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Seroprevalence of Zika (ZIKV) and Dengue (DENV) virus infection in parturients and transplacental transfer of anti-ZIKV and anti-DENV antibodies in newborns in Southeast, Brazil

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Author(s):
Rafael Rahal Guaragna Machado
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Edison Luiz Durigon; Celso Francisco Hernandes Granato; Enrique Mario Boccardo Pierulivo; Marcos Vinicius da Silva
Advisor: Edison Luiz Durigon
Abstract

Zika (ZIKV) and Dengue (DENV) viruses are arboviruses circulating in Brazil, which are of great importance for national public health. The ability to estimate the current and future spread of these viruses depends significantly on our knowledge of the serological status in exposed populations. Currently, there is few data in the literature regarding the prevalence of anti-ZIKV and anti-DENV antibodies in the general population and particularly in Brazilian pregnant women. The transplacental transfer of antibodies against infectious pathogens is an important maternal-fetal mechanism that provides protection to the newborns (NB) in the first months of life. In this context, the present study investigated the prevalence of ZIKV and DENV infection in pregnant women, evaluating the transplacental transfer of anti-ZIKV and anti-DENV antibodies to NB. Thus, a cross-sectional study was carried out with 601 pregnant women and their newborn children, attended at the University Hospital of the University of São Paulo (HU-USP), located in the city of São Paulo, Brazil. Whole blood, serum and urine samples were collected and stored in a biorepository. Sociodemographic information and maternal and neonatal clinical characteristics were obtained through interviews and analysis of medical records. To assess the seroprevalence of ZIKV and DENV infection, enzyme-linked immunosorbent assays (ELISA) were used to detect IgM and IgG antibodies and viral neutralization tests based on cytopathic effect (CPE-VNT) and plaque reduction neutralization (PRNT), for detection of neutralizing antibodies (nAbs). In addition to the serological investigation, the total nucleic acids of the biological samples were extracted by a semi-automated method, followed by RT-qPCR for an endogenous gene (RNase P) and for investigation of the presence of viral RNA of ZIKV and DENV. There was a seroprevalence of 2.39% and 31.61% of specific neutralizing antibodies against ZIKV and DENV, respectively. Most pregnant women had immunity to the four DENV serotypes (74.1%). Among the samples with detectable nAbs, no sample was positive for anti-ZIKV IgM and in 4.2% anti-DENV IgM antibodies were detected. All tested samples had satisfactory amplification for RNase P and were negative for the presence of viral RNA of the investigated viruses. Furthermore, it was possible to determine the effective transplacental transfer (TR) of specific anti-ZIKV and serotype-specific anti-DENV antibodies from previously infected mothers to the newborns. ZIKV and specific DENV IgG levels were significantly higher in the umbilical cord samples than in the respective maternal samples. Maternal and neonatal characteristics were correlated both with seropositivity for ZIKV and DENV and with the effectiveness of transferring specific DENV antibodies to newborns. Due to the relatively low seroprevalence of ZIKV and DENV in the study population, this scenario alerts to the susceptibility to infection by these pathogens. Thus, with the knowledge generated in the present study, it is expected to contribute to a better understanding of the seroprevalence of ZIKV and DENV in parturients in the region under study and the TR profile of newborns, serving as a reference for evaluating the effectiveness of transplacental transport of antibodies resulting from future vaccination schedules against ZIKV and DENV in pregnant women in Brazil. (AU)

FAPESP's process: 17/24769-2 - Zika virus in postpartum women and newborns: seroepidemiology and molecular characterization
Grantee:Rafael Rahal Guaragna Machado
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)