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HomeHealth ConditionsTropical DiseasesOld Zika and Dengue Viruses Haunt New Infections

Old Zika and Dengue Viruses Haunt New Infections

The risk of getting sick from dengue fever depends on whether you've already been infected with dengue or Zika virus in the past, and what specific type of dengue virus you're infected with this time.

A new study sheds light on how previous infections with dengue and Zika viruses can influence a person’s future risk of getting sick from different types of dengue fever. Researchers in Nicaragua followed a group of children over several years, analyzing how past encounters with these viruses impacted their susceptibility to various dengue strains.1

Dengue and Zika viruses, both spread by mosquitoes, can cause serious health issues. Dengue comes in four distinct flavors (DENV 1-4), while the Zika virus is a single strain.2 After infection with either virus, your body produces antibodies to fight it off. Usually these antibodies protect us from subsequent infections from the same or very similar viruses, but in a surprising twist, researchers have discovered that antibodies against Zika can make you more susceptible to type 3 and 4 dengue fever.

The study also emphasizes the role of past dengue infections and antibody levels. Previous exposure to dengue virus can influence sensitivity to new dengue strains, with high antibody levels offering protection against some types but potentially worsening illness for others.3 Scientists hope that by understanding these dynamics,  they can create safer and more effective vaccines against dengue and other similar viruses.

Exposure raises the risks

The Pediatric Dengue Cohort Study followed 4,000 participants between the ages of two and 17 years for arbovirus infection in Managua, Nicaragua continuously since 2004. All four dengue virus serotypes (DENV1-4) were found to be circulating simultaneously during the 2022-2023 epidemic. 

Individuals with prior exposure to dengue or Zika virus were at a higher risk of experiencing symptomatic dengue infections. 

With a prior Zika infection, they were 1.61 times more likely to develop symptomatic dengue fever, particularly for DENV3 and DENV4 serotypes. This heightened risk persisted over time, with a 1.87-fold increased risk of symptomatic dengue and a 3.62-fold increased risk of severe dengue observed even years after the initial Zika infection. 

A prior dengue infection significantly increased the risk of symptomatic DENV2 and DENV4 infections, but not DENV1 or DENV3. Interestingly, a single prior dengue infection did not increase the overall risk of symptomatic dengue, but it did increase the risk of severe dengue by 1.67 times.

Past infections make a mess of immunity

The study also revealed that the specific sequence of previous Zika infections matters, with certain combinations increasing the risk of symptomatic dengue more than others. 

In fact, those who had been infected with dengue twice were 2.66 times more likely to get sick again, especially with the DENV3 strain. This was also true for individuals who had dengue, then Zika, who faced a 1.47 times higher risk of future dengue illness, particularly with DENV2 (2.53 times higher) and DENV4 (4.05 times higher), and were 3.26 times more likely to experience severe dengue.

However, those who had been infected with dengue multiple times or a combination of dengue and Zika did not face an increased risk. 

Dengue antibodies: protection or peril?

Antibody levels against dengue were shown to fluctuate over time, influenced by previous epidemics and the type of virus involved. Pre-existing antibody levels influence the risk of dengue, depending on the infecting serotype. Low-to-intermediate antibody titers increased the risk of DENV2 and DENV4 infections, while high titers were protective against DENV1 and DENV3.

The antibodies produced after a viral infection are usually helpful, providing good protection against getting sick with the same virus again.4 However, things get trickier when it comes to similar viruses. Antibodies can sometimes cross-react with dengue’s different strains, but the effect can be a double-edged sword. In some cases, these antibodies actually increase the risk of getting sick from a different dengue serotype, especially if the antibody levels are low or moderate. This phenomenon, called antibody-dependent enhancement (ADE), explains why a first Dengue infection might make you more susceptible to a severe illness from a different dengue strain later.5,6

Double trouble for vaccine developers

These findings raise questions about the development and deployment of dengue and Zika vaccines. The discovery that Zika vaccines could potentially increase the risk of severe dengue illness in individuals who have never been exposed to the virus before, coupled with the observation that even two prior dengue infections may not offer complete protection, underscores the need for a cautious approach when designing and implementing vaccination programs for both diseases.

Health officials must carefully consider pre-existing immunity and the potential for a previous infection to worsen subsequent infections when developing future vaccine strategies. This new knowledge could help create safer and more effective vaccines for both dengue and Zika,ensuring that vaccination efforts truly protect vulnerable populations.

References

  1. Zambrana JV, Hasund CM, Aogo RA, et al. Primary exposure to Zika virus increases risk of symptomatic dengue virus infection with serotypes 2, 3, and 4 but not serotype 1. Preprint. medRxiv. 2023;2023.11.29.23299187. Published 2023 Nov 30. doi:10.1101/2023.11.29.23299187
  2. Leta S, Beyene TJ, De Clercq EM, Amenu K, Kraemer MUG, Revie CW. Global risk mapping for major diseases transmitted by Aedes aegypti and Aedes albopictus. Int J Infect Dis. 2018;67:25-35. doi:10.1016/j.ijid.2017.11.026
  3. Halstead SB, Nimmannitya S, Cohen SN. Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered. Yale J Biol Med. 1970;42(5):311-328.
  4. Gallichotte EN, Baric RS, de Silva AM. The Molecular Specificity of the Human Antibody Response to Dengue Virus Infections. Adv Exp Med Biol. 2018;1062:63-76. doi:10.1007/978-981-10-8727-1_5
  5. Katzelnick LC, Gresh L, Halloran ME, et al. Antibody-dependent enhancement of severe dengue disease in humans. Science. 2017;358(6365):929-932. doi:10.1126/science.aan6836
  6. Sangkawibha N, Rojanasuphot S, Ahandrik S, et al. Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I. The 1980 outbreak. Am J Epidemiol. 1984;120(5):653-669. doi:10.1093/oxfordjournals.aje.a113932
Melody Sayrany MSc
Melody Sayrany MSc
Melody Sayrany is a seasoned science writer with a host of experiences in cancer, neuroscience, aging, and metabolism research. She completed her BSc at The University of California, San Diego, and her MSc in biology, focusing on metabolic diseases during aging, at the University of British Columbia. Melody is passionate about science communication, and she aims to bridge the gap between complex scientific concepts and the broader community through compelling storytelling.
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