A candidate tetravalent dengue vaccine may reduce the risk for hospitalization among children living in endemic regions, although the benefit for children aged younger than 9 years remains unclear, according to recent findings.
In long-term follow-up interim analyses and integrated efficacy analyses of three clinical trials assessing the recombinant, live, attenuated vaccine (CYD-TDV, Sanofi Pasteur), researchers evaluated available data compiled during the trials’ third and fourth years. The first trial is a phase 3 study conducted in five Asian-Pacific countries (CYD14; n = 10,275), while the second is a phase 3 trial in five Latin American countries (CYD15; n = 20,869). In a third analysis, researchers invited a subset of study participants in a single-center, phase 2b trial conducted in Thailand (CYD23) to join a separate, 4-year follow-up study (CYD57; n = 4,002) evaluating safety similarly to the phase 3 trials.
Data were available for 99% of participants enrolled in CYD14, 95% of CYD15 participants and 80% of participants in CYD57. All were aged 2 to 16 years, and initially randomly assigned in a 2:1 ratio to either the vaccine (n = 22,177) or control group (n = 11,089).
The researchers defined hospitalization for virologically confirmed dengue as a surrogate safety endpoint during 3-year to 6-year follow-up, and used pooled data from the first 25 months of CYD14 and CYD15 to assess vaccine efficacy.
The researchers found that during the third year of the trials, 65 children in the vaccine group were hospitalized with virologically confirmed dengue, compared with 39 control participants. In all participants, the pooled relative risks of dengue-related hospitalization were 0.84 (95% CI, 0.56-1.24), while the risk for children aged younger than 9 years was 1.58 (95% CI, 0.83-3.02). For children aged 9 years or older, the risk was 0.5 (95% CI, 0.29-0.86). Hospitalization for severe dengue was seen in 18 participants in the vaccine group and six control patients during year 3. During the first 25 months of CYD14 and CYD15, the pooled efficacy rates for symptomatic dengue were 60.3% (95% CI, 55.7-64.5) for the total study population, 65.6% (95% CI, 60.7-69.9) for participants aged 9 years and older, and 44.6% (95% CI, 31.6-55.) for children aged younger than 9 years.
In a related editorial, Cameron P. Simmons, PhD, of the department of microbiology and immunology at the University of Melbourne, wrote that the complex nature of these findings may pose a challenge in terms of providing adequate vaccine coverage for children in the two evaluated age groups.
“If countries in which dengue is endemic were to license CYD-TDV for children 9 years of age or older, then policymakers in each setting would subsequently need to make decisions on the cost and benefit of programmatic vaccination,” Simmons wrote. “In places in which a sizable fraction of the case burden occurs in children younger than 9 years of age, this decision will be a complex one.” – by Jen Byrne
Disclosure: Hadinegoro reports grant support from Sanofi Pasteur during the conduct of this study. Please see the full study for a list of all other authors’ relevant financial disclosures.