Pilar Ciruela

Effectiveness of Pneumococcal Vaccination for Elderly People in Catalonia, Spain: A Case-Control Study

BACKGROUND Observational studies offer an approach to evaluating the effectiveness of vaccination programs. We evaluated the effectiveness of a 23-valent pneumococcal vaccination program for elderly people in Catalonia, Spain, in a matched-set case-control study. METHODS We identified 149 cases of invasive pneumococcal disease among patients aged > or =65 years who were hospitalized in 12 large hospitals in Catalonia during the period of 1 January 2001 through 31 March 2002. We selected 2 hospital control patients and 1 outpatient control subject for each case patient, matching on the basis of age and underlying medical conditions. We obtained their pneumococcal vaccination histories and used conditional logistic regression to determine effectiveness of vaccination. RESULTS Among all 149 cases of invasive pneumococcal disease, 131 (87.9%) were caused by vaccine or vaccine-related serotypes. In the adjusted analysis, overall effectiveness of vaccination against infections due to all serotypes was 70% (95% confidence interval [CI], 48%-82%). Among immunocompetent subjects with or without high-risk conditions, effectiveness of vaccination was 76% (95% CI, 51%-88%), but among immunocompromised subjects it was 50% (95% CI, -44% to 82%). Among subjects with infections due to vaccine or vaccine-related serotypes, effectiveness of vaccination was 72% (95% CI, 50%-85%) overall and 78% (95% CI, 50%-90%) in those who were immunocompetent, but it was only 46% (95% CI, -54% to 81%) in those who were immunocompromised. Overall effectiveness of vaccination was 65% (95% CI, 35%-81%) during the noninfluenza period. CONCLUSIONS Pneumococcal vaccination was effective in preventing invasive pneumococcal disease among all elderly persons in Catalonia. Effectiveness was greater in immunocompetent persons, most of whom had underlying high-risk conditions. The number of subjects was too small to determine whether vaccination was effective in those who were immunocompromised.

The epidemiology of invasive Streptococcus pneumoniae disease in Catalonia (Spain): A hospital-based study

The aim of this study was to investigate the incidence of invasive pneumococcal disease (IPD) in Catalonia. A hospital-based incidence study of the period 1997-1999 was carried out by reviewing the isolations of Streptococcus pneumoniae obtained from normally sterile sites reported by the hospitals that voluntarily participate in the Microbiological Reporting System of Catalonia (MRSC), and those obtained by active retrospective surveillance of cases recorded by microbiology laboratories of the remaining hospitals. Cases of pneumonia were included only if the blood culture was positive. The age, sex and clinical presentation of each patient were recorded. The global incidence of hospital-based IPD was 10.5 per 100,000 persons-year, and was much higher in subjects <2 years of age (59.6) and in those aged > or = 65 years (27.9). In subjects > or = 65 years, bacteremic pneumococcal pneumonias were more frequent in the months from December to March than they were in children <2 years of age (P<0.0001). The global incidence of IPD (10.5 per 100,000 persons-year) is high in Catalonia, greater than that of meningococcal or Haemophilus influenzae invasive disease. In children <2 years, the incidence is nearly six times higher (59.6 per 100,000 persons-year) with pneumonias (rate of 26.2 per 100,000 persons-year) and non-focal bacteremias (rate of 22.1 per 100,000 persons-year) being especially frequent.

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.

Changes in serotypes causing invasive pneumococcal disease (2005–2007 vs. 1997–1999) in children under 2 years of age in a population with intermediate coverage of the 7-valent pneumococcal conjugated vaccine

Serotypes causing invasive pneumococcal disease (IPD) in children aged <2 years in Catalonia (Spain) before and after licensing of the 7-valent pneumococcal conjugated vaccine (7vPCV) were assessed, using samples taken during 1997-1999 and 2005-2007 respectively. The distribution of serotypes causing IPD within these groups was obtained by serotyping strains sent by 22 Catalan hospitals to the Carlos III Health Institute, Madrid. Between 1997-99 and 2005-2007, the proportion of vaccine serotypes causing IPD in Catalonia fell from 70.54% to 31.67% (p <0.0001). The proportion of vaccine-related serotypes, mainly serotype 19A, increased from 9.82% to 32.50% (p <0.0001). The proportion of non-vaccine, non-related serotypes (serotypes not related to vaccine serotypes) rose from 19.64% to 35.83% (p <0.05). Within this group, the proportions of serotype 24F increased significantly. There has been a change in the distribution of serotypes isolated from cases of IPD in children <2 years old in Catalonia, comprising a reduction in the proportion of 7-valent vaccine serotypes, a rise in vaccine-related serotypes, especially 19A, and a smaller rise in non-vaccine, non-related serotypes, especially serotype 24F. A new 13-valent vaccine will cover 77.91% of the serotypes causing IPD in children <2 years old in Catalonia from 2005 to 2007.

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.

Prevalence and Clonal Distribution of pcpA, psrP and Pilus-1 among Pediatric Isolates of Streptococcus pneumoniae

Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths globally. The objective of this study was to determine the distribution and clonal type variability of three potential vaccine antigens: Pneumococcal serine-rich repeat protein (PsrP), Pilus-1, and Pneumococcal choline binding protein A (PcpA) among pneumococcal isolates from children with invasive pneumococcal disease and healthy nasopharyngeal carriers. We studied by Real-Time PCR a total of 458 invasive pneumococcal isolates and 89 nasopharyngeal pneumococcal isolates among children (total = 547 strains) collected in Barcelona, Spain, from January 2004 to July 2010. pcpA, psrP and pilus-1 were detected in 92.8%, 51.7% and 14.4% of invasive isolates and in 92.1%, 48.3% and 18% of carrier isolates, respectively. Within individual serotypes the prevalence of psrP and pilus-1 was highly dependent on the clonal type. pcpA was highly prevalent in all strains with the exception of those belonging to serotype 3 (33.3% in serotype 3 isolates vs. 95.1% in other serotypes; P<.001). psrP was significantly more frequent in those serotypes that are less apt to be detected in carriage than in disease; 58.7% vs. 39.1% P<.001. Antibiotic resistance was associated with the presence of pilus-1 and showed a negative correlation with psrP. These results indicate that PcpA, and subsequently Psrp and Pilus-1 together might be good candidates to be used in a next-generation of multivalent pneumococcal protein vaccine.

Serotypes and Clonal Diversity of Streptococcus pneumoniae Causing Invasive Disease in the Era of PCV13 in Catalonia, Spain

The aim of this study was to study the serotypes and clonal diversity of pneumococci causing invasive pneumococcal disease in Catalonia, Spain, in the era of 13-valent pneumococcal conjugate vaccine (PCV13). In our region, this vaccine is only available in the private market and it is estimated a PCV13 vaccine coverage around 55% in children. A total of 1551 pneumococcal invasive isolates received between 2010 and 2013 in the Molecular Microbiology Department at Hospital Sant Joan de Déu, Barcelona, were included. Fifty-two serotypes and 249 clonal types—defined by MLST—were identified. The most common serotypes were serotype 1 (n = 182; 11.7%), 3 (n = 145; 9.3%), 19A (n = 137; 8.8%) and 7F (n = 122; 7.9%). Serotype 14 was the third most frequent serotype in children < 2 years (15 of 159 isolates). PCV7 serotypes maintained their proportion along the period of study, 16.6% in 2010 to 13.4% in 2013, whereas there was a significant proportional decrease in PCV13 serotypes, 65.3% in 2010 to 48.9% in 2013 (p<0.01). This decrease was mainly attributable to serotypes 19A and 7F. Serotype 12F achieved the third position in 2013 (n = 22, 6.4%). The most frequent clonal types found were ST306 (n = 154, 9.9%), ST191 (n = 111, 7.2%), ST989 (n = 85, 5.5%) and ST180 (n = 80, 5.2%). Despite their decrease, PCV13 serotypes continue to be a major cause of disease in Spain. These results emphasize the need for complete PCV13 vaccination.

High prevalence of genetically-determined mannose binding lectin deficiency in young children with invasive pneumococcal disease

Susceptibility to invasive pneumococcal disease (IPD) correlates with age, younger children being the group with the highest burden of disease. The relevance of the innate immune response and particularly the role of mannose-binding lectin (MBL) in combating IPD is not well known. This is a 2-year prospective study (February 2011 to March 2013) including patients with IPD who attended two hospitals from Catalonia, Spain. Variables including attack rate of pneumococcal serotype (high or low invasive potential serotypes) and genotypes associated with low serum MBL levels were recorded. One hundred and forty-seven patients were included in the study. One hundred and two (69.4%) patients were children or adolescents <18 years and 45 (30.6%) were adults. Overall, low-MBL genotypes (O/O; XA/O) were detected in 23 (15.6%) patients. Children <2 years showed a higher frequency of low-MBL genotypes compared with other patients (31.0% vs. 11.9%; p = 0.031). Further sub-analysis revealed a higher proportion of low-MBL genotypes in children <2 years with IPD caused by opportunistic or low-attack-rate serotypes when compared with older patients (46.2% vs. 13.2%; p = 0.02). However, no statistically significant differences between the two groups were observed when including patients infected with invasive or high-attack-rate serotypes (18.8% vs. 10.0%; p = 0.59). Our data suggest that young children with a genetically determined low-MBL production are at a higher risk of developing IPD, particularly that caused by opportunistic or low-attack-rate pneumococcal serotypes.

Epidemiology of vaccine-preventable invasive diseases in Catalonia in the era of conjugate vaccines

We investigated the incidence and distribution of cases of invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD) and invasive Hemophilus influenzae disease (IHiD) notified by hospital laboratories to the Microbiological Reporting System of Catalonia between 2005 and 2009. Incidence rates were compared using the rate ratio (RR) and 95% CI were calculated. A value of p < 0.05 was considered statistically significant. Of the 6,661 cases, 6,012 were IPD, 436 IMD and 213 IHiD. The global annual incidence per 105 inhabitants was 16.62 (95% CI 16.20–17.04) for IPD, 1.21 (95% CI 1.09–1.32) for IMD and 0.59 (95% CI 0.51–0.67) for IHiD. IPD increased in 2009 compared with 2005 (RR:1.55, 95%CI: 1.43–1.70) and IMD and IHiD remained stable. Pneumonia was the most-frequent clinical manifestation of IPD (75.6%) and IHiD (44.1%) and meningoencephalitis with or without sepsis for IMD (70.6%). The male:female ratio was 1.37 for IPD, 1.0 for IMD and 1.15 for IHiD. The age groups with the highest incidence were the ≤ 2 y and 2–4 y groups for IPD (66.40 and 50.66/100,000 persons-year) and IMD (14.88 and 7.26/100,000 persons-year) and the ≤ 2 y and ≥ 65 y groups for IHiD (1.88 and 1.89/100,000 persons-year). The most-frequent serotypes were serotype 1 (19.0%) in IPD and untypeable serotypes (60.8%) in IHiD. Serogroup B (78.3%) was the most frequent in IMD. S. pneumoniae is the most-frequent agent causing invasive disease in Catalonia. The main clinical manifestations were pneumonia in IPD and IHiD and meningitis in IMD. The main causative agent of meningitis was N. meningitidis in people aged < 20 y and S. pneumoniae in people aged ≥ 20 y. Vaccination with conjugate vaccines may reduce the risk of infectious disease in our setting.

Impacto de la vacuna neumocócica conjugada heptavalente en una población con valores bajos-intermedios de vacunación

OBJECTIVE To analyze the changes occurring in declared cases (microbiological report) of invasive pneumococcal disease (IPD) in children <2 years old in Catalonia (Spain) after the 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use. MATERIAL AND METHODS Cases of IPD in children <2 years old were obtained from notifications to the Microbiological Reporting System of Catalonia (MRSC) in 1997-1999 and 2002-2004 by the hospitals (n=23) that have participated in the MRSC continuously and uninterruptedly since its inception in 1995. RESULTS Overall reported rates were 49.2 cases per 100,000 persons-year in 1997-1999 and 40.4 per 100,000 persons-year in 2002-2004; the difference was not statistically significant. The rate of bacteremic pneumonia fell from 25.2 per 100,000 persons-year in 1997-1999 to 21.6 per 100,000 persons-year in 2002-2004, and meningitis from 6.0 to 4.3 per 100,000 persons-year; again, differences were not statistically significant (P>0.05). CONCLUSIONS After PCV7 was licensed for use, a noticeable, but non-significant, reduction in reported IPD rates in children <2 years old occurred in Catalonia. If the results had been statistically significant, the overall reduction would have been 17.90%, not far below the theoretically expected reduction (22%), based on the protective efficacy of PCV7 (89%), the percentage of invasive disease-causing serotypes included in the vaccine (70%), and the vaccination coverage achieved during the study period (35%).