A fully liquid DTPw-HepB-Hib combination vaccine for booster vaccination of toddlers in El Salvador / Vacuna líquida combinada DTPw-HepB-Hib como dosis de refuerzo en infantes de El Salvador

Objectives:To compare the safety and immunogenicity of a booster dose of a fully liquid diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HepB-Hib) vaccine to the separate administration of commercially available DTPw and Hib vaccines in healthy toddlers. Methods:An open-label, randomized, parallel-group, Phase III study conducted at six centers in San Salvador, El Salvador, during February-June 2006. Toddlers (15-24 months of age) were eligible to participate if they had received primary immunization at 2, 4, and 6 months of age with a commercial DTPw-HepB/Hib vaccine requiring reconstitution. Participants received either one booster dose of DTPw-HepB-Hib fully liquid vaccine or DTPw and Hib vaccines administered separately. Blood samples were taken immediately prior to and at 1 month post-vaccination. For a 5-day period following vaccination, solicited adverse events were collected in subject diaries and assessed. Results:The combined DTPw-HepB-Hib fully liquid vaccine was non-inferior to the separately administered DTPw and Hib vaccines, in terms of seroprotection/seroconversion rates for all antigens evaluated. The combination vaccine elicited a strong booster response as demonstrated by a large increase in antibodies against all vaccine antigens. The geometric mean concentrations (GMCs) of all antibodies in the DTPw-HepB-Hib group exceeded the seroprotection/seroconversion thresholds by very large margins, although for some antigens they were somewhat lower than the corresponding titers in the comparator group. With the combination vaccine, considerably fewer solicited local and systemic adverse events, such as fever and irritability, were reported than with the comparator vaccines. Conclusions:This study demonstrates that the fully liquid combined DTPw-HepB-Hib vaccine is highly immunogenic and has a favorable safety profile when given as a booster vaccination to toddlers who have received...

Objetivos:Comparar la seguridad y la inmunogenicidad en infantes saludables de una dosis de refuerzo de una vacuna líquida combinada contra la difteria, el tétanos, la tosferina (de células enteras), la hepatitis B y Haemophilus influenzae tipo b (DTPw-HepB-Hib), con la aplicación por separado de vacunas DTPw y Hib disponibles comercialmente. Métodos:Se realizó un estudio de fase III abierto, aleatorizado, con grupos paralelos, en seis centros de San Salvador, El Salvador, en febrero-junio de 2006. Los infantes (de 15-24 meses) habían recibido la inmunización primaria a los 2, 4 y 6 meses de edad con una vacuna comercial DTPw-HepB/Hib que necesitaba reconstitución. Los lactantes recibieron una dosis de refuerzo con la vacuna DTPw-HepB-Hib o las vacunas DTPw y Hib por separado. Se tomaron muestras de sangre inmediatamente antes de la vacunación y un mes después. Las reacciones adversas en los cinco días siguientes a la vacunación se anotaron en diarios individuales y se evaluaron. Resultados:Según las tasas de seroprotección/seroconversión de todos los antígenos evaluados, la vacuna DTPw-HepB-Hib no fue inferior que las vacunas DTPw y Hib administradas por separado. La vacuna combinada produjo una fuerte respuesta de refuerzo, reflejada en el gran aumento de anticuerpos contra todos los antígenos presentes. Con respecto al grupo de comparación, en el grupo vacunado con DTPw-HepB-Hib las concentraciones geométricas medias de todos los anticuerpos superaron ampliamente los umbrales de seroprotección/seroconversión -aunque con títulos menores en algunos antígenos- y hubo mucho menos reacciones adversas locales y sistémicas, como fiebre e irritabilidad. Conclusiones:Se demostró que la vacuna líquida combinada DTPw-HepB-Hib es altamente inmunógena y satisfactoriamente segura cuando se aplica como dosis de refuerzo a infantes inmunizados primariamente con una vacuna pentavalente diferente que requiere reconstitución.

Culture- and antigen-negative meningitis in Guatemalan children / Meningitis negativa a pruebas antigénicas y de cultivo en niños guatemaltecos

OBJECTIVE: To compare children with confirmed bacterial meningitis (CBM) and those with culture- and latex-negative meningitis (CLN). METHODS: Children 1 to 59 months of age admitted to three major referral hospitals in Guatemala City with clinical signs compatible with bacterial infections were evaluated prospectively between 1 October 1996 and 31 December 2005. Bacterial cultures and latex agglutination antigen testing were performed on samples of cerebrospinal fluid (CSF). RESULTS: The case-fatality rate was significantly higher in the 493 children with CBM than in the 528 children with CLN (27.6 percent and 14.9 percent, respectively; P < 0.001). Children with CBM were less likely to have received antibiotics and more likely to have seizures, shock, or coma on admission than children with CLN. Among the 182 CBM survivors and 205 CLN survivors studied between October 2000 and December 2005, clinically observed sequelae were present at discharge in a higher percentage of the CBM than of the CLN group (78.6 percent and 46.8 percent, respectively; P < 0.0001). CSF glucose < 10 mg/dL, peripheral neutrophils < 2 000 cells/mm³, coma or shock at admission, and concurrent sepsis or pneumonia were risk factors for mortality in children with CBM; only coma or shock at admission predicted mortality in children with CLN. CONCLUSIONS: The high case-fatality and sequelae rates suggest that many children with CLN may have had bacterial meningitis. Estimates based on confirmed meningitis alone underestimate the true vaccine-preventable disease burden. Additional studies to determine etiologies of CLN in this population are indicated.

OBJETIVO: Comparar los casos infantiles de meningitis bacteriana confirmada (MBC) y meningitis negativa a pruebas de látex y de cultivo (MNLC). MÉTODOS: Se evaluaron los niños de 1 a 59 meses de edad ingresados en tres grandes hospitales de referencia de la Ciudad de Guatemala entre el 1 de octubre de 1996 y el 31 de diciembre de 2005 con signos clínicos de infección bacteriana. Se realizaron cultivos bacterianos y pruebas de aglutinación antigénica con látex en muestras de líquido cefalorraquídeo (LCR). RESULTADOS: La tasa de letalidad fue significativamente mayor en los 493 niños con MBC que en los 528 niños con MNLC (27,6 por ciento y 14,9 por ciento, respectivamente; P < 0,001). Los niños con MBC tuvieron menor probabilidad de recibir antibióticos y mayor de sufrir convulsiones, choques o entrar en coma al ser ingresados que los niños con MNLC. Se observó un mayor porcentaje de manifestaciones clínicas de secuelas al alta hospitalaria en los 182 niños sobrevivientes con MBC que en los 205 sobrevivientes con MNLC estudiados entre octubre de 2000 y diciembre de 2005 (78,6 por ciento y 46,8 por ciento, respectivamente; P < 0,0001). Los factores de riesgo de muerte en los niños con MBC fueron: glucosa en LCR < 10 mg/dL, neutrófilos periféricos < 2 000 células/mm³, coma o choque al ingreso, y sepsis o neumonía concurrentes; solo el coma y el choque al ingreso predijeron la muerte en niños con MNLC. CONCLUSIONES: Las altas tasas de letalidad y de secuelas indican que muchos niños con MNLC pueden haber tenido meningitis bacteriana. Las estadísticas basadas solamente en los casos confirmados de meningitis subestiman la verdadera carga de enfermedad prevenible mediante vacuna. Se deben emprender estudios adicionales para determinar las etiologías de la MNLC en esta población.

Meningitis and pneumonia in Guatemalan children: the importance of Haemophilus influenzae type b and Streptococcus pneumoniae

OBJECTIVE: To determine the epidemiology of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae invasive infections in hospitalized Guatemalan children. This is an important issue since Hib vaccine has not been incorporated into the routine immunization program in Guatemala and information from hospital records in 1995 indicated a low incidence of Hib and S. pneumoniae as causes of meningitis and invasive infections. METHODS: Children who were hospitalized in Guatemala City with clinical signs compatible with bacterial infections were evaluated for evidence of Hib or S. pneumoniae infection. Normally sterile body fluids were cultured, and antigen detection was performed on cerebrospinal fluid (CSF) and pleural fluid. RESULTS: Of 1 203 children 1-59 months of age hospitalized over a 28-month period, 725 of them (60.3 percent) had a primary diagnosis of pneumonia, 357 (29.7 percent) of meningitis, 60 (5.0 percent) of cellulitis, and 61 (5.1 percent) of sepsis and other conditions. Hib was identified in 20.0 percent of children with meningitis and S. pneumoniae in 12.9 percent. The average annual incidence of Hib meningitis was 13.8 cases per 100 000 children under 5 years of age, and 32.4 percent of meningitides caused by Hib and 58.7 percent of S. pneumoniae meningitides occurred prior to 6 months of age. Case fatality rates were 14.1 percent, 37.0 percent, and 18.0 percent, respectively, for children with Hib, S. pneumoniae, and culture-negative and antigen-negative meningitis. Prior antibiotic therapy was common and was associated with significant reductions in CSF-culture-positive results for children with other evidence of Hib or S. pneumoniae meningitis. CONCLUSIONS: Improvements in case detection, culture methods, and latex agglutination for antigen detection in CSF resulted in identification of Hib and S. pneumoniae as important causes of severe disease in Guatemalan children. Using a cutoff of > 10 white blood cells per cubic millimeter in CSF would improve the sensitivity for detection of bacterial meningitis and help estimate the burden of bacterial meningitis in Guatemala and other developing countries.