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.

Necrotizing pneumonia due to Streptococcus pneumoniae in children during the period of non-systematic use of PCV13 in Catalonia, Spain.

BACKGROUND: Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain). METHODS: A prospective observational study was conducted in patients <18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%. RESULTS: 35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children <5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13. CONCLUSIONS: Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

[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.

Necrotizing pneumonia due to Streptococcus pneumoniae in children during the period of non-systematic use of PCV13 in Catalonia, Spain.

BACKGROUND: Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain). METHODS: A prospective observational study was conducted in patients <18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%. RESULTS: 35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children <5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13. CONCLUSIONS: Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

Impact of the 13-Valent Conjugated Pneumococcal Vaccine on the Direct Costs of Invasive Pneumococcal Disease Requiring Hospital Admission in Children Aged < 5 Years: A Prospective Study.

The lack of invasive pneumococcal disease (IPD) cost studies may underestimate the eect ofpneumococcal polysaccharide conjugated vaccines (PCV). The objective of this study was to estimatethe direct costs of hospitalized IPD cases. A prospective study was made in children aged <5 yearsdiagnosed with IPD in two high-tech hospitals in Catalonia (Spain) between 2007-2009 (PCV7 period)and 2012-2015 (PCV13 period). Costs were calculated according to 2014 Catalan Health Service ratesusing diagnostic-related groups. In total, 319 and 154 cases were collected, respectively. Pneumoniahad the highest cost (65.7% and 62.0%, respectively), followed by meningitis (25.8% and 26.1%,respectively). During 2007-2015, the costs associated with PCV7 serotypes (Pearson coecient (Pc) =?0.79; p = 0.036) and additional PCV13 serotypes (Pc = ?0.75; p = 0.05) decreased, but those of otherserotypes did not (Pc = 0.23 p = 0.62). The total mean cost of IPD increased in the PCV13 period by31.4% (¿3016.1 vs. ¿3963.9), mainly due to ICU stay (77.4%; ¿1051.4 vs. ¿1865.6). During the PCV13period, direct IPD costs decreased due to a reduction in the number of cases, but cases were more severe and had a higher mean cost. During 2015, IPD costs increased due to an increase in the costsassociated with non-PCV13 serotypes and serotype 3 and this requires further investigation.

Failures of 13-Valent Conjugated Pneumococcal Vaccine in Age-Appropriately Vaccinated Children 2-59 Months of Age, Spain.

Vaccination with the 13-valent conjugated pneumococcal disease (PCV13) has reduced invasive pneumococcal disease (IPD), but there have been reports of vaccine failures. We performed a prospective study in children aged 2-59 months who received diagnoses of IPD during January 2012-June 2016 in 3 pediatric hospitals in Catalonia, Spain, a region with a PCV13 vaccination coverage of 63%. We analyzed patients who had been age-appropriately vaccinated but who developed IPD caused by PCV13 serotypes. We detected 24 vaccine failure cases. The serotypes involved were 3 (16 cases); 19A (5 cases); and 1, 6B, and 14 (1 case each). Cases were associated with children without underlying conditions, with complicated pneumonia (OR 6.65, 95% CI 1.91-23.21), and with diagnosis by PCR (OR 5.18, 95% CI 1.84-14.59). Vaccination coverage should be increased to reduce the circulation of vaccine serotypes. Continuous surveillance of cases of IPD using both culture and PCR to characterize vaccine failures is necessary.

Complicated pneumococcal pneumonia with pleural effusion or empyema in the 13-valent pneumococcal conjugate vaccine era.

AIM: The aim was to analyze the epidemiological, microbiological and clinical characteristics of patients with complicated pneumococcal pneumonia with pleural effusion (PE) or empyema. METHOD: Prospective study in three Catalan hospitals in persons aged <18 years diagnosed with complicated pneumonia with PE or empyema with isolation of Streptococcus pneumoniae in blood or pleural fluid by culture or real-time PCR between January 2012 and June 2016. Patients were divided into <2 years and 2-17 years age groups. Epidemiological, microbiological, and clinical data of patients were compared annually in both groups. PCV13 vaccination coverage increased from 48.2% in 2012 to 74.5% in 2015. RESULTS: We included 143 patients. The incidence of pneumococcal pneumonia was 6.83 cases × 10-5 persons/year in cases with PE or empyema and 2.09 cases × 10-5 person-years in cases without (rate ratio [RR]: 3.27; 2.25-4.86; P < 0.001). Empyema was more frequent than PE (79.7% vs 20.3%, P < 0.005). Of 143 cases studied, 93 (65.0%, P < 0.001) were diagnosed by real-time-PCR, 43 (30.1%) by culture and RT-PCR and 7 (4.9%) by culture only. PCV13 serotypes were more frequent in complicated than in uncomplicated pneumonia (116/142, 81.7% vs 27/45, 60.0%; P = 0.003), especially serotype 1 (41/142, 28.9% vs 6/45, 13.3%, P : 0.036). From 2012 to 2015 there was a significant reduction in serotype 1 (16/43, 37.2% vs 3/27, 11.1%, P = 0.026), and a trend to an increase in non-PCV13 serotypes (6/43, 14% vs 9/27, 33.3%, P = 0.054). CONCLUSIONS: A directly proportional relationship was observed between the reduction in pneumonia complicated with PE or empyema and a significant reduction in PCV13 serotypes, especially serotype 1, coinciding with increased PCV13 coverage.

Is antibody-mediated rejection in kidney transplant recipients a risk factor for developing cytomegalovirus or BK virus infection? Results from a case-control study.

BACKGROUND: Data are scarce on cytomegalovirus (CMV) and BK virus (BKV) infection after antibody-mediated rejection (ABMR). OBJECTIVES: We hypothesized that the immunological response in patients with ABMR or the immune modulation associated with its treatment could predispose to CMV and BKV infection. Our objective was to investigate this hypothesis. STUDY DESIGN: We conducted a single-center, matched case-control study (1:2 ratio) to analyze CMV and BKV replication during the first year after the ABMR diagnosis in kidney transplant recipients. Adult recipients with a histopathological diagnosis of ABMR between 2007-2015 were included as cases. Controls were kidney recipients who underwent transplantation immediately before and after the index case. RESULTS: Fifty-eight patients diagnosed with ABMR (33 chronic active ABMR and 25 acute ABMR), with their matched controls (116) were included. Forty-four cases received treatment for ABMR, including plasmapheresis (41), immunoglobulins (40), and rituximab (31). Within 1 year after ABMR, cases showed CMV replication more often than controls (9/58, 15.5% vs 7/116, 6%, OR = 4.21, CI 1.10-16.16, p = 0.04). Over the study period, CMV PCR determinations were requested more frequently in cases than controls (46/58, 79.3% vs 63/116, 54.3%, OR = 4.58, CI 1.92-10.9, p = 0.001). On multivariate analysis adjusted for CMV PCR determinations, retransplantation, antithymocyte globulin treatment and methylprednisolone treatment for acute rejection, CMV replication remained more common in cases than in controls (OR = 2.41, CI 0.49-11.73, p = 0.28). There were no differences in BKV replication in either urine or blood. CONCLUSIONS: ABMR may be a risk factor for CMV but not for BKV replication in kidney transplant recipients.

Community-acquired Respiratory Viruses Are a Risk Factor for Chronic Lung Allograft Dysfunction.

BACKGROUND: The relationship between community-acquired respiratory viruses (CARVs) and chronic lung allograft dysfunction (CLAD) in lung transplant recipients is still controversial. METHODS: We performed a prospective cohort study (2009-2014) in all consecutive adult patients (≥18 years) undergoing lung transplantation in the Hospital Universitari Vall d'Hebron (Barcelona, Spain). We systematically collected nasopharyngeal swabs from asymptomatic patients during seasonal changes, from patients with upper respiratory tract infectious disease, lower respiratory tract infectious disease (LRTID), or acute rejection. Nasopharyngeal swabs were analyzed by multiplex polymerase chain reaction. Primary outcome was to evaluate the potential association of CARVs and development of CLAD. Time-dependent Cox regression models were performed to identify the independent risk factors for CLAD. RESULTS: Overall, 98 patients (67 bilateral lung transplant recipients; 63.3% male; mean age, 49.9 years) were included. Mean postoperative follow-up was 3.4 years (interquartile range [IQR], 2.5-4.0 years). Thirty-eight lung transplant recipients (38.8%) developed CLAD, in a median time of 20.4 months (IQR, 12-30.4 months). In time-controlled multivariate analysis, CARV-LRTID (hazard ratio [HR], 3.00 [95% confidence interval {CI}, 1.52-5.91]; P = .002), acute rejection (HR, 2.97 [95% CI, 1.51-5.83]; P = .002), and cytomegalovirus pneumonitis (HR, 3.76 [95% CI, 1.23-11.49]; P = .02) were independent risk factors associated with developing CLAD. CONCLUSIONS: Lung transplant recipients with CARVs in the lower respiratory tract are at increased risk to develop CLAD.

Effectiveness of the 13-valent pneumococcal conjugate vaccine in preventing invasive pneumococcal disease in children aged 7-59 months. A matched case-control study.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7-59 months in a population with suboptimal vaccination coverage of 55%. METHODS: The study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI). RESULTS: 169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1-87.2) and 90% (95% CI, 63.9-97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7-97.9) against serotype 1 and 86.0% (95% CI, 51.2-99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8). CONCLUSIONS: The effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7-59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually.

Vaccine Failures in Patients Properly Vaccinated with 13-Valent Pneumococcal Conjugate Vaccine in Catalonia, a Region with Low Vaccination Coverage.

Vaccine failures occurring with 13-valent pneumococcal conjugate vaccine (PCV13) in 3 pediatric hospitals in Barcelona (2012-2013) are described. PCV13 vaccine failure was defined as the occurrence of an invasive pneumococcal infection in children properly vaccinated by PCV13. Among 84 patients with invasive pneumococcal infection, 32 had received at least one dose of PCV13. Seventeen of them had invasive pneumococcal infection produced by a PCV13 serotype. Among those, 9 patients were considered to have a PCV13 vaccine failure. Serotype 3 was isolated in 6 patients, serotype 19A in 2 and serotype 6B in 1.

Are risk factors associated with invasive pneumococcal disease according to different serotypes?

The aim of this study was to investigate risk factors for the most common serotypes of invasive pneumococcal disease (IPD). A total of 293 IPD cases were analyzed in children aged 3-59 mo in a community with intermediate vaccination coverage with the 7-valent pneumococcal vaccine (PCV7). IPD cases were reviewed during 2007-2009 in two pediatric hospitals in Catalonia (Spain). A multivariate analysis using unconditional logistic regression was performed to estimate the adjusted odds ratio. PCV7 coverage was 45.4%. Pneumonia with empyema (64.5%) was the most frequent clinical manifestation. The most common serotypes were: serotype 1 (21.2%), 19A (16.0%), 3 (12.6%) and 7F/A (6.8%). 70.0% of serotypes found were included in the 13-valent conjugate vaccine (PCV13), 39.2% in the 10-valent conjugate vaccine and 8.1% in the PCV7. PCV7 was protective in IPD cases due to PCV7-serotypes (aOR: 0.15, 95% CI:0.04-0.55). Serotype 1 was positively associated with attending day care or school (aOR: 3.55, 95% CI: 1.21-10.38) and age 24-59 mo (aOR: 7.70, 95% CI:2.70-21.98). Serotype 19A was positively associated with respiratory infection in the previous month (aOR: 2.26, 95% CI: 1.03-4.94), non-penicillin susceptible IPD (aOR: 1.89, 95% CI:1.13-3.16) and negatively associated with age 24-59 mo (aOR: 0.19, 95% CI:0.09-0.41). Serotype 3 was positively associated with vaccination (aOR: 4.87, 95% CI:2.05-11.59). No factors were associated with serotype 7F/A. Vaccination with pneumococcal vaccines including more serotypes may reduce the risk of disease in our setting.

Clinical presentation of invasive pneumococcal disease in Spain in the era of heptavalent conjugate vaccine.

BACKGROUND: The aim of this study was to analyze the rate of incidence, clinical presentation, serotype, and clonal distribution of invasive pneumococcal disease (IPD) in the era of heptavalent pneumococcal conjugate vaccine (PCV7) in Barcelona, Spain. METHODS: This was a prospective study comprising all children <5 years with IPD who were managed in 2 tertiary-care, pediatric hospitals between January 2007 and December 2009. IPD was defined as the presence of clinical findings of infection together with isolation or detection of DNA of Streptococcus pneumoniae in a sterile fluid sample. RESULTS: In this study, 319 patients (53.3% male), mean age 29.6 months, were included. Comparing rates in 2007 and 2009 (76.2 and 109.9 episodes/100,000 population, respectively), an increase of 44% (95% confidence interval, 10%-89%) was observed. The main clinical presentation was pneumonia (254 episodes, 79.6%), followed by meningitis (29, 9.1%), and bacteremia (25, 7.8%).The diagnosis was made by positive culture in 123 (38.6%) patients and in 196 (61.4%) by real-time polymerase chain reaction. Serotype study was performed in 300 episodes, and 273 (91%) were non-PCV7 serotypes. The most frequent serotypes were 1 (20.7%), 19A (15.7%), and 3 (12.3%). A minimal inhibitory concentration ≥0.12 µg/mL to penicillin was detected in 34.4% of isolates. Sequence type 306 expressing serotype 1 was the most frequent clonal type detected (20.3% of studied strains). CONCLUSIONS: IPD continues to increase in Barcelona, and the rate is higher than previously reported as a result of low sensitivity of bacterial culture. Non-PCV7 serotypes were responsible for 91% of episodes and pneumonia was the main clinical presentation.

Brote de tos ferina con elevada tasa de ataque en niños y adolescentes bien vacunados / Outbreak of whooping cough with a high attack rate in well-vaccinated children and adolescents

Introducción La tos ferina es una enfermedad reemergente. Describimos la investigación de un brote de tos ferina y las medidas de control adoptadas. Métodos Se reconstruyó el evento a través de un estudio longitudinal de incidencia. Además de los casos notificados, se realizó una búsqueda activa a partir de la lista de asistentes a las colonias a través de llamadas telefónicas. A todos los casos se les aplicó la encuesta epidemiológica, se confirmó sus antecedentes vacunales con la historia clínica informatizada y se les propuso la obtención de muestras para confirmación analítica. La descripción del brote se realizó a través de la curva epidémica, las tasas de ataque, el riesgo relativo, la prueba de tendencia lineal por edades y la cobertura vacunal. Resultados De los 30 casos que se diagnosticaron 22 (73,3%) correspondían a los integrantes de las colonias. En éstas, la tasa de ataque fue del 21,8%, del 26,7% entre los niños y preadolescentes respectivamente, aumentando linealmente con la edad. El 86,4% de este último grupo estaban correctamente vacunados incluyendo la quinta dosis a los cuatro-seis años de edad. El 90% de los casos del brote fueron detectados a partir del estudio minucioso de los primeros casos y las llamadas telefónicas a los asistentes a las colonias. Conclusiones La búsqueda activa de casos permitió el estudio de un brote de tos ferina con elevada tasa de ataque en niños y preadolescentes y elevada cobertura vacunal y la aplicación de medidas de control que contribuyeron a la detención del brote (AU)

Introduction: Whooping cough is a re-emerging disease. We describe the investigation of an outbreak of whooping cough and the measures of control adopted. Methods: The event was reconstructed through a longitudinal study of incidence. In addition to the notified cases, an active search from the list of those who attended summer camps was made through telephone calls. An epidemiological survey was applied to all cases; vaccination history was confirmed with computerised clinical history and the obtaining of samples for analytical confirmation was proposed. The description of the outbreak was made through the epidemic curve, the attack rates, the relative risk and the linear trend by ages and the vaccination coverage. Results: Of the 30 cases that appeared, 22 (73.3%) were among the members of the summer camps. In these, the attack rate was 21.8%, 26.7% among the children and adolescents increasing linearly with the age. The large majority (86.4%) of this last group were correctly vaccinated, including the fifth dose at the age of 4-6 years. Through the meticulous study of the first cases and the telephone calls to those who attended the summer camp, 90% of the cases of the outbreak were detected. (.. )(AU)

Effectiveness of 7-valent pneumococcal conjugate vaccine in the prevention of invasive pneumococcal disease in children aged 7-59 months. A matched case-control study.

The aim of this study was to evaluate the effectiveness of the administration of the 7-valent pneumococcal conjugate vaccine in a region with an intermediate vaccination coverage. A matched case-control study was carried out in children aged 7-59 months with invasive pneumococcal disease (IPD) admitted to two university hospitals in Catalonia. Three controls matched for hospital, age, sex, date of hospitalization and underlying disease were selected for each case. Information on the vaccination status of cases and controls was obtained from the vaccination card, the child's health card, the hospital medical record or the vaccination register of the primary healthcare center where the child was attended for non-severe conditions. A conditional logistic regression analysis was made to control for the effect of possible confounding variables. The adjusted vaccination effectiveness of the complete vaccination schedule (3 doses at 2, 4 and 6 months and a fourth dose at 15 months, 2 doses at least two months apart in children aged 12-23 months or a single dose in children aged >24 months) in preventing IPD caused by vaccine serotypes was 93.7% (95% CI 51.8-99.2). It was not effective in preventing cases caused by non-vaccine serotypes. The results of this study carried out in a population with intermediate vaccination coverage confirm those of other observational studies showing high levels of effectiveness of routine 7-valent pneumococcal conjugate vaccination.

[Outbreak of whooping cough with a high attack rate in well-vaccinated children and adolescents]. / Brote de tos ferina con elevada tasa de ataque en niños y adolescentes bien vacunados.

INTRODUCTION: Whooping cough is a re-emerging disease. We describe the investigation of an outbreak of whooping cough and the measures of control adopted. METHODS: The event was reconstructed through a longitudinal study of incidence. In addition to the notified cases, an active search from the list of those who attended summer camps was made through telephone calls. An epidemiological survey was applied to all cases; vaccination history was confirmed with computerised clinical history and the obtaining of samples for analytical confirmation was proposed. The description of the outbreak was made through the epidemic curve, the attack rates, the relative risk and the linear trend by ages and the vaccination coverage. RESULTS: Of the 30 cases that appeared, 22 (73.3%) were among the members of the summer camps. In these, the attack rate was 21.8%, 26.7% among the children and adolescents increasing linearly with the age. The large majority (86.4%) of this last group were correctly vaccinated, including the fifth dose at the age of 4-6 years. Through the meticulous study of the first cases and the telephone calls to those who attended the summer camp, 90% of the cases of the outbreak were detected. CONCLUSIONS: The active search of cases allowed an outbreak of whooping cough with a high attack rate to be studied in children and adolescents with a high vaccination coverage, and the application of control measures that contributed to stop the outbreak.

Epidemiology of pertussis in a country with high vaccination coverage.

INTRODUCTION: Pertussis has been a preventable disease in Catalonia since 1965, but the annual number of cases remains high. The aim of this study was to analyze the epidemiology of pertussis in Catalonia and its implications for control purposes. METHODS: An epidemiological study was carried out in Catalonia between 2004 and 2008. Pertussis cases reported to the Department of Health were collected and disease reports were filled out with the case information. Incidence rates, rate ratios (RR) and their 95% confidence intervals (CI) were calculated. RESULTS: 963 cases were reported: 555 (57.6%) were confirmed and 408 (42.4%) were suspected cases. The reported incidence rate was 2.01 × 10(-5) person years in 2004 and 4.34 in 2008. The biggest increase in cases between 2004 and 2008 was observed in the ≥35 years age group (RR: 6.98; 95%CI: 2.11-36.36). 303 (31.5%) patients were hospitalized, of whom 93.7% were aged <1 year. Clinical differences were observed in paroxysmal cough (83.8% in suspected and 76.4% in confirmed cases, p=0.005), posttussive vomiting (47.1% and 36.1%, respectively, p=0.001), apnoea (13.7% and 21.3%, respectively, p=0.003) and fever (20.1% and 12.4%, respectively, p=0.001). CONCLUSION: Pertussis incidence rates increased during the study period, with the greatest increase occurring in the ≥35 years age group. A booster dose of vaccine in young people could reduce the circulation of B. pertussis in adolescents and adults and indirectly reduce the incidence in children.

Characterization of mutations in streptomycin-resistant Mycobacterium tuberculosis clinical isolates in the area of Barcelona.

OBJECTIVES: To determine the proportion and type of mutations in Mycobacterium tuberculosis isolates resistant to streptomycin, and their relationship with the level of resistance and with the epidemiological molecular pattern of the isolates. METHODS: Sixty-nine streptomycin-resistant isolates from a M. tuberculosis strain collection (1995-2005) from Barcelona were studied. The MIC of streptomycin for each isolate was determined using the proportions method with Middlebrook 7H11 medium. The entire rpsL gene and two specific fragments of the rrs gene (the 530 loop and the 912 region) were sequenced. IS6110-restriction fragment length polymorphism and spoligotyping were performed in each isolate. RESULTS: Twenty-six (26/69, 37.7%) streptomycin-resistant isolates presented a mutation in either the rpsL gene and/or the rrs530 loop, with no mutation in the rrs912 region. Seventeen (24.6%) isolates showed rpsL mutations (codons 43 and 88) associated with high MIC levels. Nine (13.0%) isolates had alterations in the rrs gene (A513T, A513C and C516T). Nineteen isolates (19/64, 29.7%) were classified into seven clusters (containing 2-5 isolates per cluster). Nineteen different spoligotype patterns were found. All the LAM3 spoligotype isolates (10/67, 14.9%) were associated with a C491T change in the rrs gene, being also observed in all LAM3 streptomycin-susceptible isolates. CONCLUSIONS: Mutations in the rpsL and rrs genes were detected in 37.7% of streptomycin-resistant M. tuberculosis isolates. High-level resistance was associated with mutations in the rpsL gene, whereas wild-type isolates showed low MIC levels. The presence of the C491T substitution in the rrs gene in streptomycin-susceptible and -resistant isolates demonstrates that this change is an epidemiological marker associated with LAM3 sublineage.