Iolanda Jordan

Emergence of Invasive Pneumococcal Disease Caused by Nonvaccine Serotypes in the Era of 7-Valent Conjugate Vaccine

BACKGROUND Little is known about the epidemiology of invasive pneumococcal disease (IPD) after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in Spain and other European countries. METHODS We performed a 10-year prospective study including all children with culture-proven IPD admitted to Sant Joan de Deu Hospital, a childrens center in the southern area of Barcelona, Catalonia, Spain. PCV7 was introduced in June 2001, and the current estimate of PCV7 coverage is 45%-50%. RESULTS Comparing the prevaccine period (1997-2001) with the vaccine period (2002-2006), among children aged <2 years, the rate of IPD increased from 32.4 episodes per 100,000 population to 51.3 episodes per 100,000 population (an increase of 58%; 95% confidence interval, 2%-145%), and among children aged 2-4 years, the rate increased from 11.3 episodes per 100,000 population to 26.5 episodes per 100,000 population (an increase of 135%; 95% confidence interval, 31%-320%). At clinical presentation, the rate of pneumonia and/or empyema among children aged <5 years increased from 3.6 episodes per 100,000 population to 15.1 episodes per 100,000 population (an increase of 320%; 95% confidence interval, 98%-790%). These increased rates of IPD were caused by non-PCV7 serotypes, which represented 38% and 72% of infecting serotypes in the prevaccine and vaccine periods, respectively (P=.001). Penicillin resistance decreased from 48% in the prevaccine period to 27% in the vaccine period (P=.005). In the vaccine period, there was an emergence of previously established virulent clones of non-PCV7 serotypes 1 and 5. There was also an increase in the prevalence of serotypes 19A and 6A expressed with different clonal types, including Spain(23F)-1 and Spain(6B)-2. CONCLUSIONS Since the introduction of PCV7 for children, there has been an emergence of IPD caused by virulent clones of non-PCV7 serotypes that has been associated with significant clinical changes and a decrease in antibiotic resistance.

The impact of a quality improvement intervention to reduce nosocomial infections in a PICU.

Objective: To evaluate whether a quality improvement intervention could reduce nosocomial infection rates in a PICU and improve patient outcomes. Design: Prospective interventional cohort study conducted during three periods: preintervention period, intervention period, and long-term follow-up. Setting: A 14-bed medical and surgical PICU in a university hospital for children. Interventions: The quality improvement intervention consisted of the creation of an infection control team, a program targeting hand hygiene, and quality practices focused on preventing nosocomial infections. Measurements and Main Results: We included 851 patients in the preintervention period, 822 in the intervention period, and 940 in the long-term follow-up period. Compared with the preintervention period, in the intervention period, the rates of central line–associated bloodstream infection decreased from 8.1 to 6/1,000 central venous catheter-days (p = 0.640), ventilator-associated pneumonia decreased from 28.3 to 10.6/1,000 days’ ventilation (p = 0.005), and catheter-associated urinary tract infection decreased from 23.3 to 5.8/1,000 urinary catheter-days (p < 0.001). Furthermore, hospital length of stay decreased from 18.56 to 14.57 days (p = 0.035) and mortality decreased from 5.1% to 3.3% (p = 0.056). Multivariable logistic regression found that nosocomial infections was independently associated with increased mortality (odds ratio, 2.35 [95% CI, 1.02–5.55]; p = 0.046). Compared with the preintervention period, in the long-term follow-up period, central line–associated bloodstream infection decreased to 4.6/1,000 central venous catheter-days (p = 0.205); ventilator-associated pneumonia decreased to 9.1/1,000 ventilation-days (p = 0.001), and catheter-associated urinary tract infection decreased to 5.2/1,000 urinary catheter-days (p < 0.001). Hospital length of stay (14.45 days; p = 0.048) and mortality (3.2%; p = 0.058) also decreased. Conclusions: A multifaceted quality improvement intervention reduced nosocomial infection rates, hospital length of stay, and mortality in our PICU. The effects of the intervention were sustained over time.

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 childs 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.

Severe enterovirus disease in febrile neonates

INTRODUCTION Fever in newborn infants may be due to an invasive infection with potential morbidity and mortality. Our aim was to describe the characteristics and outcome of group of febrile neonates with severe enterovirus infection compared to a group of neonates with severe bacterial infection. PATIENTS AND METHODS Prospective study including all neonates (<29 days old) admitted to a teaching hospital for fever (>38 degrees C), with positive bacterial cultures or enterovirus detection in sterile samples, from September 2003 to December 2004. Clinical information, analytical data at admission (complete leukocyte count and C-reactive protein concentrations), blood, urine, and cerebrospinal fluid culture results, molecular detection of enterovirus by polymerase chain reaction (PCR), and outcome were recorded. RESULTS Invasive bacterial infections were observed in 62 patients: urinary tract infection (n=57, including 8 cases of bacteremia), sepsis (n=3), and meningitis (n=2). Molecular tests for enterovirus were positive in 10 patients. C-reactive protein values were significantly higher in neonates with bacterial infection than in those with enterovirus infection (62,3 versus 9mg/L, P=0,008). Two patients with Streptococcus agalactiae meningitis, 1 with Staphylococcus aureus sepsis and 3 with enterovirus infection (manifested as myocarditis, hepatitis, and meningoencephalitis) required admission to the pediatric intensive care unit. Among these, 1 newborn with S. agalactiae and 2 of the 3 with enterovirus infection died. CONCLUSIONS In our series, enterovirus infection was an important cause of severe invasive disease. Specific viral diagnosis can contribute to the management of febrile neonates.

Polymerase chain reaction for diagnosis and serogrouping of meningococcal disease in children.

A prospective study was performed including all children younger than 18 years with the clinical diagnosis of invasive meningococcal disease (IMD) hospitalized at the University Hospital Sant Joan de Déu in Barcelona, Spain, from January 2001 to December 2006. During the study period, 168 meningococcal disease cases were reported. Microbiologic confirmation was obtained in 118 cases. Forty-six (38.9%) of 118 cases were only detected by polymerase chain reaction (PCR); 6 patients were culture positive and PCR negative (5%). Serogroup B predominated in the 6-year period with 83.1% of the strains. A significant decrease in serogroup C was observed in the last 3 years of the study (P=0.029), and less common serogroups, such as serogroup A and W135, emerged. Serogroup distribution of patient diagnoses only by real-time PCR showed a similar distribution: serogroup B, 85.7%; serogroup C, 7.1%; and nontypeable serogroups, 7.1%. In conclusion, real-time PCR is more rapid and sensitive than culture for diagnosis and serogrouping of IMD.

Viral load at diagnosis and influenza A H1N1 (2009) disease severity in children

Please cite this paper as: Launes et al. (2012) Viral load at diagnosis and influenza A H1N1 (2009) disease severity in children. Influenza and Other Respiratory Viruses 6(601), e89–e92.

Glutamine effects on heat shock protein 70 and interleukines 6 and 10: Randomized trial of glutamine supplementation versus standard parenteral nutrition in critically ill children.

BACKGROUND & AIMS To determine whether glutamine (Gln) supplementation would have a role modifying both the oxidative stress and the inflammatory response of critically ill children. METHODS Prospective, randomized, double-blind, interventional clinical trial. Selection criteria were children requiring parenteral nutrition for at least 5 days diagnosed with severe sepsis or post major surgery. Patients were randomly assigned to standard parenteral nutrition (SPN, 49 subjects) or standard parenteral nutrition with glutamine supplementation (SPN + Gln, 49 subjects). RESULTS Glutamine levels failed to show statistical differences between groups. At day 5, patients in the SPN + Gln group had significantly higher levels of HSP-70 (heat shock protein 70) as compared with the SPN group (68.6 vs 5.4, p = 0.014). In both groups, IL-6 (interleukine 6) levels showed a remarkable descent from baseline and day 2 (SPN: 42.24 vs 9.39, p < 0.001; SPN + Gln: 35.20 vs 13.80, p < 0.001) but only the treatment group showed a statistically significant decrease between day 2 and day 5 (13.80 vs 10.55, p = 0.013). Levels of IL-10 (interleukine 10) did not vary among visits except in the SPN between baseline and day 2 (9.55 vs 5.356, p < 0.001). At the end of the study, no significant differences between groups for PICU and hospital stay were observed. No adverse events were detected in any group. CONCLUSIONS Glutamine supplementation in critically-ill children contributed to maintain high HSP-70 levels for longer. Glutamine supplementation had no influence on IL-10 and failed to show a significant reduction of IL-6 levels.

Bronchiolitis Score of Sant Joan de Déu: BROSJOD Score, validation and usefulness

To validate the bronchiolitis score of Sant Joan de Déu (BROSJOD) and to examine the previously defined scoring cutoff. Patients and Methods: Prospective, observational study. BROSJOD scoring was done by two independent physicians (at admission, 24 and 48 hr). Internal consistency of the score was assessed using Cronbachs α. To determine inter‐rater reliability, the concordance correlation coefficient estimated as an intraclass correlation coefficient (CCC) and limits of agreement estimated as the 90% total deviation index (TDI) were estimated. An expert opinion was used to classify patients according to clinical severity. A validity analysis was conducted comparing the 3‐level classification score to that expert opinion. Volume under the surface (VUS), predictive values, and probability of correct classification (PCC) were measured to assess discriminant validity. Results: About 112 patients were recruited, 62 of them (55.4%) males. Median age: 52.5 days (IQR: 32.75–115.25). The admission Cronbachs α was 0.77 (CI95%: 0.71; 0.82) and at 24 hr it was 0.65 (CI95%: 0.48; 0.7). The inter‐rater reliability analysis was: CCC at admission 0.96 (95%CI 0.94–0.97), at 24 h 0.77 (95%CI 0.65–0.86), and at 48 hr 0.94 (95%CI 0.94–0.97); TDI 90%: 1.6, 2.9, and 1.57, respectively. The discriminant validity at admission: VUS of 0.8 (95%CI 0.70–0.90), at 24 h 0.92 (95%CI 0.85–0.99), and at 48 hr 0.93 (95%CI 0.87–0.99). The predictive values and PCC values were within 38–100% depending on the level of clinical severity. Conclusion: There is a high inter‐rater reliability, showing the BROSJOD score to be reliable and valid, even when different observers apply it. Pediatr Pulmonol. 2017;52:533–539.

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.

Adrenomedullin is a useful biomarker for the prognosis of critically ill septic children

AIM To measure midregional pro-adrenomedullin (MR-pro-ADM) in critically ill septic patients to determine its prognostic usefulness as compared with other used biomarkers in pediatric intensive care units, C-reactive protein (CRP) and procalcitonin (PCT). MATERIALS & METHODS Prospective observational study conducted on 95 patients. RESULTS Mean levels of MR-pro-ADM were significantly higher when patients needed mechanical ventilation (3.2 ± 4.3 vs 1.6 ± 2.4) and inotropes (4.4 ± 5.2 vs 1.3 ± 1.2). Receiver operating characteristic curves of mortality were higher for MR-pro-ADM (cut-off value of 2.2). This marker showed higher positive predictive prognostic value than PCT and CRP (31 vs 21.6% and 15.8%, respectively). CONCLUSION MR-pro-ADM levels are good indicators of disease severity and show better reliability than PCT and CRP for predicting in-hospital mortality.