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1.
Artigo em Inglês | MEDLINE | ID: mdl-33027393

RESUMO

The Northeast of Brazil has experienced a triple epidemic, with the simultaneous circulation of dengue virus (DENV), chikungunya virus (CHIKV) and Zika virus (ZIKV), which may have contributed to the observed increase across this region of atypical forms of disease and deaths. In view of this fact, non-congenital neurological disorders related to arboviruses were compared with other etiologies, mortality and survival rates of patients admitted to referral neurology hospitals in Pernambuco State, Northeast Brazil, from 2015 to 2018. Blood and cerebrospinal fluid samples were collected and tested using molecular and serological assays. The arbovirus-exposed groups were compared with respect to epidemiological, clinical and neurologic characteristics by using the Pearson's chi-square test. For the survival analysis, the Kaplan-Meier and Hazard Ratio (HR) tests were used, with a 95% confidence interval (CI). Encephalitis and encephalomyelitis were more frequent in arboviruses, while myelitis predominated in the neurological disorders of other etiologies. Guillain-Barré Syndrome (GBS) was similarly distributed amongst the groups. Exposure to one of the arboviruses caused a six-fold increase in the risk of death (HR: 6.37; CI: 2.91 - 13.9). Amongst the arbovirus-exposed groups, infection (DENV/CHIKV) increased nine times the risk of death (HR: 9.07; CI: 3.67 - 22.4). The survival curve indicates that have been exposed to some arbovirus decreased the likelihood of survival compared to those with other etiologies (Log-Rank: p<0.001). Within this scenario, neurologic manifestations of DENV, CHIKV and ZIKV have the potential to increase mortality and decrease survival, and concomitant infection (DENV/CHIKV) is an aggravating factor in reducing the likelihood of survival when compared to monoinfections.


Assuntos
Febre de Chikungunya/diagnóstico , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Encefalite Viral/epidemiologia , Encefalomielite/virologia , Doenças do Sistema Nervoso/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Brasil , Febre de Chikungunya/complicações , Dengue/complicações , Encefalomielite/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Doenças do Sistema Nervoso/diagnóstico , Análise de Sobrevida , Infecção por Zika virus/complicações
2.
Sci Adv ; 6(39)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32978154

RESUMO

Detection of viruses is critical for controlling disease spread. Recent emerging viral threats, including Zika virus, Ebola virus, and SARS-CoV-2 responsible for coronavirus disease 2019 (COVID-19) highlight the cost and difficulty in responding rapidly. To address these challenges, we develop a platform for low-cost and rapid detection of viral RNA with DNA nanoswitches that mechanically reconfigure in response to specific viruses. Using Zika virus as a model system, we show nonenzymatic detection of viral RNA with selective and multiplexed detection between related viruses and viral strains. For clinical-level sensitivity in biological fluids, we paired the assay with sample preparation using either RNA extraction or isothermal preamplification. Our assay requires minimal laboratory infrastructure and is adaptable to other viruses, as demonstrated by quickly developing DNA nanoswitches to detect SARS-CoV-2 RNA in saliva. Further development and field implementation will improve our ability to detect emergent viral threats and ultimately limit their impact.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , DNA de Cadeia Simples/genética , Eletroforese em Gel de Ágar/métodos , Pneumonia Viral/diagnóstico , RNA Viral/genética , Análise de Sequência de RNA/métodos , Sequência de Bases , Linhagem Celular Tumoral , Infecções por Coronavirus/virologia , Dengue/diagnóstico , Dengue/virologia , Vírus da Dengue/genética , Eletroforese em Gel de Ágar/economia , Humanos , Limite de Detecção , Pandemias , Pneumonia Viral/virologia , Saliva/virologia , Análise de Sequência de RNA/economia , Zika virus/genética , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia
3.
Lancet Neurol ; 19(10): 826-839, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32949543

RESUMO

BACKGROUND: Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity. METHODS: We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics. FINDINGS: Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34-60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 [20%] had Zika, 55 [27%] had chikungunya, and two [1%] had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 [23%] patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 [47%] of 55 patients with chikungunya infection vs six [15%] of 41 with Zika infection; p=0·0008), especially myelitis (12 [22%] patients). Zika infection was more often associated with PNS disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barré syndrome (25 [61%] patients). Patients with Guillain-Barré syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days [IQR 20-30] vs 17 days [10-20]; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047). INTERPRETATION: There is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation. FUNDING: Fundação do Amparo a Ciência e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.


Assuntos
Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/epidemiologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Adulto , Idoso , Brasil/epidemiologia , Febre de Chikungunya/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Estudos Prospectivos , Infecção por Zika virus/sangue
4.
Artigo em Inglês | MEDLINE | ID: mdl-32844907

RESUMO

This study analyzed possible associations between the trimester of maternal Zika virus infection (ZIKV) in pregnancy, severity of brain computed tomography (CT) findings and the presence of microcephaly at birth in children with Congenital Zika Syndrome (CZS). It was an analytical study in a cohort of children with CZS. Symptoms of maternal infection were dichotomized into the 1st trimester of pregnancy and other trimesters. Head circumference (HC) at birth was used to calculate the z-score. Mild microcephaly was defined as HC between 2 and ≥3 standard deviations (SD) below the mean for each gestational age and sex, and severe microcephaly when HC <3 SD below average. Brain CT images were evaluated by two radiologists and classified, according to the severity, into mild, moderate and severe. Fisher's exact, Mann-Whitney and Kruskal-Wallis tests were used to verify the associations between variables. In 108 children, maternal infection in the 1st trimester of pregnancy was associated with more severe brain CT abnormalities (p=0.038), greater severity of microcephaly at birth (p=0.013) and lower HC z-scores at birth (p=0.021). The severity of brain CT lesions was also associated with lower HC z-scores at birth (p<0.001). Maternal ZIKV infection during the first trimester of pregnancy proved to be an important risk factor for a more severe spectrum of CZS, as it is associated with more severe brain CT abnormalities and, consequently, with lower HC z-scores at birth.


Assuntos
Encéfalo/diagnóstico por imagem , Microcefalia/virologia , Primeiro Trimestre da Gravidez , Tomografia Computadorizada por Raios X/métodos , Infecção por Zika virus/diagnóstico , Zika virus , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Trimestres da Gravidez , Índice de Gravidade de Doença , Infecção por Zika virus/congênito , Infecção por Zika virus/epidemiologia
5.
Arq Neuropsiquiatr ; 78(7): 403-411, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32627805

RESUMO

BACKGROUND: The congenital Zika syndrome involves structural brain changes, including ventriculomegaly, thin cerebral cortices, abnormal gyral pattern, cortical malformations, hypoplasia of the corpus callosum, myelination delay, subcortical diffuse calcifications, brainstem hypoplasia, and microcephaly in newborns. OBJECTIVE: This study aimed to describe the clinical characteristics of children with congenital Zika syndrome; to compare the outcomes of infants infected in the first (1T, n=20) and second trimesters of pregnancy (2T, n=11); to investigate correlations between birth weight, birth and follow-up head circumference, birth gestational age, and gross motor scores. METHODS: Participants were evaluated with Alberta Infant Motor Scale (AIMS) and part A of the Gross Motor Function Measure (GMFM-A). ANOVA compared head circumference, birth gestational age, birth weight, and gross motor performance of 1T and 2T. RESULTS: The correlations were investigated by Pearson correlation coefficients. ANOVA showed differences in birth and follow-up head circumferences. Head circumference was smaller in 1T, compared to 2T. Motor performance was classified as below the fifth percentile in AIMS in all children and 1T showed lower scores in prone, sitting, and total AIMS score, compared to 2T. Children ranged from 8 to 78% on GMFM-A and there was a poorer motor performance of 1T. Nineteen children showed hypertonia, six showed normal tone and six showed hypotonia. Birth head circumference was correlated with AIMS prone postural control. Follow-up head circumference was correlated to prone, supine and total AIMS scores. Smaller head circumference at birth and follow-up denoted poorer postural control. DISCUSSION: Children with congenital Zika syndrome showed microcephaly at birth and follow-up. Smaller head circumferences and poorer motor outcomes were observed in 1T. Infants showed poor visual and motor outcomes. Moderate positive correlations between birth and follow-up head circumference and gross motor function were found.


Assuntos
Microcefalia/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Encéfalo , Cefalometria , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Microcefalia/diagnóstico , Destreza Motora , Gravidez , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Infecção por Zika virus/congênito
6.
Obstet Gynecol ; 135(5): 1185-1197, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32282593

RESUMO

OBJECTIVE: To examine the relationship between prenatal diagnostics (ultrasound examination and amniotic fluid Zika virus testing) and postnatal congenital Zika syndrome abnormalities. DATA SOURCES: Systematic searches were performed in 27 databases, including ClinicalTrials.gov, from inception to July 1, 2019, for articles with the keywords "Zika," "prenatal," "ultrasound," and "amniocentesis." METHODS OF STUDY SELECTION: A total of 3,049 unique records were identified. Two reviewers independently assessed titles, abstracts, and full texts for relevance; 84 articles met the inclusion criteria. These articles describe 402 mother-fetus or mother-neonate dyads; 385 were included in the review of prenatal ultrasound examination, and 56 in the review of amniocentesis (39 in both). TABULATION, INTEGRATION, AND RESULTS: Among 195 fetuses with congenital Zika syndrome findings on prenatal ultrasound examination, postnatal congenital Zika syndrome abnormalities were reported for 153 (78%; 95% CI 7-84%). High proportions of microcephaly (76%; 95% CI 69-82%) and brain abnormalities (78%; 95% CI 69-86%) were confirmed postnatally. Among 190 fetuses without congenital Zika syndrome findings on prenatal ultrasound examination, 17% (95% CI 12-24%) had congenital Zika syndrome abnormalities identified postnatally. Structural congenital Zika syndrome abnormalities were identified postnatally in approximately equal proportions among dyads with and without Zika virus RNA detected in an amniotic fluid specimen (68% and 67%; 95% CI 52-82% and 95% CI 38-88%). In six pregnancies, Zika virus RNA was detected in amniotic fluid but not in a subsequent amniocentesis specimen. CONCLUSION: Prenatal ultrasound examination frequently detects structural findings associated with Zika virus infection; however, not all abnormalities are detected, and some may represent transient findings. As with other congenital infections, prenatal detection may vary with timing of infection, timing of ultrasound examination, technical expertise, and severity of abnormalities. The detection of Zika virus RNA in amniotic fluid in the included studies did not predict the risk for congenital Zika syndrome abnormalities in these cases, and clearance of Zika virus RNA from amniotic fluid appears possible after maternal infection. Diagnostic testing for Zika virus infection remains a shared decision between patients and clinicians, and more data are needed to define clinical predictors that will inform these decisions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018080959.


Assuntos
Amniocentese/métodos , Doenças Fetais/diagnóstico , Ultrassonografia Pré-Natal/métodos , Infecção por Zika virus/diagnóstico , Zika virus , Adulto , Feminino , Doenças Fetais/virologia , Humanos , Gravidez , Adulto Jovem , Infecção por Zika virus/embriologia , Infecção por Zika virus/virologia
7.
Proc Natl Acad Sci U S A ; 117(18): 9865-9875, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32321830

RESUMO

Recent epidemics demonstrate the global threat of Zika virus (ZIKV), a flavivirus transmitted by mosquitoes. Although infection is usually asymptomatic or mild, newborns of infected mothers can display severe symptoms, including neurodevelopmental abnormalities and microcephaly. Given the large-scale spread, symptom severity, and lack of treatment or prophylaxis, a safe and effective ZIKV vaccine is urgently needed. However, vaccine design is complicated by concern that elicited antibodies (Abs) may cross-react with other flaviviruses that share a similar envelope protein, such as dengue virus, West Nile virus, and yellow fever virus. This cross-reactivity may worsen symptoms of a subsequent infection through Ab-dependent enhancement. To better understand the neutralizing Ab response and risk of Ab-dependent enhancement, further information on germline Ab binding to ZIKV and the maturation process that gives rise to potently neutralizing Abs is needed. Here we use binding and structural studies to compare mature and inferred-germline Ab binding to envelope protein domain III of ZIKV and other flaviviruses. We show that affinity maturation of the light-chain variable domain is important for strong binding of the recurrent VH3-23/VK1-5 neutralizing Abs to ZIKV envelope protein domain III, and identify interacting residues that contribute to weak, cross-reactive binding to West Nile virus. These findings provide insight into the affinity maturation process and potential cross-reactivity of VH3-23/VK1-5 neutralizing Abs, informing precautions for protein-based vaccines designed to elicit germline versions of neutralizing Abs.


Assuntos
Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Antivirais/imunologia , Proteínas do Envelope Viral/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , Epitopos/imunologia , Células Germinativas/imunologia , Humanos , Recém-Nascido , Domínios Proteicos/imunologia , Vacinas Virais/imunologia , Vírus do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/patogenicidade , Vírus da Febre Amarela/imunologia , Vírus da Febre Amarela/patogenicidade , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia
8.
Am J Trop Med Hyg ; 102(5): 985-987, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32228787

RESUMO

We tested 700 serum samples collected throughout Panama from 2015 to 2016 for detecting antibodies and RNA of arboviruses. In convalescent specimens, microsphere immunoassay detected an antibody prevalence of 59.3% for dengue virus (DENV) and 30.3% for Zika virus (ZIKV), which included samples that were collected before the Panamanian surveillance system reported the first case of Zika in the country. For acute sera, the most common arbovirus was DENV with 18 positive samples (6%), followed by four (1.3%) of ZIKV and one (0.6%) of chikungunya virus (CHIKV). Our results indicate a change in the chronology of when ZIKV was first detected in Panama and stress the importance of integrating various approaches to enable improved surveillance of both endemic and emerging arboviruses.


Assuntos
Arbovirus , Vigilância da População/métodos , Infecção por Zika virus/diagnóstico , Zika virus , Anticorpos Antivirais/sangue , Vírus Chikungunya , Vírus da Dengue , Imunofluorescência , Humanos , Panamá/epidemiologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Infecção por Zika virus/epidemiologia
9.
Am J Trop Med Hyg ; 102(6): 1244-1248, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32157991

RESUMO

Recent expansions of vector-borne diseases highlight the need for improved surveillance, especially in resource-poor settings. Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) share the same vectors as well as similar clinical presentations, suggesting that combined surveillance would be useful. We hypothesized that blood spotted on dengue rapid diagnostic tests (RDTs) could be harnessed for sample collection in remote areas for subsequent detection of DENV, CHIKV, and ZIKV by reverse transcription real-time polymerase chain reaction (RT-qPCR). CHIKV and ZIKV dilutions were spotted on dengue RDTs (SD BIOLINE Dengue DUO, Standard Diagnostics, Gyeonggi-do, Republic of Korea), dried, and extracted. As reference, aliquots of each viral dilution were directly extracted. Using specific RT-qPCR tests, both viruses were successfully detected from RDT extracts. However, the limit of detection was slightly lower in comparison to direct extracts, two logfold for CHIKV and one logfold for ZIKV. For analysis of temperature stability, DENV dilutions were spotted on RDTs and stored for up to 2 months at -80°C, 4°C, or 35°C before testing. Storage of RDTs for 2 months at 35°C did not compromise detection of RNA by RT-qPCR; only minimal degradation was observed. This proof-of-principle study demonstrates the potential of using dengue RDTs for DENV/CHIKV/ZIKV combined surveillance in areas without access to laboratory facilities. Further investigations are needed for evaluation of tri-viral surveillance under field conditions using patient samples. Large-scale implementation of surveillance for these viruses is of crucial public health importance for the early detection of epidemics. This method also has important implications for improving understanding of the molecular epidemiology of the three viruses.


Assuntos
Febre de Chikungunya/epidemiologia , Dengue/epidemiologia , Vigilância da População/métodos , Infecção por Zika virus/epidemiologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Dengue/diagnóstico , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Humanos , Laos/epidemiologia , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico
10.
Acta Trop ; 206: 105438, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32165128

RESUMO

INTRODUCTION: Typical symptoms of primary Zika virus infection are not specific and share similarities with other arbovirus infections such as dengue fever and chikungunya. As acute infection can be asymptomatic in up to 73% of cases, infants with microcephaly represent a diagnostic challenge for pediatricians. We describe the frequency of congenital Zika syndrome (CZS) in Brazilian children born to asymptomatic pregnant mothers and its differential diagnosis. METHODS: This longitudinal, observational study was conducted on children with suspected CZS whose mothers did not report rash during pregnancy, referred to the reference hospital in a metropolitan area of ​ Rio de Janeiro, Brazil. The diagnosis of suspected CZS was based on Brazilian Ministry of Health protocol. RESULTS: Forty-three (17%) of 246 referred children were born to mothers without rash history during pregnancy. Thirteen (30%) of 43 children met the Brazilian Ministry of Health criteria for CZS, all with microcephaly (two post-natal). The other children included 11 cases with post-natal microcephaly due to hypoxic-ischemic encephalopathy (6), non-progressive encephalopathy of unknown etiology (2), microcephaly under investigation (2) and congenital toxoplasmosis (1); 17 children were misdiagnosed with microcephaly and progressed with normal head circumference during the follow-up period; one child was included because of epidemiological link and one was loss to follow-up. All children who underwent laboratory investigation for ZIKV infection during neonatal period had negative RT-qPCR tests. CONCLUSION: We emphasize the increasing importance of CZS in differential diagnosis of microcephaly at birth or post-natal period. Detailed clinical investigation assisted by neuroimaging tests may clarify the diagnosis of CZS when laboratory tests are not available during the acute phase of the disease.


Assuntos
Microcefalia/diagnóstico , Complicações Infecciosas na Gravidez , Infecção por Zika virus/congênito , Infecção por Zika virus/diagnóstico , Adulto , Infecções Assintomáticas , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Estudos Longitudinais , Gravidez
11.
PLoS One ; 15(2): e0228347, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32012191

RESUMO

The co-circulation of different arboviruses in the same time and space poses a significant threat to public health given their rapid geographic dispersion and serious health, social, and economic impact. Therefore, it is crucial to have high quality of case registration to estimate the real impact of each arboviruses in the population. In this work, a Vector Autoregressive (VAR) model was developed to investigate the interrelationships between discarded and confirmed cases of dengue, chikungunya, and Zika in Brazil. We used data from the Brazilian National Notifiable Diseases Information System (SINAN) from 2010 to 2017. There were three peaks in the series of dengue notification in this period occurring in 2013, 2015 and in 2016. The series of reported cases of both Zika and chikungunya reached their peak in late 2015 and early 2016. The VAR model shows that the Zika series have a significant impact on the dengue series and vice versa, suggesting that several discarded and confirmed cases of dengue could actually have been cases of Zika. The model also suggests that the series of confirmed and discarded chikungunya cases are almost independent of the cases of Zika, however, affecting the series of dengue. In conclusion, co-circulation of arboviruses with similar symptoms could have lead to misdiagnosed diseases in the surveillance system. We argue that the routinely use of mathematical and statistical models in association with traditional symptom-surveillance could help to decrease such errors and to provide early indication of possible future outbreaks. These findings address the challenges regarding notification biases and shed new light on how to handle reported cases based only in clinical-epidemiological criteria when multiples arboviruses co-circulate in the same population.


Assuntos
Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Dengue/diagnóstico , Dengue/epidemiologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Brasil/epidemiologia , Humanos , Modelos Estatísticos , Análise Multivariada , Análise de Regressão , Fatores de Tempo
12.
Am J Trop Med Hyg ; 102(4): 880-883, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32043455

RESUMO

Zika virus (ZIKV) caused a public health threat in the United States in 2016, leading to rapid development and implementation of blood screening assays for ZIKV RNA. Several ZIKV sequences from clinical cases have been reported, but none from asymptomatic/pre-symptomatic infections. We isolated and sequenced ZIKV from asymptomatic/pre-symptomatic blood donor (ABD-ZIKV) samples and compared with reported clinical sequences. Twelve ABD-ZIKV isolates were produced from 67 cultivated samples, and isolates were genetically similar among themselves. Most isolates shared mutations with the clinical isolate PRVABC59 2015, whereas two ABD-ZIKV isolates shared specific mutations with U.S. clinical isolates from 2016. The ABD-ZIKV strains clustered into two distinct subclades: one comprised mostly ABD-ZIKV from Puerto Rico, and another one comprised ABD-ZIKV from Florida and QTX-02 isolate (Puerto Rico). In this study, we showed the circulation of two slightly distinct virus strains among Puerto Rico blood donors, one of which was also reported in Florida.


Assuntos
Doadores de Sangue , Filogenia , Infecção por Zika virus/sangue , Zika virus/genética , Zika virus/isolamento & purificação , Adulto , Doenças Transmissíveis Emergentes/sangue , Doenças Transmissíveis Emergentes/epidemiologia , Florida/epidemiologia , Genômica , Humanos , Porto Rico/epidemiologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
13.
Virology ; 543: 34-42, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32056845

RESUMO

Zika Virus (ZIKV) is a Flavivirus transmitted primarily via the bite of infected Aedes aegypti mosquitoes. Globally, 87 countries and territories have recorded autochthonous mosquito-borne transmission of ZIKV as at July 2019 and distributed across four of the six WHO Regions. Outbreaks of ZIKV infection peaked in 2016 and declined substantially throughout 2017 and 2018 in the Americas region. There is the likely risk for ZIKV to spread to more countries. There is also the potential for the re-emergence of ZIKV in all places with prior reports of the virus transmission. The current status of ZIKV transmission and spread is, however, a global health threat, and from the aforementioned, has the potential to re-emerge as an epidemic. This review summarizes the past and present spread of ZIKV outbreak-2007-2019, the genome, transmission cycle, clinical manifestations, vaccine and antiviral drug advancement.


Assuntos
Antivirais/uso terapêutico , Mosquitos Vetores/virologia , Vacinas Virais , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissão , Zika virus/genética , Brasil/epidemiologia , Cabo Verde/epidemiologia , Surtos de Doenças , Feminino , Genoma Viral , Humanos , Masculino , Ilhas do Pacífico/epidemiologia , Vacinas Virais/imunologia , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/tratamento farmacológico
14.
Am J Trop Med Hyg ; 102(3): 625-628, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31933462

RESUMO

Arboviral diagnosis has been complicated throughout the tropical and subtropical Americas by the recent co-circulation of Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV). The aim of this study was to implement a multiplex real-time RT-PCR (rRT-PCR) for ZIKV, CHIKV, and DENV in Paraguay to test patients who were clinically suspected of having dengue. We tested 110 sera from patients who presented to the Hospital de Clínicas in 2016 and had testing for DENV nonstructural protein 1 (NS1; 40 positive and 70 negative). Using a composite reference standard, we confirmed 51 dengue cases (46.4%): 38/40 NS1 positive and 13/70 NS1 negative. Chikungunya virus and ZIKV were detected in one sample each, both were DENV NS1 negative. The NS1 test demonstrated good agreement with rRT-PCR for DENV. However, multiplex rRT-PCR identified a subset of dengue cases and additional arboviral infections that would not be detected if NS1 assays are relied upon for diagnosis.


Assuntos
Febre de Chikungunya/diagnóstico , Dengue/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Infecção por Zika virus/diagnóstico , Adolescente , Adulto , Febre de Chikungunya/epidemiologia , Criança , Dengue/epidemiologia , Doenças Endêmicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraguai/epidemiologia , Adulto Jovem , Infecção por Zika virus/epidemiologia
15.
Int J Gynaecol Obstet ; 148 Suppl 2: 45-54, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31975393

RESUMO

OBJECTIVES: To analyze the initial healthcare response to the Zika virus in Piura, Peru, and assess the perceptions of midwives and nurses regarding their role in prevention of Zika virus and management of congenital Zika syndrome (CZS). METHODS: This ethnographic study used a rapid qualitative assessment design. Data were collected through a focus group with midwives and in-depth interviews with midwives (n=11) and nurses (n=5). RESULTS: The focus of the early Zika virus response in Piura was on pregnant women and vector control. Midwives received some training on Zika-related care during the early response. Nurses did not receive any Zika-specific training. Neither nurses nor midwives were trained in neonatal CZS surveillance. Midwives were clear about the value and feasibility of incorporating Zika virus surveillance in their daily work, however nurses were not. They referred to lack of training and appropriate tools as limitations. Confusion about Zika virus and CZS symptomatology and effects persisted in both groups. Concerns about their own personal risk influenced the ways they engaged with Zika virus prevention in the community. CONCLUSION: Long-term management of endemic Zika virus in Piura will require the engagement of both nurses and midwives as primary care providers.


Assuntos
Relações Interprofissionais , Tocologia/organização & administração , Enfermeiras e Enfermeiros , Complicações Infecciosas na Gravidez/terapia , Infecção por Zika virus/terapia , Adulto , Atitude do Pessoal de Saúde , Feminino , Grupos Focais , Humanos , Tocologia/educação , Peru/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Atenção Primária à Saúde/organização & administração , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
16.
Int J Gynaecol Obstet ; 148 Suppl 2: 20-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31975400

RESUMO

OBJECTIVE: To describe the repercussions, from the perspectives of caregiver mothers, of confirmed congenital Zika syndrome (CZS) in their offspring. METHODS: A descriptive-exploratory study with a qualitative approach was carried out in the state of Espírito Santo in southeastern Brazil, with 25 women who had a child diagnosed with CZS. RESULTS: Emerging themes from the content analysis were grouped into two categories: (1) inequalities experienced by mothers, including social inequality, poverty, and gender inequality; (2) the impact of a child with CZS on mothering, including feelings at the time of diagnosis, maternal isolation and mental health, experiences of stigma and prejudice, and exhausting itineraries searching for therapeutic care. CONCLUSION: The repercussions of CZS were a huge burden on already vulnerable women, and social inequalities and poverty were important markers in the mothers' reports. Many of the families affected by CZS already lived in precarious social conditions and these conditions were exacerbated further. Robust public and social policies to support these mothers need effective implementation given that babies born with CZS need long-term care and support.


Assuntos
Mães/psicologia , Infecção por Zika virus/psicologia , Adulto , Brasil , Criança , Feminino , Disparidades nos Níveis de Saúde , Humanos , Microcefalia/psicologia , Microcefalia/virologia , Pobreza , Pesquisa Qualitativa , Isolamento Social , Estereotipagem , Infecção por Zika virus/diagnóstico
17.
Int J Gynaecol Obstet ; 148 Suppl 2: 15-19, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31975403

RESUMO

OBJECTIVES: To describe the mechanisms of implementation of Zika virus diagnosis, prevention, and management guidelines in Colombia, and to characterize their influence on efforts to defend sexual and reproductive rights. METHODS: A qualitative study performed between February and April 2018 in three municipalities in Colombia. We conducted 30 semistructured interviews and five focus groups with key informants who played a role during the epidemic. These included decision-makers, program coordinators, healthcare providers, pregnant women diagnosed with Zika virus, and members of affected communities. RESULTS: We identified barriers to and facilitators for the implementation of the national Zika virus response plan. Barriers included a lack of coordination between vector control efforts and in the realms of sexual and reproductive rights. Facilitators included healthcare providers' response to the epidemic, the development of technical skills, and the establishment of coordination and referral networks across different institutions. CONCLUSION: A multidimensional approach that considers healthcare services, gender issues, and the environment is crucial. We highlight the epidemic's effects on women's sexual and reproductive rights, mainly related to inequalities in sexual and reproductive health such as the increased risk of sexually transmitted infections experienced by the poorest and most vulnerable women.


Assuntos
Saúde Reprodutiva , Direitos Sexuais e Reprodutivos , Saúde Sexual , Infecção por Zika virus , Colômbia , Epidemias , Feminino , Grupos Focais , Humanos , Guias de Prática Clínica como Assunto , Gravidez , Pesquisa Qualitativa , Saúde da Mulher , Adulto Jovem , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/terapia
18.
Nat Microbiol ; 5(3): 443-454, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31932713

RESUMO

Metagenomic next-generation sequencing (mNGS), the shotgun sequencing of RNA and DNA from clinical samples, has proved useful for broad-spectrum pathogen detection and the genomic surveillance of viral outbreaks. An additional target enrichment step is generally needed for high-sensitivity pathogen identification in low-titre infections, yet available methods using PCR or capture probes can be limited by high cost, narrow scope of detection, lengthy protocols and/or cross-contamination. Here, we developed metagenomic sequencing with spiked primer enrichment (MSSPE), a method for enriching targeted RNA viral sequences while simultaneously retaining metagenomic sensitivity for other pathogens. We evaluated MSSPE for 14 different viruses, yielding a median tenfold enrichment and mean 47% (±16%) increase in the breadth of genome coverage over mNGS alone. Virus detection using MSSPE arboviral or haemorrhagic fever viral panels was comparable in sensitivity to specific PCR, demonstrating 95% accuracy for the detection of Zika, Ebola, dengue, chikungunya and yellow fever viruses in plasma samples from infected patients. Notably, sequences from re-emerging and/or co-infecting viruses that have not been specifically targeted a priori, including Powassan and Usutu, were successfully enriched using MSSPE. MSSPE is simple, low cost, fast and deployable on either benchtop or portable nanopore sequencers, making this method directly applicable for diagnostic laboratory and field use.


Assuntos
Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenoma , Metagenômica/métodos , Vírus/genética , Vírus/isolamento & purificação , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Biologia Computacional , DNA Viral/genética , Dengue/diagnóstico , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Ebolavirus/genética , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/diagnóstico , Humanos , Reação em Cadeia da Polimerase , RNA Viral/genética , RNA Viral/isolamento & purificação , Viroses/diagnóstico , Febre Amarela/diagnóstico , Zika virus/genética , Infecção por Zika virus/diagnóstico
19.
Int J Infect Dis ; 90: 104-110, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678190

RESUMO

OBJECTIVE: To evaluate the clinical, laboratory, and immune characteristics of Zika virus (ZIKV)-associated encephalitis in pediatric patients after the epidemic in Huila, southern Colombia. METHODS: A pediatric neuro-surveillance hospital study was conducted in a referral health center in southern Colombia, from October 2016 to October 2017. Cases of encephalitis were confirmed by nucleic acid amplification tests and serological methods in cerebrospinal fluid (CSF), plasma, and/or urine. Levels of six cytokines were evaluated by flow cytometry. Patients underwent daily clinical and laboratory follow-up. RESULTS: Twenty children with probable encephalitis were included for further studies and 16 of them were confirmed. Four cases of bacterial meningoencephalitis (Streptococcus pneumoniae, group B Streptococcus, Staphylococcus epidermidis, and Escherichia coli) and 12 cases of viral encephalitis were identified, six of them associated with ZIKV infection. Other viral encephalitis cases were caused by herpes viruses (n=3), enterovirus (n=2), and dengue virus type 2 (DENV-2; n=1) infections. ZIKV-associated encephalitis symptoms subsided faster than those of patients with encephalitis caused by other agents. CSF analysis revealed lymphocytic pleocytosis. Compared to healthy controls, children with ZIKV-associated encephalitis presented modest plasma interleukin (IL)-10 but not IL-2, IL-4, IL-6, interferon gamma (IFN-γ), or tumor necrosis factor alpha (TNF-α). Cytokine expression was differentially regulated, as dramatically elevated IL-6, IL-10, and IFN-γ levels were observed in CSF but not in paired plasma samples in one of the patients with ZIKV detectable in CSF. CONCLUSIONS: This study provides evidence that ZIKV is responsible for pediatric encephalitis in endemic areas, and the local presence of the virus may induce cephalic but not systemic expression of cytokines.


Assuntos
Encefalite Viral/virologia , Infecção por Zika virus/virologia , Adolescente , Criança , Pré-Escolar , Colômbia , Citocinas/sangue , Citocinas/líquido cefalorraquidiano , Encefalite Viral/diagnóstico , Encefalite Viral/imunologia , Feminino , Humanos , Lactente , Interferon gama/sangue , Interferon gama/líquido cefalorraquidiano , Masculino , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/imunologia
20.
Int J Infect Dis ; 92: 160-170, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31884173

RESUMO

OBJECTIVE: The re-emergence and spread of tropical viruses to new areas has raised a wave of concern worldwide. In order to treat patients at an early stage and prevent the diffusion of an outbreak, early diagnosis, and therefore fast and adequate detection, is needed. To this end, a multiplex reverse transcription real-time polymerase chain reaction TaqMan method was designed to detect Zika (ZIKV) and chikungunya (CHIKV) viruses simultaneously. METHODS: Two methods targeting different genome segments were selected from the literature for each virus. These were adapted for high genome coverage and combined in a four-plex assay that was thoroughly validated in-house. The SCREENED tool was used to evaluate the sequence coverage of the method. RESULTS: The full validation approach showed that the new four-plex method allows the specific and sensitive identification and discrimination of ZIKV and CHIKV in routine samples. The combination of two targets per virus allowing almost 100% coverage of about 500 genomes is shown for the first time. CONCLUSIONS: PCR is a reliable user-friendly technique that can be applied in remote areas. Such multiplex methods enable early and efficient diagnosis, leading to rapid treatment and effective confinement in outbreak cases. They may also serve as an aid for surveillance, and the full validation permits easy method-transfer allowing worldwide harmonization.


Assuntos
Febre de Chikungunya/diagnóstico , Vírus Chikungunya/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/classificação , Vírus Chikungunya/genética , Surtos de Doenças , Humanos , Sensibilidade e Especificidade , Zika virus/classificação , Zika virus/genética , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologia
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