Recommendations for infectious disease screening in migrants to Western Europe with inflammatory arthropathies before starting biologic agents. Results from a multidisciplinary task force of four European societies (SIR, SER, SIMET, SEMTSI) facing the largest impact of the flow of migrants today.

OBJECTIVES: Inflammatory arthritis needs infectious disease screening before starting a biologic agent, however, few data are known about migrant patients, who represent a peculiar population which requires a multidisciplinary approach among international health specialists and should also be considered by health authorities. For this reason, the Italian and Spanish Societies of Rheumatology (SIR and SER) and Tropical Medicine (SIMET and SEMTSI) promoted a multidisciplinary task force in order to produce specific recommendations about screening and advices to be considered in migrant patients with inflammatory arthritis candidate to receive biological therapy, according to their geographical origin. METHODS: The experts provided a prioritised list of research questions and the eligible spectrum of inflammatory arthritis, biologic drugs and infectious disease were defined in order to perform a systematic literature review. A search was made in Medline, Embase and Cochrane library, updated to March 2015. Ubiquitous infections and HBV, HCV, HIV and tuberculosis that are already considered in national and international recommendations, were not included. The strength of each recommendation was determined. RESULTS: The task force members agreed on 7 overarching principles. The risk of reactivation of selected potentially latent infectious disease was addressed in migrants with inflammatory arthritis candidates for biologics was considered and 15 potentially relevant infections were identified. CONCLUSIONS: Fifteen disease-specific recommendations were formulated on the basis of high level of agreement among the experts panel.

Role of Vitamin D in Hospitalized Children With Lower Tract Acute Respiratory Infections.

BACKGROUND: Vitamin D is known to have modulatory actions in the immune system. Its influence on the severity of lower tract acute respiratory infections (LT-ARIs) is unclear. OBJECTIVES: The aim of the present study was to evaluate the role of vitamin D on LT-ARI in paediatric patients. METHODS: Children admitted to hospital with LT-ARI were prospectively recruited through the GENDRES network (March 2009-May 2013). The 25-hydroxyvitamin D (25-OHD) levels were measured by immunoassay. The severity of the illness was evaluated according to clinical scales, length of hospital stay, ventilatory requirements, and pediatric intensive care unit admission. RESULTS: A total of 347 patients with a median (interquartile range) age of 8.4 (2.6-21.1) months were included. The mean (SD) 25-OHD levels in our series were 27.1 (11.3) ng/mL. In this study, a cutoff value of ≥30 ng/mL was considered optimal vitamin status. Patients with 25-OHD levels <20 ng/mL were at a higher risk of showing severe signs of respiratory difficulties (OR 5.065, 95% confidence interval 1.998-12.842; P = 0.001) than patients with normal values, and had a 117% higher risk of oxygen necessity and 217% higher risk of ventilatory requirement than those patients with normal values. An inverse correlation was found between 25-OHD levels and the severity in the evaluated scales. 25-OHD levels did not influence PICU admission rate or length of hospital stay. CONCLUSIONS: 25-OHD levels of children admitted because of a LT-ARI are <30 ng/mL. Lower levels of 25-OHD were found to be correlated with severity of the disease. The possible role of abnormal 25-OHD levels as a facilitator or consequence of the infection needs further evaluation.

[Clinical and epidemiological differences between Bordetella pertussis and respiratory syncytial virus infections in infants: a matched case control study]. / Diferencias clínicas y epidemiológicas entre las infecciones por Bordetella pertussis y por virus respiratorio sincitial en lactantes: estudio de casos controles emparejados.

INTRODUCTION: An increase in cases of pertussis, mainly in young infants, has been reported in the last few years. The clinical presentation of this disease is very similar to that produced by respiratory syncytial virus (RSV), which makes the diagnosis difficult. OBJECTIVE: To compare the clinical and epidemiological characteristics between Bordetella pertussis and RSV infections in infants admitted to hospital. MATERIAL AND METHODS: An analytical matched case-control study was conducted during the period 2008-2011. Cases were defined as infants admitted with pertussis confirmed by PCR in nasopharyngeal aspirate. Each case was matched by age, sex and date of admission to two controls defined as patients with RSV infection detected by immunochromatography in nasal aspirate. Demographic, clinical, laboratory data were compared. RESULTS: Seventy eight patients (26 cases of pertussis and 52 controls RSV+) were included. Sociodemographic characteristics were similar in both groups. Cases had more days of symptoms prior to admission, longer hospital stays, and increased frequency of epidemic family environment. Apnoea and cyanosis were more frequent. Cases of pertussis were more likely to have apnoea, cyanosis, and lymphocytosis while RSV infections had more frequent fever, vomiting and respiratory distress. CONCLUSIONS: The clinical presentations of pertussis and RSV infection are similar, but there are some characteristics that can help to distinguish between them.

Child Care Center Hand Hygiene Programs' Cost-Effectiveness in Preventing Respiratory Infections.

BACKGROUND: We previously demonstrated that a hand hygiene program, including hand sanitizer and educational measures, for day care center (DCC) staff, children, and parents was more effective than a soap-and-water program, with initial observation, in preventing respiratory infections (RIs) in children attending DCCs. We analyzed the cost-effectiveness of these programs in preventing RIs. METHODS: A cluster, randomized, controlled and open study of 911 children aged 0 to 3 years, attending 24 DCCs in Almeria. Two intervention groups of DCC-families performed educational measures and hand hygiene, one with soap-and-water (SWG) and another with hand sanitizer (HSG). The control group (CG) followed usual hand-washing procedures. RI episodes, including symptoms, treatments, medical contacts, complementary analyses, and DCC absenteeism days, were reported by parents. A Bayesian cost-effectiveness model was developed. RESULTS: There were 5201 RI episodes registered. The adjusted mean societal costs of RIs per child per study period were CG: €522.25 (95% confidence interval [CI]: 437.10 to 622.46); HSG: €374.53 (95% CI: 314.90 to 443.07); SWG: €494.51 (95% CI: 419.21 to 585.27). The indirect costs constituted between 35.7% to 43.6% of the total costs. Children belonging to the HSG had an average of 1.39 fewer RI episodes than the CG and 0.93 less than the SWG. It represents a saving of societal cost mean per child per study period of €147.72 and €119.15, respectively. The HSG intervention was dominant versus SWG and CG. CONCLUSIONS: Hand hygiene programs that include hand sanitizer and educational measures for DCC staff, children, and parents are more effective and cost less than a program with soap and water and initial observation in children attending DCCs.

TIPICO X: report of the 10th interactive infectious disease workshop on infectious diseases and vaccines.

TIPICO is an expert meeting and workshop that aims to provide the most recent evidence in the field of infectious diseases and vaccination. The 10th Interactive Infectious Disease TIPICO workshop took place in Santiago de Compostela, Spain, on November 21-22, 2019. Cutting-edge advances in vaccination against respiratory syncytial virus, Streptococcus pneumoniae, rotavirus, human papillomavirus, Neisseria meningitidis, influenza virus, and Salmonella Typhi were discussed. Furthermore, heterologous vaccine effects were updated, including the use of Bacillus Calmette-Guérin (BCG) vaccine as potential treatment for type 1 diabetes. Finally, the workshop also included presentations and discussion on emergent virus and zoonoses, vaccine resilience, building and sustaining confidence in vaccination, approaches to vaccine decision-making, pros and cons of compulsory vaccination, the latest advances in decoding infectious diseases by RNA gene signatures, and the application of big data approaches.

Effectiveness of a hand hygiene program to reduce acute gastroenteritis at child care centers: A cluster randomized trial.

We aimed to assess the effectiveness of an educational and hand hygiene program in daycare centers (DCCs) and homes on acute gastroenteritis (AGE) incidence in children attending DCCs. METHODS: A randomized, controlled, and open study of 911 children aged 0-3 years attending 24 DCCs in Almería (Spain) with an 8-month follow-up was employed. Two intervention groups of DCCs families performed educational and hand hygiene measures, 1 with soap and water (soap and water group; n = 274), another with hand sanitizer (hand sanitizer group [HSG]; n = 339), and the control group (CG; n = 298) followed usual handwashing procedures. We compared AGE episode rates with Poisson regression model. RESULTS: seven hundred fourteen AGE episodes were registered, significant differences between HSG and CG children were found during December and January. A multivariate model was applied and the adjusted incidence rate ratios by rotavirus vaccination found significant differences when children were previously vaccinated, the children in the soap and water group had a higher risk of AGE episodes (incidence rate ratio: 1.28, 95% confidence interval:1.0-1.64), compared with those in the HSG. CONCLUSIONS: This study demonstrated that hand hygiene programs that included hand sanitizer were most effective in the winter months. Further, the largest reduction of AGE episodes occurred in the children that followed hand hygiene programs including hand sanitizer and educational measures for DCC staff, parents, and children, and were vaccinated for rotavirus.

[What have we learnt about rotavirus in Spain in the last 10 years?] / ¿Qué hemos aprendido sobre rotavirus en España en los últimos 10 años?

INTRODUCTION: Vaccines against rotavirus (RV) have been available in Spain since 2006, but they are neither recommended nor financed by the National Health System. Nevertheless, through recommendations of the Spanish Association of Paediatrics vaccination has achieved intermediate coverage. MATERIAL AND METHODS: A systematic literature review was performed on studies carried out in Spain in the last 12 years (2006-2018) on RV infection and vaccination. RESULTS: A total of 43 studies were identified that met the inclusion criteria. The disease burden in children less than 5 years in the Primary Care setting ranged from 15 to 19 cases per 1,000 children, and between 120 and 480 cases per 100,000 in the hospital setting, which has a significant economic and social impact. Vaccines against RV have shown an effectiveness of between 83% and 96%, and an impact of up to 70% in reducing hospital admissions, which is dependent on the achieved vaccine coverage. New research lines are identified, such as the role of the rotavirus vaccine and protection against seizures or the impact on the gut microbiota. CONCLUSIONS: The current available information supports the significant burden of rotavirus disease in Spain and the high effectiveness of the available vaccines. This evidence should allow for an updated re-evaluation of the national recommendations on rotavirus vaccination.

Effectiveness of a Hand Hygiene Program at Child Care Centers: A Cluster Randomized Trial.

OBJECTIVES: Respiratory infections (RIs) are an important cause of morbidity and excessive antibiotic prescriptions in children attending day care centers (DCCs). We aimed to assess the effectiveness of an educational and hand hygiene program in DCCs and homes in reducing RI incidence and antibiotic prescriptions in children. METHODS: A cluster, randomized, controlled, and open study of 911 children aged 0 to 3 years attending 24 DCCs in Almería (Spain) with an 8-month follow-up. Two intervention groups of DCC families performed educational and hand hygiene measures, 1 with soap and water (SWG; n = 274), another with hand sanitizer (HSG; n = 339), and the control group (CG; n = 298) followed usual hand-washing procedures. RI episode rates were compared through multilevel Poisson regression models. The percentage of days missed were compared with Poisson exact tests. RESULTS: There were 5211 RI episodes registered. Children in the HSG had less risk of RI episodes (incidence rate ratio [IRR]: 0.77; 95% confidence interval [CI]: 0.68-0.88) and antibiotic prescriptions (IRR: 0.69; 95% CI: 0.57-0.84) compared with the those in the CG. Children in the SWG had a higher risk of RI episodes (IRR: 1.21; 95% CI: 1.06-1.39) and antibiotic prescriptions (IRR: 1.31; 95% CI: 1.08-1.56) than those in the HSG. Pupils missed 5186 DCC days because of RIs, and the percentage of days absent was significantly lower in the HSG compared with the CG (P < .001) and the SWG (P < .001). CONCLUSIONS: Hand hygiene programs that include hand sanitizer and educational measures for DCC staff, children, and parents, reduce absent days, RIs, and antibiotic prescriptions for these infections in children at DCCs.

Antibody persistence and booster responses 24-36 months after different 4CMenB vaccination schedules in infants and children: A randomised trial.

OBJECTIVES: This phase IIIb, open-label, multicentre, extension study (NCT01894919) evaluated long-term antibody persistence and booster responses in participants who received a reduced 2 + 1 or licensed 3 + 1 meningococcal serogroup B vaccine (4CMenB)-schedule (infants), or 2-dose catch-up schedule (2-10-year-olds) in parent study NCT01339923. MATERIALS AND METHODS: Children aged 35 months to 12 years (N = 851) were enrolled. Follow-on participants (N = 646) were randomised 2:1 to vaccination and non-vaccination subsets; vaccination subsets received an additional 4CMenB dose. Newly enrolled vaccine-naïve participants (N = 205) received 2 catch-up doses, 1 month apart (accelerated schedule). Antibody levels were determined using human serum bactericidal assay (hSBA) against MenB indicator strains for fHbp, NadA, PorA and NHBA. Safety was also evaluated. RESULTS: Antibody levels declined across follow-on groups at 24-36 months versus 1 month post-vaccination. Antibody persistence and booster responses were similar between infants receiving the reduced or licensed 4CMenB-schedule. An additional dose in follow-on participants induced higher hSBA titres than a first dose in vaccine-naïve children. Two catch-up doses in vaccine-naïve participants induced robust antibody responses. No safety concerns were identified. CONCLUSION: Antibody persistence, booster responses, and safety profiles were similar with either 2 + 1 or 3 + 1 vaccination schedules. The accelerated schedule in vaccine-naïve children induced robust antibody responses.

Circulating Antibody 1 and 2 Years After Vaccination With the 13-Valent Pneumococcal Conjugate Vaccine in Preterm Compared With Term Infants.

BACKGROUND: Premature infants have lower short-term immune responses to vaccination than term infants, but patterns of antibody persistence in preterm infants over longer periods are not well established. This study assessed the persistence of antibody response to the 13-valent pneumococcal conjugate vaccine (PCV13) in formerly preterm versus term infants. METHODS: In total, 100 preterm and 100 term infants received PCV13 with routine vaccines at ages 2, 3, 4 and 12 months. Serotype-specific anticapsular immunoglobulin G (IgG)-binding antibodies and opsonophagocytic activity were determined 1 and 2 years after the last PCV13 dose. RESULTS: At 1 and 2 years after the last vaccination (toddler dose), IgG geometric mean concentrations (GMCs) for all serotypes had declined from levels measured 1 month after the toddler dose but remained above pretoddler dose levels. IgG GMCs were significantly lower in preterm than term subjects for a majority of serotypes at both follow-up time points. IgG GMCs increased in both groups for some serotypes from the 1-year to 2-year follow-up, whereas others declined. Opsonophagocytic activity results supported the IgG results. CONCLUSIONS: The routine (3 + 1) vaccination schedule is likely to offer long-term protection against invasive pneumococcal disease in preterm infants and should be initiated regardless of gestational age or weight at birth, without delay of the toddler dose.

Hand Hygiene Program Decreases School Absenteeism Due to Upper Respiratory Infections.

BACKGROUND: We assessed the effectiveness of a handwashing program using hand sanitizer to prevent school absenteeism due to upper respiratory infections (URIs). METHODS: This was a randomized, controlled, and open study on a sample of 1341 children 4-12 years old, attending 5 state schools in Almería (Spain), with an 8-month follow-up. The experimental group (EG) washed their hands with soap and water, together with using hand sanitizer, and the control group followed their usual handwashing procedures. Absenteeism rates due to URIs were compared between the 2 groups through a multivariate Poisson regression analysis. The percent of days missed in both groups were compared with a z test. RESULTS: Overall, 1271 cases of school absenteeism due to URIs were registered. Schoolchildren from the EG had a 38% lower risk of absenteeism due to URIs, incidence rate ratio: 0.62, 95% confidence interval: 0.55-0.70, and a decrease in absenteeism of 0.45 episodes/child/academic year, p < .001. Pupils missed 2734 school days due to URIs and the percentage of days absent was significantly lower in the EG, p < .001. CONCLUSIONS: Use of hand sanitizer plus handwashing with soap accompanied by educational support is an effective measure to reduce absenteeism due to URIs.

Impact of vaccination uptake on hospitalizations due to rotavirus acute gastroenteritis in 2 different socioeconomic areas of Spain.

Rotavirus is the leading cause of hospitalization due to acute gastroenteritis (AGE) in infants and toddlers. However, rotavirus vaccination has been associated with a decline in hospitalization rates due to rotavirus AGE. A descriptive retrospective study was conducted to analyze the impact of rotavirus vaccination on the rate of hospitalizations due to AGE among children ≤2 years old in 2 areas of the province of Almería, Spain. After eight years of rotavirus vaccination, rates of hospitalizations due to rotavirus AGE are diminished. This decline is closely related to vaccine coverage in the studied areas.

13-valent pneumococcal conjugate vaccine (PCV13) in preterm versus term infants.

OBJECTIVES: This study evaluated the immune response and safety profile of 13-valent pneumococcal conjugate vaccine (PCV13) in preterm infants compared with term infants. METHODS: This Phase IV, open-label, 2-arm, multicenter, parallel-group study enrolled 200 healthy infants (preterm, n = 100; term, n = 100) aged 42 to 98 days. All subjects received PCV13 at ages 2, 3, 4 (infant series), and 12 (toddler dose [TD]) months, together with routine vaccines (diphtheria-tetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine and meningococcal group C conjugate vaccine). RESULTS: Most subjects achieved an anticapsular immunoglobulin G (IgG) antibody concentration ≥ 0.35 µg/mL for all serotypes: >85% after the infant series (except preterm infants for serotypes 5, 6A, and 6B) and >97% after TD (except for serotype 3). Preterm infants had overall lower IgG geometric mean concentrations compared with term infants; however, geometric mean fold increases after TD were similar for all serotypes. Opsonophagocytic activity results were consistent with IgG results and titers increased after TD in both groups for all serotypes, including serotype 3. PCV13 was generally well tolerated, with similar safety profiles in all preterm subgroups. CONCLUSIONS: Immune responses were lower in preterm infants than in term infants. However, the majority of subjects in both groups achieved both pneumococcal serotype-specific IgG antibody levels after the infant series that exceeded the World Health Organization-established threshold of protection and functional antibody responses. Responses were uniformly higher after TD, reinforcing the importance of a timely booster dose. PCV13 was well tolerated regardless of gestational age.

A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants.

BACKGROUND: Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed. METHODS: This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-µg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase. RESULTS: Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-µg rLP2086 dose, respectively. Most fevers were <39.0°C. Only 2 subjects in the 20-µg group and 1 subject in the 60-µg group experienced fevers >39.0°C; no fevers were >40.0°C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-µg dose. CONCLUSION: Due to the high fever rate experienced in the 20- and 60-µg groups, rLP2086 in the current formulation may not be acceptable for infants.

Effectiveness of a multifactorial handwashing program to reduce school absenteeism due to acute gastroenteritis.

BACKGROUND: Acute gastroenteritis (AGE) is one of the most common diseases among children and an important cause of school absenteeism. The aim of this study was to assess the effectiveness of a handwashing program using hand sanitizers for the prevention of school absenteeism due to AGE. METHODS: A randomized, controlled and open study of a sample of 1341 children between 4 and 12 years of age, attending 5 state schools in Almería (Spain), with an 8-month follow up (academic year). The experimental group (EG) washed their hands with soap and water, complementing this with the use of a hand sanitizer, and the control group (CG) followed the usual handwashing procedure. Absenteeism rates due GI were compared between the 2 groups through the multivariate Poisson regression analysis. Percent days absent in both groups were compared with a Z-test. RESULTS: 446 cases of school absenteeism due to AGE were registered. The school children from the EG had a 36% lower risk of absenteeism due to AGE (IRR: 0.64, 95% confidence interval: 0.52-0.78) and a decrease in absenteeism of 0.13 episodes/child/academic year (0.27 of EG vs 0.40 CG/episodes/child/academic year, P < 0.001). Pupils missed 725 school days due to AGE and absent days was significantly lower in the EG (EG: 0.31%, 95% confidence interval: 0.28-0.35 vs. CG: 0.44%, 95% confidence interval: 0.40-0.48, P < 0.001). CONCLUSIONS: The use of hand sanitizer as a complement to handwashing with soap is an efficient measure to reduce absent days and the number of school absenteeism cases due to AGE.

Different penetrance of disseminated infections caused by nontuberculous Mycobacteria in Mendelian susceptibility to mycobacterial disease associated with a novel mutation.

Deficiency in the interleukin12/INFgamma pathway is a genetic condition that predisposes to some infections, including nontuberculous mycobacteria infection and extraintestinal salmonellosis. We report 2 cases in sisters who were diagnosed with a genetic defect caused by a new mutation in Interleukin-12 receptor ß1 chain (IL12Rß1) leading to different clinical presentations and responses to therapy.

The impact of common infections on school absenteeism during an academic year.

BACKGROUND: School absenteeism because of infections is one of the most important problems facing both public and private primary schools. The aim of the study was to assess the impact of infections on school absenteeism and their reduction with a handwashing program using hand sanitizer. METHODS: The study was an 8-month-long, randomized, controlled open study (N = 1,609 children, aged 4-12 years old) at 5 state schools in Almeria (Spain). The experimental group (EG) washed their hands with soap and water, complemented with the use of hand sanitizer, and the control group (CG) followed the usual handwashing procedure. The total number of episodes and days missed as well as those because of upper respiratory infections and gastrointestinal infections were compared in both groups with a Z-test. RESULTS: The students were absent 12,386 days in 7,945 episodes. The incidence of total absent episodes and percent of missed days, including those because of upper respiratory infections and gastrointestinal infections, were significantly lower in the EG than the CG (P < .001), and this was maintained through the flu pandemic period. CONCLUSION: School absenteeism because of infections in schools is reduced when a hand hygiene program utilizing sanitizing gels is properly carried out, especially during the flu season.

[Health professionals' knowledge on Chagas disease in the province of Almeria, Spain]. / Conocimiento de la Enfermedad de Chagas por parte de los profesionales sanitarios de tres hospitales en la provincia de Almería.

BACKGROUND: Health professionals who care for patients with imported diseases often lack enough training. The aim of the study is to assess the knowledge of Chagas disease among doctors and nurses attending at-risk pregnant women in our province. METHOD: descriptive study through a performed anonymous and voluntary knowledge questionnaire for 278 physicians and nurses working at maternity and children's health services in the three hospitals in the province. In Poniente Hospital was established in 2007 a program of screening for the disease in pregnant women. For statistical analysis, quantitative variables were described using the mean and standard deviation. For comparison of qualitative variables we used the chi-square test or Fisher exact test as appropriate. Differences in age and years of experience depending on the hospital were measured by Brown-Forsy the robust test. RESULTS: 116 (41.7%) professionals agreed to participate in the study. 80 (69%) were women and 36 (31%) men, mean age 36.78 years. By professional categories, physicians have a mean of 73.9% correct responses, the nurses 50.7%. Poniente Hospital had the highest percentage of correct answers on aspects of the geographical distribution of the disease (73.7%), the mechanisms of transmission (86%) and diagnosis (82.5%). CONCLUSIONS: The Poniente Hospital professionals generally have a better Knowledge about Chagas disease compared with two other professionals hospitals, which probably is related to the existence of the screening program for the disease.

Evaluation of 13-valent pneumococcal conjugate vaccine and concomitant meningococcal group C conjugate vaccine in healthy infants and toddlers in Spain.

BACKGROUND: Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. METHODS: This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. RESULTS: 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35µg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. CONCLUSIONS: Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing expanded coverage against pneumococcal disease.

International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines.

BACKGROUND: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. METHODS: The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. RESULTS: We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1.28-3.42) using the meta-analytic approach. CONCLUSIONS: This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines.