NS1-Specific Antibody Response Facilitates the Identification of Children With Dengue and Zika in Hyperendemic Areas

Pediatr Infect Dis J. 2024 Feb 1;43(2):178-185. doi: 10.1097/INF.0000000000004163. Epub 2023 Nov 13.

Abstract

Background: Infections by dengue virus (DENV) and Zika virus (ZIKV) have some similar symptoms and a cross-reactive immune response, although with different risk populations and outcomes. Here, we evaluated the virologic characteristics and the nonstructural protein 1 (NS1)-specific antibody responses to DENV and ZIKV in children suspected of dengue in different epidemiologic moments in Colombia.

Methods: Viral RNA, circulating NS1 and IgM/IgG specific for DENV and ZIKV were performed by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) in 301 children suspected of dengue enrolled in a hospital setting during the ZIKV epidemic and a primary healthcare setting during a DENV epidemic. For the detection of DENV and ZIKV-specific IgM, an NS1-based ELISA was validated using characterized pediatric samples. Clinical and laboratory parameters were also evaluated.

Results: DENV RNA or NS1 antigen was detected in the plasma of 62% of children, and in none, the ZIKV RNA was found. NS1-based ELISA for DENV and ZIKV IgM showed a sensitivity/specificity of 90/84% and 73/98%, respectively. Of 114 children without detectable viremia or antigenemia, 30.7%, 17.5%, 22% and 30% were IgM-DENV + , IgM-ZIKV + , IgM-DENV + ZIKV + and IgM-DENV - ZIKV - , respectively. The ZIKV/DENV IgM-NS1 ratio allows the identification of the infecting orthoflavivirus in 88% of the children with IgM-DENV + ZIKV + , confirming a high predominance of DENV infections in the 2 pediatric settings.

Conclusion: Overall, 88% of the children with clinical suspicion of dengue had an identifiable orthoflaviviral infection, with 80% caused by DENV, 7% by ZIKV and 0.7% classified as recent infections or coinfection, demonstrating active viral cocirculation in the pediatric population of southern Colombia. The IgM-NS1 detection improved the identification of orthoflaviviral infections in children without viremia or antigenemia, suggesting it is a helpful complementary tool for medical personnel in tropical regions with high viral cocirculation and different clinical scenes.

MeSH terms

  • Adolescent
  • Antibodies, Viral* / blood
  • Child
  • Child, Preschool
  • Colombia / epidemiology
  • Dengue Virus / immunology
  • Dengue* / blood
  • Dengue* / diagnosis
  • Dengue* / epidemiology
  • Dengue* / immunology
  • Endemic Diseases*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Infant
  • Male
  • RNA, Viral / blood
  • Sensitivity and Specificity
  • Viral Nonstructural Proteins* / blood
  • Viral Nonstructural Proteins* / immunology
  • Zika Virus / immunology
  • Zika Virus Infection* / blood
  • Zika Virus Infection* / diagnosis
  • Zika Virus Infection* / epidemiology
  • Zika Virus Infection* / immunology

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin M
  • RNA, Viral
  • Viral Nonstructural Proteins