Climate change is raising temperatures around the world, and mosquitoes are on the move. As their territories expand, these pests are brining diseases like dengue with them, and cases of the viral illness are on the rise in many places. There are also newly emerging viruses to contend with, like the pandemic virus SARS-CoV-2 or the less pervasive but still threatening Zika virus, which has caused major outbreaks in several countries and is still considered a threat to public heath.
New research has highlighted the danger that can be posed when viruses occur in combination. Reporting in PLOS Neglected Tropical Diseases, scientists have shown that when people have already experienced a Zika infection, they have a higher likelihood of being hospitalized or having a severe case of dengue. These findings could also be important to the creation of a vaccine for Zika virus.
Infections with dengue virus can cause a strange phenomenon called antibody dependent enhancement, in which antibodies that are produced following infection can actually promote additional infections instead of preventing them. When a person experiences a second dengue infection, there are also high levels of inflammatory cytokines. The connection between Zika and dengue is not the same, however, according to this study, and high cytokine levels are not seen.
Instead, the link between Zika and more severe dengue cases could be connected to T cells, and an immunological process that has been called the "original antigenic sin." When this happens, T cells that have already been generated due to a previous infection trigger the production of novel T cells for a new infection. However, these T cells are not specific to the virus. Instead, this leads to the overproduction of cytokines, and inflammation that can damage tissue.
In this study, the investigators assessed samples from 1,043 patients with confirmed dengue cases that happened in 2019 around São Paulo, Brazil. Previous cases of dengue were not found to be increasing the likelihood of severe dengue cases, and in many cases, patients were experiencing their third or fourth bout of dengue infection.
But patients who had previously been infected with Zika were at 2.34 times higher risk of severe dengue and 3.39 times more likely to be hospitalized compared to people who had not been infected with dengue before. Previous Zika infections were significantly increasing the risk of severe dengue for these individuals.
"This led us to suggest novel mechanisms and renew our knowledge of the natural history of the disease," said first study author Cássia Fernanda Estofolete, an infectious disease specialist at the São José do Rio Preto Medical School (FAMERP).
Because dengue is such a widespread disease in Brazil, clinicians are encouraging patients to be vaccinated for dengue prior to receiving any Zika vaccine. However, Zika vaccines are still in development.
Dengue infections can lead to severe muscle and joint pain, headache, and nausea. In some cases, it can be fatal. Zika symptoms can be milder, but the virus is a serious threat to fetuses, who can get microcephaly from exposure to the virus. Preventing both diseases is still possible, if people can avoid being bitten by Aedes aegypti mosquitoes, which transmit both dengue and Zika.
This study confirms similar findings that were reported in Science in 2020.
Sources: FAPESP, PLOS Neglected Tropical Diseases
