Individuals with a prior Zika infection faced a 2.34 times increased risk of severe dengue and a 3.39 times higher likelihood of hospitalization compared to controls (those with no history of dengue or Zika).
Relatively advanced age (over 59) was also a higher risk factor for severe forms of dengue and hospitalization, revealed the study published in the journal PLOS Neglected Tropical Diseases.
“Our findings confirmed the results of a previous study involving children who had zika in Nicaragua. Later, when they had dengue, the risk of severity increased. We showed the same thing [risk of severe dengue increased by prior zika or dengue] for adults in Brazil,” Cassia Fernanda Estofolete, an infectious disease specialist at the Sao Jose do Rio Preto Medical School (FAMERP) told Agencia FAPESP.
“We also showed that ADE [antibody-dependent enhancement, in which, instead of providing protection, antibodies enhance viral entry into host cells and can exacerbate the disease] is non-classical,”Estofolete said.
Link Between Zika-Induced Dengue Severity and Mechanisms Uncovered
According to the scientific literature, a second infection by any of the four known dengue serotypes is known to be typically more severe than the first, but until now no correlation between this fact and the occurrence of other diseases had been investigated.The mechanism that exacerbates dengue infection following a case of zika differs from that of two consecutive infections by the dengue virus, explained the team.The viral load is higher in the second dengue episode, with high levels of inflammatory cytokines not seen in zika.
Detection of other markers suggested that the increase in severity may be due to activation of T cells, key parts of the immune system that help produce antibodies, in a pathogenic immune response that has been termed the “original antigenic sin”.The process involves so-called T-cell memory, a response in which T cells produced during a previous infection stimulate the production of more T cells to combat a new infection.
Because these new cells are not specific to the virus, they trigger an excessive release of inflammatory cytokines, which attack the organism’s proteins and tissues, potentially leading to hemorrhage.The researchers from the Sao Paulo Research Foundation (FAPESP) analysed samples from 1,043 laboratory-confirmed dengue patients, identifying those with prior zika and dengue infections.
Estofolete noted that the findings raises questions about the type of zika vaccine that should be used and the optimal timing: should it be administered with a dengue vaccine in order to avoid this problem of one following the other, for example Dengue and zika are both flaviviruses, transmitted by the same mosquito (Aedes aegypti), and have similar symptoms, often making diagnosis difficult. Dengue is more serious because in addition to fever, headache, muscle and joint pain, rash and nausea, it can cause bleeding and even death.
The symptoms of zika are milder, but the virus can cause severe problems in pregnant women and in babies, such as microcephaly and possibly Guillain-Barre syndrome, a neurological disorder that leads to paralysis.”The goal is not just to answer questions about severity, but also to know whether the mechanism we detected is the same for all dengue serotypes because this influences other factors and mechanisms. We don’t have a great deal of accumulated knowledge about zika vaccines,” Estofolete said.