RESUMO
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-1ß, 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-1ß, 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.
Assuntos
Biomarcadores/líquido cefalorraquidiano , Mediadores da Inflamação/líquido cefalorraquidiano , Microcefalia/patologia , Complicações Infecciosas na Gravidez/patologia , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Microcefalia/líquido cefalorraquidiano , Microcefalia/epidemiologia , Microcefalia/etiologia , Gravidez , Complicações Infecciosas na Gravidez/líquido cefalorraquidiano , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/etiologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Infecção por Zika virus/virologiaRESUMO
OBJECTIVE: To evaluate the utility of quantitative herpes simplex virus (HSV) polymerase chain reaction (PCR) levels for prognosis and management of neonatal HSV disease. STUDY DESIGN: Clinical and virologic data were abstracted by medical record review from neonatal HSV cases treated at Seattle Children's Hospital between 1993 and 2012. HSV PCR results from plasma (n = 47), cerebrospinal fluid (n = 56), or both (n = 40) at the time of diagnosis were available from 63 infants; 26 with skin-eye-mouth (SEM), 18 with central nervous system (CNS), and 19 with disseminated (DIS) disease. RESULTS: Plasma HSV PCR was positive in 78% of the infants with SEM, 64% with CNS and 100% with DIS disease. Mean plasma viral level was 2.8 log10 copies/mL in SEM, 2.2 log10 copies/mL in CNS, and 7.2 log10 copies/mL in DIS infants. The HSV levels were higher among infants who died compared with surviving infants, 8.1 log10 copies/mL (range 7.7-8.6) vs 3.8 log10 copies/mL (range 0.0-8.6), P = .001, however, level of HSV DNA in the cerebrospinal fluid or in plasma did not correlate with neurologic outcome. Dynamics of HSV clearance from plasma during high-dose acyclovir treatment showed single-phase exponential decay with a median viral half-life of 1.26 days (range: 0.8-1.51). CONCLUSIONS: Plasma HSV levels correlate with clinical presentation of neonatal HSV disease and mortality, but not neurologic outcome.