Jesús Ruiz-Contreras

Calendario de vacunaciones de la Asociacion Espanola de Pediatria: recomendaciones 2010

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded, as routine vaccinations, those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in special situations. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Based on the latest epidemiological trends, CAV-AEP recommends the administration of the first dose of MMR and varicella vaccines at age 12 months, with the second dose at age 2-3 years; the administration of DTaP or Tdap vaccine at age 4-6 years, always followed by another Tdap dose at 11-12 years; and the three meningococcal C scheme at 2 months, 12 months and 12 years of age. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-12 years must be increased. Universal vaccination against varicella in the second year of life is an effective strategy, and the immediate public availability of the vaccine is requested in order to guarantee the right of healthy children to be vaccinated. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. The recently authorised meningococcal B vaccine has opened a chapter of hope in the prevention of this disease. In anticipation of upcoming national and international studies, the Committee recommends the vaccine for the control of disease outbreaks, and insists on the need to be available in pharmacies. Finally, it emphasises the need to bring incomplete vaccinations up to date following the catch-up immunisation schedule.

Relationship between serotypes, age, and clinical presentation of invasive pneumococcal disease in Madrid, Spain, after introduction of the 7-valent pneumococcal conjugate vaccine into the vaccination calendar.

ABSTRACT To assess invasive pneumococcal disease (IPD) clinical presentations and relationships with age and serotype in hospitalized children (<15 years) after PCV7 implementation in Madrid, Spain, a prospective 2-year (May 2007 to April 2009) laboratory-confirmed (culture and/or PCR) IPD surveillance study was performed (22 hospitals). All isolates (for serotyping) and culture-negative pleural/cerebrospinal fluids were sent to the reference laboratory for pneumolysin (ply) and autolysin (lyt) gene PCR analysis. A total of 330 IPDs were identified: 263 (79.7%) confirmed by culture and 67 (20.3%) confirmed by PCR. IPD distribution by age (months) was as follows: 23.6% (<12), 15.8% (12 to 23), 15.5% (24 to 35), 22.4% (36 to 59), and 22.7% (>59). Distribution by clinical presentation was as follows: 34.5% bacteremic pneumonia, 30.3% pediatric parapneumonic empyema (PPE), 13.6% meningitis, 13.3% primary bacteremia, and 8.2% others. Meningitis and primary bacteremia were the most frequent IPDs in children <12 months old, and bacteremic pneumonia and PPE were most frequent in those >36 months old. Frequencies of IPD-associated serotypes were as follows: 1, 26.1%; 19A, 18.8%; 5, 15.5%; 7F, 8.5%; 3, 3.9%; nontypeable/other 30 serotypes, 27.3%. Serotype 1 was linked to respiratory-associated IPD (38.6% in bacteremic pneumonia and 38.0% in PPE) and children of >36 months (51.4% for 36 to 59 months and 40.0% for >59 months), while serotype 19A was linked to nonrespiratory IPDs (31.1% in meningitis, 27.3% in primary bacteremia, and 51.9% in others) and children of <24 months (35.9% for children of <12 months and 36.5% for those 12 to 23 months old), with high nonsusceptibility rates for penicillin, cefotaxime, and erythromycin. After PCV7 implementation, non-PCV7 serotypes caused 95.5% of IPDs. The new 13-valent conjugate vaccine would provide 79.1% coverage of serotypes responsible for IPDs in this series.

Immunogenicity and reactogenicity of primary immunization with a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type B vaccine coadministered with two doses of a meningococcal C-tetanus toxoid conjugate vaccine.

Background: This study evaluated the concurrent use of meningococcal C tetanus conjugate (MenC-TT) vaccine (NeisVac-C) with DTaP-based combinations, according to 2 vaccination schedules, one of which included hepatitis B vaccination at birth (Trial DTaP-HBV-IPV/Hib-097). Methods: Healthy infants were randomized to receive either DTaP-HBV-IPV/Hib (Infanrix hexa) at 2, 4, and 6 months (N = 115) or HBV at birth followed by DTaP-HBV-IPV/Hib at 2 and 6 months and DTaP-IPV/Hib (Infanrix-IPV Hib) at 4 months (N = 115). In both groups 2 doses of MenC-TT conjugate were coadministered at 2 and 4 months, and compared with 3 doses of MenC-CRM197 conjugate (Meningitec) coadministered at 2, 4, and 6 months with DTaP-HBV-IPV/Hib (N = 120). Antibody concentrations were measured at 2, 6 and 7 months. Solicited local and general symptoms, unsolicited symptoms, and serious adverse events (SAEs) were recorded. Results: All MenC-TT recipients had seroprotective concentrations of anti-PRP antibodies (≥0.15 μg/mL) 1 month after the third vaccine dose and all had SBA-MenC titers ≥1:8 after the second dose of MenC-TT. These responses were noninferior to those seen after 3 doses of DTaP-HBV-IPV/Hib and MenC-CRM. Anti-PRP antibody GMCs were significantly higher in MenC-TT than MenC-CRM vaccinees (7.9, 7.3, 3.8 μg/mL, respectively). Immune responses to all other coadministered antigens were unimpaired, with seroprotection/seropositivity rates ≥98.1% in MenC-TT vaccinees. All schedules studied were well tolerated, with no differences in reactogenicity between the study groups. Conclusions: Coadministration of DTaP-HBV-IPV/Hib or DTaP-IPV/Hib with 2 doses of MenC-TT conjugate vaccine is safe, well tolerated, and immunogenic, with no impairment of the response to the coadministered antigens.

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.

Expansion of Serotype Coverage in the Universal Pediatric Vaccination Calendar: Short-Term Effects on Age- and Serotype-Dependent Incidence of Invasive Pneumococcal Clinical Presentations in Madrid, Spain

ABSTRACT In Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged <15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non-PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13 serotypes.

Assessment of antibody response elicited by a 7-valent pneumococcal conjugate vaccine in pediatric human immunodeficiency virus infection.

ABSTRACT We investigated antibody responses against pneumococci of serotypes 6B, 14, and 23F in 56 children and adolescents with perinatal human immunodeficiency virus (HIV) infection who were vaccinated with 7-valent pneumococcal conjugate vaccine. Overall immune responses differed greatly between serotypes. Correlation coefficients between immunoglobulin G (IgG) measured by enzyme-linked immunosorbent assay (ELISA) and functional antibodies measured by a flow cytometry opsonophagocytosis assay (OPA) varied with serotype and time points studied. After 3 months of administering a second PCV7 dose we got the highest correlation (with significant r values of 0.754, 0.414, and 0.593 for serotypes 6B, 14, and 23F, respectively) but no significant increase in IgG concentration and OPA titers compared to the first dose. We defined a responder to a serotype included in the vaccine with two criteria: frequency of at least twofold OPA and ELISA increases for each serotype and frequency of conversion from negative to positive OPA levels. Responders varied from 43.9% to 46.3%, 28.5% to 50.0%, and 38.0% to 50.0% for serotypes 6B, 14, and 23F, respectively, depending on the response criterion. The present research highlights the importance of demonstrating vaccine immunogenicity with suitable immunological endpoints in immunocompromised patients and also the need to define how much antibody is required for protection from different serotypes, since immunogenicity differed significantly between serotypes.

Immunogenicity and reactogenicity of primary immunization with a novel combined Haemophilus influenzae Type b and Neisseria meningitidis Serogroup C-tetanus toxoid conjugate vaccine coadministered with a Diphtheria-tetanus-acellular Pertussis-hepatitis B-inactivated poliovirus vaccine at 2, 4 and 6 months.

Background: This phase II study evaluated the immunogenicity and reactogenicity of primary vaccination with a novel Hib-MenC conjugate vaccine (GlaxoSmithKline [GSK] Biologicals) coadministered with DTPa-HBV-IPV (GSK Biologicals) at 2, 4 and 6 months. Methods: Healthy infants were randomized to receive Hib-MenC coadministered with DTPa-HBV-IPV (N = 117) or MenC-CRM (Wyeth) coadministered with DTPa-HBV-IPV/Hib (GSK Biologicals; N = 120) at 2, 4 and 6 months. Antibody concentrations were measured before vaccination and after doses 2 and 3. Solicited local and general symptoms, unsolicited symptoms and serious adverse events (SAEs) were recorded. Results: All subjects in the Hib-MenC group had seroprotective titers of anti-PRP antibodies (≥0.15 μg/mL) and SBA-MenC titers (≥1:8) 1 month after the third dose. These responses were noninferior to those seen in the control group, in which a 99.1% seroprotection rate was observed for both Hib and MenC. At that time, anti-PRP and SBA-MenC GMTs were significantly higher in the Hib-MenC group (12.8 μg/mL and 2467.1 μg/mL, respectively) than in the control group (3.8 μg/mL and 1833.7 μg/mL). High seroprotection rates were already observed after the second dose of Hib-MenC; 96.4% and 100% of subjects were seroprotected to Hib and MenC, respectively. Immune responses to coadministered antigens were unimpaired; seroprotection/vaccine response rates ≥96.5% were recorded postdose 3 in the Hib-MenC group. No differences in reactogenicity were seen between the 2 study groups. Conclusions: Coadministration of a Hib-MenC conjugate vaccine with DTPa-HBV-IPV is well tolerated and immunogenic, and does not impair the immune response to any of the coadministered antigens.

Immunogenicity and reactogenicity of a booster dose of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine given to toddlers of 13-14 months of age with antibody persistence up to 31 months of age.

Background: A combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) may be a convenient alternative to separate Hib and MenC conjugate vaccines. Methods: Healthy infants randomized in a previous study for priming at 2, 4, and 6 months: Hib-MenC-TT primed group, 3 doses of Hib-MenC-TT + DTPa-HBV-IPV (N = 87); MenC-TT primed group, 2 doses of MenC-TT (NeisVac-C™; Baxter Healthcare SA, Zuürich, Switzerland) + 3 doses of DTPa/Hib containing vaccines (N = 178); MenC-CRM primed group, 3 doses of MenC-CRM197(Meningitec™; Wyeth Corporation Delaware, Madison, NJ) + DTPa-HBV-IPV/Hib (N = 93). At 13-14 months of age, Hib-MenC-TT and MenC-TT primed groups received a Hib-MenC-TT booster dose and the MenC-CRM primed group a booster dose of DTPa-HBV-IPV/Hib. Blood samples were taken before and at 1 and 18 months postbooster. Results: Before the booster dose, persistence of anti-polyribosyl ribitol phosphate (PRP) antibody concentration ≥0.15 &mgr;g/mL in the Hib-MenC-TT (96.4%) and MenC-TT (96.1%) primed groups and of MenC bactericidal titers ≥1:8 in the Hib-MenC-TT primed group (96.3%) was statistically significantly higher than in the MenC-CRM primed group (86.4% and 85.4%, respectively). One month after the Hib-MenC-TT booster, 99.2% subjects in the Hib-MenC-TT primed + MenC-TT primed pooled groups had anti-PRP levels ≥1 &mgr;g/mL, and 99.6% had SBA-MenC titers ≥1:128. The Hib-MenC-TT booster tended to be less reactogenic than the DTPa-HBV-IPV/Hib control and no serious adverse events related to vaccination were reported. Eighteen months after boosting with Hib-MenC-TT, SBA-MenC titers ≥1:8 persisted in 92.7% subjects and anti-PRP ≥0.15 &mgr;g/mL persisted in 99.4%. Conclusions: Primary immunization with 3 doses of Hib-MenC-TT coadministered with DTPa-HBV-IPV induced antibodies that persisted up to the second year of life. The Hib-MenC-TT booster administered to primed toddlers induced robust and persistent antibody responses to both the Hib and MenC components and had an acceptable safety profile.

Laboratory-based, 2-year surveillance of pediatric parapneumonic pneumococcal empyema following heptavalent pneumococcal conjugate vaccine universal vaccination in Madrid.

Background: In October 2006, the heptavalent pneumococcal conjugate vaccine was included in the Madrid vaccination calendar, warranting serotype (St) surveillances in pneumococcal pediatric parapneumonic empyema (PPE). Methods: A prospective 2-year (May 2007–April 2009) laboratory-confirmed PPE surveillance was performed in 22 hospitals. All isolates (for serotyping) and culture-negative pleural fluids were sent to the reference laboratory for polymerase chain reaction (PCR) analysis. Results: We identified 138 PPEs. Pneumococcal etiology was confirmed in 100 cases: 38 by culture, 62 by PCR. Mean age was 44.64 ± 26.64 months; 51.0% were male. Similar pneumococcal PPE distribution was found by age: 21% to 28% in <24, ≥24–<36, ≥36–<60, and ≥60 months. PPE-associated Sts were St 1 (38%), St 5 (15%), St 19A (11%), St 7F (9%), St 3 (8%), and others (19%). St 1 was the most common in >36 months, with similar rates to St 19A in <24 months (≈30%). In ≥24–≤36 months, St 3 (21.7%), St 1 and St 5 (17.4% each) were the most frequent. No differences in demographic data, vaccination status, length of hospitalization, and outcome were found between culture-negative (PCR positive) and culture-positive PPE patients, with significantly higher percentages of St 1 and St 5 in culture-positive PPEs. Total rates of St 1 (38%), St 5 (15%), and St 7F (9%) would have been over-represented considering only positive-culture PPEs (n = 38), by increasing to 52.6% (St 1), 23.7% (St 5), and 10.5% (St 7F). The 13-valent pneumococcal conjugate vaccine would cover 84.0% of Sts causing PPEs. Conclusions: PCR is essential for determining the specific etiology of PPE.

Chagas disease travels to Europe.

In his Correspondence letter, Ricardo Pereira Igreja revisits the impor tance of Chagas disease 100 years after its discovery. Immigration from South America to Europe is increasing, so European countries are now facing some neglected diseases they are not used to dealing with. 97·5% of Bolivians who emigrate to Europe (the most popular desti nation after the USA) settle in Spain. The prevalence of Chagas disease in Bolivia is 20–40%. We have been assessing the prevalence of Chagas disease in Bolivian pregnant women in our Spanish hospital for the past 2 years and have found a 17·7% rate (71/401), with a 1·4% vertical transmission rate (1/71). Chagas disease has been included in the routine assessment for LatinAmerican blood donors in Spain since 2005, but no national screening protocol for pregnant woman has been established. Because of the noted high prevalence of Chagas disease in Bolivian pregnant women in Spain, we suggest that all such women should be screened. Early treatment of infected children could avoid most of the severe complications associated with this disease. Furthermore, identifi cation of the mothers would allow treatment of this group and could off er them a better life expectancy.