Previous Zika infection increases the risk of severe dengue – 11/30/2023 – Health

Research led by Brazilians shows that previous Zika infection increases the risk of serious cases and hospitalization due to dengue fever subsequently contracted. The finding is an important piece for studies looking for a vaccine against Zika.

The scientific literature highlights that the second infection with any dengue serotype (there are currently four known) is predominantly more serious than the first, without being correlated with the other disease.

Published in PLOS Neglected Tropical Diseases, the new work, however, signals that the mechanism that exacerbates dengue infection after Zika is different. In cases of a second episode of dengue, there is an increase in viral load, with high concentrations of inflammatory cytokines, which did not occur with Zika.

Scientists detected other markers, suggesting that the increase in severity is due to the activation of T cells (whose function is to help produce antibodies). This is the so-called “original antigenic sin”, that is, when T cells produced during a previous infection stimulate the production of more lymphocytes when a new infection occurs. As they are not specific to destroy the virus, they end up inducing an uncontrolled production of inflammatory cytokines that attack proteins and cause damage to the body’s tissues and even hemorrhages.

The study analyzed samples from 1,043 patients with dengue, with laboratory confirmation, in 2019 in the city of São José do Rio Preto (in the interior of São Paulo). Previous Zika and dengue infections were investigated.

The municipality is considered a hyperendemic region, with geoclimatic characteristics that favor the circulation of arboviruses (which cause both diseases) throughout the year. The largest epidemics reported in the city occurred in 2010, 2013, 2015, 2016 and 2019, when there was a record number of cases with the recirculation of dengue serotype 2.

“We saw that a previous case of dengue, in this study, was not a risk factor for worsening because we believe that the patients were already on their third or even fourth infection. Previous Zika infection was an important and aggravating factor for a second episode of dengue. With this, we suggest new mechanisms and renew knowledge of the natural history of the disease”, infectologist Cássia Fernanda Estofolete, from the Faculty of Medicine of São José do Rio Preto (Famerp) and first author of the article, told Agência Fapesp. .

The work received support from Fapesp through research assistance to Estofolete, a Post-Doctoral Scholarship to Alice Freitas Versiani and a Thematic Project granted to Famerp professor Maurício Lacerda Nogueira, corresponding author of the article.

“Our results confirm those obtained in a previous study, carried out with children who had Zika in Nicaragua. Then, when they had dengue, the risk increased for severe cases. We showed that this also occurs in adults in Brazil. And the second finding is that the ADE [sigla em inglês para antibody-dependent enhancement ou amplificação dependente de anticorpos] It’s not classic. This raises questions about the type of Zika vaccine that should be used and when is the best time. Would it be applied together with the dengue vaccine so as not to create a situation of one after the other, for example? These are possibilities to understand how to prescribe them. But, in Brazil, it is still more important to vaccinate first for dengue due to the number of cases”, explains Nogueira.

The ADE that the professor refers to happens when antibodies produced by a previous infection, instead of completely neutralizing a virus in the subsequent infection, end up facilitating their entry into the body’s cells, worsening the infection.

Notifications

Brazil has already surpassed the number of dengue cases in 2022 this year, with 1.372 million notifications, of which 1 million were confirmed between January and July (latest bulletin available). São Paulo and Minas Gerais are the most affected states, according to the Ministry of Health.

In relation to Zika, there are 4,773 probable cases this year in the country, of which 1,725 ​​are confirmed, with Bahia and Rio Grande do Norte with the highest number of records. Epidemiologists point out that, in general, there are underreporting of arbovirus cases, either due to the difficulty of detecting them or because the symptoms can be mild and people do not even seek health services.

In 2016, when the world experienced outbreaks of the disease, Brazil had more than 1.5 million of the 2.38 million confirmations in the Americas. In 2019, South America recorded a dengue epidemic with more than 3.13 million reported cases and four years after the emergence of the Zika virus (ZIKV, of the Flavivirus genus) on the continent.

In March this year, the National Health Surveillance Agency (Anvisa) approved a vaccine against dengue from a Japanese manufacturer, which is currently available in the private health network. The Butantan Institute is also developing an immunizer. For Zika, there are studies, however, at earlier stages.

In addition to being transmitted by the same mosquito (Aedes aegypti), the two diseases present similar symptoms, often making diagnosis difficult. Dengue is more serious because, in addition to causing fever, body aches and headaches, spots on the skin and feeling unwell, it can cause bleeding and lead to death.

Zika, on the other hand, causes milder symptoms, however, it causes serious problems in pregnant women and their babies, such as microcephaly, and may also be related to a neurological syndrome that causes paralysis, Guillain-Barré syndrome.

Experts have highlighted that higher temperatures resulting from climate change are causing diseases transmitted by Aedes spread even to colder regions. Furthermore, deforestation contributes to worsening the situation, as forests rich in biodiversity tend to inhibit the transmitting mosquito with a greater number of predators of the species. Method

Samples from patients with confirmed infection were evaluated for dengue and Zika virus history using an immunoenzymatic assay (Elisa type) developed in partnership with researcher Lee Gehrke, from the Massachusetts Institute of Technology (United States). The assay was specifically designed to eliminate the cross-reactivity between Flaviviruses observed in commercial kits available on the market.

Analyzes showed that patients with a history of Zika infection had a 2.34 times higher risk of developing severe forms of dengue and a 3.39 times higher risk of hospitalization compared to controls (individuals without a history of dengue or Zika). Furthermore, patients over the age of 59 were also at greater risk.

Having studied the topic for years, the group coordinated by Professor Nogueira published a study in 2021 showing that previous dengue infection does not increase the risk of a pregnant woman infected with Zika giving birth to a baby with microcephaly.

Now, Estofolete has started a new stage of research, expanding the samples to cases from 2022, with a different serotype.

“The idea is not only to answer about the severity, but to know if this detected mechanism is the same for all dengue serotypes because this has other influences, even in relational mechanisms. We have little accumulated knowledge in relation to the Zika vaccine”, he states the infectious disease specialist.

The article Influence of previous Zika virus infection on acute dengue episode can be read here.