Investigating Local Patterns of Mumps Virus Circulation, Using a Combination of Molecular Tools.

Mumps is a vaccine-preventable disease caused by the mumps virus (MuV). However, MuV has re-emerged in many countries with high vaccine coverage. The World Health Organization (WHO) recommends molecular surveillance based on sequencing of the small hydrophobic (SH) gene. Additionally, the combined use of SH and non-coding regions (NCR) has been described in different studies, proving to be a useful complement marker to discriminate general patterns of circulation at national and international levels. The aim of this work is to test local-level usefulness of the combination of SH and MF-NCR sequencing in tracing hidden transmission clusters and chains during the last epidemic wave (2015-2020) in Spain. A database with 903 cases from the Autonomous Community of Madrid was generated by the integration of microbiological and epidemiological data. Of these, 453 representative cases were genotyped. Eight different SH variants and thirty-four SH haplotypes were detected. Local MuV circulation showed the same temporal pattern previously described at a national level. Only two of the thirteen previously identified outbreaks were caused by more than one variant/haplotype. Geographical representation of SH variants allowed the identification of several previously undetected clusters, which were analysed phylogenetically by the combination of SH and MF-NCR, in a total of 90 cases. MF-NCR was not able to improve the discrimination of geographical clusters based on SH sequencing, showing limited resolution for outbreak investigations.

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.

[Public funding impact of the pneumococcal vaccine on compliance with the vaccination schedule.] / Impacto de la financiación pública de la vacuna frente a neumococo en el cumplimiento de la pauta vacunal.

OBJECTIVE: It is important to know the impact of public financing on routine vaccination on compliance with the vaccination regimen. Few studies have been carried out on this topic. The objective of this study was to describe the effect of public financing of pneumococcal vaccine on vaccination coverage and the degree of compliance with the vaccination regimen in the child population of the Community of Madrid (CM). METHODS: A descriptive observational study was carried out. The study population were children vaccinated in the period of public (2008 and 2010) and private (2012 and 2013) funding. Data source was the vaccination information system. We estimated the coverage of "full inmunization" at 24 months and the coverage of "vaccination on time" of the primary vaccination and the complete schedule. Comparison according to the type of financing was made using the prevalence ratio (PR) and the relative percentage of change. The delay between vaccine doses was calculated at 24 months of age. RESULTS: On-time vaccination coverage was 72% when public financing of the vaccine and 64% when private financing (PR= 1.12). The delay between doses was greater than 10% when funding was private. CONCLUSIONS: Public financing of the vaccine improves compliance with the vaccine regimen.

OBJETIVO: Es importante conocer el impacto de la financiación pública de la vacunación sistemática sobre el cumplimiento de la pauta vacunal. Se han realizado pocos estudios sobre este tema. El objetivo de este estudio fue describir el efecto de la financiación pública de la vacuna antineumocócica sobre la cobertura de vacunación y el grado de cumplimiento de la pauta vacunal en la población infantil de la Comunidad de Madrid (CM). METODOS: Se realizó un estudio observacional descriptivo. La población de estudio fueron niños residentes en la Comunidad de Madrid que alcanzaron la edad de vacunación en los períodos de financiación pública (2008 y 2010) y privada (2012 y 2013). La fuente de datos fue el sistema de información vacunal de la CM. Se estimó la cobertura de "vacunación completa" a los 24 meses y la cobertura de "vacunación a tiempo" de la primovacunación y de la pauta completa. La comparación según el tipo de financiación se efectuó mediante la razón de prevalencias (RP) y el porcentaje relativo del cambio. Se calculó el retraso entre dosis vacunales a los veinticuatro meses de edad. RESULTADOS: La cobertura de vacunación a tiempo fue del 72% cuando la financiación de la vacuna fue pública y del 64% cuando fue privada (RP=1,12). El retraso entre dosis fue mayor del 10% cuando la financiación fue privada. CONCLUSIONES: La financiación pública de la vacuna mejora el cumplimiento de la pauta vacunal.

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.

Evolución de la distribución de serotipos de Streptococcus pneumoniae aislados en líquido pleural en la Comunidad de Madrid entre los años 2007 y 2018 / Evolution of the distribution of Streptococcus pneumoniae serotypes isolated in pleural fluid in the Madrid Autonomous Community between the years 2007-2018

INTRODUCCIÓN: El objetivo de este estudio es describir la distribución de serotipos de Streptococcus pneumoniae aislados de líquido pleural en la Comunidad de Madrid entre los años 2007 y 2018. MÉTODOS: Se estudiaron las cepas de episodios de enfermedad neumocócica invasiva aisladas en la Comunidad de Madrid durante el periodo 2007-2018. La frecuencia de serotipos en líquido pleural se comparó con la observada en otras muestras. RESULTADOS: Se procesaron 6.115 cepas invasivas de neumococo; de ellas, 182(3%) se aislaron en muestras de líquido pleural. El 70,9% de los aislados pertenecía a alguno de los 6 siguientes serotipos: 1, 3, 19A, 8, 7F y 5. Los serotipos 3 y 8 aumentaron de manera significativa: pasaron del 9,6 al 30,8%, y del 5,3% al 20,5%, respectivamente, entre los periodos 2007-2010 y 2015-2018. CONCLUSIÓN: Los serotipos 3 y 8 son causas importantes de infección del líquido pleural en nuestra área en la actualidad

INTRODUCTION: The aim of this study was to describe the distribution of Streptococcus pneumoniae serotypes in isolates from pleural fluid in the Madrid Autonomous Community between the years 2007-2018. METHODS: Invasive pneumococcal disease strains isolated during the period 2007-2018 were studied. The frequency of serotypes from pleural fluid was compared with that observed in other samples. RESULTS: A total of 6,115 pneumococcal invasive isolates were processed. Of them, 182 (3%) were isolated from pleural fluid. A total of 70.9% of isolates belonged to some of the following 6 serotypes: 1, 3, 19A, 8, 7F and 5. The serotypes 3 and 8 increased significantly from 9.6% to 30.8%, and from 5.3% to 20.5%, respectively, over the periods 2007-2010 to 2015-2018. CONCLUSIONS: Pneumococcal serotypes 3 and 8 are currently significant causes of infection of pleural fluid in our region

Hepatitis C and hepatitis C-related advanced liver disease hospitalisation trends before and after the Strategic Plan for Tackling Hepatitis C in the National Health System.

INTRODUCTION: This work evaluates the burden and trends of hepatitis C virus (HCV)-associated hospitalisations in Spain before and after the implementation of the Strategic Plan for Tackling Hepatitis C in the National Health System in 2015. METHODS: HCV-related hospitalisation discharges from 2005 to 2017 were obtained from the National Registry of Hospitalisations. A descriptive analysis of the hospitalisations was performed. RESULTS: From 2005 to 2017, there were 674 067 HCV-related hospitalisations: 1.2%, 29.9%, 63.9% and 5% of them due to acute, carriers, chronic and unspecified hepatitis C. Average age of the patients was 57.7 years (SD: 16.4), average hospital stay was 9.1 days (SD: 12.2) and intra-hospital case-fatality rate was 6.5%. Hospitalisation rates decreased notably (P < 0.05) in 2016-2017 compared to 2005-2015 for all [hospitalisation rate ratio (HRR): 0.77], males (HRR: 0.80), females (HRR: 0.74), chronic hepatitis C (HRR: 0.84), non-advanced liver disease (N-AdLD) (HRR: 0.80) and AdLD (HRR: 0.73). Acute HCV (HRR: 0.54) and carriers (HRR: 0.49) show decreases in 2016-2017 vs. 2005-2015, although their rates started to decrease in 2008/2009. Unspecified HCV hospitalisation rates increased (P < 0.05) in 2016-2017 (HRR: 2.02) vs. 2005-2015. From 2015 to 2017, cost per patient increased from 5981 euros to 6349 euros, but overall cost decreased, as hospitalisations rates decreased from 302 to 264 million euros. DISCUSSION: HCV-related hospitalisation rates decreased notably in 2016 and 2017 after the strategic plan for tackling hepatitis C was launched. Although cost per AdLD patient increased in 2016 and 2017, globally costs were reduced around 35 million euros per year.

Evolution of the distribution of Streptococcus pneumoniae serotypes isolated in pleural fluid in the Madrid Autonomous Community between the years 2007-2018. / Evolución de la distribución de serotipos de Streptococcus pneumoniae aislados en líquido pleural en la Comunidad de Madrid entre los años 2007 y 2018.

INTRODUCTION: The aim of this study was to describe the distribution of Streptococcus pneumoniae serotypes in isolates from pleural fluid in the Madrid Autonomous Community between the years 2007-2018. METHODS: Invasive pneumococcal disease strains isolated during the period 2007-2018 were studied. The frequency of serotypes from pleural fluid was compared with that observed in other samples. RESULTS: A total of 6,115 pneumococcal invasive isolates were processed. Of them, 182 (3%) were isolated from pleural fluid. A total of 70.9% of isolates belonged to some of the following 6serotypes: 1, 3, 19A, 8, 7F and 5. The serotypes 3 and 8 increased significantly from 9.6% to 30.8%, and from 5.3% to 20.5%, respectively, over the periods 2007-2010 to 2015-2018. CONCLUSIONS: Pneumococcal serotypes 3 and 8 are currently significant causes of infection of pleural fluid in our region.

Serotipos de Streptococcus pneumoniae con tropismo meníngeo en casos de enfermedad neumocócica invasora. Comunidad de Madrid, 2007-2018 / Streptococcus pneumoniae serotypes with meningeal tropism in cases of invasive pneumococcal disease. Community of Madrid, 2007-2018

INTRODUCCIÓN: Se describe la distribución de serotipos de Streptococcus pneumoniae aislados en líquido cefalorraquídeo (LCR) entre los años 2007-2018 en la Comunidad de Madrid (CM) identificando aquellos con mayor tropismo meníngeo. MÉTODOS: Se estudiaron las cepas de episodios de enfermedad neumocócica invasora enviadas al Laboratorio Regional de Salud Pública por los servicios de microbiología de hospitales públicos y privados de la CM. La frecuencia de serotipos procedentes de LCR se comparó con la observada en otras muestras. RESULTADOS: Se procesaron 6.115 cepas. El 5% (n = 304) se aislaron en LCR. Siete serotipos (11A, 19F, 23B, 10A, 24F, 23A y 35F) mostraron una frecuencia en LCR significativamente mayor que en otras muestras habitualmente estériles. Los serotipos 24F, 11A y 23B mostraron alta resistencia a la penicilina. CONCLUSIÓN: La frecuencia y la resistencia de determinados serotipos de neumococo con elevado tropismo meníngeo podría comprometer el tratamiento de las infecciones del sistema nervioso central

INTRODUCTION: To describe the distribution of Streptococcus pneumoniae serotypes isolated in cerebrospinal fluid (CSF) between 2007-2018 in the Community of Madrid (CM) and to identify those with higher meningeal tropism. METHODS: Strains isolated from invasive pneumococcal disease were sent to the Regional Laboratory of Public Health by Microbiology laboratories of public and private hospitals of the CM. The frequency of serotypes from CSF was compared with that observed in other samples. RESULTS: A total of 6,115 strains were processed and 5% (n=304) were isolated from CSF. Seven serotypes (11A, 19F, 23B, 10A, 24F, 23A and 35F) showed a frequency significantly higher in CSF than in other usually sterile samples. Serotypes 24F, 11A and 23B showed high penicillin-resistance. CONCLUSION: The frequency and resistance of certain pneumococcal serotypes with high meningeal tropism could compromise the treatment of central nervous system infections

Increase of serotype 8, ST53 clone, as the prevalent strain of Streptococcus pneumoniae causing invasive disease in Madrid, Spain (2012-2015) / Incremento del serotipo 8, clon ST53, como la cepa más prevalente causante de enfermedad neumocócica invasora en Madrid, España (2012-2015)

INTRODUCTION: In recent years, Streptococcus pneumoniae serotype 8 has become the most prevalent cause of invasive pneumococcal disease (IPD) in Madrid, Spain. The objective of this study was to characterize the invasive clones of S. pneumoniae serotype 8 in Madrid over the 2012-2015 period. METHODS: From January 2012 to December 2015, a total of 1543 invasive isolates were studied. Serotyping was carried out by Pneumotest-Latex agglutination and Quellung reaction. Susceptibilities to penicillin, erythromycin and levofloxacin were determined by the Etest®. All serotype 8 strains were typed by multilocus sequence typing (MLST) and by pulsed-field gel electrophoresis (PFGE). RESULTS: Two hundred and forty-eight (248) serotype 8 strains were detected (16.1%) and 243 of them were available for molecular typing. Nine sequence types (STs) by MLST (8-ST53, 8-ST63, 8-ST404, 8-ST1107, 8-ST989, 8-ST1110, 8-ST2231, 8-ST3544 and 8-ST4301), and nine PFGE profiles were identified (one corresponding to each ST). The 8-ST53 clone was the most widespread, and increased from 53.8% among all serotype 8 isolates in 2012, to 90.1% in 2015. In contrast, the 8-ST63 clone, resistant to levofloxacin and erythromycin, decreased from 30.8%, among all serotype 8 strains in 2012, to 5.0% in 2015. CONCLUSIONS: The increase in our region of S. pneumoniae serotype 8, not included in conjugated vaccines, occurred at the expense of the 8-ST53 clone. On the contrary, the 8-ST63 clone decreased. Since clone 8-ST63 has the theoretical advantage of its levofloxacin-erythromycin resistance in comparison to 8-ST53, the predominance of 8-ST53 over 8-ST63 is striking

INTRODUCCIÓN: En los últimos años Streptococcus pneumoniae serotipo 8 ha sido la causa más prevalente de enfermedad neumocócica invasora (ENI) en la Comunidad de Madrid. El objetivo de este estudio fue caracterizar los clones invasores de S. pneumoniae serotipo 8 circulantes en Madrid ente los años 2012 y 2015. MÉTODOS: Se estudiaron 1.543 cepas causantes de ENI aisladas entre enero de 2012 y diciembre de 2015. El serotipado se realizó mediante aglutinación con Pneumotest-Latex y reacción de Quellung. La determinación de la sensibilidad frente a penicilina, eritromicina y levofloxacino se realizó mediante Etest(R). Las cepas del serotipo 8 se tipificaron por MLST (multi-locus sequence typing) y electroforesis en campo pulsado (PFGE). RESULTADOS: Se detectaron 248 cepas del serotipo 8 (16,1%) y 243 de ellas estuvieron disponibles para tipado molecular. Se identificaron 9 tipos de ST: 8-ST53, 8-ST63, 8-ST404, 8-ST1107, 8-ST989, 8-ST1110, 8-ST2231, 8-ST3544 y 8-ST4301, y 9 perfiles de PFGE (uno correspondiente a cada ST). El clon 8-ST53 fue el más prevalente dentro del serotipo 8 y aumentó del 53,8% en 2012 al 90,1% en 2015. Por el contrario el clon 8-ST63 asociado con resistencia a levofloxacino y eritromicina disminuyó del 30,8% en 2012 al 5,0% en 2015. CONCLUSIONES: El incremento del serotipo 8 en nuestra región, no cubierto por las actuales vacunas conjugadas, se produjo a expensas del clon 8-ST53. Inversamente, el clon 8-ST63 disminuyó. Dado que el clon 8-ST63 presenta sobre el 8-ST53 la ventaja teórica de su resistencia frente a levofloxacino y eritromicina, resulta llamativo el predominio de 8-ST53 sobre 8-ST63

Increase of serotype 8, ST53 clone, as the prevalent strain of Streptococcus pneumoniae causing invasive disease in Madrid, Spain (2012-2015).

INTRODUCTION: In recent years, Streptococcus pneumoniae serotype 8 has become the most prevalent cause of invasive pneumococcal disease (IPD) in Madrid, Spain. The objective of this study was to characterize the invasive clones of S. pneumoniae serotype 8 in Madrid over the 2012-2015 period. METHODS: From January 2012 to December 2015, a total of 1543 invasive isolates were studied. Serotyping was carried out by Pneumotest-Latex agglutination and Quellung reaction. Susceptibilities to penicillin, erythromycin and levofloxacin were determined by the Etest®. All serotype 8 strains were typed by multilocus sequence typing (MLST) and by pulsed-field gel electrophoresis (PFGE). RESULTS: Two hundred and forty-eight (248) serotype 8 strains were detected (16.1%) and 243 of them were available for molecular typing. Nine sequence types (STs) by MLST (8-ST53, 8-ST63, 8-ST404, 8-ST1107, 8-ST989, 8-ST1110, 8-ST2231, 8-ST3544 and 8-ST4301), and nine PFGE profiles were identified (one corresponding to each ST). The 8-ST53 clone was the most widespread, and increased from 53.8% among all serotype 8 isolates in 2012, to 90.1% in 2015. In contrast, the 8-ST63 clone, resistant to levofloxacin and erythromycin, decreased from 30.8%, among all serotype 8 strains in 2012, to 5.0% in 2015. CONCLUSIONS: The increase in our region of S. pneumoniae serotype 8, not included in conjugated vaccines, occurred at the expense of the 8-ST53 clone. On the contrary, the 8-ST63 clone decreased. Since clone 8-ST63 has the theoretical advantage of its levofloxacin-erythromycin resistance in comparison to 8-ST53, the predominance of 8-ST53 over 8-ST63 is striking.

Streptococcus pneumoniae serotypes with meningeal tropism in cases of invasive pneumococcal disease. Community of Madrid, 2007-2018. / Serotipos de Streptococcus pneumoniae con tropismo meníngeo en casos de enfermedad neumocócica invasora. Comunidad de Madrid, 2007-2018.

INTRODUCTION: To describe the distribution of Streptococcus pneumoniae serotypes isolated in cerebrospinal fluid (CSF) between 2007-2018 in the Community of Madrid (CM) and to identify those with higher meningeal tropism. METHODS: Strains isolated from invasive pneumococcal disease were sent to the Regional Laboratory of Public Health by Microbiology laboratories of public and private hospitals of the CM. The frequency of serotypes from CSF was compared with that observed in other samples. RESULTS: A total of 6,115 strains were processed and 5% (n=304) were isolated from CSF. Seven serotypes (11A, 19F, 23B, 10A, 24F, 23A and 35F) showed a frequency significantly higher in CSF than in other usually sterile samples. Serotypes 24F, 11A and 23B showed high penicillin-resistance. CONCLUSION: The frequency and resistance of certain pneumococcal serotypes with high meningeal tropism could compromise the treatment of central nervous system infections.

Impacto de la vacuna triple vírica sobre la incidencia de la parotiditis en la Comunidad de Madrid y evaluación de la efectividad de la cepa Jeryl-Lynn entre 1998 y 2016 / Impact of the MMR vaccine on the incidence of mumps in the Community of Madrid and evaluation of the effectiveness of the Jeryl-Lynn strain. Years 1998-2016

Introducción y objetivo: La parotiditis se caracteriza por la inflamación de la glándula parótida y fiebre, y es prevenible mediante vacunación con triple vírica (TV). El objetivo es evaluar el impacto y la efectividad vacunal (EV). Material y métodos: Se seleccionaron los casos notificados al Sistema de Enfermedades de Declaración Obligatoria entre 1998 y 2016. La EV se calculó en cohortes vacunadas con 2 dosis de Jeryl-Lynn, y el impacto comparando las incidencias por edad y por cohortes Rubini (1995-1998) y Jeryl-Lynn (1999-2002) en los periodos 1998-2004, 2005-2009 y 2010-2015. Las estimaciones por grupo de edad y período se compararon con las del período anterior y las estimaciones por cohortes se compararon entre sí dentro de cada período mediante razones de incidencia (RI) empleando modelos de Poisson. La EV se estimó empleando el método de cribado mediante modelos de regresión logística. Resultados: Se notificaron 13.816 casos. La incidencia en 2005-2009 fue superior a la de 1998-2004 (RI: 1,46; IC 95%: 1,40-1,53), y en 2010-2015 se mantuvo estable (RI: 0,99; IC 95%: 0,95-1,03). La incidencia anual media de las cohortes Rubini fue de 69,43 casos por 100.000 habitantes y la de las cohortes Jeryl-Lynn de 32,24. La RI fue de 0,25 (IC 95%: 0,22-0,29), 0,55 (IC 95%: 0,49-0,61) y 0,88 (IC 95%: 0,76-1,00) para cada periodo, respectivamente. Se incluyeron 2.574 casos en el estudio de EV. La EV disminuyó con el tiempo al alcanzar valores no significativos tras 7 años de seguimiento (EV: 55%; IC 95%: 82 a -12%). Conclusiones: El comportamiento de la parotiditis se caracteriza por presentar fluctuaciones, cambios en la presentación etaria y una disminución de la EV

Introduction: Mumps is characterised by parotid inflammation and fever and is preventable by vaccination with MMR vaccine. The objective of the study is to assess the impact and effectiveness of the vaccine. Material and methods: Cases notified to the Notifiable Disease System between 1998 and 2016 were used for the study. The vaccine effectiveness (VE) was calculated in cohorts vaccinated with two doses of Jeryl-Lynn, and the impact was calculated by comparing incidences by age and by Rubini (1995-1998) and Jeryl-Lynn (1999-2002) cohorts during the periods 1998-2004, 2005-2009 and 2010-2015. The incidences for age group and period were compared with the previous period and the incidences for cohorts were compared within a period with incidence ratios (IR) using Poisson models. The VE was estimated using the screening method using logistic regression models. Results: 13,816 cases were reported. The incidence in 2005-2009 was higher than in 1998-2004 (IR: 1.46, 95% CI: 1.40-1.53), and it remained stable in 2010-2015 (IR: 0.99, 95% CI: 0.95-1.03). The average incidence rate of the Rubini cohort was 69.43 and the Jeryl-Lynn cohort was 32.24. The IR was 0.25 (95% CI: 0.22-0.29), 0.55 (95% CI: 0.49-0.61) and 0.88 (95% CI: 0.76-1.00) for each period respectively. 2,574 cases were included in the VE study. EV decreased over time reaching not significant values after seven years of follow-up (VE: 55%, 95% CI: 82 to -12%). Conclusions: Parotiditis behavior is characterised by fluctuations, changes in presentation and a decrease in VE

Prevalence of asymptomatic Leishmania infection and associated risk factors, after an outbreak in the south-western Madrid region, Spain, 2015.

BackgroundA large outbreak of leishmaniasis with 758 cutaneous and visceral leishmaniasis cases occurred in 2009 in Fuenlabrada, in the south-west of the Madrid region of Spain.AimWe aimed to determine the prevalence of asymptomatic Leishmania infection after this outbreak, and its associated risk factors.MethodsA cross-sectional study of 804 healthy individuals living in Fuenlabrada who had no history of leishmaniasis, was conducted between January and July 2015. Asymptomatic infections were sought by either a combination of PCR, immunofluorescent antibody titre, and direct agglutination tests, or by whole blood stimulation assay (WBA) with interleukin-2 (IL-2) quantification.ResultsUsing the first approach, prevalence of asymptomatic individuals was 1.1% (9/804), while the second returned a value of 20.7% (143/804). Older age, being male, proximity to the park where the focus of infection was identified, and living in a detached house, were all strongly associated with the prevalence of asymptomatic infection.ConclusionsThe true number of infected individuals may be underestimated if only serological methods are used. The combination of WBA with IL-2 quantification may allow to better determine the prevalence of asymptomatic Leishmania infection, which would be useful in establishing control measures and in quantifying their impact. In our study, the use of WBA with IL-2 quantification also helped establish the risk factors that influence exposure to and infection by Leishmania.

Impact of the MMR vaccine on the incidence of mumps in the Community of Madrid and evaluation of the effectiveness of the Jeryl-Lynn strain. Years 1998-2016. / Impacto de la vacuna triple vírica sobre la incidencia de la parotiditis en la Comunidad de Madrid y evaluación de la efectividad de la cepa Jeryl-Lynn entre 1998 y 2016.

INTRODUCTION: Mumps is characterised by parotid inflammation and fever and is preventable by vaccination with MMR vaccine. The objective of the study is to assess the impact and effectiveness of the vaccine. MATERIAL AND METHODS: Cases notified to the Notifiable Disease System between 1998 and 2016 were used for the study. The vaccine effectiveness (VE) was calculated in cohorts vaccinated with two doses of Jeryl-Lynn, and the impact was calculated by comparing incidences by age and by Rubini (1995-1998) and Jeryl-Lynn (1999-2002) cohorts during the periods 1998-2004, 2005-2009 and 2010-2015. The incidences for age group and period were compared with the previous period and the incidences for cohorts were compared within a period with incidence ratios (IR) using Poisson models. The VE was estimated using the screening method using logistic regression models. RESULTS: 13,816 cases were reported. The incidence in 2005-2009 was higher than in 1998-2004 (IR: 1.46, 95% CI: 1.40-1.53), and it remained stable in 2010-2015 (IR: 0.99, 95% CI: 0.95-1.03). The average incidence rate of the Rubini cohort was 69.43 and the Jeryl-Lynn cohort was 32.24. The IR was 0.25 (95% CI: 0.22-0.29), 0.55 (95% CI: 0.49-0.61) and 0.88 (95% CI: 0.76-1.00) for each period respectively. 2,574 cases were included in the VE study. EV decreased over time reaching not significant values after seven years of follow-up (VE: 55%, 95% CI: 82 to -12%). CONCLUSIONS: Parotiditis behavior is characterised by fluctuations, changes in presentation and a decrease in VE.

Evolución de la enfermedad neumocócica invasora y sus serotipos en la Comunidad de Madrid / nfermedad neumocócica invasiva pediátrica en la isla de Gran Canaria: estudio prospectivo durante 16 años (2001-2016)

INTRODUCCIÓN: Streptococcus pneumoniae es una causa importante de morbilidad, y la vacuna es la medida más eficaz para prevenirla. El objetivo de este estudio es analizar la evolución de la enfermedad neumocócica invasora (ENI). MATERIAL Y MÉTODOS: Estudio observacional de los casos de ENI residentes en la Comunidad de Madrid notificados a la Red de Vigilancia Epidemiológica entre los años 2008 y 2015. El caso de ENI se definió como la enfermedad producida por Streptococcus pneumoniae, con aislamiento, detección de ADN o detección de antígeno, en muestras procedentes de sitios normalmente estériles. Las cepas aisladas se enviaron al Laboratorio Regional de Salud Pública para la identificación del serotipo. Los serotipos se clasificaron según su inclusión en la vacuna heptavalente (VCN7), en la vacuna trecevalente pero no en la heptavalente (VCN13 adicional) y no incluidos en la VCN13 (no VCN). Se calcularon las razones de incidencia (RI) comparando los períodos 2011-2012 y 2013-2015 con el período 2008-2010. RESULTADOS: Se notificaron 4.307 casos. El 86,6% fueron serotipados. La RI de ENI para todos los serotipos fue de 0,67 y de 0,67; la RI para los serotipos VCN7 fue de 0,43 y de 0,45; la RI para los VCN13 adicional fue de 0,46 y de 0,25, y la RI para los no VCN fue de 1,01 y de 1,32 en los períodos 2011-2012 y 2013-2015. Los serotipos 8, 9 N, 10A, 23B, 24F y el serogrupo 33 incrementaron su incidencia de manera significativa en el período 2013-2015. Los serotipos 15B y 24F supusieron el 24% de los casos no VCN13 en menores de 5años, los serotipos 8 y 9 N el 51% en población de 5 a 59 años y los serotipos 8 y 22F el 25% en mayores de 59 años. CONCLUSIONES: La incidencia de serotipos no incluidos en vacunas conjugadas ha aumentado, especialmente en menores de 5 años, pero la incidencia total de ENI ha disminuido. Es imprescindible continuar con los programas de vigilancia epidemiológica y microbiológica para valorar el efecto de la vacunación sobre la incidencia de la ENI

INTRODUCTION: Streptococcus pneumoniae is an important cause of morbidity. Vaccination is the most effective measure to prevent it. The aim of this study is to analyse the evolution of invasive pneumococcal disease (IPD). MATERIAL AND METHODS: Observational study of IPD cases notified to the Epidemiological Surveillance Network of the Autonomous Community of Madrid between 2008 and 2015. The IPD case was defined as the disease caused by Streptococcus pneumoniae, with isolation and DNA or antigen detection, in samples from normally sterile sites. The isolated strains were sent to the Regional Public Health Laboratory for identification of the serotype. Serotypes were classified according to their inclusion in the 7-valent conjugate vaccine (PCV7), in the 13-valent vaccine, but not in the 7-valent vaccine (PCV13-additional) and not included in the 13-valent vaccine (non-PCV). The Incidence Rate Ratios (IRRs) were calculated comparing the 2011-2012 and 2013-2015 periods with the 2008-2010 period. RESULTS: 4,307 cases were reported. 86.6% were serotyped. The IRR of IPD was 0.67 and 0.67 for all serotypes; 0.43 and 0.45 for PCV7 serotypes; 0.46 and 0.25 for PCV13-additional serotypes, and 1.01 and 1.32 for non-PCV13 serotypes in the 2011-2012 and 2013-2015 periods. The incidence of serotypes 8, 9 N, 10A, 23B, 24F and serogroup 33 increased significantly in the 2013-2015 period. Serotypes 15B and 24F accounted for 24% of non-PCV13 cases in children under 5 years, serotypes 8 and 9 N for 51% in the population aged 5 to 59 years and serotypes 8 and 22 F for 25% in the population aged over 59 years. CONCLUSIONS: The incidence of serotypes not included in conjugate vaccines has increased, especially in children under 5years, but the total incidence of IPD has decreased. It is important to continue with the epidemiological and microbiological surveillance programmes to assess the effect of vaccination on the incidence of IPD

Effectiveness and impact of a single-dose vaccine against chickenpox in the community of Madrid between 2001 and 2015.

BACKGROUND: Chickenpox is a contagious airborne disease. Immunization by varicella vaccine is an effective preventive measure. The objective of this study is to evaluate the impact and effectiveness of a single-dose vaccination against chickenpox at 15 months of age. METHODS: Observational study based on data from the Epidemiological Surveillance System of the Autonomous Community of Madrid from 2001 to 2015. The years were grouped into 4 periods according to epidemic cycles and vaccination schedule: 2001-06, 2007-10, 2011-13 and 2014-15. The impact was calculated as Relative Risk (RR) between the incidence of chickenpox in children between 15 months and 13 years of age between 2011-13 and 2001-06 through Poisson regression using notifications made to the Diseases of Compulsory Declaration (DCD) system, the Sentinel Physicians Network (SPN) and hospital discharge records noted as Minimum Basic Data Set (MBDS). The vaccine effectiveness (VE) was calculated using the screening method and a 1:2 case-control study paired by age and paediatrician in population from 15 months to 13 years and between 2007 and 2015 using SPN source data. RESULTS: The RR2011-13/2001-06 using data from the DCD was 0.14 (95% CI: 0.14 to 0.15), 0.07 (95% CI: 0.06 to 0.08) from SPN and 0.17 (95% CI: 0.15 to 0.20) from MBDS. A total of 338 cases were included in the VE screening obtaining an overall of 76.7% (IC 95%: 71.9 to 80.7%). For a case-control study, 120 cases and 247 controls were recruited obtaining a VE of 92.4% (IC 95%: 80.8 to 97.0%). CONCLUSIONS: The single-dose vaccination against chickenpox at 15 months of age has high impact and effectiveness.

Diagnóstico serológico de parotiditis epidémica: valor de la titulación de IgG específica / Serological diagnosis of mumps: Value of the titration of specific IgG

Introducción: El objetivo del estudio fue determinar un punto de corte de la titulación de IgG mediante ELISA en el diagnóstico de parotiditis. Métodos: Se estudiaron sueros de 85 casos de parotiditis (confirmados por PCR en saliva) y de 2.351 controles de la población de la Comunidad de Madrid. Resultados: La detección de IgM fue positiva en 21 casos (sensibilidad del 24,7). El mejor punto de corte de IgG correspondía a títulos ≥4.900 (sensibilidad del 64,7% y especificidad del 86,1%). De 42 pacientes vacunados con ≥1 dosis de triple vírica se detectó IgM en 4, mientras que la detección de IgG ≥4.900 fue positiva en 29 (sensibilidad del 69,0%). Conclusiones: Un resultado de IgG ≥4.900 fue casi 5 veces más probable en un paciente con parotiditis que en otro sujeto no infectado. La detección de títulos elevados de IgG frente a parotiditis puede mejorar el rendimiento diagnóstico de la IgM en vacunados (AU)

Introduction: The aim of this study was to evaluate a cut-off point of the titration of IgG by ELISA in the diagnosis of mumps. Methods: A study was made of serum samples from 85 mumps cases (confirmed by PCR in saliva) and 2,351 controls of the general population of the Region of Madrid. Results: The IgM detection was positive in 21 cases (sensitivity of 24.7%). The best cut-off point corresponded to IgG titres ≥4,900 (sensitivity of 64.7% and specificity of 86.1%). Among 42 patients immunised with at least one dose of measles mumps, rubella vaccine IgM was detected in 4 cases. However, the detection of IgG ≥4,900 was positive in 29 (sensitivity of 69.0%). Conclusions: An IgG result of ≥4.900 was almost 5 times more probable in a patient with mumps than in a non-infected patient. The detection of high titres of IgG against mumps could improve the IgM results in vaccinated people (AU)

Descenso de la incidencia de la varicela en la Comunidad de Madrid tras la vacunación infantil universal. Años 2001-2015 / Decrease in the incidence of chickenpox in the Community of Madrid after universal childhood immunization. Years 2001-2015

Objetivo: La vacuna frente a la varicela se recomendó en la Comunidad de Madrid (CM) a los 15 meses de edad entre noviembre de 2006 y diciembre de 2013. El objetivo fue describir el impacto de la vacunación sobre la incidencia de la varicela en la CM durante el período 2001-2015. Diseño: Estudio descriptivo de los casos de varicela notificados a la Red de Médicos Centinela de la CM y de los casos registrados en el Conjunto Mínimo Básico de Datos al alta hospitalaria. Se calculó la incidencia de casos y de ingresos de varicela, total y específica por edad y sexo. Resultados: La incidencia fue un 94,0% menor en el período 2012-2013 que en el período 2001-2003. En el período 2014-2015 la incidencia fue un 61,8% superior que en el período 2012-2013. La incidencia más alta se apreció en los niños de 0-4 años excepto en el período 2010-2014, en el que fue superada por la del grupo de 5-9 años. La tendencia de los ingresos hospitalarios también fue decreciente, siendo el grupo de menores de un año el de mayor incidencia. Conclusiones: La recomendación de vacunar a los 15 meses de edad ha producido un importante descenso de la incidencia de casos y de ingresos por varicela en todos los grupos de edad, lo que es compatible con la efectividad de una dosis y su capacidad para producir inmunidad de grupo. La retirada de esta recomendación en 2014 y 2015 ha conllevado un incremento de la incidencia (AU)

Objective: Varicella vaccine was recommended in the Community of Madrid (CM) at 15 months of age between November 2006 and December 2013. The objective was to describe the impact of vaccination on the incidence of varicella in the CM during the period 2001-2015. Design: A descriptive study of cases of varicella reported to the Sentinel Physician Network of the CM and the cases recorded in the Minimum Basic Data Set at hospital discharge was carried out. Total incidence of cases and of hospital admissions were calculated, as well as specific incidence by age and sex. Results: The incidence was 94.0% lower between 2012 and 2013 than between 2001 and 2003. Between 2014 and 2015 the incidence was 61.8% higher than between 2012 and 2013. The highest incidence was observed in children aged 0 to 4 years except for 2010-2014, which was exceeded by the incidence in children aged 5 to 9. The trend in hospital admissions was also decreasing, with the highest incidence in children aged 0 to 1 year, followed by 1-4 years. Conclusions: There has been a significant decrease in the incidence of cases and of hospital admissions by varicella in all age groups after the recommendation to vaccinate at 15 months of age, which is compatible with the effectiveness of a dose and its ability to produce immunity group. The withdrawal of this recommendation between 2014 and 2015 has led to an increase in the incidence (AU)

Trends of invasive pneumococcal disease and its serotypes in the Autonomous Community of Madrid. / Evolución de la enfermedad neumocócica invasora y sus serotipos en la Comunidad de Madrid.

INTRODUCTION: Streptococcus pneumoniae is an important cause of morbidity. Vaccination is the most effective measure to prevent it. The aim of this study is to analyse the evolution of invasive pneumococcal disease (IPD). MATERIAL AND METHODS: Observational study of IPD cases notified to the Epidemiological Surveillance Network of the Autonomous Community of Madrid between 2008 and 2015. The IPD case was defined as the disease caused by Streptococcus pneumoniae, with isolation and DNA or antigen detection, in samples from normally sterile sites. The isolated strains were sent to the Regional Public Health Laboratory for identification of the serotype. Serotypes were classified according to their inclusion in the 7-valent conjugate vaccine (PCV7), in the 13-valent vaccine, but not in the 7-valent vaccine (PCV13-additional) and not included in the 13-valent vaccine (non-PCV). The Incidence Rate Ratios (IRRs) were calculated comparing the 2011-2012 and 2013-2015 periods with the 2008-2010 period. RESULTS: 4,307 cases were reported. 86.6% were serotyped. The IRR of IPD was 0.67 and 0.67 for all serotypes; 0.43 and 0.45 for PCV7 serotypes; 0.46 and 0.25 for PCV13-additional serotypes, and 1.01 and 1.32 for non-PCV13 serotypes in the 2011-2012 and 2013-2015 periods. The incidence of serotypes 8, 9N, 10A, 23B, 24F and serogroup 33 increased significantly in the 2013-2015 period. Serotypes 15B and 24F accounted for 24% of non-PCV13 cases in children under 5years, serotypes 8 and 9N for 51% in the population aged 5 to 59years and serotypes 8 and 22F for 25% in the population aged over 59years. CONCLUSIONS: The incidence of serotypes not included in conjugate vaccines has increased, especially in children under 5years, but the total incidence of IPD has decreased. It is important to continue with the epidemiological and microbiological surveillance programmes to assess the effect of vaccination on the incidence of IPD.