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

Emerg Infect Dis. 2019 Aug;25(8):1485-1493. doi: 10.3201/eid2508.190113. Epub 2019 Aug 17.

Abstract

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.

Keywords: Brazil; T-cell specificity; Zika virus; antibody-dependent enhancement; congenital Zika syndrome; cross protection; dengue virus; flaviviridae; viral plaque assay; viruses.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brazil / epidemiology
  • Cross Protection / immunology*
  • Dengue / epidemiology
  • Dengue / history
  • Dengue / immunology*
  • Dengue Virus / classification
  • Dengue Virus / genetics
  • Dengue Virus / immunology*
  • Female
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Phylogeny
  • Pregnancy
  • Pregnancy Complications, Infectious / epidemiology*
  • Prevalence
  • Public Health Surveillance
  • Serogroup
  • Time Factors
  • Zika Virus / immunology*
  • Zika Virus Infection / epidemiology*
  • Zika Virus Infection / history
  • Zika Virus Infection / prevention & control*
  • Zika Virus Infection / transmission