Efficacy of a tetravalent dengue vaccine in children in Latin America.

BACKGROUND: In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development. METHODS: In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection. RESULTS: A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events. CONCLUSIONS: The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.).

Zika and Dengue Interactions in the Context of a Large Dengue Vaccine Clinical Trial in Latin America.

A phase III dengue vaccine trial including 9- to 16-year-olds in Latin America (NCT01374516) was ongoing at the time of a Zika outbreak. We explored interactions between dengue and Zika, in the context of dengue vaccination. Symptomatic virologically confirmed Zika (VCZ) was evaluated using acute-phase sera from febrile participants (January 2013-March 2018). Neutralizing antibody geometric mean titers (GMTs) were evaluated pre- and post-Zika outbreak (months 25 and 72) in 2,000 randomly selected participants. Baseline dengue serostatus was determined using the plaque reduction neutralization test or inferred post hoc using nonstructural protein 1 IgG ELISA at M13 (case-cohort analysis). Vaccine efficacy against VCZ and serologically suspected Zika (SSZ) was estimated. Overall, 239/10,157 (2.4%) acute-phase samples were VCZ positive during the study. Dengue vaccine efficacy against VCZ was 27.8% (95% CI: 0.3; 47.7) among baseline dengue-seropositive participants. No vaccine effect was evident against SSZ. Zika antibody GMTs increased from pre- to post-Zika epidemic, with smaller increases observed for participants who were dengue seropositive at baseline than for those who were dengue seronegative: post-/pre-Zika GMT ratios for baseline dengue-seropositive participants were 21.5 (vaccine group) and 30.8 (placebo); and for dengue seronegatives, 88.1 and 89.5, respectively. Dengue antibody GMTs post-Zika were higher in dengue vaccine and placebo recipients with SSZ than those without SSZ in both dengue seropositives and seronegatives. Dengue vaccine did not enhance symptomatic Zika illness in dengue-seropositive individuals, rather it reduced the risk of VCZ. Zika infection boosted preexisting vaccine-induced or naturally occurring dengue-neutralizing antibodies.

Immune Response Persistence and Safety of a Booster Dose of the Tetravalent Dengue Vaccine in Adolescents and Adults Who Previously Completed the 3-dose Schedule 4-5 Years Earlier in Latin America: A Randomized Placebo-controlled Trial.

BACKGROUND: We previously described an increased immune response 28 days after a booster dose of the live, attenuated, tetravalent dengue vaccine (CYD-TDV) in healthy adolescents and adults in Latin America (CYD64, NCT02623725). This follow-up study evaluated immune response persistence and safety of a CYD-TDV booster dose up to Month (M) 24 post-booster. METHODS: This study included 250 participants who previously received 3 primary doses of CYD-TDV in the CYD13 (NCT00993447) and CYD30 (NCT01187433) studies, and who were randomized 4-5 years later to receive a CYD-TDV booster or placebo (3:1). Dengue neutralizing antibodies against the parental dengue virus strains were assessed using the plaque reduction neutralization test (PRNT50) at M6, M12, and M24 post-booster. Post-booster memory B-cell responses were assessed in a subset of participants using the FluoroSpot assay up to M12 post-booster. RESULTS: In the CYD-TDV group (n = 187), dengue neutralizing antibody geometric mean titers (GMTs) declined from the peak at day 28 through to M24 for all serotypes. GMTs at M24 were similar to those at pre-booster among baseline dengue seropositives. A similar trend was observed for baseline dengue seronegatives, albeit at a lower magnitude. Previous vaccination-induced detectable B-cell memory responses in seropositives and seronegatives that decreased to pre-booster levels at M12 post-booster. The CYD-TDV booster dose was well-tolerated. CONCLUSIONS: In baseline dengue seropositives, following a CYD-TDV booster dose administered 4-5 years after primary immunization, dengue neutralizing antibody GMTs and B-cell memory responses peaked in the short-term before gradually decreasing over time. A CYD-TDV booster dose could improve protection against dengue during outbreak periods.

Vigilancia de infecciones nosocomiales: experiencia en Hospital de especialidades del Instituto Hondureño de Seguridad Social, 2006-2012 / Surveillance of healthcare associated infections: experience in Hospital de Especialidades

Antecedentes: Las Infecciones asociadas a la atención en salud representan un problema de salud pública a nivel mundial, aumentan la morbilidad y mortalidad, ponen en riesgo la vida de los pacientes y aumentan los costos hospitalarios y sociales. Materiales y método: Se realizó estudio descriptivo, retrospectivo en Hospital de especialidades del Instituto Hondureño de Seguridad Social de Tegucigalpa MDC, periodo 2006 a 2012. Se describen los informes del comité de prevención y control de infecciones intrahospitalarias. Resultados: Durante el periodo hubo una tasa de incidencia de 5.2 infecciones nosocomiales por mil días de hospitalización y una prevalencia de 1.8 por cien ingresos. Las infecciones más frecuentes fueron las infecciones de sitio quirúrgico, bacteriemias asociadas a catéter venoso central o periférico y neumonías nosocomiales. En el Instituto Hondureño de Seguridad Social la vigilancia ha permitido detectar factores de riesgo asociados a infecciones intrahospitalarias y tomar las medidas para disminuir algunas tasas de infecciones, como las infecciones del tracto urinario asociadas a uso de catéter vesical, neumonías asociadas a ventilador mecánico. Conclusiones: El trabajo de vigilancia presentado en este reporte refuerza la importancia que tienen los programas de prevención y control de infecciones nosocomiales para mejorar los indicadores de calidad de atención dentro de las instituciones de salud...

Resistencia antimicrobiana en bacterias aisladas, en el Instituto Hondureño de Seguridad Social / Antimicrobial resistance in isolated bacteria in the Instituto Hondureño de Seguridad Social

Introducción. La resistencia de las bacterias a los antimicrobianos es un problema creciente a nivel mundial, produciendo un incremento en los costos hospitalarios y en la morbimortalidad. El objetivo de este trabajo es presentar la sensibilidad a los antibióticos de las bacterias aisladas en el Hospital de Especialidades del Instituto Hondureño de Seguridad Social. Materiales y Métodos. Se realizó un estudio descriptivo de la sensibilidad de las bacterias aisladas en pacientes hospitalizados en el Hospital de Especialidades del Instituto Hondureño de Seguridad Social de Tegucigalpa, Honduras del 2006 al 2009. Resultados. Se registraron 4,812 aislamientos procedentes de diversas muestras: 986(20.4%) urocultivos,824(17%) hemocultivos , 627(13%) de secreciones varias y de diversas fuentes. Las bacterias Gram negativas fueron las aisladas con mayor frecuencia, siendo las mas comunes Klebsiella pneumoniae, Echerichia coli y Burkholderia cepacia. La Echerichia coli presentó alta resistencia a quinolonas, de 37% a 42%; Pseudomona aeruginosa presentó alta resistencia a cefalosporina de tercera generación y quinolonas, aumentando de 30% en el 2006 a más del 40% en el 2009. Acinetobacter baumanii tiene una alta resistencia a todos los antibióticos incluso a los carbapenémicos. Stafilococcus aureus resistente a meticilina incrementó de 20% en 2007 hasta 36% en el 2009. El primer caso de neumococo resistente a penicilina se documento en el 2009. Discusió. Los resultados demuestran la necesidad de crear políticas a nivel institucional para contener y controlar el aumento de la resistencia antimicrobiana...