Influence of previous Zika virus infection on acute dengue episode
Cássia Fernanda Estofolete, Alice F. Versiani, Fernanda Simões Dourado, Bruno Henrique Gonçalves de Aguiar Milhim, Carolina Colombelli Pacca, Gislaine Celestino Dutra da Silva, Nathália Zini, Bárbara F. dos Santos, Flora de Andrade Gandolfi, Natalia Franco Bueno Mistrão, Pedro H. C. Garcia, Rodrigo S. Rocha, Lee Gehrke, Irene Bosch, Rafael Elias Marques, Mauro Martins Teixeira, Flávio Guimarães da Fonseca, Nikos Vasilakis, Maurício Lacerda Nogueira
Abstract
BACKGROUND: The co-circulation of flaviviruses in tropical regions has led to the hypothesis that immunity generated by a previous dengue infection could promote severe disease outcomes in subsequent infections by heterologous serotypes. This study investigated the influence of antibodies generated by previous Zika infection on the clinical outcomes of dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 1,043 laboratory confirmed dengue patients and investigated their prior infection to Zika or dengue. Severe forms of dengue disease were more frequent in patients with previous Zika infection, but not in those previously exposed to dengue. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that previous Zika infection may represent a risk factor for subsequent severe dengue disease, but we did not find evidence of antibody-dependent enhancement (higher viral titer or pro-inflammatory cytokine overexpression) contributing to exacerbation of the subsequent dengue infection.