Laboratory Testing Requirements for Vaccination with Dengvaxia Dengue Vaccine
Dengvaxia is available for use in children and adolescents 9–16 years old with laboratory-confirmed previous dengue virus infection and living in an area where dengue is endemic (occurs frequently or continuously).
Laboratory confirmation of previous dengue virus infection is required and can be obtained by:
- Evidence of prior acute dengue virus infection with
- Positive dengue RT-PCR test result, or
- Positive dengue NS1 antigen test result
- OR, positive results on BOTH of the following anti-dengue virus immunoglobulin G (dengue IgG antibody) tests in a two-step testing algorithm:
A single positive anti-dengue virus immunoglobulin M (dengue IgM) test result is not sufficient proof of dengue virus infection for vaccination with Dengvaxia due to potential cross-reactivity with other circulating flaviviruses (e.g., Zika virus) in dengue-endemic areas.
Rationale for Pre-vaccination Serologic Screening: To Provide Evidence of Previous Dengue Virus Infection
Detection of dengue IgG provides evidence of previous dengue virus infection. Not all dengue IgG tests can be used for pre-vaccination screening. Some dengue IgG tests can be cross-reactive with other flaviviruses, such as Zika virus, or are not intended to detect infections that occurred several years ago. In addition, some tests may have unacceptably high rates of false-positive or false-negative test results.
To determine vaccine eligibility and minimize the risk of false-positive test results, CDC recommends the use of highly specific pre-vaccination screening tests for dengue IgG. The specificity of a test is determined by the percentage of correctly identified negative cases. Patients with a negative test result in the dengue vaccine pre-vaccination screening should be re-tested every 1-2 years from the ages of 9–16 years or based on clinical judgement of their healthcare provider.
Pre-vaccination screening testing standards
All serologic tests recommended for pre-vaccination screening are required to meet the following standards.
| Test Characteristic | Minimum |
|---|---|
| Sensitivity | ≥75% |
| Specificity† | ≥98% |
†Zika virus and other epidemiologically relevant flaviviruses are included in the evaluation for specificity.
Dengue IgG tests for pre-vaccination screening must have a minimum specificity of 98% to minimize the chance of misclassifying a true negative test result for a person as positive.
Pre-vaccination screening tests must also have a sensitivity of at least 75% to accurately identify a high proportion of children and adolescents with past dengue virus infections who can benefit from vaccination.
Beginning in 2022, anti-dengue IgG antibody tests will become available as enzyme-linked immunosorbent assays (ELISA) and rapid diagnostic tests (RDTs).
- ELISAs are suitable for simultaneously testing several samples in the laboratory.
- RDTs can be used for testing individual samples in a variety of settings, including high- and low-complexity laboratories and healthcare provider offices in accordance with local regulations.
Tests Meeting the Required Criteria for Pre-vaccination Screening
- CDC has evaluated all dengue IgG tests available for purchase in the U.S. market.
- Tests with performance characteristics near CDC requirements were evaluated for sensitivity and specificity using samples collected from children living in Puerto Rico who were 9–16 years old.
- These evaluations showed that, when run individually, two tests performed well for sensitivity and specificity but neither meets the required 98% specificity.
- The evaluation found that the following two IgG tests, when used together in a two-test algorithm, met the test performance requirements (sensitivity ≥75% and specificity ≥98%).
- EUROIMMUN Anti-Dengue Virus NS1 Type 1-4 ELISA (IgG)*
- CTK BIOTECH OnSite Dengue IgG Rapid Test*
- These tests are not yet cleared by the U.S. Food and Drug Administration. To perform pre-vaccination screening with EUROIMMUN Anti-Dengue Virus NS1 Type 1-4 ELISA (IgG)* and the CTK BIOTECH OnSite Dengue IgG Rapid Test*, laboratories must validate and implement these tests in accordance with federal and local regulations.
- The list of requirements and/or tests will be updated as additional evaluations of test performance become available.
- The EUROIMMUN Anti-Dengue Virus NS1 Type 1-4 ELISA (IgG)* and the CTK BIOTECH OnSite Dengue IgG Rapid Test* should be performed using a two-step algorithm with one test for screening and a second test for confirmation.
- Only children with positive results on BOTH tests are considered eligible for vaccination with Dengvaxia.
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