title: Efficacy of a tetravalent dengue vaccine in children in Latin America.
abstract: 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.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Luis
authors.initials: L
authors.lastname: Villar
authors.forename: Gustavo Horacio
authors.initials: GH
authors.lastname: Dayan
authors.forename: José Luis
authors.initials: JL
authors.lastname: Arredondo-García
authors.forename: Doris Maribel
authors.initials: DM
authors.lastname: Rivera
authors.forename: Rivaldo
authors.initials: R
authors.lastname: Cunha
authors.forename: Carmen
authors.initials: C
authors.lastname: Deseda
authors.forename: Humberto
authors.initials: H
authors.lastname: Reynales
authors.forename: Maria Selma
authors.initials: MS
authors.lastname: Costa
authors.forename: Javier Osvaldo
authors.initials: JO
authors.lastname: Morales-Ramírez
authors.forename: Gabriel
authors.initials: G
authors.lastname: Carrasquilla
authors.forename: Luis Carlos
authors.initials: LC
authors.lastname: Rey
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Dietze
authors.forename: Kleber
authors.initials: K
authors.lastname: Luz
authors.forename: Enrique
authors.initials: E
authors.lastname: Rivas
authors.forename: Maria Consuelo
authors.initials: MC
authors.lastname: Miranda Montoya
authors.forename: Margarita
authors.initials: M
authors.lastname: Cortés Supelano
authors.forename: Betzana
authors.initials: B
authors.lastname: Zambrano
authors.forename: Edith
authors.initials: E
authors.lastname: Langevin
authors.forename: Mark
authors.initials: M
authors.lastname: Boaz
authors.forename: Nadia
authors.initials: N
authors.lastname: Tornieporth
authors.forename: Melanie
authors.initials: M
authors.lastname: Saville
authors.forename: Fernando
authors.initials: F
authors.lastname: Noriega
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D003715:Dengue / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053059:Dengue Vaccines / Q000276:immunology; D003716:Dengue Virus / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D019353:Endemic Diseases / Q000517:prevention & control; D005260:Female; D006760:Hospitalization; D006801:Humans; D057194:Intention to Treat Analysis; D007843:Latin America; D008297:Male; D065288:Serogroup; D012720:Severity of Illness Index; D016037:Single-Blind Method; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D053059:Dengue Vaccines; D014613:Vaccines, Attenuated