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Clin Infect Dis. 2018 Apr 3;66(8):1164-1172. doi: 10.1093/cid/cix966.

Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials.

Author information

1
Dengue Company, Sanofi Pasteur, Lyon, France.
2
Clinical Development, Sanofi Pasteur, Marcy l'Etoile, France.
3
Instituto Nacional de Pediatría, Unidad de Apoyo a la Investigación Clínica, Mexico City, Mexico.
4
Clinical Epidemiology Unit, School of Medicine, Universidad Industrial de Santander, Bucaramanga, Colombia.
5
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
6
Pasteur Institute, Ho Chi Minh City, Vietnam.
7
Global Clinical Immunology Department, Sanofi Pasteur, Swiftwater, Pennsylvania.
8
Clinical Sciences, Sanofi Pasteur, Bangkok, Thailand.
9
Clinical Sciences, Sanofi Pasteur, Mexico City.
10
Global Epidemiology, Sanofi Pasteur, Lyon, France.
11
Medical Affairs, Sanofi Pasteur, Lyon, France.
12
Research and Development, Sanofi Pasteur, Swiftwater, Pennsylvania.
13
Clinical Sciences, Sanofi Pasteur, Singapore.

Abstract

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.

Clinical Trials Registration:

NCT01373281 and NCT01374516.

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