunal infantil. Conclusiones: El descenso de ENI por STVCN13 resistentes se asoció con el incremento de la cobertura vacunal infantil...(AU)

Objectives: To study the spatio-temporal distribution of cases of invasive pneumococcal disease (IPD) due to serotypes resistant to erythromycin and its relationship with community consumption of macrolides and childhood vaccination coverage. Methods: We selected IPD cases in adults over 59 years old, residents in the Community of Madrid (MC), notified in the period 2007-2016. The variables studied were obtained from the Vaccination Information Systems and the Pharmaceutical Service. The cut-off point (minimum inhibitory erythromycin concentration > 0.5 mg/L) of the EUCAST classification was used to define erythromycin resistant serotypes. We used JointPoint to estimate the incidence trends by erythromycin resistant serotypes included in the 13-valent vaccine (STPCV13) and not included in it (STnoPCV13). The association of these incidences with the community consumption of macrolides and vaccination coverage was made using Poisson models. Statistical scanning was used for the detection of temporal-spaces clusters of cases. Results: 1936 cases were identified, of which 427 erythromycin resistant serotypes were identified. The incidence of all cases due to resistant serotypes was decreasing (AAPC: -5,40%). During the period studied, the incidence of cases due to erythromycin resistant STPCV13 was decreasing with an annual percentage change (APC): -13.8 and was inversely associated with childhood vaccination coverage (IRR 0.641), while that of cases due to erythromycin resistant STnoPCV13 was ascending (APC): 4.5; and was not associated with coverage. 1 cluster was detected by STnoPCV13 and none by STPCV13 after the date of inclusion of the 13-valent in the childhood vaccination calendar. Conclusions: The decrease in IPD due to resistant STPCV13 was associated with an increase in childhood vaccination coverage...(AU)

Spatial and temporal analysis of invasive pneumococcal disease due to erythromycinresistant serotypes.

OBJECTIVES: To study the spatio-temporal distribution of cases of invasive pneumococcal disease (IPD) due to serotypes resistant to erythromycin and its relationship with community consumption of macrolides and childhood vaccination coverage. METHODS: We selected IPD cases in adults over 59 years old, residents in the Community of Madrid (MC), notified in the period 2007-2016. The variables studied were obtained from the Vaccination Information Systems and the Pharmaceutical Service. The cut-off point (minimum inhibitory erythromycin concentration > 0.5 mg/L) of the EUCAST classification was used to define erythromycin resistant serotypes. We used JointPoint to estimate the incidence trends by erythromycin resistant serotypes included in the 13-valent vaccine (STPCV13) and not included in it (STnoPCV13). The association of these incidences with the community consumption of macrolides and vaccination coverage was made using Poisson models. Statistical scanning was used for the detection of temporal-spaces clusters of cases. RESULTS: 1936 cases were identified, of which 427 erythromycin resistant serotypes were identified. The incidence of all cases due to resistant serotypes was decreasing (AAPC: -5,40%). During the period studied, the incidence of cases due to erythromycin resistant STPCV13 was decreasing with an annual percentage change (APC): -13.8 and was inversely associated with childhood vaccination coverage (IRR 0.641), while that of cases due to erythromycin resistant STnoPCV13 was ascending (APC): 4.5; and was not associated with coverage. 1 cluster was detected by STnoPCV13 and none by STPCV13 after the date of inclusion of the 13-valent in the childhood vaccination calendar. CONCLUSIONS: The decrease in IPD due to resistant STPCV13 was associated with an increase in childhood vaccination coverage. The presence of clusters due to STnoPCV13 after the date of inclusion of the 13-valent vaccine in the childhood vaccination calendar indicates serotypes replacement. The increase in cases of resistant STnoPCV13 could be related to the replacement of vaccine serotypes in nasopharyngeal colonization, facilitated by the consumption of macrolides still at high levels in MC.

Carga de hospitalización y comorbilidades relacionadas con la enfermedad neumocócica en España (2019-2021) / Burden of hospitalisation and comorbidities related to pneumococcal disease in Spain (2019-2021

Introducción: La enfermedad neumocócica (EN) presenta una sustancial morbimortalidad en España, con gran impacto asistencial y económico en el sistema sanitario español. Objetivos: El objetivo del presente trabajo es describir la carga hospitalaria de la EN y comorbilidades asociadas. Metodología: Estudio descriptivo transversal con base en el conjunto mínimo básico de datos y serie 2019-2021. En el análisis de las comorbilidades potencialmente asociadas a EN se empleó el Índice de Comorbilidad de Charlson (CCI). Resultados: La edad media fue 67 años con una tasa total de hospitalización de 10,65 × 10.000 habitantes y tasa de letalidad de 14,90 × 10.000 habitantes, con valores mayores en el sexo masculino. Se identificó un descenso en el caso de las hospitalizaciones y un aumento de la letalidad. El 58,34% de los pacientes ingresó por neumonía. Las enfermedades más prevalentes relacionadas con los ingresos por EN fueron: la enfermedad pulmonar obstructiva crónica, la insuficiencia cardiaca congestiva, el cáncer y la diabetes. La estancia media fue de 13 días y el coste medio total 8533 euros por episodio. El coste anual fue de 370, 455 y 462 millones de euros en 2019, 2020 y 2021, respectivamente. Conclusiones: Debido a la gran carga que continúa suponiendo para el sistema sanitario de España, la EN y las comorbilidades más frecuentes asociadas a la misma deben abordarse desde un punto de vista preventivo, considerando medidas esenciales como la vacunación y una correcta vigilancia epidemiológica de la enfermedad.(AU)

Introduction: Pneumococcal disease (PCD) has a substantial morbidity and mortality in Spain, with a large health care and economic impact on the Spanish health care system. Objectives: The aim of this study is to describe the hospital burden of pneumococcal disease and associated comorbidities. Methodology: Cross-sectional descriptive study based on the minimum basic data set and series 2019-2021. The Charlson Comorbidity Index (CCI) was used in the analysis of comorbidities potentially associated with invasive pneumococcal disease. Results: The mean age was 67 years with a total hospitalisation rate of 10.65 × 10,000 population and case fatality rate of 14.90 × 10,000 population, with higher values in males. A decrease in hospitalisations and an increase in case fatality was identified. Pneumonia accounted for 58.34% of patients admitted. The most prevalent diseases associated with invasive pneumococcal disease admissions were: chronic obstructive pulmonary disease, congestive heart failure, cancer and diabetes. The average length of stay was 13 days and the average total cost was 8533 euros per episode. The annual cost was €370m, €455m and €462m in 2019, 2020 and 2021, respectively. Conclusions: Due to the large burden it continues to place on Spain’s healthcare system, pneumococcal disease and the most frequent comorbidities associated with it must be approached from a preventive standpoint, considering essential measures such as vaccination and proper epidemiological surveillance of the disease.(AU)

Enfermedad neumocócica invasiva en niños menores de 60 meses, antes y después de la introducción de la vacuna conjugada 13-valente / Invasive pneumococcal disease in children under 60 months before and after availability of 13-valent conjugate vaccine

Introducción: La enfermedad neumocócica invasiva (ENI) es la infección bacteriana más relevante en niños pequeños y la introducción de las vacunas antineumocócicas conjugadas (VNC) ha cambiado su presentación clínica. En este estudio se analizaron los cambios en la incidencia, características clínicas y distribución de serotipos en los casos de ENI antes y después de la disponibilidad de la VNC13. Métodos: Se incluyeron prospectivamente pacientes con ENI menores de 60 meses ingresados en 2 hospitales pediátricos terciarios desde enero de 2007 a diciembre de 2009 (período pre-VNC13) y de enero de 2012 a junio de 2016 (período VNC13). Resultados: Se identificaron 493 casos, 319 en el período pre-VNC13 y 174 en el período VNC13. La incidencia de ENI disminuyó de 89,7 a 34,4 casos por 100.000 habitantes (−62%, p<0,001). Esta disminución de la incidencia se dio por igual en todas las presentaciones clínicas de la enfermedad excepto en la neumonía necrotizante (aumentó de 0,8 a 3,7 casos por 100.000 habitantes). Todos los serotipos incluidos en la VNC13 pero no incluidos en la VNC7 disminuyeron significativamente. No se encontraron diferencias significativas en la estancia hospitalaria, muerte y/o secuelas entre ambos períodos, aunque durante el período VNC13, los pacientes requirieron más días en la unidad de cuidados intensivos pediátricos y de ventilación mecánica (p=0,00). La incidencia del serotipo 3 disminuyó de 10,4 a 6,9 casos por 100.000 habitantes, aunque fue el serotipo más frecuente en los pacientes con un cuadro clínico grave. Conclusiones: Luego de la introducción de la VNC13 se ha producido una disminución significativa de los casos de ENI. El serotipo 3 sigue siendo una causa importante de casos graves de ENI. (AU)

Background: Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). Methods: Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). Results: We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 cases per 100,000 population (−62%; P<.001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 cases/100,000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P=.00). The incidence of serotype 3 decreased from 10.4 to 6.9 cases per 100,000 population, although it was the serotype involved most frequently in patients with severe disease. Conclusions: After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD. (AU)

Invasive pneumococcal disease in children under 60 months before and after availability of 13-valent conjugate vaccine.

BACKGROUND: Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). METHODS: Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). RESULTS: We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 casos per 100 000 habitantes ( -62%; P < .001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 casos/100 000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P = .00). The incidence of serotype 3 decreased from 10.4 to 6.9 casos per 100 000 population, although it was the serotype involved most frequently in patients with severe disease. CONCLUSIONS: After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD.

Disminución de la vigilancia de la enfermedad neumocócica invasiva tras el inicio de la pandemia de COVID-19, Cuba 2020

RESUMEN Durante la pandemia de COVID-19 deben mantenerse activos los sistemas de vigilancia de enfermedades prevenibles mediante vacunación. El objetivo de la presente comunicación es alertar sobre el debilitamiento de la vigilancia de la enfermedad neumocócica invasiva en Cuba durante el 2020. Para ello se realizó un análisis retrospectivo del número de casos con enfermedad neumocócica invasiva confirmado en el Laboratorio Nacional de Referencia, Cuba 2014-2020. Entre el 2014 y 2019 el número de aislados de Streptococcus pneumoniae osciló entre 81 y 121. Durante el 2020 solo se confirmaron 31 aislados; 19 de ellos se recuperaron de meningitis y únicamente cinco de neumonía. Las medidas sanitarias implementadas para contener el avance de la pandemia COVID-19 pueden haber influido en la disminución de aislados responsables de enfermedad neumocócica invasiva. Esto parece obedecer al debilitamiento de la vigilancia, pues las pruebas para el diagnóstico de la COVID-19 se convirtieron en una prioridad durante el 2020.

ABSTRACT During the COVID-19 pandemic, surveillance systems for vaccine-preventable diseases should remain active. The purpose of the present communication is to warn about the weakening of invasive pneumococcal disease surveillance in Cuba during the year 2020. To achieve such an end, a retrospective analysis was conducted of the number of invasive pneumococcal disease cases confirmed at the Cuban National Reference Laboratory in the period 2014-2020. From 2014 to 2019 the number of Streptococcus pneumoniae isolates ranged between 81 and 121. In 2020 only 31 isolates were confirmed, 19 of which were retrieved from meningitis and a mere five from pneumonia. The health actions implemented to contain the spread of the COVID-19 pandemic may have influenced the decline in the number of isolated responsible for invasive pneumococcal disease. This situation seems to be a consequence of the weakening of surveillance, since COVID-19 diagnostic tests became a priority during 2020.

Spatial and temporal analysis of invasive pneumococcal disease due to erythromycinresistant serotypes. / Análisis espacial y temporal de la enfermedad neumocócica invasora por serotipos resistentes a eritromicina.

OBJECTIVES: To study the spatio-temporal distribution of cases of invasive pneumococcal disease (IPD) due to serotypes resistant to erythromycin and its relationship with community consumption of macrolides and childhood vaccination coverage. METHODS: We selected IPD cases in adults over 59 years old, residents in the Community of Madrid (MC), notified in the period 2007-2016. The variables studied were obtained from the Vaccination Information Systems and the Pharmaceutical Service. The cut-off point (minimum inhibitory erythromycin concentration > 0.5 mg/L) of the EUCAST classification was used to define erythromycin resistant serotypes. We used JointPoint to estimate the incidence trends by erythromycin resistant serotypes included in the 13-valent vaccine (STPCV13) and not included in it (STnoPCV13). The association of these incidences with the community consumption of macrolides and vaccination coverage was made using Poisson models. Statistical scanning was used for the detection of temporal-spaces clusters of cases. RESULTS: 1936 cases were identified, of which 427 erythromycin resistant serotypes were identified. The incidence of all cases due to resistant serotypes was decreasing (AAPC: -5,40%). During the period studied, the incidence of cases due to erythromycin resistant STPCV13 was decreasing with an annual percentage change (APC): -13.8 and was inversely associated with childhood vaccination coverage (IRR 0.641), while that of cases due to erythromycin resistant STnoPCV13 was ascending (APC): 4.5; and was not associated with coverage. 1 cluster was detected by STnoPCV13 and none by STPCV13 after the date of inclusion of the 13-valent in the childhood vaccination calendar. CONCLUSIONS: The decrease in IPD due to resistant STPCV13 was associated with an increase in childhood vaccination coverage. The presence of clusters due to STnoPCV13 after the date of inclusion of the 13-valent vaccine in the childhood vaccination calendar indicates serotypes replacement. The increase in cases of resistant STnoPCV13 could be related to the replacement of vaccine serotypes in nasopharyngeal colonization, facilitated by the consumption of macrolides still at high levels in MC.

[Invasive pneumococcal disease in children under 60 months before and after availability of 13-valent conjugate vaccine]. / Enfermedad neumocócica invasiva en niños menores de 60 meses, antes y después de la introducción de la vacuna conjugada 13-valente.

BACKGROUND: Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). METHODS: Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). RESULTS: We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 cases per 100,000 population (-62%; P<.001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 cases/100,000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P=.00). The incidence of serotype 3 decreased from 10.4 to 6.9 cases per 100,000 population, although it was the serotype involved most frequently in patients with severe disease. CONCLUSIONS: After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD.

[Characteristics of patients with invasive pneumococcal disease requiring admission to intensive care units]. / Características de los pacientes con enfermedad neumocócica invasora que requieren ingreso en la unidad de cuidados intensivos.

INTRODUCTION: Patients with invasive pneumococcal disease (IPD) may require admission into paediatric intensive care units (PICU). The aim of this study is to analyse the epidemiological, clinical, and microbiological characteristics associated with IPD that may require admission to the PICU. MATERIAL AND METHODS: A prospective study was conducted on cases of IPD diagnosed in three Paediatric Hospitals in Barcelona between January 2012 and June 2016. An analysis was made of the associations between the admission to PICU and the epidemiological, clinical, and microbiological variables. RESULTS: A total of 263 cases with IPD were included, of which 19% (n = 50) required admission to PICU. Patients with septic shock (7; 100%), meningitis (16; 84.2%), and those with complicated pneumonia (23; 15.2%) were admitted to the PICU. The most frequent complications were pulmonary (35.2%) and neurological (39.5%). The ratio between admission and non-admission to PICU was 4.7 times higher in subjects with an underlying disease. The serotypes associated with PICU admission were 19A (23% of the total of this serotype), serotype 14 (20%), serotype 3 (17%), and serotype 1 (12.5%). CONCLUSIONS: IPD required PICU admission in cases of septic shock and meningitis, and less so with complicated pneumonia. The percentage of admissions is greater in children with an underlying disease. Admission into the PICU involves a longer stay, complications during the acute phase, as well as sequelae, particularly neurological ones. The serotypes of the patients that were admitted to PICU were predominantly vaccine serotypes.

Distribution of PCV13 and PPSV23 Streptococcus pneumoniae serotypes in Argentinean adults with invasive disease, 2013-2017 / Distribución de los serotipos PCV13 y PPSV23 de Streptococcus pneumoniae en adultos argentinos con enfermedad invasiva, 2013-2017

Abstract Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. To identify the serotypes most commonly associated with infection in adults in Argentina, 791 pneumococcal isolates from 56 hospitals belonging to 16 provinces and Buenos Aires city were serotyped. The isolates were submitted as part of a National Surveillance Program for invasive pneumococcal disease in adults, which started in 2013. Serotypes 3, 8, 12F, 7F and 1 were the most prevalent among adult patients. During the study period there was no significant difference in serotype distribution between the age groups studied (18-64 and >65 years old), except for serotype 1, 3 and 23A. Most prevalent serotypes in pneumonia were serotype 7F, 1, 12F, 8, and 3. When the clinical diagnosis was meningitis, serotype 3 and 12F were the most prevalent, whereas when the diagnosis was sep-sis/bacteremia the most prevalent was serotype 8. In this work, for the 18-64-year-old group, PPSV23 and PCV13 serotypes accounted for 74.56% and 44.54% respectively of the cases in the studied period. On the other hand, for the >65-year-old group, these serotypes represented 72.30% and 41.42% respectively. The aim of this work was to establish the knowledge bases of the serotypes that cause invasive pneumococcal diseases in the adult population in Argentina and to be able to detect changes in their distribution over time in order to explore the potential serotype coverage of the vaccines in current use.

Resumen Streptococcus pneumoniae es una causa importante de enfermedad invasiva grave asociada con una alta mortalidad y morbilidad en todo el mundo. Para identificar los serotipos principales asociados con la infección en adultos en Argentina, 791 aislamientos de neumococo de 56 hospitales pertenecientes a 16 provincias y la ciudad de Buenos Aires fueron serotipificados. Los aislamientos fueron remitidos como parte del Programa Nacional de Vigilancia para la enfermedad neumocócica invasiva en adultos, que comenzó en 2013. Los serotipos 3, 8, 12F, 7F y 1 fueron los más prevalentes. Durante el período de estudio no hubo diferencias significativas en la distribución de serotipos entre los dos grupos de adultos estudiados (18-64 y >65 años), excepto para los serotipos 1, 3 y 23A. Los serotipos más prevalentes en casos de neumonía fueron 7F, 1, 12F, 8 y 3. Cuando el diagnóstico clínico fue meningitis, los serotipos 3 y 12F fueron los más prevalentes. Y el serotipo 8 fue el más prevalente en la sepsis/bacteriemia. En el grupo de 18-64 años, los serotipos PPSV23 y PCV13 representaron, respectivamente, el 74,56 y el 44,54% de los casos de enfermedad invasiva en el período estudiado. En el grupo de >65 años, estos serotipos representaron el 72,30 y 41,42%, respectivamente. Es importante conocer los serotipos causantes de infecciones neumocócicas invasivas en la población adulta en Argentina y detectar eventuales cambios en su distribución a lo largo del tiempo, para explorar la potencial cobertura de las vacunas utilizadas.

Distribution of PCV13 and PPSV23 Streptococcus pneumoniae serotypes in Argentinean adults with invasive disease, 2013-2017.

Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. To identify the serotypes most commonly associated with infection in adults in Argentina, 791 pneumococcal isolates from 56 hospitals belonging to 16 provinces and Buenos Aires city were serotyped. The isolates were submitted as part of a National Surveillance Program for invasive pneumococcal disease in adults, which started in 2013. Serotypes 3, 8, 12F, 7F and 1 were the most prevalent among adult patients. During the study period there was no significant difference in serotype distribution between the age groups studied (18-64 and ≥65 years old), except for serotype 1, 3 and 23A. Most prevalent serotypes in pneumonia were serotype 7F, 1, 12F, 8, and 3. When the clinical diagnosis was meningitis, serotype 3 and 12F were the most prevalent, whereas when the diagnosis was sepsis/bacteremia the most prevalent was serotype 8. In this work, for the 18-64-year-old group, PPSV23 and PCV13 serotypes accounted for 74.56% and 44.54% respectively of the cases in the studied period. On the other hand, for the ≥65-year-old group, these serotypes represented 72.30% and 41.42% respectively. The aim of this work was to establish the knowledge bases of the serotypes that cause invasive pneumococcal diseases in the adult population in Argentina and to be able to detect changes in their distribution over time in order to explore the potential serotype coverage of the vaccines in current use.

Enfermedad neumocócica en pacientes menores de 5 años / Pneumoccocal disease in a patient under 5 years

Introducción: La enfermedad neumocócica afecta prioritariamente a las personas en las edades extremas de la vida. En este sentido, el Hospital Docente Infantil Sur Dr. Antonio María Béguez César constituye un sitio de vigilancia centinela del Proyecto Nacional Neumococo, lo cual sirvió de motivación para desarrollar la presente investigación sobre esta enfermedad. Objetivo: Describir las características epidemiológicas, clínicas, microbiológicas e imagenológicas en pacientes menores de 5 años ingresados por presentar enfermedad neumocócica. Métodos: Se realizó un estudio observacional, descriptivo y prospectivo de 170 pacientes menores de 5 años de edad, ingresados en el mencionado centro hospitalario en el período 2014-2016 por presentar enfermedad neumocócica. Resultados: En la serie predominaron la supresión precoz de la lactancia materna (52,3 %) y la existencia de fumadores convivientes (44,7 %) como principales factores de riesgo, además de la fiebre (100,0 %), la tos (96,0 %), el tiraje (74,1%) y la polipnea (70,0 %) como síntomas más frecuentes; mientras que la neumonía se presentó en 82,3 % y hubo 10,0 % de positividad al neumococo, por serotipos 19A, 19F, 14 y 6A, con 66,6 % de colonización en lactantes. Por su parte, la letalidad y la mortalidad proporcional por neumonía fueron de 2,85 y 8,0 %, respectivamente, sin decesos por neumococo. Conclusiones: El aislamiento de neumococo resultó bajo, con predominio en lactantes colonizados y con indicadores de mortalidad por neumonía no neumocócica, lo cual sugiere que la corta edad es un riesgo de deceso por dicha causa.

Introduction: Pneumococcal disease affects mainly people in the extreme ages of life. In this sense, Dr. Antonio María Béguez Caesar Southern Teaching Pediatric Hospital constitutes a place of centinel surveillance of the Pneumococcus National Project, which served as motivation to develop the present investigation on this disease. Objective: To describe the epidemiological, clinical, microbiological and imaging characteristics in patients younger than 5 years admitted due to a pneumoccocical disease. Methods: An observational, descriptive and prospective study of 170 patients younger than 5 years admitted to the above mentioned hospital in the period 2014-2016 was carried out, for presenting pneumoccocal disease. Results: The early suppression of the maternal feeding (52.3 %) and the presence of coexisting smokers (44.7 %) as main risk factors, besides fever (100.0 %), cough (96.0 %), chest indrawing (74.1 %) and polypnea (70.0 %) as the most frequent symptoms prevailed in the series; while the pneumonia was presented in 82.3 % and there was 10.0 % positiveness to pneumoccocus, by serotypes 19A, 19F, 14 and 6A, with 66.6 % colonization in infants. On the other hand, lethality and proportional mortality for pneumonia were of 2.85 and 8.0 %, respectively, without deaths due to pneumoccocus. Conclusions: Pneumoccocus isolation was low, with prevalence in colonized infants and with mortality indicators due to non pneumoccocal pneumonia, which suggests that the short age is a death risk due to this cause.

Treatment and prevention of invasive pneumococcal disease. / Tratamiento y prevención de la enfermedad neumocócica invasiva.

Invasive pneumococcal disease is a severe infection that mainly affects patients with associated comorbidity. The paediatric conjugate vaccination has resulted in a change in the adult vaccination strategy. The antibiotic resistance of pneumococcus is not currently a severe problem. Nevertheless, the World Health Organisation has included pneumococcus among the bacteria whose treatment requires the introduction of new drugs, such as ceftaroline and ceftobiprole. Although the scientific evidence is still limited, the combination of beta-lactams and macrolides is recommended as empiric therapy for bacteraemic pneumococcal pneumonia.

Paediatric invasive pneumococcal disease on the island of Gran Canaria: 16-year prospective study (2001-2016).

OBJECTIVES: To calculate the incidence of invasive pneumococcal disease (IPD) in the paediatric population of Gran Canaria (Spain), its clinical and epidemiological characteristics, serotype distribution, antibiotic resistance, and variations in these variables before and after the introduction of the PCV13 vaccine. METHODS: Prospective hospital-based study including all patients (190) aged 0-14 years admitted with confirmed IPD between January 2001-May 2010 (152 cases) and June 2010-December 2016 (38 cases). Patients were divided into 3 age groups (<2 years; 2-5 years; and >5 years). Clinical symptoms were mutually-exclusively classified as meningitis, bacteraemic pneumonia, pleural effusion (PE), empyema or bacteraemia without a focus. RESULTS: Most cases occurred in boys (59.47%), during autumn-winter (65.79%), in children aged <2 years (55.79%) and with mean age increasing from the pre-PCV13 to the post-PCV13 period (2.5 vs 3.1 years). Incidence between periods reduced by 66.4% (p<0.001): from 13.1/100,000 to 4.4/100,000. PEs (3.9% vs 18.4%, p<0.005) and empyemas (1.5% vs 16.7%, p=NS) increased in the post-PCV13 period whereas all other symptoms decreased, although this was not statistically significant. Vaccine serotypes (77% vs 40.6%, p=0.000), particularly serotypes 19A (23.9% vs 12.5%) and 14 (14.2% vs 9.4%), as well as erythromycin resistance (57.2% vs 7.9%, p=0.000) decreased in the post-PCV13 period. CONCLUSION: IPD incidence, vaccine serotypes and erythromycin resistance decreased in the post-PCV13 period whereas PEs increased.

Clinical and microbiological characteristics of unusual manifestations of invasive pneumococcal disease.

INTRODUCTION: Invasive pneumococcal disease (IPD) typically presents as bacterial pneumonia, meningitis or primary bacteraemia. However, Streptococcus pneumoniae can produce infection at any level of the body (endocarditis, arthritis, spontaneous bacterial peritonitis, etc.), which is also known as unusual IPD (uIPD). There are very limited data available about the clinical and microbiological profile of these uncommon manifestations of pneumococcal disease. Our aim was to analyse clinical forms, microbiological profile, epidemiology and prognosis of a cohort of patients with unusual invasive pneumococcal disease (uIPD). METHODS: We present a retrospective study of 389 patients (all adult and paediatric patients diagnosed during the period) diagnosed with IPD at our hospital (Complejo Hospitalario Universitario de Vigo) between 1992 and 2014. We performed an analysis of clinical, microbiological and demographical characteristics of patients comparing the pre-pneumococcal conjugate vaccine (PCV) period with the post-vaccination phase. IPD and uIPD were defined as follows; IPD: infection confirmed by the isolation of S. pneumoniae from a normally sterile site, which classically presented as bacterial pneumonia, meningitis or primary bacteraemia; uIPD: any case of IPD excluding pneumonia, meningitis, otitis media, rhinosinusitis or primary bacteraemia. RESULTS: A total of 22 patients (6%) met the criteria of uIPD. A Charlson index >2 was more prevalent in uIPD patients than IPD patients (45% vs 24%; p=0.08). The most common clinical presentation of uIPD was osteoarticular infection (8 patients, 36%), followed by gastrointestinal disease (4 patients, 18%). Infection with serotypes included in PCV-13 was significantly higher in IPD patients (65%) than in patients with uIPD, 35% (p=0.018). Conversely, infection with multidrug-resistant strains was higher among patient with uIPD (27% vs 9%; p=0.014). The all-cause mortality rate was 15%, 13% in the IPD group and 32% among patients with uIPD (p=0.07). According to the multivariate analysis, a Charlson Index >2 (OR 5.1, 95% CI, 1.8-14.0) and a Pitt Score >2 (OR 1.4, 95% CI, 1.2-1.9) were independent predictors of mortality. CONCLUSION: uIPD is a rare entity that affects patients with more comorbidities than typical IPD and it is usually caused by non-vaccine serotypes with greater antimicrobial resistance.

Bases conceptuales y metodológicas para estimar el costo de las enfermedades neumocócicas en niños en el primer nivel de atención de salud / Conceptual and methodological bases for estimating the cost of pneumococcal diseases in children in the primary health care

Introducción: Conocer el costo de la enfermedad neumocócica en niños es necesario para la asignación y gestión de los recursos destinados a su tratamiento y para respaldar los estudios dirigidos al costo efectividad de intervenciones preventivas. Objetivo: Describir las estrategias metodológicas empleadas para la estimación del costo de la atención a la enfermedad neumocócica en niños en el primer nivel de atención de salud. Fuente de los datos: Se realizó una revisión bibliográfica y documental.Se utilizó como estrategia de búsqueda: costo, enfermedad neumocócica, atención primaria de salud y niños. Se incluyeron aquellos artículos en español e inglés, indexados en Scielo, PubMed o en el Schoolar Google. Se identificaron 17 publicaciones. Síntesis de los datos: El tratamiento dado a los aspectos conceptuales y metodológicos fue similar en todos los estudios. Entre los desenlaces clínicos se consideró la meningitis, la sepsis, la neumonía y la otitis media. La perspectiva más frecuentemente empleada fue la institucional. Los estudios se enfocaron en el costo directos médicos a partir de las partidas de salario, pruebas diagnósticas y medicamentos. Como estrategia para el costeo se combinaron los métodos Arriba-Abajo, Abajo-Arriba o Microcosteo y Caso Tipo o Estándar. Conclusiones: Son escasos los estudios de costos de la enfermedad neumocócica en niños que incluyan el primer nivel de atención. Los diseños metodológicos se asociaron a evaluaciones económicas completas, incluyen a la mayoría de los desenlaces clínicos y se enfocan en los costos institucionales. La combinación de diferentes métodos de costeo caracteriza el estudio de esta temática(AU)

Introduction: It is required to know the cost of pneumococcal disease in children in order to allocate and manage the adequate resources for treatment and to support the cost-effectiveness study of preventive interventions. Objective: To describe the methodological strategies for estimation of the cost of care for pneumococcal disease in children at the primary health care. Data source: A literature and documentary review was made in which the search strategy comprised cost, pneumococcal disease, primary health care and children. Those articles in Spanish and English indexed in Scielo, PubMed and in Schoolar Google were included. Seventeen publications were identified. Data synthesis: The conceptual and methodological aspects were addressed in a similar way in all the studies. Among the clinical outcomes were meningitis, sepsis, pneumonia and otitis media. The most frequently used perspective was institutional one. The studies focused on direct medical costs on the basis of salary items, diagnostic tests and medications. The cost strategy combined the Top-Down, the Down-Up or Microcosts and Type or Standard Case methods. Conclusions: There are few studies on the pneumococcal disease cost in children at the primary health care. The methodological designs are associated with comprehensive economic assessments, include most of the clinical outcomes, and focus on institutional costs. The combination of different costing methods characterizes the study of this topic(AU)

Enfermedad neumocócica invasiva por serotipo 38, reporte de caso clínico / Invasive pneumococcal disease by serotype 38, a clinical case report

La enfermedad neumocócica invasiva (ENI) es causa de morbimortalidad prevenible en pediatría. Con la introducción de vacunas antineumocócicas conjugadas disminuyó la prevalencia de ENI en 61,9% en los menores de 2 años, y se produjo un cambio en la distribución de serotipos y un aumento de ENI por serotipos no vaccinales. En este contexto, es relevante la vigilancia epidemiológica de los serotipos emergentes causantes de ENI en la población. Se presentará el caso de una lactante de 11 meses con diagnóstico de meningitis causada por neumococo serotipo 38, su evolución y consecuencias clínicas, y se realiza un análisis de la situación epidemiológica actual.

In pediatrics,invasive pneumococcal disease is a preventable cause ofmorbidity andmortality.The introduction of conjugated pneumococcal vaccines has reduced the prevalence of invasive pneumococcal disease by 61.9% in the under two's and has brought about a change in the distribution of serotypes and a rise in invasive pneumococcal disease caused by non-vaccine serotypes.This being the case,itis very importanttomonitorthe epidemiology ofthe emerging serotypes causing the disease in the population.We presentthe case of an 11 month old infant diagnosed with meningitis caused by serotype 38, describing his clinical course andclinical consequences; andweperforman analysis ofthepresent epidemiologica lsituation