Zika Virus Infection and Associated Neurologic Disorders in Brazil.
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ABSTRACT:
SUBMITTER: de Oliveira WK
PROVIDER: S-EPMC5544116 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Zika Virus Infection and Associated Neurologic Disorders in Brazil.
de Oliveira Wanderson K WK Carmo Eduardo H EH Henriques Claudio M CM Coelho Giovanini G Vazquez Enrique E Cortez-Escalante Juan J Molina Joaquin J Aldighieri Sylvain S Espinal Marcos A MA Dye Christopher C
The New England journal of medicine 20170329 16
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Project description:BackgroundZika virus (ZIKV) is an emerging flavivirus of global concern. ZIKV infection of the central nervous system has been linked to a variety of clinical syndromes, including microcephaly in fetuses and rare but serious neurologic disease in adults. However, the potential for ZIKV to influence brain physiology and host behavior following apparently mild or subclinical infection is less well understood. Furthermore, though deficits in cognitive function are well-documented after recovery from neuroinvasive viral infection, the potential impact of ZIKV on other host behavioral domains has not been thoroughly explored.MethodsWe used transcriptomic profiling, including unbiased gene ontology enrichment analysis, to assess the impact of ZIKV infection on gene expression in primary cortical neuron cultures. These studies were extended with molecular biological analysis of gene expression and inflammatory cytokine signaling. In vitro observations were further confirmed using established in vivo models of ZIKV infection in immunocompetent hosts.ResultsTranscriptomic profiling of primary neuron cultures following ZIKV infection revealed altered expression of key genes associated with major psychiatric disorders, such as bipolar disorder and schizophrenia. Gene ontology enrichment analysis also revealed significant changes in gene expression associated with fundamental neurobiological processes, including neuronal development, neurotransmission, and others. These alterations to neurologic gene expression were also observed in the brain in vivo using several immunocompetent mouse models of ZIKV infection. Mechanistic studies identified TNF-α signaling via TNFR1 as a major regulatory mechanism controlling ZIKV-induced changes to neurologic gene expression.ConclusionsOur studies reveal that cell-intrinsic innate immune responses to ZIKV infection profoundly shape neuronal transcriptional profiles, highlighting the need to further explore associations between ZIKV infection and disordered host behavioral states.
| S-EPMC9036774 | biostudies-literature
Project description:The Zika virus (ZIKV) has rapidly reached epidemic proportions, especially in northeastern Brazil, and has rapidly spread to other parts of the Americas. A recent increase in the prevalence of microcephaly in newborn infants and vision-threatening findings in these infants is likely associated with the rapid spread of ZIKV.To evaluate the ocular findings in infants with microcephaly associated with presumed intrauterine ZIKV infection in Salvador, Bahia, Brazil.Case series at a tertiary hospital. Twenty-nine infants with microcephaly (defined by a cephalic circumference of ≤32 cm) with a presumed diagnosis of congenital ZIKV were recruited through an active search and referrals from other hospitals and health unities. The study was conducted between December 1 and December 21, 2015.All infants and mothers underwent systemic and ophthalmic examinations from December 1 through December 21, 2015, in the Roberto Santos General Hospital, Salvador, Brazil. Anterior segment and retinal, choroidal, and optic nerve abnormalities were documented using a wide-field digital imaging system. The differential diagnosis included toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and human immunodeficiency virus, which were ruled out through serologic and clinical examinations.Ocular abnormalities associated with ZIKV.Twenty-three of 29 mothers (79.3%) reported suspected ZIKV infection signs and symptoms during pregnancy, 18 in the first trimester, 4 in the second trimester, and 1 in the third trimester. Of the 29 infants (58 eyes) examined (18 [62.1%] female), ocular abnormalities were present in 17 eyes (29.3%) of 10 children (34.5%). Bilateral findings were found in 7 of 10 patients presenting with ocular lesions, the most common of which were focal pigment mottling of the retina and chorioretinal atrophy in 11 of the 17 eyes with abnormalities (64.7%), followed by optic nerve abnormalities in 8 eyes (47.1%), bilateral iris coloboma in 1 patient (2 eyes [11.8%]), and lens subluxation in 1 eye (5.9%).Congenital infection due to presumed ZIKV exposure is associated with vision-threatening findings, which include bilateral macular and perimacular lesions as well as optic nerve abnormalities in most cases.
| S-EPMC5444996 | biostudies-other
Project description:ImportanceThere are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults.ObjectiveTo evaluate the rates of acute ZIKV infection among patients hospitalized with Guillain-Barré syndrome (GBS), meningoencephalitis, or transverse myelitis.Design, setting, and participantsA prospective, observational cohort study was conducted at a tertiary referral center for neurological diseases in Rio de Janeiro, Brazil, between December 5, 2015, and May 10, 2016, among consecutive hospitalized adults (>18 years of age) with new-onset acute parainfectious or neuroinflammatory disease. All participants were tested for a series of arbovirosis. Three-month functional outcome was assessed.InterventionsSamples of serum and cerebrospinal fluid were tested for ZIKV using real-time reverse-transcriptase-polymerase chain reaction and an IgM antibody-capture enzyme-linked immunosorbent assay. Clinical, radiographic (magnetic resonance imaging), electrophysiological, and 3-month functional outcome data were collected.Main outcomes and measuresThe detection of neurologic complications secondary to ZIKV infection.ResultsForty patients (15 women and 25 men; median age, 44 years [range, 22-72 years]) were enrolled, including 29 patients (73%) with GBS (90% Brighton level 1 certainty), 7 (18%) with encephalitis, 3 (8%) with transverse myelitis, and 1 (3%) with newly diagnosed chronic inflammatory demyelinating polyneuropathy. Of these, 35 patients (88%) had molecular and/or serologic evidence of recent ZIKV infection in the serum and/or cerebrospinal fluid. Of the patients positive for ZIKV infection, 27 had GBS (18 demyelinating, 8 axonal, and 1 Miller Fisher syndrome), 5 had encephalitis (3 with concomitant acute neuromuscular disease), 2 had transverse myelitis, and 1 had chronic inflammatory demyelinating polyneuropathy. Admission to the intensive care unit was required for 9 patients positive for ZIKV infection (26%), and 5 (14%) required mechanical ventilation. Compared with admission during the period from December 5, 2013, to May 10, 2014 (before the Brazilian outbreak of ZIKV), admissions for GBS increased from a mean of 1.0 per month to 5.6 per month, admissions for encephalitis increased from 0.4 per month to 1.4 per month, and admissions for transverse myelitis remained constant at 0.6 per month. At 3 months, 2 patients positive for ZIKV infection (6%) died (1 with GBS and 1 with encephalitis), 18 (51%) had chronic pain, and the median modified Rankin score among survivors was 2 (range, 0-5).Conclusions and relevanceIn this single-center Brazilian cohort, ZIKV infection was associated with an increase in the incidence of a diverse spectrum of serious neurologic syndromes. The data also suggest that serologic and molecular testing using blood and cerebrospinal fluid samples can serve as a less expensive, alternative diagnostic strategy in developing countries, where plaque reduction neutralization testing is impractical.
| S-EPMC5710239 | biostudies-literature
Project description:We describe a case of a 20-month-old girl with probable congenital Zika virus infection and normal neurodevelopment, despite microcephaly and abnormal neuroimaging. This case raises questions about early prognostic markers and draws attention to the need for investigation in suspected Zika cases, even if the child's early neurodevelopment is normal.
| S-EPMC6200011 | biostudies-literature
Project description:Zika virus (ZIKV) has been detected in blood, urine, semen, cerebral spinal fluid, saliva, amniotic fluid, and breast milk. In most ZIKV infected individuals, the virus is detected in the blood to one week after the onset of symptoms and has been found to persist longer in urine and semen. To better understand virus dynamics, a prospective cohort study was conducted in Brazil to assess the presence and duration of ZIKV and related markers (viral RNA, antibodies, T cell response, and innate immunity) in blood, semen, saliva, urine, vaginal secretions/menstrual blood, rectal swab and sweat. The objective of the current manuscript is to describe the cohort, including an overview of the collected data and a description of the baseline characteristics of the participants. Men and women ≥ 18 years with acute illness and their symptomatic and asymptomatic household contacts with positive reverse transcriptase-polymerase chain reaction test for ZIKV in blood and/or urine were included. All participants were followed up for 12 months. From July 2017 to June 2019, a total of 786 participants (284 men, 502 women) were screened. Of these, 260 (33.1%) were enrolled in the study; index cases: 64 men (24.6%), 162 (62.3%) women; household contacts: 12 men (4.6%), 22 (8.5%) women. There was a statistically significant difference in age and sex between enrolled and not enrolled participants (p<0.005). Baseline sociodemographic and medical data were collected at enrollment from all participants. The median and interquartile range (IQR) age was 35 (IQR; 25.3, 43) for men and 36.5 years (IQR; 28, 47) for women. Following rash, which was one of the inclusion criteria for index cases, the most reported symptoms in the enrollment visit since the onset of the disease were fever, itching, arthralgia with or without edema, non-purulent conjunctivitis, headache, and myalgia. Ten hospitalizations were reported by eight patients (two patients were hospitalized twice) during follow up, after a median of 108 days following symptom onset (range 7 to 266 days) and with a median of 1.5 days (range 1 to 20 days) of hospital stay. A total of 4,137 visits were performed, 223 (85.8%) participants have attended all visits and 37 (14.2%) patients were discontinued.
| S-EPMC7785242 | biostudies-literature
Project description: Not available
| S-EPMC4593454 | biostudies-literature
Project description:We report two patients that developed severe thrombocytopenia after Zika virus (ZIKV) infection. The first patient had 1000 platelets/μL and died after multiple hemorrhages. The second patient had 2000 platelets/μL, had melena and ecchymoses, and recovered after receiving intravenous immunoglobulin. ZIKV may be associated with immune-mediated severe thrombocytopenia.
| S-EPMC5176332 | biostudies-literature
Project description:The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)-mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case-control framework in northeastern Brazil among 29 Zika virus-seropositive mothers of neonates with CZS and 108 Zika virus-seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.
| S-EPMC6649334 | biostudies-literature
Project description:Long known to be endemic in Africa and Southeast Asia and a rare cause of acute febrile illness, Zika virus (ZIKAV) arose from obscurity when an Asian genotype ZIKAV caused an outbreak of mild febrile illness in 2007 in Yap State, Federated States of Micronesia. Subsequent viral spread in the Pacific led to a large outbreak in French Polynesia commencing in 2013. After its recognition in the Americas through March 2017, the Pan American Health Organization has received reports of >750000 suspected and laboratory-confirmed cases of autochthonous ZIKAV transmission. Outbreaks in most countries in the Americas peaked in early to mid-2016. Increased surveillance in several Southeast Asian counties has led to increased case recognition, including an outbreak in Singapore, and the first reports of birth defects linked to ZIKAV in the region. As of April 2017, the World Health Organization reported 84 countries or territories with current or previous ZIKAV transmission.
| S-EPMC5853392 | biostudies-other