Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

BACKGROUND: Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. METHODS: We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. RESULTS: In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. CONCLUSIONS: With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

Immunogenicity and safety of a quadrivalent meningococcal polysaccharide CRM conjugate vaccine in infants and toddlers.

OBJECTIVES: This phase III study assessed the safety and immunogenicity of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, administered with routine vaccines starting at 2 months of age. METHODS: Healthy infants received MenACWY-CRM in a two- or three-dose primary infant series plus a single toddler dose. In addition, a two-dose toddler catch-up series was evaluated. Immune responses to MenACWY-CRM were assessed for serum bactericidal activity with human complement (hSBA). Reactogenicity and safety results were collected systematically. RESULTS: After a full infant/toddler series or two-dose toddler catch-up series, MenACWY-CRM elicited immune responses against the four serogroups in 94-100% of subjects. Noninferiority of the two- versus three-dose MenACWY-CRM infant dosing regimen was established for geometric mean titers for all serogroups. Following the three-dose infant primary series, 89-98% of subjects achieved an hSBA ≥ 8 across all serogroups. Immune responses to concomitant routine vaccines given with MenACWY-CRM were noninferior to responses to routine vaccines alone, except for pertactin after the two-dose infant series. Noninferiority criteria were met for all concomitant antigens after the three-dose infant series. CONCLUSIONS: MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed.

Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in young Latin American children: A double-blind randomized controlled trial.

BACKGROUND: The relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. METHODS AND FINDINGS: This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15-18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization-defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28-30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: -1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n = 11,798; 0.16%) in the PHiD-CV group and 26 deaths (n = 11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases. CONCLUSIONS: Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00466947.

Immunogenicity, safety, and tolerability of two trivalent subunit inactivated influenza vaccines: a phase III, observer-blind, randomized, controlled multicenter study.

The objective of this study was to evaluate and compare the immunogenicity, safety, and tolerability of two influenza subunit vaccines, a primarily European-marketed trivalent vaccine (Agrippal®, Novartis Vaccines), and a predominantly U.S.-marketed control trivalent vaccine (Fluvirin®, Novartis Vaccines), in subjects aged 3-64 y. The immunogenicity of both vaccines was evaluated according to the Center for Biologics Evaluation and Research (CBER) criteria. This clinical trial was performed between April and December 2007 in Argentina. A total of 1893 subjects were stratified into three age groups (3-8 y, 9-17 y, and 18-64 y), and randomized in a 2:1 ratio to receive either Agrippal or Fluvirin. Adolescents and adults received one dose of vaccine intramuscularly, whereas children aged 3-8 years received two vaccine doses, administered 4 wk apart. Antibody levels were measured by means of hemagglutination inhibition assay before vaccination (baseline); 21 d after the first vaccination (adults and adolescents); and, for children aged 3-8 y, 28 d after the first vaccination and 21 d after the second vaccine dose. Adverse reactions were solicited via diary cards for 7 d after each vaccination, and unsolicited adverse events were reported throughout the study period. Both vaccines were safe and well-tolerated, and elicited robust immunogenic responses in all age groups, meeting both CBER licensure criteria for all three viral strains after completion of the age-recommended vaccination schedule. These findings support the use of the trivalent subunit influenza vaccines Agrippal and Fluvirin for universal vaccination campaigns on an annual basis. ClinicalTrials.gov: NCT00464672.

Immunogenicity and safety of an investigational hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae B conjugate combined vaccine in healthy 2-, 4-, and 6-month-old Argentinean infants.

BACKGROUND AND AIMS: Assessment of a new, fully liquid, investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim, Sanofi Pasteur), containing the same active ingredients as Pentaxim (DTaP-IPV//PRT-T) and 10 µg Hansenula polymorpha-derived recombinant hepatitis B (Hep B) surface antigen, Sanofi Pasteur, in Argentinean infants. METHODS: Infants born to Hep B surface antigen seronegative mothers were randomized to receive the DTaP-IPV-Hep B-PRP-T vaccine or Pentaxim and Engerix B Pediatrico (Hep B monovalent) vaccines at 2, 4, 6 months of age. Antibody titers were measured before and 1 month after 3-month primary vaccination. Noninferiority analyses were performed on seroprotection/seroconversion rates. Safety was evaluated descriptively up to 1 month after primary vaccination. RESULTS: A total of 624 participants were enrolled, 312 participants were randomized to each group, and 604 participants completed the trial. The DTaP-IPV-Hep B-PRP-T vaccine was demonstrated as noninferior to the Pentaxim and Hep B monovalent vaccines with seroprotection/seroconversion rates 1 month postdose 3 for each valence. The anti-Hep B geometric mean titer 1-month postdose 3 for the investigational DTaP-IPV-Hep B-PRP-T primary series was similar to the monovalent Hep B control. The overall incidence of adverse events was similar among the 2 groups. CONCLUSIONS: The new, fully liquid, investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) is highly immunogenic and safe when compared with licensed comparators, warranting further development.

Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization vaccines including oral poliovirus vaccine in Latin America.

BACKGROUND: The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Expanded Program on Immunization (EPI) vaccines including oral polio vaccine (OPV) was evaluated in this study. METHODS: Double-blind, randomized (2:1), placebo-controlled study conducted across 6 Latin American countries. Healthy infants (N = 6568) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0, 1- to 2-month schedule. Routine vaccines including OPV were coadministered according to local EPI schedule. Vaccine efficacy (VE) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95% confidence interval [CI]. Safety was assessed during the entire study period. Immunogenicity of RIX4414 and OPV was also assessed. RESULTS: During the efficacy follow-up period (mean duration = 7.4 months), 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups, respectively, with a VE of 81.6% (95% CI: 54.4-93.5). VE against severe rotavirus gastroenteritis caused by G1 type was 100% (95% CI: <0-100) and 80.6% (95% CI: 51.4-93.2) against the pooled non-G1 rotavirus types, respectively. There was no difference (P = 0.514) in the incidence of serious adverse events reported in the 2 groups. Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4% (95% CI: 53.7-68.6) in the RIX4414 group; similar seroprotection rates (≥96.0%) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups. CONCLUSION: RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus (G1 and non-G1) when coadministered with routine EPI vaccines including OPV.

Primary and booster vaccination in Latin American children with a DTPw-HBV/Hib combination: a randomized controlled trial.

BACKGROUND: Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and Haemophilus influenzae type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (Tritanrix™-HBV/Hib). METHODS: This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months. RESULTS: One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses. CONCLUSIONS: Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00332566.

Immunogenicity and safety of a novel yeast Hansenula polymorpha-derived recombinant Hepatitis B candidate vaccine in healthy adolescents and adults aged 10-45 years.

The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10-15 years, 10 microg HBsAg/dose) and one in Uruguay (344 participants aged 16-45 years, 20 microg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer <0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titers >or=10 mIU/mL; delta non-inferiority limit of -10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10-15 year and 16-45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines.

Efficacy and safety of 1 and 2 doses of live attenuated influenza vaccine in vaccine-naive children.

BACKGROUND: We investigated the efficacy and safety of 1 versus 2 doses of live attenuated influenza vaccine (LAIV) in influenza vaccine-naive children aged 6 to <36 months. PATIENTS/METHODS: Subjects were randomized to 1 of 4 regimens in year 1: 2 doses LAIV, 1 dose LAIV, excipient placebo, or saline placebo. In year 2, LAIV recipients were to receive 1 dose of LAIV and placebo recipients were to receive saline placebo. Because of an unintended treatment allocation error in year 2, 1 block of subjects who were randomized to LAIV received saline placebo and 1 block who were randomized to placebo received LAIV. RESULTS: In year 1, vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAIV was 73.5% and 57.7%, respectively, against antigenically similar strains. In year 2, absolute efficacy of a single dose of LAIV was 73.6% and 65.2%, respectively, in recipients of 2 and 1 doses of LAIV in year 1. Year 2 efficacy was 57.0% in subjects who received 2 doses of LAIV in year 1 and placebo in year 2. Safety and tolerability of LAIV were consistent with previous studies. Reactogenicity was similar between placebo groups. Seroconversion rates were significantly higher in the 2-dose versus the 1-dose LAIV group in year 1 and in both LAIV groups versus placebo in years 1 and 2. CONCLUSIONS: One dose of LAIV provided clinically significant protection against influenza in young children previously unvaccinated against influenza; 2 doses provided additional protection. Protection after 2 doses in year 1 persisted through a second season without revaccination. LAIV excipients were not a major contributor to reactogenicity. These benefits provide support for increased use of LAIV in children > or =2 years of age.

A new serotype 14 variant of the pneumococcal Spain9V-3 international clone detected in the central region of Argentina.

The penicillin-resistant Spain(9V)-3 clone of Streptococcus pneumoniae is widespread and presents different serotype variants originating from recombination of the capsular genes. In this work, the genetic relatedness of 29 invasive pneumococci isolated from the central region of Argentina (Cordoba, Buenos Aires, Santa Fe and La Pampa provinces) was assessed by multilocus sequence typing (MLST). All of the penicillin-non-susceptible isolates studied (21/29) belonged to a serotype 14 variant of the Spain(9V)-3 clone. This clone was predominant, suggesting that it was responsible for the penicillin resistance spread in this region. Interestingly, this serotype 14 variant (named Cordoba S14V) could be differentiated from the European one by its pbp1a gene, suggesting a different recombinational replacement of the capsular genes. The putative recombination sites were analysed, resulting in the proximal crossover point being clearly localized in the spr0309 gene, with the distal site restricted to the recU gene, confirming a different recombination event. Analysis of the dexB, cpsB, aliA and pbp1a genes from these strains showed a high similarity with the corresponding genes of the Spain(14)-5 clone, suggesting that the capsular genes were provided by this international clone. Analysis of the genetic polymorphisms of the pbp1a (nt 1473-1922) and spr0309 (nt 1-790) genes is proposed as an epidemiological tool to help recognize the Cordoba S14V of the Spain(9V)-3 clone. On the other hand, BOX-repeat-based PCR and MLST analyses of serotype 14 strains revealed a divergent epidemiology of the Cordoba S14V, suggesting a non-recent dissemination in the paediatric population. It is suggested that this molecular epidemiology work will be a reference for monitoring the evolution of S14Vs of Spain(9V)-3, the emergence of new clones and the impact of pneumococcal vaccination programmes in Argentina.

A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of infants in Latin America.

OBJECTIVES: In 1998 the World Health Organization (WHO) recommended the inclusion of Haemophilus influenza type B (Hib) conjugate vaccines in infant immunization programs, whenever in accordance with national priorities. GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib (DTPw-HB/Hib) vaccine containing 5 microg of polyribosylribitol phosphate (PRP), and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB (Tritanrix) and Hib (Hiberix) vaccines given as simultaneous concomitant injections. METHODS: We performed a randomized, double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine given as a single injection, compared with the reference regimen. RESULTS: Both vaccination regimens elicited excellent immune responses, with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of > or = 0.15 microg/mL one month after primary vaccination. The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components. Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups, and a marked increase of all antibody concentrations was observed after the booster dose. Both vaccine regimens were similar in terms of their overall reactogenicity profiles. CONCLUSIONS: Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis.

Active epidemiologic surveillance of pneumonia and invasive pneumococcal disease in ambulatory and hospitalized infants in Cordoba, Argentina.

Active surveillance of ambulatory and hospitalized children 2-23 months old in Cordoba, Argentina for invasive pneumococcal disease and radiographically confirmed "obvious" pneumonia revealed annual incidences of 206.8 and 2422 cases, respectively, per 100,000 children. The invasive pneumococcal disease incidence was substantially higher than those previously reported from Latin America and Europe.

A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of infants in Latin America / Nueva vacuna combinada DTPw-HB/Hib para la vacunación primaria y de refuerzo de menores de un año en América Latina

Objectives. In 1998 the World Health Organization (WHO) recommended the inclusion of Haemophilus influenza type B (Hib) conjugate vaccines in infant immunization programs, whenever in accordance with national priorities. GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib (DTPwHB/Hib) vaccine containing 5 µg of polyribosylribitol phosphate (PRP), and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB (Tritanrix) and Hib (Hiberix) vaccines given as simultaneous concomitant injections. Methods. We performed a randomized, double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine given as a single injection, compared with the reference regimen. Results. Both vaccination regimens elicited excellent immune responses, with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of ≥ 0.15 µg/mL one month after primary vaccination. The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components. Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups, and a marked increase of all antibody concentrations was observed after the booster dose. Both vaccine regimens were similar in terms of their overall reactogenicity profiles. Conclusions. Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis.

OBJETIVOS: En 1998, la Organización Mundial de la Salud (OMS) recomendó que se incluyeran vacunas conjugadas contra Haemophilus influenzae tipo B (Hib) en los programas de vacunación de niños menores de un año, siempre que ello estuviera en consonancia con las prioridades nacionales. La compañía GlaxoSmithKline Biologicals ha creado una nueva vacuna pentavalente que es una combinación de la vacuna contra la difteria (D), el tétanos (T) y la tos ferina (P) (con antígeno tosferínico a base de células completas) y las vacunas contra la hepatitis B (HB) y contra Haemophilus influenzae tipo B (Hib) (DTPw-HB/Hib), con un total de 5 µg de fosfato de polirribosilrribitol (FPR). Hemos evaluado la inmunogenia y reactogenia observadas al aplicarse las dosis primaria y de refuerzo de esta nueva vacuna a niños sanos y las hemos comparado con las observadas al aplicar un régimen de referencia a base de las vacunas autorizadas DTPw-HB (Tritanrix) y antiHib (Hiberix) en forma de inyecciones simultáneas. MÉTODOS: Llevamos a cabo un estudio aleatorizado y con doble enmascaramiento de septiembre de 1998 a agosto de 1999 para establecer la inmunogenia y reactogenia observadas al administrarles a niños sanos la nueva vacuna combinada pentavalente (DTPw-HB/Hib) en una sola inyección, y compararlas con las observadas con el régimen de referencia. RESULTADOS: Se obtuvieron excelentes respuestas inmunitarias con ambos regímenes. Todos los niños vacunados en ambos grupos alcanzaron concentraciones séricas protectoras de anticuerpos antiFPR > 0,15 µg un mes después de recibir la dosis primaria. La vacuna combinada DTPw-HB/Hib no dio resultados inferiores a los obtenidos con las vacunas autorizadas en términos de los porcentajes de seroprotección, seropositividad y respuesta frente a todos los componentes antigénicos de la vacuna. La persistencia de anticuerpos contra todos los antígenos contenidos en ella hasta el momento en que se administró la dosis de refuerzo fue parecida en ambos grupos, y se observó un marcado aumento de las concentraciones de todos los anticuerpos después del refuerzo. La reactogenia general observada con ambos regímenes de vacunación fue parecida. CONCLUSIONES: Nuestros resultados indican que la nueva vacuna combinada pentavalente DTPw-HB/Hib ofrece una manera eficiente y confiable de poner en práctica las recomendaciones de la OMS para el control de la hepatitis B y de las infecciones por Hib en el mundo entero.

Vigilancia epidemiológica activa de la enfermedad neumocócica en lactantes, en el ámbito ambulatorio y en la internación / An active epidemiologic surveillance of neumococcal disease in the outpatient and hospitalization settings

RESUMENIntroducción. El objetivo del trabajo fue investigar laincidencia de enfermedad invasiva por Streptococcuspneumoniae en pacientes hospitalizados y ambulatoriosatendidos en centros de la ciudad deCórdoba, Argentina.Población, material y métodos. Este estudio de incidenciase realizó entre diciembre de 1999 y noviembrede 2002.Se obtuvieron hemocultivos en todos los pacientesde 2 a 23 meses de edad con sospecha de la enfermedad(temperatura axilar 39 ºC, sospecha clínica deneumonía o sospecha clínica de otra enfermedadinvasiva por Streptococcus pneumoniae). A los pacientescon sintomatología respiratoria y temperatura<39 °C, se les realizó radiografía de tórax y a losque presentaban neumonías con condensación, seles realizó hemocultivo.Tanto la información demográfica y patológica comola evolución de la enfermedad se consignaron enuna hoja de toma de datos.Resultados. La incidencia global de enfermedad invasivapor S. pneumoniae fue de 206,8 por 105/año,mayor en los pacientes de 6 a 17 meses. Entre lasformas de presentación de la enfermedad se encontraron:47,5 por ciento (IC 95 por ciento 40,0 menos 55,0) de bacteriemia sinfoco; 45,8 por ciento (IC 95 por ciento 38,4 menos 53,4) de neumonía; 3,9 por ciento (IC 95 por ciento 1,7 menos 8,2) de meningitis y 2,8 por ciento (IC 95 por ciento1,0 menos 6,7) de abscesos. El serotipo más frecuente fue el 14en el 45,6 por ciento de los aislamientos, seguido del 6B y 1con ambos en el 10,8 por ciento de los casos. Durante lavigilancia se encontró un 68 por ciento de cepas sensibles,26 por ciento con resistencia intermedia y por ciento resistentes apenicilina.Conclusiones. La tasa de incidencia de la enfermedadinvasiva por S. pneumoniae en niños de Córdobase sitúa en valores elevados en comparación conLatinoamérica y Europa, probablemente reveladapor la pesquisa de la enfermedad, que en esteestudio se realizó en pacientes ambulatorios querepresentaron más de la mitad del total de aislamientos.Palabras clave: incidencia, enfermedad invasiva,pesquisa

Reduced-antigen-content-diphtheria-tetanus-acellular-pertussis and inactivated polio vaccine as a booster for adolescents 10 to 14 years of age.

UNLABELLED: High rates of pertussis disease in adolescents suggest that additional boosting against pertussis would be beneficial. A combined acellular-pertussis-containing booster vaccine (dTpa-IPV; Boostrixtrade mark Polio, n =440) was compared to separately administered dTpa (Boostrixtrade mark) and inactivated polio virus (IPV; Imovax Polio((R)), n =219), and to DTPa-IPV (Infanrixtrade mark IPV, n =111) vaccine in a partially blind, randomised controlled trial in 10-14 year olds. One month after vaccination, seroprotection/seropositivity rates for all antigens were similar for all groups. Although pertussis and diphtheria antibody geometric mean antibody concentrations were higher after DTPa-IPV, all subjects had protective antibodies against diphtheria, tetanus and polio, and at least 97% had a vaccine response to pertussis antigens. Reactogenicity of dTpa-IPV was comparable to dTpa + IPV, but dTpa-IPV was generally better tolerated than DTPa-IPV. CONCLUSION: The combined reduced-antigen-content-diphtheria-tetanus-acellular-pertussis and IPV vaccine is immunogenic and well tolerated when administered to adolescents and could be used to improve the control of pertussis disease in this age group.

Comparison of two recombinant hepatitis B vaccines and their interchangeability in Argentine infants.

OBJECTIVE: To compare two pediatric recombinant hepatitis B vaccines-the Engerix-B reference vaccine and the Euvax-B vaccine-in terms of immunogenicity and reactogenicity, and also to investigate their interchangeability, that is, whether a three-dose hepatitis B vaccination schedule begun with a first dose of Engerix-B could be completed with two doses of Euvax-B. METHODS: This study was conducted in the city of Córdoba, Argentina, from March 1999 through February 2000. Three groups of Argentine newborns (100 per group) were vaccinated at 0, 1, and 6 months of age with hepatitis B vaccine: group A, three doses of Euvax-B; group B, three doses of Engerix-B; and group C, one dose of Engerix-B followed by two doses of Euvax-B. Reactogenicity was evaluated based on parental reporting of any solicited local or systemic event occurring during the 7-day period following vaccination. Whether Euvax-B and Engerix-B were clinically identical was assessed in terms of the seroprotection rates (antibodies to hepatitis B surface antigen (anti-HBsAg) >/= 10 milli-international units per mL (mIU/mL) 2 months after the third vaccination). RESULTS: Reactogenicity was low in all three groups. Five months after the second dose (that is, immediately prior to the third vaccination), seroprotection rates were 95.9%, 94.7%, and 90.2% for groups A, B, and C, respectively. Two months after the third dose all subjects were seroprotected, with geometric mean concentrations of anti-HBsAg of 2 468.1, 1 714.8, and 2 075.3 mIU/mL for groups A, B, and C, respectively. CONCLUSIONS: Both of the recombinant hepatitis B vaccines that we studied were well tolerated and highly immunogenic. Euvax-B was clinically identical (not inferior) to the EngerixB reference vaccine, and either vaccine could be used to achieve the World Health Organization goal of immunizing all infants against hepatitis B. Further, Euvax-B can be safely used in infants given an initial dose of either Euvax-B or Engerix-B.

Comparison of two recombinant hepatitis B vaccines and their interchangeability in Argentine infants / Comparación de dos vacunas recombinantes contra la hepatitis B y su intercambiabilidad en lactantes argentinos

OBJETIVO: Comparar dos vacunas pediátricas recombinantes contra la hepatitis B ùEuvax-B y la vacuna de referencia Engerix-Bù en cuanto a su inmunogenicidad y reactogenicidad, e investigar su intercambiabilidad, es decir, si el esquema de vacunación contra la hepatitis B de tres dosis comenzado con una primera dosis de Engerix-B puede completarse con dos dosis de Euvax-B. MÉTODOS: Este estudio se llevó a cabo en la ciudad de Córdoba, Argentina, entre marzo de 1999 y febrero de 2000. Se vacunó contra la hepatitis B a tres grupos de 100 lactantes argentinos a los 0, 1 y 6 meses de edad. El grupo A recibió tres dosis de Euvax-B; el grupo B, tres dosis de Engerix-B; y el grupo C, una dosis de Engerix-B seguida de dos dosis de Euvax-B. Para evaluar la reactogenicidad se utilizó la información brindada por los padres acerca de determinados fenómenos locales o sistémicos solicitados por los investigadores que hubieran ocurrido durante los siete días posteriores a la vacunación. Para establecer si eran idénticas clínicamente las vacunas Euvax-B y Engerix-B se utilizaron las tasas de seroprotección ùes decir, títulos de anticuerpos contra el antígeno de superficie de hepatitis B (anti-HBsAg) > 10 miliunidades internacionales por mililitro (mUI/mL)ù alcanzados dos meses después de la tercera dosis. RESULTADOS: La reactogenicidad fue baja en los tres grupos de estudio. A los 5 meses de la segunda dosis (es decir, inmediatamente antes de la tercera dosis), las tasas de seroprotección fueron 95,9%, 94,7% y 90,2% en los grupos A, B y C, respectivamente. Dos meses después de la tercera dosis, todos los lactantes se encontraban protegidos, con concentraciones medias geométricas de anti-HBsAg de 2 468,1 mUI/mL en el grupo A, de 1 714,8 mUI/mL en el grupo B y de 2 075,3 mUI/mL en el grupo C. CONCLUSIONES: Las dos vacunas recombinantes contra la hepatitis B estudiadas fueron bien toleradas y altamente inmunogénicas. La vacuna Euvax-B fue clínicamente idéntica (no inferior) a la vacuna de referencia Engerix-B y cualquiera de ellas puede utilizarse para alcanzar la meta propuesta por la Organización Mundial de la Salud de inmunizar a todos los recién nacidos contra la hepatitis B. Además, puede emplearse con seguridad la vacuna Euvax-B en lactantes que recibieron una primera dosis con Euvax-B o Engerix-B

Objective. To compare two pediatric recombinant hepatitis B vaccines­the Engerix-B reference vaccine and the Euvax-B vaccine­in terms of immunogenicity and reactogenicity, and also to investigate their interchangeability, that is, whether a three-dose hepatitis B vaccination schedule begun with a first dose of Engerix-B could be completed with two doses of Euvax-B. Methods. This study was conducted in the city of Córdoba, Argentina, from March 1999 through February 2000. Three groups of Argentine newborns (100 per group) were vaccinated at 0, 1, and 6 months of age with hepatitis B vaccine: group A, three doses of Euvax-B; group B, three doses of Engerix-B; and group C, one dose of Engerix-B followed by two doses of Euvax-B. Reactogenicity was evaluated based on parental reporting of any solicited local or systemic event occurring during the 7-day period following vaccination. Whether Euvax-B and Engerix-B were clinically identical was assessed in terms of the seroprotection rates (antibodies to hepatitis B surface antigen (anti-HBsAg) ≥ 10 milli-international units per mL (mIU/mL) 2 months after the third vaccination). Results. Reactogenicity was low in all three groups. Five months after the second dose (that is, immediately prior to the third vaccination), seroprotection rates were 95.9%, 94.7%, and 90.2% for groups A, B, and C, respectively. Two months after the third dose all subjects were seroprotected, with geometric mean concentrations of anti-HBsAg of 2 468.1, 1 714.8, and 2 075.3 mIU/mL for groups A, B, and C, respectively. Conclusions. Both of the recombinant hepatitis B vaccines that we studied were well tolerated and highly immunogenic. Euvax-B was clinically identical (not inferior) to the EngerixB reference vaccine, and either vaccine could be used to achieve the World Health Organization goal of immunizing all infants against hepatitis B. Further, Euvax-B can be safely used in infants given an initial dose of either Euvax-B or Engerix-B

Linezolid versus cefadroxil in the treatment of skin and skin structure infections in children.

BACKGROUND: Skin and skin structure infections are common reasons for visits to pediatricians, accounting for up to 18%. Staphylococcus aureus and Streptococcus pyogenes are the most frequently isolated Gram-positive pathogens in uncomplicated skin infections. Increasingly outpatient infections involve antibiotic-resistant Gram-positive pathogens including methicillin-resistant S. aureus. METHODS: This randomized, blinded, comparator-controlled, multinational trial compared the efficacy and safety of linezolid and cefadroxil for treatment of uncomplicated skin/skin structure infections in pediatric patients. Children ages 5 to 11 years were to receive linezolid suspension [10 mg/kg (up to 600 mg)] or cefadroxil suspension [15 mg/kg (up to 500 mg)] every 12 h. Patients ages 12 to 17 years were to receive linezolid tablets (600 mg) or cefadroxil capsules (500 mg) every 12 h. Therapy lasted 10 to 21 consecutive days with a follow-up visit 10 to 21 days posttherapy. RESULTS: Linezolid and cefadroxil were consistently effective treatments across all primary and secondary efficacy assessments. At follow-up cure rates were 88.7% (205 of 231) for linezolid-treated and 86.2% (193 of 224) for cefadroxil-treated intent-to-treat patients; cure rates were 91.0% (201 of 221) for linezolid-treated and 90.0% (189 of 210) for cefadroxil-treated clinically evaluable patients. S. aureus was eradicated in 89.6% (120 of 134) linezolid-treated and 88.8% (111 of 125) cefadroxil-treated microbiologically evaluable patients. Gastrointestinal complaints were the most common adverse events reported, without significant differences between treatment groups, and myelosuppression was not observed in this study. CONCLUSIONS: Linezolid is well-tolerated and as effective as cefadroxil in treating uncomplicated skin infections in pediatric patients. Linezolid effectively treated infections caused by S. aureus, methicillin-resistant S. aureus and S. pyogenes.