WHAT:

Children with a history of prior dengue virus infection had a significantly lower risk of being symptomatic when infected by Zika virus, according to a study in Nicaragua of more than 3,000 children aged 2 to 14 years. Experts have worried that prior dengue virus infection could exacerbate severe Zika disease. However, the new findings, published in PLOS Medicine, indicate that prior dengue immunity in children may in fact be protective against symptomatic Zika disease.

The research was conducted by investigators at the University of Michigan in Ann Arbor; the University of California, Berkeley; the Ministry of Health in Managua, Nicaragua; and the Sustainable Sciences Institute, also in Managua. The research was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

While dengue virus has been entrenched in the Americas for decades, Zika virus was not reported in the region until 2015. Zika virus and dengue virus are both transmitted by Aedes aegypti mosquitoes and cause similar symptoms, including fever, rash, and joint pain. In some cases, Zika virus infection can cause neurological issues, and infection during pregnancy can lead to birth defects and developmental problems in babies (a condition called congenital Zika syndrome). However, many people do not show symptoms when infected with either Zika virus or dengue virus.

It has been observed that in some epidemiological settings, a second dengue infection can be much more severe than a first dengue infection. Since dengue and Zika are closely related, it is important to know whether Zika following a dengue infection could also be more severe. To examine this potential relationship, the authors studied the 2016 epidemic of Zika in a longstanding cohort of children in Managua, many of whom had dengue infection histories.

Among the 3,893 children aged 2 to 14 years in the study, the authors estimate there were 1,356 Zika infections--560 of which were symptomatic cases--from January 2016 through February 2017. Case counts are based on infections confirmed by laboratory detection of Zika virus in the body using a method called RT-PCR (used to confirm symptomatic cases at the time of infection), and an algorithm developed to serologically classify--a process that involves examining antibodies in blood samples--cases not confirmed by RT-PCR (primarily clinically inapparent cases). Using data from the 15 years of the pediatric cohort, the investigators determined exposure histories for 3,027 of the children, of which 743 children had at least one dengue infection.

In statistical models adjusted for sex and age (younger children are less likely to have had dengue virus infection), children with a previous dengue virus infection before March 2015 had a significantly lower risk of symptomatic Zika virus infection. However, prior dengue virus infections did not affect the rate of total Zika virus infections, which includes both symptomatic and clinically inapparent cases.

These data indicate that prior dengue immunity in children may be protective against symptomatic Zika infection, according to the authors. They note that future research should investigate the immunological mechanisms of cross-protection between dengue virus and Zika virus and examine whether dengue immunity is protective against congenital Zika syndrome or Zika-related neurological complications.

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ARTICLE:

A Gordon et al. Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua. PLOS Medicine DOI: 10.1371/journal.pmed.1002726 (2019).

WHO:

NIAID Director Anthony S. Fauci, M.D., is available for comment. Mark Challberg, Ph.D., flaviviruses program officer, Virology Branch in NIAID's Division of Microbiology and Infectious Diseases, is also available for comment.

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