1. Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid.
- Author
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Nascimento-Carvalho GC, Nascimento-Carvalho EC, Ramos CL, Vilas-Boas AL, Moreno-Carvalho OA, Vinhaes CL, Barreto-Duarte B, Queiroz ATL, Andrade BB, and Nascimento-Carvalho CM
- Subjects
- Brazil epidemiology, Case-Control Studies, Female, Follow-Up Studies, Humans, Infant, Newborn, Male, Microcephaly cerebrospinal fluid, Microcephaly epidemiology, Microcephaly etiology, Pregnancy, Pregnancy Complications, Infectious cerebrospinal fluid, Pregnancy Complications, Infectious epidemiology, Pregnancy Complications, Infectious etiology, Prognosis, Prospective Studies, Retrospective Studies, Zika Virus Infection virology, Biomarkers cerebrospinal fluid, Inflammation Mediators cerebrospinal fluid, Microcephaly pathology, Pregnancy Complications, Infectious pathology, Zika Virus isolation & purification, Zika Virus Infection complications
- Abstract
Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same laboratory, we identified 14 ZIKV-exposed neonates during the ZIKV epidemic (2015-2016), 7(50%) with and 7(50%) without microcephaly, without any other congenital infection, and 14 neonates (2017-2018) eligible to be controls and to match cases. 29 inflammation mediators were measured using Luminex immunoassay and multidimensional analyses were employed. Neonates with ZIKV-associated microcephaly presented substantially higher degree of inflammatory perturbation, associated with uncoupled inflammatory response and decreased correlations between concentrations of inflammatory biomarkers. The groups of microcephalic and non-microcephalic ZIKV-exposed neonates were distinguished from the control group (area under curve [AUC] = 1; P < 0.0001). Between controls and those non-microcephalic exposed to ZIKV, IL-1β, IL-3, IL-4, IL-7 and EOTAXIN were the top CSF markers. By comparing the microcephalic cases with controls, the top discriminant scores were for IL-1β, IL-3, EOTAXIN and IL-12p70. The degree of inflammatory imbalance may be associated with microcephaly in CZI and it may aid additional investigations in experimental pre-clinical models testing immune modulators in preventing extensive damage of the Central Nervous System.
- Published
- 2021
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