According to a study conducted by Brazilian experts, those who have contracted the Zika virus are more likely to get severe dengue and require hospitalization. The discovery has significant implications for the creation of a Zika vaccine.
The scientific literature states that a second infection by any of the four known dengue serotypes is usually more severe than the first, but up to this point, no studies had investigated the relationship between this fact and the prevalence of other diseases.
The research has been released in the PLOS Neglected Tropical Diseases publication.
The authors conclude that the mechanism that makes dengue illness worse after a Zika case is different from that of two consecutive dengue infections. In contrast to Zika, the second dengue episode has a larger viral load and higher levels of inflammatory cytokines.
Other indicators pointed to the possibility that the pathogenic immune response known as the “original antigenic sin,” which activates T cells—important immune system components that aid in the production of antibodies—may be the cause of the severity rise.
T-cell memory, a response in which T cells generated during an earlier infection promotes the generation of more T cells to combat a new infection, is involved in the process. Since these newly formed cells are not virus-specific, they cause an overabundance of inflammatory cytokines to be released, attacking the organism’s tissues and proteins and perhaps causing bleeding.
To decide whether patients had previously contracted dengue and Zika, the researchers examined samples from 1,043 laboratory-confirmed dengue patients. The instances happened in São José do Rio Preto, a big city in the Brazilian state of São Paulo, which is known to be hyperendemic for dengue because over 70% of the population has the illness.
Due to its location and environment, arboviruses can spread year-round. There were dengue epidemics in 2010, 2013, 2015, 2016, and 2019, with serotype 2 accounting for a record number of infections.
Because the patients were likely to have their third or fourth infection, we concluded that a prior dengue infection was not a risk factor for severity. Nonetheless, a prior Zika infection played a significant role and worsened a later dengue outbreak. The article’s first author, Cássia Fernanda Estofolete, an infectious disease specialist at the São José does Rio Preto Medical School (FAMERP), told Agência FAPESP, “This led us to suggest novel mechanisms and renew our knowledge of the natural history of the disease.”
“Our results supported those of an earlier study involving Zika-affected children in Nicaragua. Afterwards, the likelihood of severity rose when they contracted dengue. For adults in Brazil, we found the same phenomenon (risk of severe dengue increased by preceding Zika or dengue).
According to corresponding author Maurício Lacerda Nogueira, “We also demonstrated 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.”
This begs the question of what kind of Zika vaccine to use and when to provide it. For example, should it be given in conjunction with a dengue vaccine to prevent the issue of one vaccination spreading to another? To ensure proper prescription, it is important to understand the many alternatives. Given the number of cases in Brazil, it’s still more crucial to administer the dengue vaccination initially, Nogueira continued.
Journal Reference
Cassia F. Estofolete et al, Influence of previous Zika virus infection on acute dengue episode, PLOS Neglected Tropical Diseases (2023). DOI: 10.1371/journal.pntd.0011710.
