Zika infection increases future risk for severe dengue
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Prior Zika virus infection can significantly increase the risk for severe dengue, similar to a prior dengue infection, which may pose issues for vaccine development for both viruses, according to a study published in Science.
“While the dengue epidemic was going on, we were noticing that there were a lot more cases than we were expecting, and so we were analyzing this and started seeing this tendency for more cases,” Eva Harris, PhD, professor of infectious diseases and vaccinology and director of the Center for Global Public Health at the University of California, Berkeley School of Public Health, told Healio.
Credit: CDC/James Gathany
“From there, we were able to perform a finer analysis and extend that to look at disease severity. What we found was not only was there more symptomatic disease, but there was also an enhancement of severe disease,” Harris said.
Harris and colleagues estimated the probability of symptomatic dengue virus serotype 2 (DENV2) during the 2019 to 2020 epidemic based on Zika virus and dengue infection histories. They analyzed pediatric cohorts in Nicaragua that experienced sequential dengue virus 1 (DENV1), DENV2 and dengue virus 3 (DENV3) epidemics from 2004 to 2015, Zika epidemics from 2016 to 2017 and DENV2 epidemics from 2018 to 2020.
In the study, the researchers found that the risk for symptomatic DENV2 and severe disease was increased by the presence of one prior Zika infection, one prior dengue infection or one prior dengue infection, followed by one Zika infection. However, multiple prior dengue infections reduced dengue risk.
The researchers also noted that high pre-existing anti-dengue antibody titers had a protective effect against DENV1, DENV3 and Zika, and intermediate titers activated by previous dengue or Zika infection increased future risk of DENV2 disease and severity and DENV3 severity.
“The most important thing that we want to do in the future is to maintain this cohort so that we can look not only at the effect on DENV2 because we happen to have a DENV2 epidemic, but the other serotypes,” Harris said.
Perspective
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Sarah B. Mulkey, MD, PhD
The host’s immune system interaction to a viral threat is complex. As discussed in this study by Katzelnick and colleagues, our past viral exposure experience, or lack thereof, may impact illness severity for new viruses or new viral strains. In the case of flaviviruses, it seems fairly complicated. Previous infection with Zika virus or dengue virus appears to increase the risk for severe DENV2 disease compared with not having been exposed to these viruses before. However, if one has been exposed to dengue several times, this then seems to become protective. These findings certainly may complicate the development of a vaccine for Zika and dengue infection. In consideration of the current SARS-CoV-2 pandemic, how might past exposure to other coronaviruses impact our immune system response and risk of asymptomatic or severe COVID-19 illness? To understand risk for disease severity following viral infection, attention to past viral exposures may be of key importance.
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