Response to letter to the editor re “Severe dengue hemorrhagic fever after TAK-003 dengue vaccination: A case report of a potential vaccine-associated adverse reaction”

We thank the authors for their letter commenting on our case report, "Severe dengue hemorrhagic fever after TAK-003 dengue vaccination: A case report of a potential vaccineassociated adverse reaction" [1].We acknowledge their perspective suggesting that the severe dengue observed in our patient could have resulted from a naturally acquired infection; however, in our assessment, this case is highly unlikely to represent natural infection when considering the complete clinical course and available laboratory evidence.The authors primarily suggested that the NS1 antigen detection in this patient was unlikely to be attributable to the TAK-003 vaccine, citing the absence of NS1 positivity in their phase 2 trial.Building upon a closer examination of that study, however, several important distinctions present [2].The trial enrolled only 351 participants with a mean age of 31.1 years, 53.6% of whom were seropositive at baseline.This relatively small sample size and younger, predominantly seropositive population differ substantially from the characteristics of our patient.Such a cohort would be expected to mount a more robust immune response, potentially leading to lower levels of vaccine viremia and, consequently, negative NS1 test results.