Enrique Otheo

Impact of introduction of conjugate vaccines in the vaccination schedule on the incidence of pediatric invasive pneumococcal disease requiring hospitalization in Madrid 2007 to 2011.

Background: Differences in invasive pneumococcal disease (IPD) in children are expected after a change from 7-valent pneumococcal conjugate vaccine (PCV7) to 13-valent pneumococcal conjugate vaccine (PCV13). Universal vaccination with PCV7 started in Madrid in November 2006, and it switched to PCV13 in June 2010. Methods: A prospective, laboratory-confirmed (by culture or polymerase chain reaction), clinical surveillance including all pediatric IPD requiring hospitalization in Madrid was performed in all hospitals with a pediatric department and included four 1-year periods from May 2007 to April 2011. Incidence rate (IR) was calculated as number cases per 100,000 inhabitants using children population data. Results: Six hundred fourteen IPDs were identified: 209 parapneumonic pneumococcal empyema, 191 bacteremic pneumonia, 75 primary bacteremia, 72 meningitis, 38 IPDs secondary to otic foci and 29 others. The incidence of IPD remained unchanged during 2007-2010 (IR=≈17.0), with a marked decrease in 2010-2011 (IR=11.34; P<0.05) attributable to reduction in children younger than 24 months (50.19 in 2008-2009 compared with 24.92 in 2010-2011; P<0.005). The incidence of bacteremic pneumonia (R2=0.966; &bgr;=1.132; P=0.017) and meningitis (R2=0.898; &bgr;=0.505; P=0.052) showed decreasing linear trends over time. The incidence of parapneumonic pneumococcal empyema increased in 2009-2010 but decreased in 2010-2011 (6.73 vs. 4.14; P=0.019). The incidence of IPDs by PCV13 serotypes was significantly (P⩽0.004) lower in 2010-2011 (8.78) than in previous periods (IR=≈13.5). Conclusions: Early data regarding changing from PCV7 to PCV13 use in the childhood vaccination calendar indicate that reductions in IR of bacteremic pneumonia and meningitis after PCV7 introduction (by reduction of cases by serotypes 1 and 19A) further decreased and there was a reversion of the increase in IR of parapneumonic pneumococcal empyema from 2010-2011, mainly because of reduction in serotype 1 and 19A cases.

Pandemic H1N1 influenza-associated hospitalizations in children in Madrid, Spain.

Please cite this paper as: del Rosal et al. (2011) Pandemic H1N1 influenza‐associated hospitalizations in children in Madrid, Spain. Influenza and Other Respiratory Viruses 5(6), e544–e551.

Oseltamivir treatment for influenza in hospitalized children without underlying diseases.

Aim: To determine whether the treatment with oseltamivir improves the outcome of children with confirmed influenza infection and no other underlying disease. Methods: Multicentric, retrospective study performed in 10 hospitals of Madrid between September 2010 and June 2012. All children admitted to the hospitals with confirmed influenza infections were eligible. Children with risk factors for serious disease and nosocomial influenza infections were excluded. Asthma was not considered an exclusion factor. The study compared patients treated and untreated with oseltamivir. Fever duration, oxygen support, antibiotics administration, length of hospital stay, intensive care admission and bacterial complications were analyzed. To compare variables, &khgr;2 test, Fisher exact test, ANOVA or Mann-Whitney U test were used. Results: Two hundred eighty-seven children were included and 93 of them were treated with oseltamivir (32%). There were no significant differences between treated and untreated patients in days of fever after admission (1.7 ± 2; 2.1 ± 2.9, P > 0.05), length of stay (5.2 ± 3.6; 5.5 ± 3.4, P > 0.05), days of hypoxia (1.6 ± 2.3; 2.1 ± 2.9, P > 0.05), diagnosis of bacterial pneumonia (10%; 17%, P > 0.05), intensive care admission (6.5%; 1.5%,P > 0.05) or antibiotic prescription (44%; 51%, P > 0.05). There were no differences when the population was stratified by age (below or over 1 year) or by the presence or absence of asthma. Conclusions: There were no proven benefits of treatment with oseltamivir in hospitalized pediatric patients without the underlying diseases or risk factors for developing a serious illness, including those with asthma.

Dexamethasone for Parapneumonic Pleural Effusion: A Randomized, Double-Blind, Clinical Trial

Objective To assess whether dexamethasone (DXM) decreases the time to recovery in patients with parapneumonic pleural effusion. Study design This was a multicenter, randomized, double blind, parallel‐group, placebo‐controlled clinical trial of 60 children, ranging in age from 1 month to 14 years, with community‐acquired pneumonia (CAP) and pleural effusion. Patients received either intravenous DXM (0.25 mg/kg/dose) or placebo every 6 hours over a period of 48 hours, along with antibiotics. The primary endpoint was the time to recovery in hours, defined objectively. We also evaluated complications and adverse events. Results Among the 60 randomized patients (mean age, 4.7 years; 58% female), 57 (95%) completed the study. Compared with placebo recipients, the patients receiving DXM had a shorter time to recovery, after adjustment by severity group and stratification by center (hazard ratio, 1.95; 95% CI, 1.10‐3.45; P = .021). The median time to recovery for patients receiving DXM was 68 hours (2.8 days) shorter than patients receiving placebo (109 hours vs 177 hours; P = .037). In exploratory subgroup analysis, the median time to recovery for patients with simple effusion receiving DXM was 76 hours (3.1 days) shorter than for patients with simple effusion receiving placebo (P = .017). The median time to recovery for patients with complicated effusion receiving DXM was 14 hours (0.5 days) shorter than for patients with complicated effusion receiving placebo (P = .66). The difference in the effect of DXM in the 2 severity groups was not statistically significant (P = .138 for interaction). There were no significant differences in complications or adverse events attributable to the study drugs, except for hyperglycemia. Conclusion In this trial, DXM seemed to be a safe and effective adjunctive therapy for parapneumonic pleural effusion. Trial registration ClinicalTrials.gov: NCT01261546.

Effect of the different 13-valent pneumococcal conjugate vaccination uptakes on the invasive pneumococcal disease in children: Analysis of a hospital-based and population-based surveillance study in Madrid, Spain, 2007-2015

In the Community of Madrid, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) in the fully government-funded Regional Immunization Program (RIP) in May, 2010, but was later excluded in May, 2012, and included again in January, 2015. These unique changes allowed us to assess the impact of the different pneumococcal vaccination policies on PCV13 uptake in infants and on the incidence rate (IR) of invasive pneumococcal disease (IPD) in children <15 years old. In this prospective, active, surveillance study, we estimated PCV13 uptakes, IR and incidence rate ratios (IRR) for total IPD and for IPD caused by PCV13- and non-PCV13 serotypes in children <15 years, stratified by age, in four periods with different vaccination policies: fully government-funded PCV7 vaccination, fully government-funded PCV13, mixed public/private funding and only private funding. Vaccine uptakes reached 95% in periods with public-funded pneumococcal vaccination, but fell to 67% in the private funding period. Overall, IR of IPD decreased by 68% (p<0.001) in 2014–15, due to 93% reduction in the IR of PCV13-type IPD (p<0.001) without significant changes in non-PCV13-type IPD. A fully government-funded PCV13 vaccination program lead to high vaccine uptake and dramatic reductions in both overall and PCV13-type IPD IR. When this program was switched to private PCV13 vaccination, there was a fall in vaccine coverage and stagnation in the decline of PCV13-type IPD with data suggesting a weakening of herd immunity.

Complications of Pneumococcal Bacteremia After Thirteen-valent Conjugate Vaccine Withdrawal

Background: In the Region of Madrid, universal immunization with the 13-serotypes pneumococcal conjugate vaccine (PCV13) started in May 2010. In July 2012, public funding ceased. Vaccination coverage decreased from >95% to 82% in 2013 and to 67% in 2014. Our aim was to investigate the impact of PCV13 withdrawal from Madrid Region universal immunization program on the incidence of complicated pneumococcal bacteremia. Methods: We performed a multicenter retrospective cohort study, from 2009 to 2014. Participants were children aged <14 years with Streptococcus pneumoniae bacteremia. Complications were defined as any condition requiring intensive care or surgery. Sequelae were conditions lasting ≥90 days. Results: A total of 168 patients were recruited. One-fourth of both immunized and nonimmunized patients had complications. Global complications increased after PCV13 withdrawal. About 28% of PCV13 serotypes presented complications. Complications caused by PCV13 serotypes did not increase after July 2012. Non-PCV13 serotypes increased progressively from 2009 on, and 23% presented complications. A significant risk of complications was found for patients with meningitis, empyema, C-reactive protein >100 mg/L and serotype 1. A multivariate analysis indicated that complications were associated with meningitis and hospital admission after July 2012. Sequelae were significantly associated with children <2 years of age, meningitis and non-PCV13 serotypes. Conclusions: The incidence of complications caused by PCV13 serotypes did not increase 2 years after PCV13 withdrawal. Nevertheless, all-serotypes complications increased. The likely cause was that non-PCV13 serotypes (associated with meningitis) are on the rise.

Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children.

OBJECTIVES To evaluate the impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children. METHODS Children younger than 15years of age attending 27 hospitals in the Region of Madrid with confirmed pneumococcal meningitis were identified in a prospective surveillance study, from 2007 to 2015. Clinical data, neurological sequelae, pneumococcal vaccination status, serotyping and antibiotic susceptibility were recorded. RESULTS One hundred and four cases of pneumococcal meningitis were identified, 63 during the period of routine 7-valent pneumococcal conjugate vaccine immunisation (May 2007-April 2010) and 41 during the period of 13-valent pneumococcal conjugate vaccine immunisation (May 2010-April 2015). When both periods were compared, a 62% (95% CI: 45-75%) decrease in the incidence of pneumococcal meningitis was observed, from 2.19 cases per 100,000 inhabitants in the PCV7 period to 0.81 per 100,000 inhabitants in the PCV13 period (p=0.0001), mainly due to an 83% (95% CI: 30-96%) reduction in cases caused by serotype 19A. Isolates not susceptible to cefotaxime (MIC>0.5μg/L) decreased from 27% to 8%, (p=0.02). Mean patient ages rose from 28.7months to 38.5months (p<0.05). Case fatality rate across both periods was 5%. An unfavourable outcome (death or neurological sequelae) occurred in 27% of patients, while the rate was similar in both periods. There was no increase in meningitis caused by pneumococcal serotypes not included in 13-valent pneumococcal conjugate vaccine throughout the years of the study. CONCLUSIONS Immunisation with 13-valent pneumococcal conjugate vaccine has reduced the rate of pneumococcal meningitis in children less than 15years, with a near-elimination of cefotaxime-resistant isolates, but morbidity has remained unchanged. A shift of pneumococcal meningitis towards slightly higher age groups was also observed.

Hyponatremia in children with pneumonia rarely means SIADH

Abstract Background Hyponatremia (HN) < 135 mmol/L is a frequent finding in children with community-acquired pneumonia (CAP). We aimed to determine the proportion of syndrome of inappropriate antidiuretic hormone secretion (SIADH) among patients with CAP and HN. Moreover, we wished to investigate the relationship between HN and inflammatory markers, bacterial etiology and prognosis in hospitalized children with CAP. Methods We carried out a prospective, observational, multicentre, prospective cohort study. Eligible participants were children from 1 month to 17 years old hospitalized due to CAP from 2012 to 2015. Results A total of 150 children were analyzed. Forty-five (30%) patients had serum sodium levels of less than 135 mmol/L. Patients with HN had significantly higher concentrations of inflammatory biomarkers. They also had significantly lower osmolality and urine sodium. They also had longer hospitalizations and more days of fever. Only 16 out of the 45 (35%) patients with HN had confirmed calculated plasma osmolality (<275 mOsm/kg). Only 5 out of 37 (13%) patients with available measurements of plasma osmolality and urine sodium fulfilled the criteria for SIADH. Among the 16 patients with HN and hypo-osmolality, 15 had a fractional sodium excretion (EFNa) levels of less than 1%. We found a significant inverse linear correlation between serum sodium and C-reactive protein, as well as serum sodium and procalcitonin. We found a significant direct correlation between serum sodium and urine sodium. Conclusion HN is a common finding in hospitalized children with CAP. True SIADH is a rare event. HN has a good correlation with inflammatory biomarkers.