New study refutes suspicions that dengue fever increases risk of zika-related microcephaly

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A pregnant woman infected with the zika virus is not at greater risk of giving birth to a baby with microcephaly if she has been previously exposed to the dengue virus, according to a Brazilian study comparing data from pregnant women in Rio de Janeiro and in Manaus.

A zika epidemic broke out in Brazil in 2015-16 in areas where dengue is endemic. Both viruses are transmitted by mosquitoes Aedes aegypti. Some of the states affected by the zika outbreak have reported an increase in cases of microcephaly, a rare neurological disorder in which a baby’s brain fails to fully develop. Others have not seen such an increase.

According to this new study by Brazilian researchers, two factors explain the increase in microcephaly in only certain areas: the high rate of attack of zika, and the fact that the mother contracted the virus during the first trimester of the 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 was carried out under the aegis of the Zika Virus Research Network in São Paulo (Rede Zika). The results are described in an article by Virus, a peer-reviewed open access journal published by the Multidisciplinary Digital Publishing Institute (MDPI). The article appeared at the end of April in a special issue on zika and pregnancy.

“The differences between regions in terms of the number of reported cases of microcephaly during the zika epidemic were puzzling. One of the hypotheses was that previous exposure to dengue might make zika worse, but in São Paulo state there wasn’t much. adverse effects of zika even though the region is highly endemic for dengue, so we decided to try to find out what could explain the differences, ”said virologist Maurício Lacerda Nogueira, professor at the Faculty of Medicine of São José do Rio Preto (FAMERP) in São Paulo, and co-principal investigator of the study alongside Patrícia Brasil, researcher at the Oswaldo Cruz Foundation (FIOCRUZ) in Rio de Janeiro.

According to Nogueira, their attention was drawn to the attack rate when they analyzed the data for the two state capitals. In Rio de Janeiro, where many cases of microcephaly have been reported, the number of people infected with the zika virus was 10 per 10,000 population, while in Manaus, where relatively few babies were born with microcephaly, the attack rate was 0.6 per 10,000.

Microcephaly caused by zika is a rare occurrence, but when there are many cases of zika in an area, it becomes more noticeable. It had been suggested earlier that getting zika in the first trimester of pregnancy might be relevant, and now we’ve proven it to be. “

Mauricio Lacerda Nogueira, virologist

Methodology

Researchers set out to understand the differences in adverse pregnancy outcomes and in babies from the two populations by studying 114 pregnant women infected with the zika virus between September 2015 and June 2016. The infection was confirmed by RT- tests. qPCR of blood and / or urine samples. Subjects were recruited from the Heitor Vieira Dourado Tropical Medicine Foundation (FMT-HVD), a hospital specializing in infectious diseases in Manaus, and the FIOCRUZ Acute Febrile Disease Clinic in Rio de Janeiro.

Previous exposure to dengue was assessed by serological tests to detect, among other things, neutralizing antibodies. The aim was to explore potential 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.

Overall, 31 women had unfavorable results (27 in Rio and 4 in Manaus). In this group, four babies died before birth and 27 were born with brain abnormalities. “Only Zika virus attack rates and infection during the first trimester of pregnancy have been associated with adverse pregnancy and infant outcomes. status of the article in the summary.

And they conclude: “The strengths of our study include careful classification of infant outcomes, made possible through detailed birth assessments by a multidisciplinary team. […] In addition, the use of a highly sensitive and specific product [plaque reduction neutralizing antibody] The assay to characterize pre-existing immunity to dengue fever and the use of sera collected during the acute phase of zika infection confirmed by RT-PCR lend credibility to our results. […] Our main limitations are the modest sample size and convenience sample selection. “

An earlier study conducted by Nogueira in 2017 showed that patients infected with zika after exposure to dengue did not get more seriously ill than others. This is the first scientific study to show it in humans. Previous research involving cells and rodents had suggested otherwise (more on: revistapesquisa.fapesp.br/en/dengue-may-attenuate-zika).

Background

Microcephaly is a rare neurological disease in which an infant’s head and brain are significantly smaller than normal due to alterations 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.

The causes of microcephaly include genetic factors and exposure to chemicals, bacteria, and viruses. Scientists have recently shown that zika acquired during pregnancy can adversely affect the development of the fetus.

During the epidemic in Brazil, zika affected people of all ages and was associated with the occurrence of a large number of cases of microcephaly. In November 2015, Brazil declared a public health emergency due to the growing number of cases. The World Health Organization (WHO) then issued an epidemiological alert, highlighting the possibility of congenital neurological malformations in babies born to women infected with zika.

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

In 2016, there were some 214,000 probable cases of zika. That 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 epidemiological bulletin of the Ministry of Health.

The symptoms of zika are similar to those of dengue. In most people who are infected, it causes fever, headache, red eyes, joint pain, and rash. On average, the symptoms disappear in ten days.

Researchers are continuing their analysis of the interactions between zika and dengue fever, in particular to see whether zika modulates infection with the dengue virus. Nogueira is also participating in an international group that is working on models to predict epidemics of zika, dengue and yellow fever (more on: agencia.fapesp.br/35240/).

The article “Why do the perinatal results of ZIKV differ in different regions of Brazil?” A two-cohort exploratory study ”can be found at: www.mdpi.com/1999-4915/13/5/736/htm.

Source:

Fundação de Amparo in Pesquisa do Estado de São Paulo

Journal reference:

Damasceno, L., et al. (2021) Why were the perinatal results of ZIKV different in some areas of Brazil? An exploratory study of two cohorts. Virus. doi.org/10.3390/v13050736.


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