Ask the Experts: Dengue: Prevaccination Testing

Administration of Dengvaxia to a person who has never been infected with DENV may result in an increased risk of hospitalization and severe dengue illness if they are infected with natural (wild type) DENV for the first time after vaccination. Multiple complex mechanisms likely contribute to increased disease severity during a second DENV infection. The published ACIP recommendation provides a detailed description of these mechanisms at www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7006a1-H.pdf. In addition, CDC has developed simple illustrations and descriptions to explain this phenomenon at https://www.cdc.gov/dengue/hcp/vaccine/eligibility.html.

In a person who has never been infected with DENV, vaccination with Dengvaxia may “stand in” (immunologically) for the first natural infection, resulting in an increased risk of severe dengue in response to the first natural infection because the immune system responds as if that infection were the “second” infection.

CDC has established strict accuracy criteria for the laboratory tests considered acceptable proof of past DENV infection before vaccination of a child.

No test is perfectly accurate: wrong results lead to different types of risk. A false negative test result means a child who is at increased risk of severe dengue would not be protected by vaccination. A false positive test means a child who was not at high risk of severe dengue would be vaccinated, potentially increasing the child’s risk of severe dengue if the child experiences a subsequent DENV infection.

All dengue IgG tests for pre-vaccination screening must have a minimum specificity of at least 98% to minimize the chance of misclassifying a person who should have a true negative test result as positive. This high specificity minimizes the risk of vaccinating a person who should not be vaccinated.

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.

Acceptable laboratory confirmation of previous dengue virus infection 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 IgG antibody tests in a two-step testing algorithm:
  • EUROIMMUN Anti-Dengue Virus NS1 Type 1-4 ELISA (IgG) and
  • CTK BIOTECH OnSite Dengue IgG Rapid Test

Visit www.cdc.gov/dengue/vaccine/hcp/testing.html. for additional information about laboratory testing requirements for vaccination with Dengvaxia. As additional tests are evaluated and approved as acceptable, information will be updated by CDC.

Vaccinators are encouraged to use the CDC prevaccination checklist to evaluate patient eligibility: www.cdc.gov/dengue/resources/DVBD_FS_Vaccination_Checklist-508.pdf.

No. IgM tests for acute DENV infection are not sufficiently accurate to be acceptable evidence for the purposes of vaccination. These tests may be falsely positive as a result of other flavivirus infections that may cause similar symptoms (such as Zika).

Acceptable evidence of acute infection with DENV is either a positive dengue RT-PCR test result, or a positive dengue NS1 antigen test result.

Visit CDC’s website on laboratory testing requirements for vaccination with Dengvaxia for additional information: www.cdc.gov/dengue/vaccine/hcp/testing.html.