Fatal encephalitis associated with Zika virus infection in an adult

Soares, Cristiane; Brasil, Patrícia; Medialdea-Carrera, Raquel; Sequeira, Patrícia Carvalho de; Filippis, Ana Bispo de; Borges, Vitor A.; Theophilo, Fernando; Ellul, Mark; Solomon, Tom

doi:10.1016/j.jcv.2016.08.297

Cited by 108 publications

(92 citation statements)

References 13 publications

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“…It is formally possible that some portion of the ZIKV RNA positive neutrophils represent the phagocytosis of infected material or cells, although evidence from other flaviviruses seems to contradict this notion 33 . The demonstration of rapid and high-level ZIKV infection of cerebellar neurons is concerning, and might help to explain the neurologic outcomes associated with ZIKV infection observed in adults and early gestational neonates 34–36 . These findings might also warrant enhanced clinical vigilance in Zika-endemic areas for adults who present with neurologic symptoms 37,38 .…”

Section: Discussionmentioning

confidence: 99%

Zika viral dynamics and shedding in rhesus and cynomolgus macaques

Osuna

Lim

Deléage

et al. 2016

Nat Med

276

335

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Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection was cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans.

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Section: Discussionmentioning

confidence: 99%

Zika viral dynamics and shedding in rhesus and cynomolgus macaques

Osuna

Lim

Deléage

et al. 2016

Nat Med

276

335

View full text Add to dashboard Cite

show abstract

“…The rapid spread of ZIKV within the Americas has unveiled microcephaly 1 and Guillain-Barré syndrome 2,3 as ZIKV-associated neurological complications. Recent reports have further indicated other neurological manifestations to be associated with ZIKV including myelitis 4 , meningoencephalitis 5 and fatal encephalitis 6 . Here, we investigate the neuropathogenesis of ZIKV infection in IFNAR knockout ( Ifnar1 −/− ) mice, an infection model that exhibits high viral burden within the central nervous system (CNS).…”

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confidence: 99%

Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice

et al. 2017

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Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly1 and Guillain-Barré syndrome 2,3 as ZIKV-associated neurological complications. Recent reports have further indicated other neurological manifestations to be associated with ZIKV including myelitis 4, meningoencephalitis 5 and fatal encephalitis6. Here, we investigate the neuropathogenesis of ZIKV infection in IFNAR knockout (Ifnar1−/−) mice, an infection model that exhibits high viral burden within the central nervous system (CNS). We show that systemic spread of ZIKV from the site of infection to the brain requires Ifnar1-deficiency in the hematopoietic compartment. However, spread of ZIKV within the CNS is supported by Ifnar1-deficient non-hematopoietic cells. Within this context, ZIKV infection of astrocytes results in breakdown of the blood-brain barrier and a large influx of CD8+ effector T cells. Further, we find antiviral activity of CD8+ T cells within the brain markedly limits ZIKV infection of neurons, but as a consequence instigates ZIKV-associated paralysis. Taken together, our study uncovers mechanisms underlying ZIKV-neuropathogenesis within a susceptible mouse model and suggests BBB breakdown and T cell mediated neuropathology as potential underpinnings of ZIKV-associated neurological complications in humans.

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“…Amidst the current outbreak in the Americas, ZIKV has been associated with severe neurological manifestations in adults, including Guillain–Barré syndrome (GBS; Cao-Lormeau et al, 2016; Dirlikov et al, 2016; do Rosario et al, 2016; Dos Santos et al, 2016), acute myelitis (Mecharles et al, 2016), and encephalitis (Carteaux et al, 2016; Soares et al, 2016). GBS has been the best studied neurological presentation in adults, and the association between recent ZIKV infection and GBS has been principally demonstrated in studies that have relied on serologic testing for ZIKV diagnosis (Cao-Lormeau et al, 2016; Dos Santos et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Zika Virus, Chikungunya Virus, and Dengue Virus in Cerebrospinal Fluid from Adults with Neurological Manifestations, Guayaquil, Ecuador

et al. 2017

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Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) have been associated with clinical presentations that involve acute neurological complaints. In the current study, we identified ZIKV, CHIKV, and DENV in cerebrospinal fluid (CSF) samples from patients admitted to the Hospital Luis Vernaza (Guayaquil, Ecuador) to the Emergency Room or the Intensive Care Unit, with neurological symptoms and/or concern for acute arboviral infections. Viral RNA from one or more virus was detected in 12/16 patients. Six patients were diagnosed with meningitis or encephalitis, three with Guillain–Barré Syndrome, and one with CNS vasculitis. Two additional patients had a systemic febrile illness including headache that prompted testing of CSF. Two patients, who were diagnosed with encephalitis and meningoencephalitis, died during their hospitalizations. These cases demonstrate the breadth and significance of neurological manifestations associated with ZIKV, CHIKV, and DENV infections.

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Fatal encephalitis associated with Zika virus infection in an adult

Abstract: In endemic areas, ZIKV should be considered as an aetiological agent in cases of encephalitis, and clinicians should be aware of its potential severity.

Cited by 108 publications

References 13 publications

Zika viral dynamics and shedding in rhesus and cynomolgus macaques

Zika viral dynamics and shedding in rhesus and cynomolgus macaques

Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice

Zika Virus, Chikungunya Virus, and Dengue Virus in Cerebrospinal Fluid from Adults with Neurological Manifestations, Guayaquil, Ecuador

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