Cristina Esteva

Pediatric Parapneumonic Empyema, Spain

Increased incidence is principally due to highly invasive nonvaccine serotypes of pneumococci, especially serotype 1.

Emergence of invasive pneumococcal disease caused by multidrug-resistant serotype 19A among children in Barcelona☆

OBJECTIVE To describe the epidemiology of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 19A. METHODS We studied all children and adolescents with IPD caused by serotype 19A who were admitted to a Childrens Hospital in Barcelona (1997-2007). Serotyping, antibiotic susceptibility and clonal analysis were performed. RESULTS Comparing the pre-vaccine period (1997-2001) with the early vaccine period (2002-2004) and the late vaccine period (2005-2007) there was an increase of IPD caused by serotype 19A: 1 of 58 episodes (1.7%) vs. 8 of 54 episodes (14.8%) vs. 27 of 123 episodes (21.9%), respectively (P = 0.002). All S. pneumoniae serotype 19A isolated in the pre-vaccine and early vaccine periods (n = 9) were penicillin susceptible, while in the late vaccine period, 12 of 27 (44%) were penicillin nonsusceptible (P = 0.01). A clonal analysis revealed 15 different sequence types (STs) expressing serotype 19A. 10 of them were preexisting STs associated with serotype 19A including the multidrug-resistant ST320 and ST276. CONCLUSION There was an increase of IPD caused by S. pneumoniae serotype 19A which was mainly related with the emergence of preexisting clones several of them closely related with international multidrug-resistant clones. These results should be considered when selecting the new conjugate pneumococcal vaccines.

Serotypes and clones causing invasive pneumococcal disease before the use of new conjugate vaccines in Catalonia, Spain

OBJECTIVES The objective of this study was to learn the serotype distribution and clonal composition of pneumococci causing invasive pneumococcal disease (IPD) in children and adults in Spain before the introduction of new 10-valent (PCV10) and 13-valent (PCV13) conjugate vaccines. METHODS This is a 1-year prospective study including all patients with culture-proved IPD admitted to 30 medical centers in Catalonia, Spain, during the year 2009. RESULTS A total of 614 episodes of IPD occurred in 612 patients. The rates of IPD were highest in children aged <24 months and adults >64 years (64.5 and 44.7 per 100,000 population). The burden of disease was mainly due to pneumonia in all age ranges. 609 of 614 strains were serotyped and 47 different serotypes were found. Among the 609 IPD cases with known serotype, 12.2% were caused by PCV7 serotypes, 51% by PCV10 serotypes, and 71.7% by PCV13 serotypes. 608 of 614 isolates were characterized by MLST. The main clonal types detected were ST306, CC191 and CC230. CONCLUSIONS PCV13 conjugate vaccine offers good coverage against IPD in Catalonia, Spain. However, the high genetic diversity of pneumococci highlights the importance of molecular surveillance systems for monitoring IPD during the vaccination period. SUMMARY This study shows that 13-valent conjugate vaccine offers good coverage against invasive pneumococcal disease in children and adults in Spain. However, the high genetic diversity of pneumococci highlights the importance of molecular surveillance systems for monitoring IPD during the vaccination period.

Pediatric parapneumonic pleural effusion: epidemiology, clinical characteristics, and microbiological diagnosis.

In recent years an increase in the incidence and severity of parapneumonic pleural effusion (PPE) in pediatric populations has been observed. Streptococcus pneumoniae remains the main causal agent. New molecular and antigen techniques have increased the microbiological diagnosis of this pathology.

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 &mgr;g/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.

Identification of vaccine human papillomavirus genotypes in squamous intraepithelial lesions (CIN2–3)

OBJECTIVE To identify the prevalence of human papillomavirus vaccine genotypes and non-vaccine genotypes implicated in the appearance of cervical intraepithelial neoplasia (CIN2-3). METHODS Prospective study of 519 women with abnormal cytology. All the women underwent a second Papanicolaou test, cervicovaginal sampling for type-specific HPV detection and colposcopy, and women with abnormal colposcopy results were referred to biopsy. Pearsons chi-square test was used for statistical analysis. RESULTS HPV was detected in 340 patients (65.5%), and in 125 (24%) more than one HPV genotype was present. We selected 206 patients with CIN2 or CIN3 confirmed by biopsy. In 88 (42.7%) of these patients, HPV types 16 and 18 were detected, but only 58 (28.2%) without co-infection by other high-risk or probable high-risk HPV types. In 115 (55.8%) women diagnosed with CIN2 or CIN3 high-risk or probable high-risk HPV types other than 16 or 18 were found. High-risk and/or probable high-risk HPV genotypes not included in the vaccine were isolated in this study more frequently than 16 or 18, and this difference was statistically significant (p=0.047). Of the 206 women diagnosed with CIN2 or CIN3, 19 tested negative for HPV and 14 tested positive for low-risk HPV types. CONCLUSION Only 28.2% of women with CIN2 or CIN3 confirmed by biopsy were infected exclusively by HPV type 16 or 18, a finding that places in doubt the degree of protection afforded by HPV vaccination.

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.

PsrP, a protective pneumococcal antigen, is highly prevalent in children with pneumonia and is strongly associated with clonal type.

ABSTRACT Invasive pneumococcal disease (IPD) is a major health problem worldwide. Due to ongoing serotype replacement, current efforts are focused in an attempt to identify the pneumococcal antigens that could be used in a next-generation multivalent protein vaccine. The objective of our study was to use real-time PCR to determine the distribution and clonal type variability of PsrP, a protective pneumococcal antigen, among pneumococcal isolates from children with IPD or healthy nasopharyngeal carriers. psrP was detected in 52.4% of the 441 strains tested. While no differences were determined when the prevalence of psrP in colonizing strains (n = 89) versus that in all invasive strains (n = 352) was compared, a strong trend was observed when the prevalence of psrP in all pneumonia isolates (n = 209) and colonizing isolates (P = 0.067) was compared, and a significant difference was observed when the prevalence in all pneumonia isolates and those causing bacteremia (n = 76) was compared (P = 0.001). An age-dependent distribution of psrP was also observed, with the incidence of psrP being the greatest in strains isolated from children >2 years of age (P = 0.02). Strikingly, the presence of psrP within a serotype was highly dependent on the clonotype, with all isolates of invasive clones such as clonal complex 306 carrying psrP (n = 88), whereas for sequence type 304, only 1 of 19 isolates carried psrP; moreover, this was inversely correlated with antibiotic susceptibility. This finding suggests that inclusion of psrP in a vaccine formulation would not target resistant strains. We conclude that psrP is highly prevalent in strains that cause IPD but is most prevalent in strains isolated from older children with pneumonia. These data support the potential use of PsrP as one component in a multivalent protein-based vaccine.

Streptococcus pneumoniae serotype 1 causing invasive disease among children in Barcelona over a 20‐year period (1989–2008)

Fifty-six isolates of serotype 1 were identified during a 20-year prospective study (1989-2008), including all children with culture-proven invasive pneumococcal disease (IPD) admitted to a childrens hospital in Barcelona. Forty-eight of them (85.7%) were in children aged >2 years. Complicated pneumonia (n = 28) and non-complicated pneumonia (n = 20) were the main clinical presentations. The frequency of serotype 1 IPD increased from 1999-2003 to 2004-2008: 1.2 to 4.4 episodes/100 000 children (p <0.001). The ST306 clone were identified in 70.4% of isolates. As IPD caused by serotype 1 is mainly detected in older children, a vaccination programme for children >2 years should be considered.

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.