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

Sebastián Castro-Trujillo; Katherine Segura; Sara Bolívar-Marín; Doris M Salgado; Irene Bosch; Rocío Vega; María Clemencia Rojas; Carlos F Narváez

doi:10.1097/INF.0000000000004163

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

Pediatr Infect Dis J. 2023 Nov 13. doi: 10.1097/INF.0000000000004163. Online ahead of print.

Authors

Sebastián Castro-Trujillo¹, Katherine Segura^{2

3}, Sara Bolívar-Marín¹, Doris M Salgado⁴, Irene Bosch^{5

6}, Rocío Vega^{4

7}, María Clemencia Rojas³, Carlos F Narváez^{4

3}

Affiliations

¹ From the División de Inmunología, Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Huila, Colombia.
² Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia.
³ Dirección Laboratorio de Salud Pública, Secretaría de Salud Departamental, Gobernación del Huila, Neiva, Huila, Colombia.
⁴ Área de Pediatría, Departamento de Ciencias Clínicas, Facultad de Salud, Universidad Surcolombiana, Neiva, Huila, Colombia.
⁵ Department of Microbiology, Harvard Medical School, Boston, Massachusetts.
⁶ Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.
⁷ Departamento de Pediatría, Hospital Universitario de Neiva, Neiva, Huila, Colombia.

PMID: 37963312
DOI: 10.1097/INF.0000000000004163

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 virological characteristics and the nonstructural protein 1 (NS1)-specific antibody responses to DENV and ZIKV in children suspected of dengue in different epidemiological 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 ortho flavivirus 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 ortho flaviviral 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 ortho flaviviral 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.