Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil

• Published in: Emerging infectious diseases Vol. 25; no. 8; pp. 1485 - 1493
• Main Authors: Pedroso, Celia, Fischer, Carlo, Feldmann, Marie, Sarno, Manoel, Luz, Estela, Moreira-Soto, Andrés, Cabral, Renata, Netto, Eduardo Martins, Brites, Carlos, Kümmerer, Beate M, Drexler, Jan Felix
• Format: Journal Article
• Language: English
• Published: United States U.S. National Center for Infectious Diseases 01.08.2019; Centers for Disease Control and Prevention
• Subjects: antibody-dependent enhancement; Birth defects; Brazil; Brazil - epidemiology; cross protection; Cross Protection - immunology; Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil; Dengue - epidemiology; Dengue - history; Dengue - immunology; Dengue virus; Dengue Virus - classification; Dengue Virus - genetics; Dengue Virus - immunology; Female; flaviviridae; Genetic disorders; Genomes; Genomics; History, 20th Century; History, 21st Century; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical - prevention & control; Newborn infants; Phylogeny; Pregnancy; Pregnancy Complications, Infectious - epidemiology; Prevalence; Public Health Surveillance; Serogroup; Time Factors; Zika virus; Zika Virus - immunology; Zika Virus Infection - epidemiology; Zika Virus Infection - history; Zika Virus Infection - prevention & control; Zika Virus Infection - transmission; Brazil; flaviviridae; T-cell specificity; cross protection; viruses; congenital Zika syndrome; dengue virus; Brazil; Zika virus; antibody-dependent enhancement; viral plaque assay
• ISSN: 1080-6040; 1080-6059
• DOI: 10.3201/eid2508.190113

The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)-mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case-control framework in northeastern Brazil among 29 Zika virus-seropositive mothers of neonates with CZS and 108 Zika virus-seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.