Immune response to 13-valent pneumococcal conjugate vaccine with a reduced dosing schedule.

BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) has demonstrated effectiveness against pneumococcal illnesses when administered as 3 infant doses plus a toddler dose (3+1 schedule) or as an abbreviated schedule of 2 infant doses plus a toddler dose (2+1 schedule). The 13-valent pneumococcal conjugate vaccine (PCV13) is approved and World Health Organization-prequalified for administration in a 2+1 schedule when used as part of routine immunization programs. OBJECTIVE: To summarize immunologic responses elicited by PCV13 administered in a 2+1 schedule and following 2 doses in a 3+1 schedule. METHODS: Studies were double-blind, randomized, active-controlled, multicenter studies except the Mexico study (open-label, single-arm). In 2+1 studies, PCV13 was administered at 2, 4, and 12 (UK) or 3, 5, and 11 (Italy) months. In 3+1 studies (Spain and Mexico), assessment was made postdose 2 of the primary series (2, 4, and 6 months). The primary immunogenicity endpoint was the proportion of participants achieving serotype-specific antipolysaccharide immunoglobulin (Ig)G concentrations ≥ 0.35µg/mL (i.e., responders) 1 month postdose 2. Pneumococcal IgG geometric mean concentrations (GMCs), opsonophagocytic activity (OPA), and concomitant vaccine responses were assessed. RESULTS: PCV13 and PCV7 elicited comparable immune responses for the 7 common serotypes after 2 infant doses. The proportion of PCV13 responders postdose 2 was >85% for most of the 7 common and 6 additional serotypes, except common serotypes 6B (27.9-81.4%) and 23F (55.8-77.5%) and additional serotypes 3 (73.8-96.9%) and 6A (79.2-94.4%). Serotypes 6B and 23F elicited lower IgG GMCs postdose 2 compared with other serotypes; all serotypes demonstrated boosting posttoddler dose. All serotypes demonstrated functional activity; >95% of participants achieved OPA levels ≥ 1:8 postdose 2. Concomitant vaccine responses were similar between PCV13 and PCV7 groups. CONCLUSION: Immune responses elicited by PCV13 following 2 infant doses support transition from PCV7 to PCV13 in countries using a 2+1 schedule.

Vigilancia epidemiológica prospectiva de la enfermedad neumocócica invasora y de la neumonía en niños de San José, Costa Rica / Prospective epidemiologic surveillance of invasive pneumoccal disease and pneumonia in children in San Jos‚, Costa Rica

Justificación y objetivo: Streptococcus pneumoniae es globalmente la primera causa de muertes inmunoprevenibles en niños menores de 5 años. Métodos: entre 2007 y 2009 se realizó una vigilancia prospectiva con base poblacional en niños de 28 días a 36 meses en San José, Costa Rica. Se determinaron la incidencia de la enfermedad neumocócica invasora y de neumonía confirmada clínicamente y por radiografía, la distribución de serotipos y la sensibilidad a los antibióticos. Resultados: participaron 8801 sujetos (mediana de edad: 13,0 meses). En 25 niños se detectó enfermedad neumocócica invasora mediante aislamiento en cultivos (22) o mediante reacción de polimerasa en cadena y un cuadro clínico compatible con enfermedad neumocócica invasora. En los casos diagnosticados únicamente por cultivo, la tasa de incidencia de enfermedad neumocócica invasora en niños de 28 días a 36 meses de edad fue de 33,7/100000 por año para los años 1 y 2 combinados. Al considerar los casos adicionales diagnosticados por reacción de polimerasa en cadena, la incidencia aumnetó a 46,/100 000. El serotipo más frecuente fue el 14 (28,6 por ciento), seguido por los serotipos 3, 4, 6A, 19A, 22F. 42,9 por ciento de los aislamientos eran insensibles a la penicilina y al cotrimoxazol. La incidencia de neumonía confirmada clínicamente y de neumonía confirmada por radiografía fue de 1968/100 000 y 551/100 000, respectivamente. Conclusión: la incidencia de enfermedad neumocócica invasora y neumonía en niños de San José es considerable. Estos datos epidemiológicos sirven como línea de base para evaluar la efectividad de nuevas vacunas antineumocócicas conjugadas.

Bacteriology of community-acquired invasive disease found in a multicountry prospective, population-based, epidemiological surveillance for Pneumococcus in children in Latin America.

Several bacteria cause community-acquired invasive bacterial disease in children; many are vaccine preventable. Knowledge of pathogens causing community-acquired invasive bacterial disease is important when selecting antimicrobial therapy and implementing vaccine prevention strategies. We describe bacteriology of community-acquired invasive disease observed among 31,641 blood and sterile fluid cultures from children aged 28 days to 36 months in 3 Latin American countries over 2 years.

Population-based surveillance for invasive pneumococcal disease and pneumonia in infants and young children in Bogotá, Colombia.

BACKGROUND: In children <5 years of age, Streptococcus pneumoniae (SP) is, globally, the leading cause of vaccine-preventable death. Surveillance conducted in Bogotá, Colombia estimated incidence rates of invasive pneumococcal disease (IPD), clinical and chest radiograph-confirmed pneumonia (CXR+Pn); SP serotype distribution and antimicrobial susceptibility. METHODS: This prospective population-based surveillance was conducted from 2006 to 2008 in children 28 days to <36 months of age seeking care at SaludCoop centers. We determined incidence rates of IPD and pneumonia (clinical and CXR+Pn). Eligibility criteria included: temperature ≥39.0°C within 24h and/or clinical suspicion of IPD or pneumonia. Blood was obtained for culture in all children. Other sterile site specimens were obtained per routine practice. RESULTS: Of 8261 subjects enrolled, a total of 64 had invasive pneumococcal disease detected by isolation of SP from nonduplicative cultures (62) or detected solely by PCR and a clinical picture consistent with IPD (2). The overall IPD incidence rates for culture-positive only cases for children aged 28 days to <36 months was 76.4/100,000 per year for years 1 and 2 combined. Age stratification found the highest rates in children 6-12 and 12 to <24 months of age. IPD incidence rates were assessed for bacteremic pneumonia (54.2/100,000), bacteremia (17.2/100,000), meningitis (3.7/100,000), and sepsis (1.2/100,000). Most common serotypes causing IPD were: 14 (51.6%), 6B (9.7%), and 19F (9.7%). Coverage of IPD cases by pneumococcal conjugate vaccine (PCV) 7, PCV10, and PCV13 was 77.4%, 85.5%, and 91.9%, respectively. Twenty-eight isolates (45.2%) were penicillin-nonsusceptible; PCV7 covered 96.3% of these; PCV10 covered 96.3% and PCV13 covered 100%. The overall incidence of clinical pneumonia and CXR+Pn was 6276/100,000 and 2120/100,000, respectively. CONCLUSION: Pneumococcal disease and pneumonia burden is considerable in children in Bogotá, Colombia. Vaccination with pneumococcal conjugate vaccines has the potential to decrease this burden. Epidemiologic data are critical in assessing the potential impact of introduction of PCVs into national immunization schedules.

Prospective epidemiologic surveillance of invasive pneumococcal disease and pneumonia in children in San José, Costa Rica.

BACKGROUND: Streptococcus pneumoniae (SP) is the leading cause of vaccine-preventable death in children <5 years of age, globally. This surveillance determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest radiograph-confirmed pneumonia (CXR+Pn); and SP serotype distribution and antimicrobial susceptibility in children in San José, Costa Rica. METHODS: This was a 2-year prospective, population-based surveillance conducted in 2007-2009 in children aged 28 days to 36 months presenting to participating healthcare centers. Eligibility criteria for study inclusion were as follows: temperature ≥ 39.0°C within 24h and/or clinical suspicion of IPD or pneumonia. RESULTS: 8801 subjects were enrolled. Median age: 14.5 months. A total of 25 children had invasive pneumococcal disease with S. pneumoniae isolated from nonduplicative cultures (22) or detected solely by PCR and a clinical picture consistent with IPD (3). Sources of positive cultures (some children had >1 positive culture) were: blood (20), pleural fluid (4), and cerebrospinal fluid (3). Of the 3 cases detected solely by PCR, 2 were from cerebrospinal fluid and 1 from pleural fluid. The overall IPD incidence rates for culture-positive only cases for children aged 28 days to <3 years was 33.7/100,000 per year for years 1 and 2 combined. Age stratification of culture-positive only subjects showed a peak during year 1 (106.8/100,000) in children 28 days to <6 months of age group, and in year 2 (45.5/100,000) in children 12 months to <24 months of age group. Most common serotypes were 14 (28.6%), followed by 3, 4, 6A, 19A, and 22F (9.5% each). Of 22 nonduplicative IPD isolates, 42.9% were penicillin- and trimethoprim/sulfamethoxazole nonsusceptible isolates. Consideration of PCR-positive cases increases the incidence of IPD for children aged 28 days to <3 years to 46.0/100,000. Overall incidence of clinical pneumonia and CXR+Pn was 1968/100,000 and 551/100,000, respectively. CONCLUSIONS: There is a considerable burden of IPD and pneumonia in children in San José. These epidemiologic data serve as a baseline to evaluate the effectiveness of the incorporation of new conjugate pneumococcal vaccines into the National Immunization Program in Costa Rican children.

Population-based surveillance for invasive pneumococcal disease and pneumonia in infants and young children in Goiânia, Brazil.

BACKGROUND: Streptococcus pneumoniae is the leading cause of vaccine-preventable death in children <5 years of age globally. We determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest X-ray-confirmed pneumonia (CXR+Pn), S. pneumoniae serotype distribution, and antimicrobial susceptibility in children in Goiânia, Brazil. METHODS: Prospective, population-based surveillance was conducted from May 2007 to May 2009 in children 28 days to <36 months of age presenting to all 33 pediatric healthcare services (outpatient departments, emergency rooms, hospitals) in Goiânia. Eligibility criteria were temperature ≥39.0 °C in the previous 24h and/or clinical suspicion of pneumonia or IPD. RESULTS: 14,509 subjects were enrolled. Median age was 14.0 months. S. pneumoniae was detected in 64 samples from 62 subjects: 58 (90.6%) blood; 4 (6.3%) cerebrospinal fluid; and 2 (3.1%) pleural fluid. Incidence rate of IPD (culture- and polymerase chain reaction-positive) for all children aged 28 days to <36 months was 57.5/100,000; overall incidence for culture-positive only was 54.9/100,000. Age stratification of culture-positive-only subjects found the highest rates were, 114.6/100,000 and 69.8/100,000, respectively, for the 6 months to <12 months and 12 months to <24 months age groups. The overall incidence of invasive pneumonia and pneumococcal meningitis was 37.2/100,000 and 5.3/100,000, respectively. The most common IPD serotypes were 14 (45.0%), 6B (13.3%), 18C (6.7%), and 23F (5.0%). Eight isolates (13.3%) were penicillin nonsusceptible. The cumulative percentages of serotypes included in 7-valent, 10-valent, and 13-valent pneumococcal conjugate vaccines were 78.3%, 80.0%, and 88.3%, respectively. The overall incidence of clinical pneumonia and CXR+Pn was, 9598/100,000 and 3428/100,000, respectively. CXR+Pn rates for hospitalized and non-hospitalized subjects were 1751/100,000 and 1677/100,000, respectively. CONCLUSIONS: The burden of IPD and pneumonia is considerable in children in a large Brazilian city, and is seen in hospitalized as well as ambulatory subjects. Vaccination with pneumococcal conjugate vaccines has the potential to decrease this burden.