Dengue is a mosquito-borne viral illness that causes hundreds of millions of infections each year. No specific therapy exists. In a randomized, controlled trial involving Latin American children, a tetravalent dengue vaccine showed significant protective efficacy.
Several dengue vaccine candidates are in development. As part of the clinical development of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), twin phase 3 clinical trials were initiated in Asia and Latin America to assess the efficacy of a schedule of three doses (administered at 0, 6, and 12 months) against symptomatic, virologically confirmed dengue (VCD).
• How have rates of dengue infection in endemic areas changed over the past decade?
Dengue is a mosquito-borne disease that is present in many parts of the world. From 2003 through 2013, the number of dengue cases that were reported to the Pan American Health Organization (PAHO) increased by a factor of five. The disease is caused by one of four closely related virus serotypes from the genus flavivirus. Mosquitoes that transmit the virus are present in tropical and subtropical regions worldwide and in some temperate areas of the United States, Europe, Africa, and the Middle East. Dengue is an increasing public health problem despite efforts to manage epidemics through vector control.
• Is there evidence that the CYD-TDV vaccine under development is effective?
In the Latin American trial, the CYD-TDV vaccine had an efficacy of 60.8% against symptomatic VCD after a three-dose vaccination schedule among children between the ages of 9 and 16 years. In the per-protocol analysis, the vaccine efficacy was 60.8% (95% confidence interval [CI], 52.0 to 68.0), on the basis of 176 cases of VCD in the vaccine group and 221 in the control group that were diagnosed more than 28 days after the third dose. In the intention-to-treat analysis, which included all children who received at least one injection from month 0 to 25, the vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). These efficacy results are consistent with those of the similarly designed Asian trial.
Morning Report Questions
Q: Is the CYD-TDV vaccine effective against all 4 dengue serotypes, and in both seropositive and seronegative recipients?
A: In the two studies, efficacy was higher against serotypes 3 and 4 than against serotypes 1 and 2. In Asia, efficacy against serotype 2 was 35% after the third injection, which was not significant in comparison with placebo, whereas in the Latin American study, the point estimate was 42.3%, which was significant. Efficacy in the small subgroup of children who had seronegative status at baseline was 43.2%, which was not significant in comparison with placebo but was similar to that in the Asian study (35.5%).
Q: Is this vaccine safe?
A: In the Latin American study, safety and reactogenicity profiles from 25 months of active surveillance were consistent with previous reports that identified no major concerns. No pattern of serious adverse events was identified.