BACKGROUND: Dengue diagnosis confirmation and surveillance are widely based on serological assays to detect anti-dengue IgM or IgG antibodies since such tests are affordable/user-friendly. The World Health Organization identified serological based diagnosis as a potential tool to define probable dengue cases in the context of vaccine trials, while acknowledging that this may have to be interpreted with caution. METHODS: In a phase IIb randomized, placebo-controlled trial assessing the efficacy of a tetravalent dengue vaccine (CYD-TDV) in Thai schoolchildren, case definition was based on virological confirmation by either serotype-specific RT-PCRs or by NS1-antigen ELISA (Clinicaltrials.gov NCT00842530). Here, we characterized suspected dengue cases using IgM and IgG ELISA to assess their utility in evaluating probable dengue cases in the context of vaccine efficacy trials, comparing virologically-confirmed and serologically diagnosed dengue in the vaccine and placebo groups. Serologically probable cases were defined as: (1) IgM positive acute- or convalescent-phase samples, or (2) IgG positive acute-phase sample and ≥4-fold IgG increase between acute and convalescent-phase samples. RESULTS: Serological diagnosis had good sensitivity (97.1%), but low specificity (85.1%) compared to virological confirmation. A high level of false positivity through serology diagnosis particularly in the 2 months post-vaccination was observed, and is most likely related to detection of the immune response to the dengue vaccine. This lack of specificity and bias with vaccination demonstrates the limitation of using IgM and IgG antibody responses to explore vaccine efficacy. CONCLUSION: Reliance on serological assessments would lead to a significant number of false positives during routine clinical practice and surveillance following the introduction of the dengue vaccine.
RCT Entities:
BACKGROUND: Dengue diagnosis confirmation and surveillance are widely based on serological assays to detect anti-dengue IgM or IgG antibodies since such tests are affordable/user-friendly. The World Health Organization identified serological based diagnosis as a potential tool to define probable dengue cases in the context of vaccine trials, while acknowledging that this may have to be interpreted with caution. METHODS: In a phase IIb randomized, placebo-controlled trial assessing the efficacy of a tetravalent dengue vaccine (CYD-TDV) in Thai schoolchildren, case definition was based on virological confirmation by either serotype-specific RT-PCRs or by NS1-antigen ELISA (Clinicaltrials.gov NCT00842530). Here, we characterized suspected dengue cases using IgM and IgG ELISA to assess their utility in evaluating probable dengue cases in the context of vaccine efficacy trials, comparing virologically-confirmed and serologically diagnosed dengue in the vaccine and placebo groups. Serologically probable cases were defined as: (1) IgM positive acute- or convalescent-phase samples, or (2) IgG positive acute-phase sample and ≥4-fold IgG increase between acute and convalescent-phase samples. RESULTS: Serological diagnosis had good sensitivity (97.1%), but low specificity (85.1%) compared to virological confirmation. A high level of false positivity through serology diagnosis particularly in the 2 months post-vaccination was observed, and is most likely related to detection of the immune response to the dengue vaccine. This lack of specificity and bias with vaccination demonstrates the limitation of using IgM and IgG antibody responses to explore vaccine efficacy. CONCLUSION: Reliance on serological assessments would lead to a significant number of false positives during routine clinical practice and surveillance following the introduction of the dengue vaccine.
Authors: Eric Plennevaux; Annick Moureau; José L Arredondo-García; Luis Villar; Punnee Pitisuttithum; Ngoc H Tran; Matthew Bonaparte; Danaya Chansinghakul; Diana L Coronel; Maïna L'Azou; R Leon Ochiai; Myew-Ling Toh; Fernando Noriega; Alain Bouckenooghe Journal: Clin Infect Dis Date: 2018-04-03 Impact factor: 9.079
Authors: Elizabeth A Hunsperger; Claudia N Duarte Dos Santos; Huong Thi Que Vu; Sutee Yoksan; Vincent Deubel Journal: PLoS Negl Trop Dis Date: 2017-09-07
Authors: Judith Kirstein; William Douglas; Manoj Thakur; Mark Boaz; Thomas Papa; Anna Skipetrova; Eric Plennevaux Journal: BMC Infect Dis Date: 2018-09-21 Impact factor: 3.090
Authors: Nur Alia Sheh Omar; Yap Wing Fen; Jaafar Abdullah; Yasmin Mustapha Kamil; Wan Mohd Ebtisyam Mustaqim Mohd Daniyal; Amir Reza Sadrolhosseini; Mohd Adzir Mahdi Journal: Sci Rep Date: 2020-02-11 Impact factor: 4.379