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Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2020.tde-08022021-143715
Document
Author
Full name
Mayara Rovariz Agostinho
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2020
Supervisor
Committee
Fonseca, Benedito Antonio Lopes da (President)
Boulos, Marcos
Lima, Danielle Malta
Title in Portuguese
Investigação de parâmetros virológicos e imunológicos no desenvolvimento de doença neonatal resultante da infecção pelo vírus Zika na gestação
Keywords in Portuguese
Citocinas
Gestantes
Microcefalia
Síndrome congênita pelo vírus Zika
Zika vírus
Abstract in Portuguese
O surto causado pelo vírus Zika (ZIKV) no Brasil gerou um estado de alerta no período de 2015 e 2016 pela associação ao crescente número de casos de microcefalia em neonatos e Síndrome de Guillain-Barré em adultos. O objetivo deste estudo foi investigar parâmetros virológicos e imunológicos de gestantes infectadas pelo ZIKV para compreender a associação desta infecção com o desenvolvimento de doença neonatal. Foi estabelecido uma coorte de gestantes admitidas no pré-natal da rede básica de saúde de Ribeirão Preto. Amostras de sangue foram coletadas a cada consulta e analisadas quanto a positividade ao ZIKV e quanto à concentração de citocinas pró e anti-inflamatórias. A caracterização do desfecho gestacional foi feito pelo acesso aos sistemas de informação de saúde CeVeSP e Hygia WEB. Analisou-se amostras de 312 pacientes e 252 demonstram positividade ao ZIKV. 42 gestantes infectadas apresentaram desfecho negativo, exibindo em maior proporção a evolução para aborto (61,9%), seguido de malformação fetal (23,8%), óbito neonatal (9,5%) e em menor proporção natimorto (4,8%). Notou-se infecção pelo ZIKV em gestantes com desfecho negativo em todos os períodos gestacionais, no entanto, mulheres que foram infectadas no primeiro trimestre obtiveram piores prognósticos sendo observada a evolução para aborto, óbito neonatal e natimorto. Gestantes infectadas pelo ZIKV apresentaram menores níveis de IL-13, IL-5 e IL-17A em relação as gestantes sem infecção que apresentaram neonatos saudáveis. Não se observou diferença nos níveis de mediadores imunológicos entre pacientes com diferentes desfechos gestacionais infectadas pelo ZIKV na fase aguda da doença. Entretanto, pacientes com ZIKV com desfecho gestacional negativo apresentaram maiores concentrações de TNF-α em relação as que exibiram neonatos saudáveis na fase de convalescença. Esses resultados indicam que o TNF-α está envolvido na forma mais grave de infecção do ZIKV, prejudicando na evolução gestacional e no desenvolvimento fetal.
Title in English
Immunological and virological parameters investigation in the development of neonatal disease resulted from Zika virus infection during the pregnancy
Keywords in English
Congenital Zika syndrome
Cytokines
Microcephaly
Pregnant women
Zika virus
Abstract in English
Zika virus (ZIKV) outbreak in Brazil was of great concern because it was related with a massive number of microcephaly cases in neonates and Guillain-Barré Syndrome in adults during the period of 2015 and 2016. The aim of this study was investigate immunological and virological parameters of ZIKV infected pregnant women to understand the association of this infection with the development of neonatal disease. A cohort of pregnant women admitted in the pre-natal appointments of Ribeirão Preto primary health care units was constructed. Blood samples were collected in every appointment and analyzed for ZIKV positivity and for pro and anti-inflammatory cytokines concentration. The access of health information system CeVeSP e Hygia WEB was necessary for the characterization of the gestational outcome. Samples of 312 patients were analyzed being 252 positive for ZIKV. Only 42 infected pregnant presented a negative gestational outcome, exhibiting a greater proportion of evolution to miscarriages (61,9%), followed by fetal malformation (23,8%), neonatal death (9,5%) and stillbirths (4,8%). ZIKV infection was observed in all gestational periods of patients that presented a negative gestational outcome, however, pregnant women infected in the first trimester had a worst gestational prognosis once it was observed the evolution to miscarriages, neonatal death and stillbirth. The quantification of cytokines identified lower concentrations of IL-13, IL-5 e IL-17A in ZIKV infected pregnant women than pregnant women without infection that exhibited healthy neonates. No differences were identified in the immunologic mediators levels between patients with different gestational outcomes during disease acute phase. However, ZIKV infected patients with negative gestational outcome expressed greater levels of TNF-α than infected patients that exhibited healthy newborns in the convalescence phase. These results indicate that TNF-α is involved in the severe forms of the ZIKV infection, impairing the gestation evolution and fetal growth.
 
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Publishing Date
2021-03-23
 
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