Tetravalent Dengue Vaccine Reduces Symptomatic and Asymptomatic Dengue Virus Infections in Healthy Children and Adolescents Aged 2-16 Years in Asia and Latin America

• Published in: Journal of Infectious Diseases Vol. 214; no. 7; pp. 994 - 1000
• Main Authors: Olivera-Botello, Gustavo, Coudeville, Laurent, Fanouillere, Karen, Guy, Bruno, Chambonneau, Laurent, Noriega, Fernando, Jackson, Nicholas
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.10.2016; Oxford University Press (OUP)
• Subjects: Adolescent; Aged; Antibodies, Neutralizing; Antibodies, Neutralizing - blood; Antibodies, Viral; Antibodies, Viral - blood; Asia; Asia - epidemiology; Asymptomatic Diseases; Asymptomatic Diseases - epidemiology; Child; Child, Preschool; Clinical Trials, Phase III as Topic; Dengue; Dengue - epidemiology; Dengue - prevention & control; Dengue Vaccines; Dengue Vaccines - administration & dosage; Dengue Vaccines - immunology; Dengue Virus; Dengue Virus - immunology; Female; Flaviviridae; Humans; Latin America; Latin America - epidemiology; Major and Brief Reports; Major Articles and Brief Reports; Male; Placebos; Placebos - administration & dosage; Treatment Outcome; VIRUSES; Asia; Latin America; Asia; adolescents; children; dengue vaccine; symptomatic dengue virus infection; Latin America; asymptomatic dengue virus infection
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiw297

Background. Asymptomatic dengue virus-infected individuals are thought to play a major role in dengue virus transmission. The efficacy of the recently approved quadrivalent CYD-TDV dengue vaccine against asymptomatic dengue virus infection has not been previously assessed. Methods. We pooled data for 3 736 individuals who received either CYD-TDV or placebo at 0, 6, and 12 months in the immunogenicity subsets of 2 phase 3 trials (clinical trials registration NCT01373281 and NCTO1374516). We defined a seroconversion algorithm (ie, a ≥4-fold increase in the neutralizing antibody titer and a titer of ≥40 from month 13 to month 25) as a surrogate of asymptomatic infection in the vaccine and placebo groups. Results. The algorithm detected seroconversion in 94% of individuals with a diagnosis of virologically confirmed dengue between months 13 and 25, validating its discriminatory power. Among those without virologically confirmed dengue (n = 3 669), 219 of 2 485 in the vaccine group and 157 of 1 184 in the placebo group seroconverted between months 13 and 25, giving a vaccine efficacy of 33.5% (95% confidence interval [CI], 17.9%-46.1%) against asymptomatic infection. Vaccine efficacy was marginally higher in subjects aged 9-16 years (38.6%; 95% CI, 22.1%-51.5%). The annual incidence of asymptomatic dengue virus infection in this age group was 14.8%, which was 4.4 times higher than the incidence for symptomatic dengue (3.4%). Conclusions. The observed vaccine efficacy against asymptomatic dengue virus infections is expected to translate into reduced dengue virus transmission if sufficient individuals are vaccinated in dengue-endemic areas.