Maternal Th17 Profile after Zika Virus Infection Is Involved in Congenital Zika Syndrome Development in Children.

Brazil is one of the countries that experienced an epidemic of microcephaly and other congenital manifestations related to maternal Zika virus infection which can result in Congenital Zika Syndrome (CZS). Since the Zika virus can modulate the immune system, studying mothers' and children's immune profiles become essential to better understanding CZS development. Therefore, we investigated the lymphocyte population profile of children who developed CZS and their mothers' immune response in this study. The study groups were formed from the Plaque Reduction Neutralization Test (PRNT) (CZS+ group) result. To evaluate the lymphocyte population profile, we performed phenotyping of peripheral lymphocytes and quantification of serum cytokine levels. The immunophenotyping and cytokine profile was correlated between CSZ+ children and their mothers. Both groups exhibited increased interleukin-17 levels and a reduction in the subpopulation of CD4+ T lymphocytes. In contrast, the maternal group showed a reduction in the population of B lymphocytes. Thus, the development of CZS is related to the presence of an inflammatory immune profile in children and their mothers characterized by Th17 activation.

Maternal Immune Response to ZIKV Triggers High-Inflammatory Profile in Congenital Zika Syndrome.

The immunological mechanisms involved in the development of congenital Zika syndrome (CZS) have yet to be fully clarified. This study aims to assess the immuno-inflammatory profile of mothers and their children who have been diagnosed with CZS. Blood samples, which were confirmed clinically using the plaque reduction neutralization test (PRNT), were collected from children with CZS and their mothers (CZS+ group). Samples were also collected from children who did not develop CZS and had a negative PRNT result and from their mothers (CZS- group). The data demonstrated a correlation between the leukocyte profile of CZS+ children and their mothers, more evident in monocytes. Monocytes from mothers of CZS+ children showed low expression of HLA and elevated hydrogen peroxide production. CZS+ children presented standard HLA expression and a higher hydrogen peroxide concentration than CZS- children. Monocyte superoxide dismutase activity remained functional. Moreover, when assessing the monocyte polarization, it was observed that there was no difference in nitrite concentrations; however, there was a decrease in arginase activity in CZS+ children. These data suggest that ZIKV infection induces a maternal immuno-inflammatory background related to the child's inflammatory response after birth, possibly affecting the development and progression of congenital Zika syndrome.

Plaque Reduction Neutralization Test (PRNT) in the Congenital Zika Syndrome: Positivity and Associations with Laboratory, Clinical, and Imaging Characteristics.

The short duration of viremia, low blood viral load, inaccessibility to timely specific diagnostic tests, and cross-reactions with other flaviviruses have hindered laboratory confirmation of Congenital Zika Syndrome (CZS). This study analyzes the positivity of the plaque reduction neutralization test (PRNT) in children with clinical or imaging characteristics of CZS and its association with laboratory, clinical, and imaging characteristics. The 94 clinical cases of CZS submitted to the ZIKV PRNT90 test were followed from 2016 to 2018. The mean age of children at PRNT90 collection was 22 ± 6 months Standard Deviation. The ZIKV PRNT90 was positive (titer ≥ 10) in 40 (42.5%) children. ZIKV PRNT90 positivity was associated with severe microcephaly in newborns (p = 0.016), lower head circumference z-score at birth (p = 0.043) and 24 months of age (p = 0.031), and severe reduction of the cerebral parenchyma volume (p = 0.021), expressing greater disease severity. Negative PRNT90 in children with characteristic signs of CZS may be due to false-negative results, indicating that the diagnosis of CZS should be primarily syndromic.