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Zika virus - Top 30 Publications

Current views on Zika virus vaccine development.

Infectious disease: Musashi-1 protein could mediate the effects of Zika virus on brain development.

Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus.

Zika virus (ZIKV) is a re-emerging virus that has recently spread into dengue virus (DENV) endemic regions and cross-reactive antibodies (Abs) could potentially affect ZIKV pathogenesis. Using DENV-immune serum, it has been shown in vitro that antibody-dependent enhancement (ADE) of ZIKV infection can occur. Here we study the effects of pre-existing DENV immunity on ZIKV infection in vivo. We infect two cohorts of rhesus macaques with ZIKV; one cohort has been exposed to DENV 2.8 years earlier and a second control cohort is naïve to flaviviral infection. Our results, while confirming ADE in vitro, suggest that pre-existing DENV immunity does not result in more severe ZIKV disease. Rather our results show a reduction in the number of days of ZIKV viremia compared to naïve macaques and that the previous exposure to DENV may result in modulation of the immune response without resulting in enhancement of ZIKV pathogenesis.

Effect of ZIKA virus on adult eyes.

Evaluation of Placental and Fetal Tissue Specimens for Zika Virus Infection - 50 States and District of Columbia, January-December, 2016.

Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1), and detection of Zika virus RNA in clinical and tissue specimens can provide definitive laboratory evidence of recent Zika virus infection. Whereas duration of viremia is typically short, prolonged detection of Zika virus RNA in placental, fetal, and neonatal brain tissue has been reported and can provide key diagnostic information by confirming recent Zika virus infection (2). In accordance with recent guidance (3,4), CDC provides Zika virus testing of placental and fetal tissues in clinical situations where this information could add diagnostic value. This report describes the evaluation of formalin-fixed paraffin-embedded (FFPE) tissue specimens tested for Zika virus infection in 2016 and the contribution of this testing to the public health response. Among 546 live births with possible maternal Zika virus exposure, for which placental tissues were submitted by the 50 states and District of Columbia (DC), 60 (11%) were positive by Zika virus reverse transcription-polymerase chain reaction (RT-PCR). Among 81 pregnancy losses for which placental and/or fetal tissues were submitted, 18 (22%) were positive by Zika virus RT-PCR. Zika virus RT-PCR was positive on placental tissues from 38/363 (10%) live births with maternal serologic evidence of recent unspecified flavivirus infection and from 9/86 (10%) with negative maternal Zika virus immunoglobulin M (IgM) where possible maternal exposure occurred >12 weeks before serum collection. These results demonstrate that Zika virus RT-PCR testing of tissue specimens can provide a confirmed diagnosis of recent maternal Zika virus infection.

Clinical Impact of Non-Congenital Zika Virus Infection in Infants and Children.

While the Zika virus (ZIKV) has been noted for its distinct neurotropism and identified as a significant cause for a congenital infection syndrome, there has been increased recognition of the importance to better understand the clinical impact of non-congenital ZIKV infection in infants and children. This article reviews reports of perinatal and breast milk transmission of ZIKV and summarizes current clinical outcome data of pediatric non-congenital ZIKV infection.

Detection of the Northeastern African Rift Valley Fever Virus Lineage During the 2015 Outbreak in Mauritania.

Rift Valley fever (RVF) is an acute viral anthropozoonosis that causes epizootics and epidemics among livestock population and humans. Multiple emergences and reemergences of the virus have occurred in Mauritania over the last decade. This article describes the outbreak that occurred in 2015 in Mauritania and reports the results of serological and molecular investigations of blood samples collected from suspected RVF patients.

Global Alert: Zika Virus-an Emerging Arbovirus.

Zika virus (ZIKV) is an arbovirus of the Flavivirus genus, and it has an envelope and a single RNA molecule. In early 2016, the World Health Organization declared ZIKV infection to be an emerging global health threat. The major transmission route of the virus to humans is Aedes mosquitoes. ZIKV can be transmitted between humans by transplacental, perinatal, and sexual routes and via blood and body fluids. ZIKV infection usually results in a mild and self-limiting disease with low-grade fever, conjunctivitis, and periorbital edema. Neurological complications such as Guillain-Barré syndrome, meningoencephalitis, acute disseminated encephalomyelitis, acute myelitis, and transverse myelitis have been reported during ZIKV infection. Intrauterine and congenital ZIKV infections have strong teratogenic effects on the fetus. Intrauterine or congenital ZIKV infection can lead to microcephaly, ocular anomalies (such as macular atrophy, pigment mottling, and optic nerve anomalies), and cardiac anomalies (such as atrial or ventricular septal defect). Calcification in the brain between the cortical and subcortical areas, ventriculomegaly, cerebellar hypoplasia, corpus callosum hypoplasia, cortical/subcortical atrophy, delayed myelination, enlarged cisterna magna, and craniofacial disproportion have been reported as brain development defects. ZIKV infection usually results in a mild disease, and it does not require specific therapy. However, complications of infection during the early period of life are serious. Thus, many drugs have been investigated, and vaccine development studies have been conducted to prevent ZIKV infection. Vector control and personal protection from mosquito-borne transmission are important for decreasing the prevalence of ZIKV infection. In particular, pregnant residents or travelers to endemic areas should be carefully protected against mosquito-borne transmission.

Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype-anti-idiotype Fab complex.

A detailed understanding of the fine specificity of serotype-specific human antibodies is vital for the development and evaluation of new vaccines for pathogenic Flaviviruses such as Dengue virus (DENV) and Zika virus. In this study, we thoroughly characterize the structural footprint of an anti-idiotype antibody (E1) specific for a potent, fully human DENV serotype 1-specific antibody termed HM14c10, derived from a recovered patient. The crystal structure at a resolution of 2.5 Å of a complex between the Fab fragments of E1 and HM14c10 provides the first detailed molecular comparison of an anti-idiotype paratope specific for a human antibody with its analogous epitope- a discontinuous quaternary structure located at the surface of the viral particle that spans adjacent envelope (E) proteins. This comparison reveals that the footprints left by E1 and E on HM14c10 largely overlap, explaining why formation of the binary complexes are mutually exclusive. Structural mimicry of the DENV E epitope by the E1 combining site is achieved via the formation of numerous interactions with heavy chain CDRs of HM14c10, while fewer interactions are observed with its light chain, compared to the E protein. We show that E1 can be utilized to detect HM14c10-like antibodies in sera from patients recovered from a DENV-1 infection suggesting that this is a public (common) idiotype. These data demonstrate the utility of employing an anti-idiotype antibody to monitor a patient's specific immune responses and suggest routes for improvement of E 'mimicry' by E1 through increasing its recognition of the FabHM14c10 light chain CDRs.IMPORTANCE A chimeric yellow fever/dengue live-attenuated tetravalent vaccine is now marketed. Dengue remains a significant public health problem, because protection conferred by this vaccine is uneven against the four circulating serotypes. Reliable tools must be developed to measure the immune response of individuals exposed to DENV, either via viral infection or through vaccination. Anti-idiotypic antibodies provide precision tools for analyzing the pharmacokinetics of antibodies in an immune response and also for measuring the amount of circulating anti-infective therapeutic antibodies. Here, we characterize how an anti-idiotypic antibody (E1) binds the antibody HM14c10, which potently neutralizes DENV serotype 1. We report the crystal structure at a resolution of 2.5 Å of a complex between the Fab fragments of E1 and HM14c10 and provide the first detailed molecular comparison between the anti-idiotype surface and its analogous epitope located at the surface of the Dengue viral particle.

RNA-dependent RNA polymerase: Addressing Zika outbreak by a phylogeny-based drug target study.

Since the first major outbreak of Zika virus (ZIKV) in 2007, ZIKV is spreading explosively through South and Central America and recent reports in highly populated developing countries alarm the possibility of a more catastrophic outbreak. ZIKV infection in pregnant women leads to embryonic microcephaly and Guillain-Barré syndrome in adults. At present there is limited understanding of the infectious mechanism and no approved therapy has been reported. Despite the withdrawal of public health emergency, the WHO still considers the ZIKV as a highly significant and long-term public health challenge that the situation has to be addressed rapidly. Nonstructural protein 5 (NS5) is essential for capping and replication of viral RNA and comprises a methyltransferase (MTase) and RNA dependent RNA polymerase (RdRp) domain. We used molecular modeling to obtain the structure of ZIKV RdRp and by molecular docking and phylogeny analysis we here demonstrate the potential sites for drug screening. Two metal binding sites and an NS3-interacting region in ZIKV RdRp are demonstrated as potential drug screening sites. The docked structures reveal a remarkable degree of conservation at the substrate binding site and the potential drug screening sites. A phylogeny-based approach is provided for an emergency preparedness, where similar class of ligands could target phylogenetically related proteins. This article is protected by copyright. All rights reserved.

Zika Virus in Ontario: Evaluating a Rapid Risk Assessment Tool for Emerging Infectious Disease Threats.

To determine the Ontario-specific risk of local and travel-related Zika virus transmission in the context of a public health emergency of international concern, Public Health Ontario (PHO) completed a rapid risk assessment (RRA) on January 29, 2016, using a newly developed RRA guidance tool. The RRA concluded that risk of local mosquito-borne transmission was low, with a high risk of imported cases through travel. The RRA was updated 3 times based on predetermined triggers. An independent evaluation assessed both the application of the RRA guidance tool (process evaluation) and the usefulness of the RRA (outcome evaluation). We conducted face-to-face, semi-structured interviews with 7 individuals who participated in the creation or review of the Zika virus RRA and 4 end-users at PHO and the Ministry of Health and Long-Term Care. An inductive thematic analysis of responses was undertaken, whereby themes were directly informed by the data. The process evaluation determined that most steps outlined in the RRA guidance tool were adhered to, including forming a cross-functional writing team, clarifying the scope and describing context, completing the RRA summary report, and updating the RRA based on predefined triggers. The outcome evaluation found that end-users judged the Zika virus RRA as evidence-informed, useful, consistent, and timely. The evaluation established that the locally tailored guidance tool, adapted from national and international approaches to RRAs, facilitated a systematic, evidence-informed, and timely formal RRA process at PHO for the Zika virus RRA, which met the needs of end-users. Based on the evaluation, PHO will modify future RRAs by incorporating some flexibility into the literature review process to support timeliness of the RRA, explicitly describing the limitations of studies used to inform the RRA, and refining risk algorithms to better suit emerging infectious disease threats. It is anticipated that these refinements will improve upon the timely assessment of novel or reemerging infectious diseases.

Full-genome amplification and sequencing of Zika viruses using a targeted amplification approach.

We have developed methods for full-genome sequencing of Zika viruses (ZIKVs) based on a targeted amplification approach. We used alignments of publicly available complete genome data to design a primer set that selectively amplifies ZIKVs. The approach includes amplification strategies for templates present at both high- and low-copy number, and PCR cycling conditions that have been normalized across genome fragments in order to streamline laboratory handling. Abundant templates can be amplified using a strategy that uses 6 overlapping amplicons to cover the complete viral genome, whereas scarce templates can be amplified using a strategy that uses 11 overlapping amplicons of smaller size. The workflow is sequencing platform agnostic, and thus, can be used in low resource settings where access to traditional Sanger sequencing is the only option available. Given the scarcity of tools for ZIKV, this approach should facilitate epidemiological surveillance and other studies that require the generation of complete viral genomic information quickly and cost-effectively.

AIDS, Avian flu, SARS, MERS, Ebola, Zika… what next?

Emerging infections have threatened humanity since times immemorial. The dramatic anthropogenic, behavioral and social changes that have affected humanity and the environment in the past century have accelerated the intrusion of novel pathogens into the global human population, sometimes with devastating consequences. The AIDS and influenza pandemics have claimed and will continue to claim millions of lives. The recent SARS and Ebola epidemics have threatened populations across borders. The emergence of MERS may well be warning signals of a nascent pandemic threat, while the potential for geographical spread of vector-borne diseases, such as Zika, but also Dengue and Chikungunya is unprecedented. Novel technologies and innovative approaches have multiplied to address and improve response preparedness towards the increasing yet unpredictable threat posed by emerging pathogens.

An update on Zika vaccine developments.

The devastating consequences of congenital Zika virus (ZIKV) infection led to a global response directed toward a better understanding of the epidemiology and pathogenesis of ZIKV and to efforts at vaccine development. As a result, there are currently 45 ZIKV vaccine candidates in development. Areas covered: Both traditional (purified inactivated, live attenuated, viral-vectored, recombinant sub-unit) and novel (DNA, self-replicating RNA, mRNA) vaccine platforms are being utilized. For emergency use, vaccines that are appropriate for women of child-bearing age (including pregnant women) are being developed. Live vaccines that may be contraindicated in pregnancy are also in development for potential inclusion in national immunization programmes in childhood or pre-teenage age groups. WHO developed a target product profile for Zika vaccines for use in an emergency. Expert commentary: Although ZIKV vaccine development had a quick head start, further development may be hampered because of the inability to conduct large efficacy trials with the decline in cases globally and unpredictability of new outbreaks. Furthermore, there are complex ethical issues involved in conducting efficacy trials in pregnant women.

Infección por el virus Zika en el embarazo y su impacto.

Zika virus: a cause of concern in transplantation?

Worldwide, the number of countries reporting Zika virus (ZKV) infection continues to increase. Although 80% of cases are asymptomatic, ZKV has been identified as a neurotropic virus associated with congenital microcephaly, Guillain-Barre' syndrome, and meningoencephalitis. Until recently, infection in transplant recipients has not been identified. This study will review the existing literature on ZKV infection, laboratory testing, and management in transplant recipients.

Zika virus infection in Vietnam: current epidemic, strain origin, spreading risk, and perspective.

Zika virus infection and its associated microcephaly have being receiving global concern. This infection has spread widely since the first outbreak was recorded in Africa in 1952. Now, it has been reported in over 70 countries on five continents including Africa, North and South America, Asia, and Europe. Vietnam is one of the most recent countries which had cases of Zika virus infection at the end of 2016. This country has also reported the first case of a microcephaly-born baby which was probably linked to Zika virus infection. However, information on the Zika virus epidemic in Vietnam is still limited. This brief report intends to update the current Zika virus epidemic, and to discuss challenges and perspectives in controlling this infection in Vietnam.

Travel-Associated Zika Virus Disease.

Travel-Associated Zika Virus Disease.

What Are People Tweeting About Zika? An Exploratory Study Concerning Its Symptoms, Treatment, Transmission, and Prevention.

In order to harness what people are tweeting about Zika, there needs to be a computational framework that leverages machine learning techniques to recognize relevant Zika tweets and, further, categorize these into disease-specific categories to address specific societal concerns related to the prevention, transmission, symptoms, and treatment of Zika virus.

Early Evidence for Zika Virus Circulation among Aedes aegypti Mosquitoes, Rio de Janeiro, Brazil.

During 2014-2016, we conducted mosquito-based Zika virus surveillance in Rio de Janeiro, Brazil. Results suggest that Zika virus was probably introduced into the area during May-November 2013 via multiple in-country sources. Furthermore, our results strengthen the hypothesis that Zika virus in the Americas originated in Brazil during October 2012-May 2013.

Zika Virus Screening among Spanish Team Members After 2016 Rio de Janeiro, Brazil, Olympic Games.

We evaluated the risk for the Spanish Olympic Team acquiring Zika virus in Rio de Janeiro, Brazil, during 2016. We recruited 117 team members, and all tested negative for Zika virus. Lack of cases in this cohort supports the minimum risk estimates made before the Games.

Zika virus: practical guidelines.

Zika virus suddenly emerged in Latin America in 2015‑2016. Congenital malformations have been observed in infected pregnant women, causing a major public health impact in affected countries, particularly in Brazil. In addition, sexual transmission of Zika virus has been well documented. This led to the development of prevention strategies and recommendations for travellers visiting at risk countries. These documents are regularly amended depending on the evolution of scientific knowledge, the epidemiologic trends and the national and international guidelines. Through practical cases, we present here the guidelines developed by the Geneva University Hospitals.

School-Based Health Education in Yucatan, Mexico about the Chikungunya Virus and Mosquito Illness Prevention.

The Chikungunya virus (CHIKV) has been rapidly spreading throughout Latin America, utilizing pre-existing vectors to infiltrate the immunologically naïve populations. With the current rise of the Zika Virus, there is an urgent need for more rigorous vector control efforts to prevent further Zika breakout. We designed a school-based education module on CHIKV and mosquito prevention and presented it to the local students of ages of 6-18 in a rural town called Sudzal in Yucatan, Mexico. We distributed questionnaires before and after education to test the students' knowledge of CHIKV and mosquito prevention. Chi-squared test was performed to determine the efficacy of the presentation in increasing their knowledge. The education presentation has proven to effectively educate the local residents in several critical methods of mosquito prevention, increasing the average test scores by 67% post-education. These include applying repellent, staying hydrated during recuperation, and cleaning indoor water containers to eliminate breeding sites (P<0.001). Furthermore, the questionnaire captured the residents' behavioral patterns regarding CHIKV and mosquito prevention and identified cultural, ecological, and socioeconomic factors hindering effective implementation of vector control.

Zoonotic and Vector-Borne Diseases in Urban Slums: Opportunities for Intervention.

Urban slums provide conditions that increase the risk of exposure to vector-borne and zoonotic pathogens. Large interventions, such as social and sanitary changes, are a priority but their implementation is challenging. Integration between the multidisciplinary understanding of pathogens' dynamics and community participatory approaches is a key prevention strategy.

Ocular Effects of Zika Virus - A review.

Zika virus (ZIKV) was considered an innocent pathogen while restricted to the African and Asian population; however, after reaching the Americas in March 2015, it became a global threat. Despite usually causing mild or no symptoms in infected adults, ZIKV displays a different behavior towards fetuses. When infected during gestation, fetuses have their immature neural cells killed by the virus and consequently have devastating findings at birth. In the past year, the drastic effects of ZIKV infection in newborns include neurological, ophthalmological, audiological, and skeletal abnormalities. These findings represent a new entity called Congenital Zika Syndrome. We summarize the ocular findings of congenital Zika Syndrome, as well as the current understanding of the illness, systemic manifestations, laboratory investigation, differential diagnosis, prophylaxis, and treatment for this disorder.

Flavivirus and Filovirus EvoPrinters: New alignment tools for the comparative analysis of viral evolution.

Flavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest.

Author's Reply: Zika Virus Infection and Ophthalmic Examination in Newborn.

See Something, Say Something: Correction of Global Health Misinformation on Social Media.

Social media are often criticized for being a conduit for misinformation on global health issues, but may also serve as a corrective to false information. To investigate this possibility, an experiment was conducted exposing users to a simulated Facebook News Feed featuring misinformation and different correction mechanisms (one in which news stories featuring correct information were produced by an algorithm and another where the corrective news stories were posted by other Facebook users) about the Zika virus, a current global health threat. Results show that algorithmic and social corrections are equally effective in limiting misperceptions, and correction occurs for both high and low conspiracy belief individuals. Recommendations for social media campaigns to correct global health misinformation, including encouraging users to refute false or misleading health information, and providing them appropriate sources to accompany their refutation, are discussed.

Lessons learned on Zika virus vectors.