Primary exposure to Zika virus is linked with increased risk of symptomatic dengue virus infection with serotypes 2, 3, and 4, but not 1

  1. José Victor Zambrana
  2. Chloe M. Hasund
  3. Rosemary A. Aogo
  4. Sandra Bos
  5. Sonia Arguello
  6. Karla Gonzalez
  7. Damaris Collado
  8. Tatiana Miranda
  9. Guillermina Kuan
  10. Aubree Gordon
  11. Angel Balmaseda
  12. Leah C. Katzelnick
  13. Eva Harris

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Abstract

Infection with any of the four dengue virus serotypes (DENV1–4) can protect against or enhance subsequent dengue depending on preexisting antibodies and infecting serotype. Additionally, primary infection with the related flavivirus Zika virus (ZIKV) is associated with increased risk of DENV2 disease. Here, we measured how prior DENV and ZIKV immunity influenced risk of disease caused by DENV1–4 in a pediatric Nicaraguan cohort. Of 3412 participants in 2022, 10.6% experienced dengue cases caused by DENV1 ( n = 139), DENV4 ( n = 133), DENV3 ( n = 54), DENV2 ( n = 9), or an undetermined serotype ( n = 39). Longitudinal clinical and serological data were used to define infection histories, and generalized linear and additive models adjusted for age, sex, time since last infection, and year, and repeat measurements were used to predict disease risk. Compared with flavivirus-naïve participants, primary ZIKV infection was associated with increased risk of disease caused by DENV4 (relative risk = 2.62, 95% confidence interval: 1.48 to 4.63) and DENV3 (2.90, 1.34 to 6.27), but not DENV1 infection. Primary DENV infection or DENV followed by ZIKV infection was also associated with increased risk of DENV4 disease. We reanalyzed 19 years of cohort data and demonstrated that prior flavivirus immunity and antibody titer had distinct associations with disease risk depending on incoming serotype. We thus find that prior ZIKV infection, like prior DENV infection, is associated with increased risk of disease with certain DENV serotypes. Cross-reactivity among flaviviruses should be considered when assessing vaccine safety and efficacy.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Annie Ngono

    Review 1: "Primary Exposure to Zika Virus Increases Risk of Symptomatic Dengue Virus Infection with Serotypes 2, 3, and 4 but not Serotype 1"

    Overall, the reviewer found the study to be well-designed with strong evidence to support the claims.

  2. Rapid Reviews Infectious Diseases

    Annie Ngono

    Review of: "Primary Exposure to Zika Virus Increases Risk of Symptomatic Dengue Virus Infection with Serotypes 2, 3, and 4 but not Serotype 1"

    Reviewers: A Ngono (La Jolla Institute for Immunology) | 📘📘📘📘📘

  3. Version published to 10.1126/scitranslmed.adn2199
  4. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/10393624.

    Does the introduction explain the objective of the research presented in the preprint? Yes The introduction clearly explains the objective of the study by presenting information on how antibody titers can be cross-reactive that are both neutralizing and increase the risk of infection. This is further built upon in how the paper describes the implication of previous DENV or ZIKV infections and the increased risk they pose.
    Are the methods well-suited for this research? Somewhat appropriate The methods and materials that were described were thorough and properly executed and produced a solid foundation on which one would be able to generate meaningful discourse. The methods could be further enhanced if the study design had accounted for potential confounding variables that may have been prevalent during the time of the study that was being observed.
    Are the conclusions supported by the data? Highly supported
    Are the data presentations, including visualizations, well-suited to represent the data? Somewhat appropriate and clear
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Somewhat clearly
    Is the preprint likely to advance academic knowledge? Somewhat likely
    Would it benefit from language editing? No
    Would you recommend this preprint to others? Yes, it's of high quality
    Is it ready for attention from an editor, publisher or broader audience? Yes, after minor changes

    Competing interests

    The author declares that they have no competing interests.

  5. Version published to 10.1101/2023.11.29.23299187v1 on medRxiv