Acute-Phase Dengue Antibody Profiles in Pediatric Patients: Influence on Viremia and Disease Manifestations

Secondary dengue infections are often linked to more severe clinical outcomes, yet pre-existing antibodies may exert either protective or pathogenic effects. To evaluate the role of acute-phase dengue antibodies in pediatric dengue, we analyzed clinical and laboratory features, viremia, and antibody profiles in children infected with DENV-1. We conducted a retrospective study of patients under 18 years diagnosed with DENV-1 in Salta, Argentina. Viremia was quantified by real-time RT-PCR; acute-phase IgG antibodies (within 7 days from symptom onset) against DENV, DENV-1, and DENV-NS1 were measured by immunoassays, and neutralizing antibodies by plaque reduction neutralization tests. Among 151 patients (median age 12 years), 62% presented dengue with warning signs and one case progressed to severe dengue. Viremia was higher in probable primary infections than in probable secondary infections and did not correlate with disease severity. Probable secondary infections were characterized by acute-phase antibody profiles that did not associate with DENV viremia. Age-stratified analyses revealed that adolescents exhibited higher viremia levels than younger children in probable primary infections, while viremia levels were comparable across age groups in probable secondary infections. Furthermore, children younger than 10 years displayed acute-phase antibody levels similar to those of adolescents. In adolescents with probable secondary infections, anti-DENV and anti-DENV-1 IgG were inversely correlated with platelet counts, whereas neutralizing and anti-DENV-NS1 antibodies showed no association. Collectively, these findings indicate that probable secondary DENV infections in our pediatric cohort were characterized by acute-phase antibodies that were not associated with viremia control, and that in adolescents, anti-DENV and anti-DENV-1 IgG antibodies likely associated with platelet depletion. These results highlight important implications for vaccine design, underscoring the need for vaccines that elicit strong neutralizing responses while minimizing cross-reactivity and the risk of antibody dependent enhancement.