RESULTS
dengue, VCD, infection, DENV-1
VIRUS, DENGUE HEMORRHAGIC FEVER, DENGUE, INFECTION, REINFECTION, PLAQUE, DENGUE
In total, 13,380 participants in the TAK-003 group and 6,687 in the placebo group received at least one dose of TAK-003 or placebo between September 2016 and March 2017, and were included in the safety population by vaccination group. There were an additional four participants who received both TAK-003 and placebo as a result of an administrative error. Of the 20,063 participants who were tested at baseline, 5,547 (27.6%) were seronegative to all four serotypes.In ∼57 months after the first dose, 442 participants (3.3%) in the TAK-003 group and 547 (8.2%) in the placebo group experienced at least one VCD episode (Number of participants and relative risk of a subsequent episode of virologically confirmed dengue (VCD) from the first dose to 4.5 years after the second dose (approximately month 57), safety set dataVCD = virologically confirmed dengue.Based on total safety set.Ten of the sequential episodes of VCD occurred at the sites in the Philippines, four in Colombia, three in Sri Lanka, and one in Thailand (Clinical and laboratory data of participants who experienced two episodes of virologically confirmed dengue infection during the trial from the first dose to 4.5 years after the second dose (approximately month 57), safety set dataDENV = dengue virus; F = female; M = male; N = no; ULoQ = upper limit of quantification; Y = yes.Age at randomization.Classified as severe dengue by the adjudication committee.Treatment group is not provided to prevent participant-level unblinding because the trial is ongoing and remains blinded. Dengue RNA was detected and quantified with a validated dengue detection reverse transcription–polymerase chain reaction. The ULoQ of the method was determined to be 85,714,286 genome copy equivalents for all four dengue serotypes. Microneutralization test results are expressed as the reciprocal of the dilutions of test serum that show a 50% reduction in plaque counts compared to the virus controls.In the 18 participants who experienced two VCD episodes, five of the first episodes after trial vaccination were diagnosed clinically as dengue by the investigators, and three participants were hospitalized (one episode each of DENV-1, -2, and -3). Two of the subsequent episodes (DENV-1 homotypic reinfection and DENV-4 following DENV-2) were diagnosed clinically as dengue and both required hospitalization. One of the first VCD episodes (DENV-3 in a baseline seronegative participant) was classified as severe by the adjudication committee; none of the other episodes were classified as severe or dengue hemorrhagic fever.