Eric PlennevauxAnnick MoureauJosé L. Arredondo-GarcíaLuis VillarPunnee PitisuttithumNgoc H. TranMatthew BonaparteDanaya ChansinghakulDiana L. CoronelMaïna L'AzouR. Leon OchiaiMyew Ling TohFernando NoriegaAlain BouckenooghePasteur Institute in Ho Chi Minh CitySanofi Pasteur SAUniversidad Industrial de SantanderMahidol UniversityInstituto Nacional de PediatríaClinical SciencesGlobal EpidemiologySanofi PasteurClinical SciencesSanofi Pasteur2019-08-282019-08-282018-04-03Clinical Infectious Diseases. Vol.66, No.8 (2018), 1164-117215376591105848382-s2.0-85045137183https://repository.li.mahidol.ac.th/handle/20.500.14594/46761© 2017 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. Background We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. Methods We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2-16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. Results There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Conclusions Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries.Mahidol UniversityMedicineArticleSCOPUS10.1093/cid/cix966