New study refutes the suspicion that dengue increases the risk of Zika-related microcephaly

Publicado em 21 julho 2021

A pregnant woman infected with Zika virus is no greater risk of giving birth to a baby with microcephaly if she was previously exposed to dengue virus, according to a Brazilian study that compared data for pregnant women in Rio de Janeiro and Manaus .

In 2015/16, a Zika epidemic broke out in Brazil in areas where dengue is endemic. Both viruses are transmitted by the mosquito Aedes aegypti. Some of the states hit by the Zika epidemic reported an increase in cases of microcephaly, a rare neurological condition in which the baby?

7;s brain does not develop fully. Others did not see such a surge.

According to this new study by Brazilian researchers, two factors explain the rise in microcephaly in only a few areas: the high rate of Zika attack and the mother’s infection with the virus in the first trimester of pregnancy. The term attack rate in epidemiology refers to the number of cases divided by the total population.

The study was supported by FAPESP through two projects (16 / 15021-1 and 13 / 21719-3) and carried out under the auspices of the Network for Research on the Zika Virus in São Paulo (Rede Zika). The results are in an article in. described Viruses, a peer-reviewed open access journal published by the Multidisciplinary Digital Publishing Institute (MDPI). The article appeared in a special issue on Zika and pregnancy at the end of April.

“The discrepancies between regions in the number of reported cases of microcephaly during the Zika epidemic were puzzling. One of the hypotheses was that previous dengue exposure might make Zika more severe, but there weren’t many side effects from Zika in São Paulo state, although dengue fever is highly endemic to the area, so we decided to find out what could explain the differences, “said the virologist Maurício Lacerda Nogueira, professor at the São José do Rio Preto Medical School (FAMERP) in São Paulo and together with Patrícia Brasil, a researcher at the Oswaldo Cruz Foundation (FIOCRUZ) in Rio de Janeiro, Co – Study director of the study.

When analyzing the data for the two state capitals, they became aware of the attack rate, according to Nogueira. In Rio de Janeiro, where many cases of microcephaly have been reported, the number of people infected with Zika virus was 10 per 10,000 people, while in Manaus, where relatively few babies were born with microcephaly, the rate of infection was 0.6 per 10,000 .

Microcephaly caused by Zika is a rare phenomenon, but when there are many cases of Zika in an area it becomes more noticeable. It was previously suggested that Zika infection might be relevant in the first trimester of pregnancy and now we have proven that it is. “

Maurício Lacerda Nogueira, virologist


Researchers tried to understand the differences in the negative outcomes of pregnancy and babies in the two populations by studying 114 pregnant women who were infected with Zika virus between September 2015 and June 2016. The infection was determined by RT-qPCR testing of blood and / or urine samples. The subjects were recruited by the Heitor Vieira Dourado Tropical Medicine Foundation (FMT-HVD), a hospital for infectious diseases in Manaus and the FIOCRUZ clinic for acute febrile diseases in Rio de Janeiro.

Previous exposure to dengue was assessed using serological tests to detect neutralizing antibodies, among other things. The aim was to investigate possible associations between pregnancy outcomes and the Zika attack rate, defined as the number of officially reported cases during the study period divided by the population of each city.

A total of 31 women had adverse outcomes (27 in Rio and 4 in Manaus). In this group, four babies died before birth and 27 were born with brain abnormalities. “Only Zika attack rates and infections in the first trimester of pregnancy were associated with adverse pregnancy and infant outcomes. Pre-existing immunity to dengue was not associated with outcomes (normal or abnormal) in patients with Zika during pregnancy,” according to the authors of the article status in the abstract.

And they conclude: “One of the strengths of our study is a careful classification of infant outcomes made possible by detailed assessments at birth by a multidisciplinary team. […] In addition, the use of a highly sensitive and specific[[[[Plaque reduction of neutralizing antibodies]Assay to characterize pre-existing dengue immunity and the use of sera collected during the acute phase of RT-PCR-confirmed Zika infection give credibility to our results. […] Our main limitations are the modest sample size and the convenience of sample selection. “

An earlier study led by Nogueira in 2017 showed that patients who became infected with Zika after dengue exposure did not get more seriously ill than other people. It was the first scientific study to show this in humans. Previous research on cells and rodents had suggested the opposite (more at:


Microcephaly is a rare neurological condition in which an infant’s head and brain are significantly smaller than normal due to changes in the formation of the nervous system during development in the womb. Children with microcephaly usually suffer from delayed or blocked mental, physical, and motor development.

Causes of microcephaly include genetic factors and exposure to chemicals, bacteria, and viruses. Scientists recently showed that Zika can affect the development of the fetus during pregnancy.

During the epidemic in Brazil, Zika affected people of all ages and has been linked to the occurrence of a wide variety of cases of microcephaly. In November 2015, Brazil declared a health emergency due to the increasing number of cases. The World Health Organization (WHO) then issued an epidemiological warning, highlighting the possibility of congenital neurological malformations in babies born to Zika-infected women.

In 2015 alone, more than 2,400 cases of microcephaly were reported in Brazil. They occurred in approximately 540 parishes in 20 states. In 2010-14, the total number of reported cases was 781.

In 2016 there were around 214,000 likely Zika cases. The number fell to 17,000 in 2017 and 8,000 in 2018. In the first three months of this year it was 448, according to the Ministry of Health’s epidemiological bulletin.

The symptoms of Zika are similar to those of dengue. In most infected people, it causes a fever, headache, red eyes, joint pain, and a rash. On average, symptoms go away in ten days.

Researchers continue their analysis of the interactions between Zika and dengue, specifically to determine whether Zika modulates infection with the dengue virus. Nogueira also participates in an international group working on models to predict Zika, dengue and yellow fever epidemics (more at:

The article “Why did the perinatal results of the ZIKV differ in different regions of Brazil? An exploratory study with two cohorts” can be found at:


Foundation for Research Promotion of the State of São Paulo

Journal reference:

Damaszener, L., et al. (2021) Why do the perinatal results of the ZIKV differ in different regions of Brazil? An exploratory study of two cohorts. Viruses.