Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: an individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium

Summary Background Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%. Funding National Council for Scientific and Technological Development - Brazil (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq); Wellcome Trust and the United Kingdom's Department for International Development; European Union's Horizon 2020 research and innovation program; Medical Research Council on behalf of the Newton Fund and Wellcome Trust; National Institutes of Health/National Institute of Allergy and Infectious Diseases; Foundation Christophe et Rodolphe Mérieux; Coordination for the improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Capes); Ministry of Health of Brazil; Brazilian Department of Science and Technology; Foundation of Research Support of the State of São Paulo (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP); Foundation of Research Support of the State of Rio de Janeiro (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ); Foundation of Support for Research and Scientific and Technological Development of Maranhão; Evandro Chagas Institute/Brazilian Ministry of Health (Instituto Evandro Chagas/Ministério da Saúde); Foundation of Research Support of the State of Goiás (Fundação de Amparo à Pesquisa do Estado de Goiás – FAPEG); Foundation of Research Support of the State of Rio Grande do Sul (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul – FAPERGS); Foundation to Support Teaching, Research and Assistance at Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto (Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto); São Paulo State Department of Health (Secretaria de Saúde do Estado de São Paulo); Support Foundation of Pernambuco Science and Technology (Fundação de Amparo à Ciência e Tecnologia de Pernambuco – FACEPE).

Field validation of the performance of paper-based tests for the detection of the Zika and chikungunya viruses in serum samples

In low-resource settings, resilience to infectious disease outbreaks can be hindered by limited access to diagnostic tests. Here we report the results of double-blinded studies of the performance of paper-based diagnostic tests for the Zika and chikungunya viruses in a field setting in Latin America. The tests involved a cell-free expression system relying on isothermal amplification and toehold-switch reactions, a purpose-built portable reader and onboard software for computer vision-enabled image analysis. In patients suspected of infection, the accuracies and sensitivities of the tests for the Zika and chikungunya viruses were, respectively, 98.5% (95% confidence interval, 96.2–99.6%, 268 serum samples) and 98.5% (95% confidence interval, 91.7–100%, 65 serum samples) and approximately 2 aM and 5 fM (both concentrations are within clinically relevant ranges). The analytical specificities and sensitivities of the tests for cultured samples of the viruses were equivalent to those of the real-time quantitative PCR. Cell-free synthetic biology tools and companion hardware can provide de-centralized, high-capacity and low-cost diagnostics for use in low-resource settings.

Você conhece os impactos do vírus Zika sobre as famílias?

*Portuguese content* Com objetivo de avaliar como as famílias dessas crianças foram impactadas, a pesquisa Impactos econômicos e sociais do vírus Zika foi realizada no IFF-Fiocruz, hospital público federal situado no Rio de Janeiro, que atua em ensino, pesquisa e atendimento a mulheres, crianças e adolescentes.

Pregnant Women Infected with Zika Virus Show Higher Viral Load and Immunoregulatory Cytokines Profile with CXCL10 Increase

Results in this paper reveal that the anti-inflammatory response in pregnant women infected with ZIKA is characterized by high CXCL10, a cytokine correlated with congenital malformations.

Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia

This article provides a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia.

Uma Antropologia da Transmissão: mosquitos, mulheres e a epidemia de Zika no Brasil

Low Aedes aegypti Vector Competence for Zika Virus from Viremic Rhesus Macaques

This paper finds that Ae. aegypti vector competence for ZIKV from macaques is low, likely to be due to low viral load and the short duration of ZIKV viremia in primates suitable for infecting susceptible mosquitoes.

Zika virus transmission by Brazilian Aedes aegypti and Aedes albopictus is virus dose and temperature-dependent

Results indicate that Brazilian populations of Ae. aegypti exhibit a much higher transmission potential for ZIKV than Ae. albopictus.

Vector Competence of Aedes aegypti, Aedes albopictus and Culex quinquefasciatus from Brazil and New Caledonia for Three Zika Virus Lineages

Viral surveillance and mosquito control measures must be strengthened to avoid the spread of new ZIKV lineages and minimize the transmission of viruses currently circulating.

Forced Zika Virus Infection of Culex pipiens Leads to Limited Virus Accumulation in Mosquito Saliva

In this study, researchers provide the first demonstration of ZIKV accumulation in the saliva of Cx. pipiens upon forced infection. Nevertheless, they consider Cx. pipiens as a highly inefficient vector for ZIKV.

Rapid decline of Zika virus NS1 antigen-specific antibody responses, northeastern Brazil

Researchers have found that ZIKV immunity might be shorter-lived than previously thought, which may contribute to local ZIKV resurgence once individual immune responses wane sufficiently to reduce community protective immunity in addition to birth and migration.

Zika Virus Circulation in Mali

This study demonstrates the circulation of ZIKV in Mali and provides evidence of a previously unidentified outbreak that occurred in the late 1990s.

The invasive Asian bush mosquito Aedes japonicus found in the Netherlands can experimentally transmit Zika virus and Usutu virus

Given that Ae. japonicus can experimentally transmit arthropod-borne viruses (arboviruses) like ZIKV and USUV and is currently expanding its territories, we should consider this mosquito as a potential vector for arboviral diseases in Europe.

The global scientific research response to the public health emergency of Zika virus infection

Mapping the response to Zika, a public health emergency, demonstrated a clear pattern of the participation of countries in the scientific advances. The pattern of knowledge production found in this study represented varying country perspectives, research capacity and interests based first on their level of exposure to the epidemic and second on their financial positions regarding science.

Gender mainstreaming as a pathway for sustainable arbovirus control in Latin America

Building on the UN’s Sustainable Development Goals commitment to “leave no one behind” and the recent championing of a need for a people-centered approach to epidemic preparedness and response, the authors call for more evidence that can support policy recommendations and advocacy efforts for gender-mainstreamed arbovirus control programs in Latin America.

Genomic and Epidemiological Surveillance of Zika Virus in the Amazon Region

This study reveals how the ZIKV epidemic was ignited and maintained within the largest urban metropolis in the Amazon. These results might contribute to improving the public health response to outbreaks in Brazil.

A new class of broadly neutralizing antibodies that target the glycan loop of Zika virus envelope protein

Results showed in this article have strong implications for developing anti-ZIKV vaccines and therapeutic mAbs.

Uncertainty in times of medical emergency: Knowledge gaps and structural ignorance during the Brazilian Zika crisis

Uncertainty was a defining feature of the Brazilian Zika crisis of 2015–2016. This article identifies three forms of uncertainty: global health, public health and clinical uncertainty, and it suggests that “emergency research” was effective in tackling global health uncertainty.    

Recombination of B- and T-cell epitope-rich loci from Aedes- and Culex-borne flaviviruses shapes Zika virus epidemiology

Findings from this article explain why explosive ZIKV epidemics occurred in DENV-endemic regions of Micronesia, Polynesia and the Americas where Culex-borne flavivirus outbreaks are infrequent, and why ZIKV did not cause major epidemics in Asia where Culex-borne flaviviruses are widespread.

Zika seroprevalence declines and neutralizing antibodies wane in adults following outbreaks in French Polynesia and Fiji

Data from this study suggest that immunity against the Zika virus may not last as long as previously thought, which could affect the chances of future outbreaks.

Spatiotemporal Analysis of the Population Risk of Congenital Microcephaly in Pernambuco State, Brazil

This study emphasizes the burden of microcephaly during the outbreak in Pernambuco, with estimates higher than in some previous studies, and with high risk in an inland region of the state for reasons which are yet to be clarified.

A literary history of Zika: Following Brazilian state responses through documents of emergency

Book chapter in Locating Zika Social Change and Governance in an Age of Mosquito Pandemics; Edited by Kevin Bardosh  

Viral emergence and immune interplay in flavivirus vaccines

Comment

Low vector competence in sylvatic mosquitoes limits Zika virus to initiate an enzootic cycle in South America

These results suggest that genetically determined tissue barriers, especially in the midgut, play a vital role in inhibiting ZIKV for transmission in the tested sylvatic mosquito species. Thus, an independent enzootic transmission cycle for ZIKV in South America is very unlikely.

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium

Results of large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV.

Estimating the risk of arbovirus transmission in Southern Europe using vector competence data

Based on vector competence data and vector distribution, the auhtors generate a prediction risk map for CHIKV stressing the fear of CHIKV and to a lesser extent, of other arboviruses for Europe, calling us for new public health strategies.

Zika virus threshold determines transmission by European Aedes albopictus mosquitoes

Results in this study stress the poor ability of Ae. albopictus to sustain a local transmission of ZIKV in Europe and provide a promising tool to evaluate the risk of ZIKV transmission in future outbreaks.

Zika Virus Outbreak on Curaçao and Bonaire, a Report Based on Laboratory Diagnostics Data

ZIKV cases confirmed by qRT-PCR indicate that the virus was circulating on Curaçao between at least December 2015 and March 2017, and on Bonaire between at least October 2016 and February 2017, with peak cases occurring in November 2016.

REALM: An Altmetrics-based Framework to Map Science Impacts on Society. A Case Study on Zika Research

In this paper the authors describe an altmetrics-based framework which allows the identification of specialists and important research in specific research scenarios.

Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infection

Yeast-derived EDIII is a safe and effective ZIKV vaccine candidate with desirable production traits.

High specificity and sensitivity of Zika EDIII-based ELISA diagnosis highlighted by a large human reference panel

Researchers developed a ZEDIII-based ELISA that can discriminate between past or current DENV and ZIKV infections, allowing the detection of a serological scar from other flaviviruses. This could be used to confirm exposure of pregnant women or to follow the spread of an endemic disease.

Complex Scenario of Homotypic and Heterotypic Zika Virus Immune Enhancement

Letter to the Editor

Impact of Zika Virus Emergence in French Guiana: A Large General Population Seroprevalence Survey

This study described a large-scale representative ZIKV seroprevalence study in South America from the recent 2015–2016 Zika epidemic. The findings reveal that the majority of the population remains susceptible to ZIKV, which could potentially allow future reintroductions of the virus.

Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil

The results reported in this study suggest that multitypic dengue virus infection may protect from, rather than enhance, development of congenital Zika syndrome.

Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway

Results from this research show that the differentiation state of hNPCs is a significant factor contributing to the outcome of ZIKV infection and furthermore suggest that ZIKV infection might initiate early activation of the Notch pathway resulting in an abnormal differentiation process, implicated in ZIKV-induced brain injury.

Whole-Blood Testing for Diagnosis of Acute Zika Virus Infections in Routine Diagnostic Setting

Comparison of Zika virus quantitative reverse transcription PCR results in single timepoint whole blood–plasma pairs from 227 patients with suspected Zika virus infection resulted in confirmation of 8 additional patients with Zika virus infection.

Phylogeography and invasion history of Aedes aegypti, the Dengue and Zika mosquito vector in Cape Verde islands (West Africa)

The authors of this study performed a phylogeographic and population genetics study of A. aegypti in Cape Verde in order to infer the geographic origin and evolutionary history of this mosquito.

Assessing the Potential Interactions between Cellular miRNA and Arboviral Genomic RNA in the Yellow Fever Mosquito, Aedes aegypti

This study shows a broad picture of possible interactions between mosquito cellular miRNAs and the viral RNA of different genotypes/lineages of arboviruses, providing a list of mosquito cellular miRNAs candidates for experimental validations in future studies.

Zika virus infection: an update

Since the ZIKV outbreak in Brazil in 2015, the scientific community has joined efforts to gather more information on the epidemiology, clinical features and pathogenicity of the virus. Here, you can read a summary of the most important advances made recently and the discussion of promising, innovative approaches to understand and control ZIKV infection.

A snapshot on the impact of ZIKAlliance's scientific publications between December 2018 and April 2019

Transmission potential of African, Asian and American Zika virus strains by Aedes aegypti and Culex quinquefasciatus from Guadeloupe (French West Indies)

Culex quinquefasciatus mosquitoes from Guadeloupe are not able to experimentally transmit ZIKV. It was also noticed better transmission of ZIKV strain from Senegal by Ae. aegypti from Guadeloupe compared to Malaysia and Martinique strains.

A computational method for the identification of Dengue, Zika and Chikungunya virus species and genotypes

In this study, the authors developed an efficient method to classify virus sequences with respect to their species and sub-species (i.e. serotype and/or genotype).

Second ZIKAlliance’s Annual Meeting in Rotterdam, 2-3 May 2019

Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus

This study offers an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.

A Viral Polymerase Inhibitor Reduces Zika Virus Replication in the Reproductive Organs of Male Mice

In this study, the authors explore the potential of antivirals to serve as an effective strategy to prevent sexual transmission. The data illustrate the value of a mouse model to validate the efficacy of new potential ZIKV drugs at the level of the male reproductive system.

Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cells

In this study, the authors provide in vitro evidence that infection of HUVECs with ZIKV induces apoptosis and elevation of TF expression that leads to activation of secondary hemostasis.

The possible role of cross-reactive dengue virus antibodies in Zika virus pathogenesis

In this review, the authors summarize the results of the evidence to date and elaborate on other possible detrimental effects of cross-reactive flavivirus antibodies, both for ZIKV infection and the risk of ZIKV-related congenital anomalies, DENV infection, and dengue hemorrhagic fever.

Assessing Zika Virus Transmission Within Households During an Outbreak in Martinique, 2015–2016

This study characterized the contribution of household transmission in ZIKV epidemics, demonstrating the benefits of integrating multiple data sets to gain more insight into epidemic dynamics.

The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses

Data in this study suggest that the human upper respiratory tract epithelium is a target for flaviviruses and could potentially play a role in the spread of infection to other body compartments through basolateral virus release. Further work is required to evaluate the risks and define the adapted measures to protect individuals exposed to flavivirus-contaminated body fluids.

Lipidomic Analysis Reveals Serum Alteration of Plasmalogens in Patients Infected With ZIKA Virus

Data provided in this article add important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV.

Zika virus infection among symptomatic patients from two healthcare centers in Sao Paulo State, Brazil: prevalence, clinical characteristics, viral detection in body fluids and serodynamics

This study shows that urine ZIKV RT-PCR testing in the acute phase of infection can improve the sensitivity of diagnosis, while testing serum is probably less useful despite more sustained shedding in some cases. Higher sensitivity and specificity serological tests are needed for the diagnosis of patients who seek medical attention after the period of ZIKV detection by RT-PCR and for surveillance purposes in settings of high DENV background infection.

Scientific collaboration in Zika: identification of the leading research groups and researchers via social network analysis

This study shows that a Zika researcher’s influence is basically determined by three factors: (a) number of publications; (b) diversified partnerships; and (c) the links established with the research area’s pioneers.

SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts

In this study, the authors determined the global proteomic profile of CHIKV and ZIKV infections in human skin fibroblasts using Stable Isotope Labelling by Amino acids in Cell culture (SILAC)-based mass-spectrometry analysis.

The Unfolded Protein Response: A Key Player in Zika Virus-Associated Congenital Microcephaly

The discovery of the link between ZIKV infection and UPR activation has a broader relevance, since this pathway plays a crucial role in many distinct cellular processes and its induction by ZIKV may account for several reported ZIKV-associated defects.

Vector-borne transmission and evolution of Zika virus

The authors of this study review the mosquito and vertebrate host species potentially involved in ZIKV vector-borne transmission worldwide; provide an evidence-supported analysis regarding the possibility of ZIKV spillback from an urban cycle to a zoonotic cycle outside Africa; and review hypotheses regarding recent emergence and evolution of ZIKV.

Low Zika Virus Seroprevalence in Vientiane, Laos, 2003–2015

With a low herd immunity in the Vientiane population, ZIKV represents a risk for future large-scale outbreaks. Implementation of a nationwide ZIKV surveillance network and epidemiological studies throughout Laos is needed.

The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million births

This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate lead the authors to hypothesize that the Northeast region of Brazil was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.

The difficulties in obtaining reliable Zika virus diagnostics

Correspondence re: Familiar barriers still unresolved - a perspective on the Zika virus outbreak research response

Zika Virus Seroprevalence in Urban and Rural Areas of Suriname, 2017

In Suriname, 770 participants were recruited from 1 urban area and 2 rural villages in the tropical rainforest in order to conduct a ZIKV serosurvey. Researchers found that 35.1% of the participants had neutralizing antibodies against ZIKV. In 1 remote village in the rainforest, 24.5% of the participants had neutralizing antibodies against ZIKV, suggesting that ZIKV was widely spread across the country.

Monocyte-Derived Dendritic Cells as Model to Evaluate Species Tropism of Mosquito-Borne Flaviviruses

The authors of this study demonstrate Flavivirus-dependent differences in the interaction with monocyte-derived dendritic cells. These may play a role in pathogenesis but appear to only partially reflect the expected species tropism.

Differential Shedding and Antibody Kinetics of Zika and Chikungunya Viruses, Brazil

Recurrent recent arbovirus infections suggested by serologic data and unspecific symptoms highlight the need for exhaustive virologic testing.

Optimization of a fragment linking hit toward Dengue and Zika virus NS5 methyltransferases inhibitors

A fragment-based drug design approach on flavivirus methyltransferase.

Combination of ELISA screening and seroneutralisation tests to expedite Zika virus seroprevalence studies

The authors of this study propose a strategy allowing implementing efficient and practicable large-scale seroepidemiological studies for Zika Virus (ZIKV).

Human stem cell-derived hepatocyte-like cells support Zika virus replication and provide a relevant model to assess the efficacy of potential antivirals

The authors of this study demonstrate that both human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) and the Huh7 hepatoma cell line support the complete ZIKV replication cycle.

Neurodevelopment in Infants Exposed to Zika Virus In Utero

Letter to the Editor

A yellow fever–Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in mice

The authors of this study report the engineering of a chimeric virus vaccine candidate (YF-ZIKprM/E) by replacing the antigenic surface glycoproteins and the capsid anchor of YFV-17D with those of a prototypic Asian lineage ZIKV isolate.

Within the Zika virus (ZIKV) research community, a new and remarkable kind of collaboration is taking place

ZIKAlliance travels to Peru and Ecuador

Familiar barriers still unresolved - a perspective on the Zika virus outbreak research response

The authors of this study have identified three major bottlenecks in the implementation of a swift response to the increasing frequency of widespread infectious disease outbreaks: the absence of a timeline for the funding process, delays in regulatory and ethical approval, and the challenging logistics of laboratory support, including diagnostics.

Estimating the risk of Dengue, Chikungunya and Zika outbreaks in a large European city

The model provided in this study correctly estimates the number of imported cases and can be easily adapted to other urban areas where Ae. albopictus is the only potential vector present.

Research Models and Tools for the Identification of Antivirals and Therapeutics against Zika Virus Infection

This review focuses on the recent advances regarding research models, as well as available experimental tools that can be used for the identification and characterization of potential antiviral targets and therapeutic intervention strategies.

Potential effect of Zika virus infection on human male fertility?

The findings from this study suggest a possible long-term detrimental effect of ZIKV infection on human male fertility that has to be further explored in well-characterized samples from cohort studies conducted in ZIKV-endemic areas.

Zika virus infection modulates the metabolomic profile of microglial cells

In the present study, the authors investigate the metabolomic profile of ZIKV-infected microglia.

Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis

The findings in this article suggest that the ZIKV epidemic is by and large over within LAC, with incidence projected to be low in most cities in 2018. Local low levels of transmission are probable, but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.

Zika virus infects human testicular tissue and germ cells

This study provides key insights into how ZIKV may persist in semen and alter semen parameters, as well as a valuable tool for testing antiviral agents.

Differential transmission of Asian and African Zika virus lineages by Aedes aegypti from New Caledonia

The results of this study demonstrate that Ae. aegypti from New Caledonia can become infected and replicate different ZIKV strains belonging to all lineages. These data emphasize the importance of studying the interaction between vectors and their arboviruses according to each local geographic context.

Lessons learnt from the emergence of Zika virus

Comment

Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil

Data from this study support a link between maternal ZIKV infection and congenital malformations and suggest the occurrence of predominantly vector-borne ZIKV transmission in these cases. In addition, some highly prevalent TORCH pathogens may be misinterpreted as representative of ongoing ZIKV activity in the absence of exhaustive diagnostics in northeastern Brazil.

Zika virus outbreak in the Pacific: Vector competence of regional vectors

Results from this study indicate a low ZIKV transmission by Ae. aegypti and Ae. polynesiensis tested from the Pacific region. These results were unexpected and suggest the importance of other factors especially the vector density, the mosquito lifespan or the large immunologically naive fraction of the population that may have contributed to the rapid spread of the ZIKV in the Pacific region during the 2013–2017 outbreak.

Re-visiting the evolution, dispersal and epidemiology of Zika virus in Asia. A commentary from the authors.

Pettersson et al provide a short commentary on their research article Re-visiting the evolution, dispersal and epidemiology of Zika virus in Asia published in Emerging Microbes & Infections in May 2018. This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement no. 734548 and ZikaPLAN Grant Agreement no. 734584.

4 EU-funded Zika consortia met in Marseille during the International Symposium to discuss a common strategy for vaccine development

Re-visiting the evolution, dispersal and epidemiology of Zika virus in Asia

In this study, the authors have traced the phylogenetic history and spatio-temporal dispersal pattern of ZIKV in Asia prior to its explosive emergence in the Pacific region and the Americas.

External Quality Assessment for Zika Virus Molecular Diagnostic Testing, Brazil

The results from this study emphasize the need for continuous quality assessments of Zika virus diagnostic testing globally.

Zika virus and Guillain–Barré syndrome in Bangladesh

Researchers found no significant association between ZIKV infection and GBS in Bangladesh, but GBS following ZIKV infection was characterized by a distinct clinical and electrophysiological subtype compared to C. jejuni infection. These findings indicate that ZIKV may precede a specific GBS subtype but the risk is low.

Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas

The risk of congenital neurologic defects related to Zika virus (ZIKV) infection has ranged from 6 to 42% in various reports. The aim of this study was to estimate this risk among pregnant women with symptomatic ZIKV infection in French territories in the Americas.

Zika virus epidemiology in Bolivia: A seroprevalence study in volunteer blood donors

The authors conclude that ZIKV has been circulating in Bolivian tropical areas but not in highlands, and that the epidemic has not been limited by previous immunity against dengue. Specific attention should be paid to the region of Santa Cruz, where the seroprevalence is still limited, but the density of Aedes aegypti populations makes plausible further spreading of the disease.

The structural proteins of epidemic and historical strains of Zika virus differ in their ability to initiate viral infection in human host cells

In this study researchers show that ZIKV containing BeH819015 structural proteins is much less efficient in cell-attachment leading to a reduced susceptibility ofepithelial A549 and neuronal SH-SY5Y cells to viral infection.

Limited Evidence for Infection of Urban and Peri-urban Nonhuman Primates with Zika and Chikungunya Viruses in Brazil

The authors of this study tested nonhuman primates (NHP) sampled during 2012 to 2017 in urban and peri-urban areas severely affected by ZIKV and CHIKV in Brazil. Seroprevalence and antibody titers were low for both viruses. Additionally, they found evidence for infection by heterologous viruses eliciting cross-reactive antibodies. These data suggest that urban or peri-urban NHP are not easily infected by ZIKV and CHIKV despite intense local transmission, and they may also imply that the ZIKV and CHIKV outbreaks in the Americas cannot be sustained in urban or peri-urban NHP once human population immunity limits urban transmission cycles.

Emerging trends of Zika apprehension in an epidemic setting

The findings of this study have implications for the development of multifaceted infection control programs, including strategies for prevention and awareness, helping the population to develop an accurate perception of the threat they are facing and encouraging behavior changes.

The Zika Virus Epidemic in Brazil: From Discovery to Future Implications

The authors of this study discuss gaps in the knowledge and the challenges ahead to anticipate, prevent, and control emerging and re-emerging epidemics of arboviruses in Brazil and worldwide.

Recombinant Zika NS1 Protein Secreted from Vero Cells Is Efficient for Inducing Production of Immune Serum Directed against NS1 Dimer

The authors of this article demonstrated that recombinant ZIKV NS1 expressed in mammalian cells stably transduced with a lentiviral vector is suitable for inducing the production of specific antibody directed against NS1 oligomer. According to the authors, anti-ZIKV immune serum could be a great tool for the specific detection of secreted NS1 hexamer in human cells infected with ZIKV of African and Asia lineages, including contemporary epidemic strains.

Zika virus can be venereally transmitted between Aedes aegypti mosquitoes

In this study, researchers assessed for the first time the venereal transmission of ZIKV between Aedes aegypti under laboratory conditions. Their conclusion is that venereal transmission between Aedes mosquitoes might contribute to Zika virus maintenance in nature.

Zika virus evolution on the edges of the Pacific ocean

In this study, by adding 13 new full ZIKAV genome sequences, isolated from different places in the Pacific region and at different periods of time, along with other published genomes, the authors provide for the first time a map of the whole ZIKAV Pacific sublineage, from the Western to the Eastern edges of the Pacific ocean.

Stress-induced unfolded protein response contributes to Zika virus–associated microcephaly

In order to understand the mechanism of Zika virus-associated microcephaly, the authors combined analysis of human fetuses infected with Zika virus, cultures of human neuronal stem cells and mice embryos. They showed that ZIKV infection of cortical progenitors controlling neurogenesis triggers a stress in the endoplasmic reticulum in the embryonic brain, inducing signals in response to incorrect protein con-formation.

Vectorial status of the Asian tiger mosquito Aedes albopictus of La Réunion Island for Zika virus

The authors performed an experimental oral infection with the Asian genotype of ZIKV in Ae. albopictus from La Réunion and found a strong midgut barrier to dissemination. This result is discussed in the light of previous vector competence assays for DENV and CHIKV performed on other Ae. albopictus populations from La Réunion.

ZIKAlliance’s Annual Meeting in Guadeloupe 23-24 November, 2017

High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks

In this article, authors find that the high burden of Zika virus infection in a northeastern Brazilian metropolis questions the fate of the outbreak due to population protective immunity; that Zika virus infection predominantly affects geographic areas with low socioeconomic status, demonstrating a clear link between poverty and Zika virus infection; and, finally, additional evidence for the link between Zika virus infection and microcephaly.

High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks [Press Release]

A study published this week in mBio demonstrates rapid spread of ZIKV in Salvador, a metropolis in northeastern Brazil representing one of the most affected areas during the American ZIKV outbreak, and infection rates exceeding 60%.

Infection of a French Population of Aedes albopictus and of Aedes aegypti (Paea Strain) with Zika Virus Reveals Low Transmission Rates to These Vectors’ Saliva

This study shows that the extrinsic incubation period of Ae. aegypti for transmission is shorter than that of Ae. albopictus.

Zika virus displacement by a chikungunya outbreak in Recife, Brazil

In 2015–2016 in the Recife Metropolitan Region, the authors of this study detected the tail end of a Zika epidemic, which was displaced by a chikungunya epidemic. Few dengue cases were identified despite a high number of official dengue notifications in the area during this period. This study shows here important epidemiological features of these cases.

InFocus interview with Anna-Bella Failloux

Culex quinquefasciatus mosquitoes do not support replication of Zika virus

The authors of this study found that Culex quinquefasciatus does not support ZIKV replication and Wolbachia is not involved in producing this phenotype. These mosquitoes are therefore very unlikely to play a role in transmission of ZIKV.

New reverse genetics and transfection methods to rescue arboviruses in mosquito cells

In order to overcome potential technological issues related to the study of arboviruses, the authors of this study designed an improved DNA transfection protocol for insect cells and then demonstrated that the simple and flexible ISA (Infectious Subgenomic Amplicons) reverse-genetics method can be efficiently applied to both mammalian and mosquito cells to generate in days recombinant infectious positive-stranded RNA viruses belonging to genera Flavivirus (Japanese encephalitis, Yellow fever, West Nile and Zika viruses) and Alphavirus (Chikungunya virus). 

Lineage-Specific Real-Time RT-PCR for Yellow Fever Virus Outbreak Surveillance, Brazil

The authors of this study developed novel multiplex real-time reverse transcription PCRs. The new PCRs enable yellow fever (YFV) detection with diagnostic sensitivity. Although the dual-target assay is superior to the single-target assay in sensitivity and robustness to target competition, the single-target assay – as stated by the researchers – may be advantageous in resource-limited settings and may be more convenient for multiplex usage in combination with assays targeting co-circulating arboviruses, such as chikungunya, Zika, and dengue viruses.

Characterization of the Zika virus induced small RNA response in Aedes aegypti cells

Results from this study suggest that ZIKV has mechanisms to evade mosquito innate immunity and it is therefore important to understand virus-vector interactions and the implications they have on transmission.

Three EU-funded Zika Consortia Meetings at ECTMIH

During the European Congress on Tropical Medicine and International Health (ECTMIH) conference in Antwerp, the three EU-funded Zika Consortia, ZIKAlliance, ZIKAction and ZikaPLAN organized a joint symposium, with an afternoon of presentations packed with up-to-date science regarding ZIKV on October 17th.

First outbreak of Zika virus in the continental United States: a modelling analysis. A commentary from the authors

Marini et al provide a short commentary on their research article First outbreak of Zika virus in the continental United States: a modelling analysis published in September 2017 in Eurosurveillance. This was supported by the European Union’s Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement no. 734548.

ClearColi BL21(DE3)-based expression of Zika virus antigens illustrates a rapid method of antibody production against emerging pathogens

The remarkable efficacy of the ClearColi BL21(DE3)-based expression system at eliciting the rapid production of specific anti-ZIKV antibodies endorses an innovative method, which can be extended to emerging viruses for which development of immunological tools is an urgent prerequisite.

Evidence for congenital Zika virus infection from neutralizing antibody titers in maternal sera, north-eastern Brazil

Results from this study suggest that despite the inter-individual variability in immune responses, the magnitude of the maternal ZIKV-specific neutralizing antibody response may prove useful to corroborate congenital ZIKV infection, contributing to reliable estimates of the manifestation index of ZIKV-associated congenital disease. Further studies will be needed to evaluate the time-course of maternal neutralizing antibody responses to identify whether a high maternal PRNT titer can be used as an early marker of congenital infection aiding potential antiviral intervention strategies.

InFocus interview with Vivian Avelino-Silva

First outbreak of Zika virus in the continental United States: a modelling analysis

In this work, the authors analysed the transmission dynamics of the Wynwood outbreak, recorded in Florida at the end of July 2016, using a mathematical model calibrated to outbreak data, and assessed the efficacy of the implemented vector control measures in containing viral transmission. Results from this analysis provide useful insights for prevention and control of possible future outbreaks in European areas.

Update on activities from Work Package 2: Clinical Biology & Immunology

Work Package 8: An update on ZIKAlliance communication activities

Zika genomics urgently need standardized and curated reference sequences

In this letter, the authors address the need for curation and standardized annotation of ZIKV reference genomes in order to guide researchers and clinicians in genomic analyses and the translation of research findings.

InFocus interview with Sarah Bethencourt

Replication of the Zika virus in different iPSC-derived neuronal cells and implications to assess efficacy of antivirals

This study demonstrates for the first time that motor neurons support ZIKV replication and these cells are as a consequence of ZIKV replication destroyed by the virus, and that human iPSC derived neuronal cells offer a physiologically relevant system to assess the potential antiviral effect of small molecule inhibitors of viral replication that are being developed to clear ZIKV infections in the nervous system.

Re-evaluation of routine dengue virus serology in travelers in the era of Zika virus emergence

Researchers have demonstrated that the recent ZIKV outbreak in Latin America substantially affects the DENV serology in routine diagnostic laboratories.

Neotropical bats that co-habit with humans function as dead-end hosts for dengue virus

Results from this study indicate that bats do not sustain sufficient virus amplification in order to function as reservoirs and exclude them as players in the dengue virus transmission cycle.

ZIKAlliance’s Clinical Meeting in Cuba 12-14 August, 2017

InFocus interview with Dra Carmen Soria

Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies

Researchers found that in order for an antiviral treatment to effectively reduce the time to plasma viral clearance therapy should be initiated at the time of infection or given prophylactically.

Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells

Taken together, this study shows that African and Asian ZIKV strains differ in their abilities to infect and replicate in different neural cells, as well as their abilities to cause cell death early after infection. This implies that caution is necessary against extrapolation of experimental data obtained using historical African ZIKV strains to the current outbreak. In addition, the fact that Asian ZIKV strains infect only a minority of cells with a relatively low burst size together with the lack of early cell death induction might contribute to their ability to cause chronic infections within the CNS.

Insecticide resistance is mediated by multiple mechanisms in recently introduced Aedes aegypti from Madeira Island (Portugal)

This study showed the up-regulation of several detoxification genes of multiple enzyme families associated with metabolic resistance, and the presence of the two kdr mutations, with the F1534C being fixed. Another suggested mechanism probably involved in the resistance phenotype is cuticle thickening, as several cuticle genes were found overexpressed. This study reinforces the importance of alternative control strategies to suppress Ae. aegypti population and thus reduce the likelihood of arbovirus transmission in the region.

Establishment and cryptic transmission of Zika virus in Brazil and the Americas

Results from this study further indicate that viruses from northeast Brazil were important for the continental spread of ZIKV. Within Brazil, the authors find instances of virus lineage movement from northeast to southeast Brazil; most of these events are dated to the second half of 2014 and led to onwards transmission in Rio de Janeiro and São Paulo states. The authors infer that ZIKV lineages disseminated from northeast Brazil to elsewhere in Central America, the Caribbean, and South America.

Culex quinquefasciatus from areas with the highest incidence of microcephaly associated with Zika virus infections in the Northeast Region of Brazil are refractory to the virus

The study shows that Culex quinquefasciatus should not be considered a potential vector of ZIKV in Brazil.

Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking

This study shows that imipramine strongly inhibits the replication of several Flaviviridae family members, including Zika, West Nile and Dengue virus. These data show that this compound is a potential drug candidate for anti-arboviral treatment.

Low seroprevalence of Zika virus in Cameroonian blood donors

The findings from this study indicate that the immunity of the Cameroonian population against ZIKV is low and that circulation in urban populations is uncommon. Hence, the risk of epidemic spread of ZIKV does exist. The virus is likely to be imported by infected travelers coming from epidemic areas and has the potential to be transmitted by local peri-domestic mosquitoes. This study provides biological evidence that such introduction would occur in populations that are globally immunologically naïve against ZIKV infection and live in areas where potential epidemic vectors exist.

Suramin inhibits Zika virus replication by interfering with virus attachment and release of infectious particles

The authors of this article describe inhibition of ZIKV replication by suramin, originally an anti-parasitic drug. They suggest that the inhibitory effect of suramin on ZIKV attachment and virion biogenesis and its broadspectrum activity warrant further evaluation of this compound as a potential therapeutic.

Successful technology transfer of a Zika vaccine developed by Institut Pasteur Shanghai-Chinese Academy of Sciences (IPS-CAS) to Chongqing Zhifei Biological Products Co., Ltd.

Institut Pasteur Shanghai-Chinese Academy of Sciences (IPS-CAS), a partner of the ZIKAlliance consortium, announced that it has entered into a collaborative research agreement with Chongqing Zhifei Biological Products Stock Co., Ltd. (Zhifei) for the clinical studies and commercialization of a recombinant Zika virus subunit vaccine developed by IPS-CAS.

Call for support - Global Vector Control Response grant application

In response to the recent World Health Organisation (WHO) Global Vector Control Response document (http://www.who.int/malaria/global-vector-control-response/en/), ARCTEC at the London School of Hygiene & Tropical Medicine is working with The Global Health Network, the WHO and the Centres for Disease Control and Prevention (CDC) to develop an exciting new initiative called The Global Vector Hub. The project is being part-funded by an EU H2020 grant as part of the recently formed ZikaPLAN consortium.  We have been invited by the Wellcome Trust to submit an application for a Biomedical Resource and Technology Development Grant to help fund the website. We have successfully advanced through the first round of grant proposals. The full application is now being prepared and is due for submission on 3rd April, 2017. To demonstrate the need for the Global Vector Hub, we are collecting letters of support from potential stakeholders. It would be great if you could distribute this e-mail to your contacts and ask them to provide letters of support.

Risk of microcephaly after Zika virus infection in Brazil, 2015 to 2016

The key message from this study is that the large uncertainty around the risk estimate needs to be further investigated because of a) the possible existence of co-factors that are yet to be validated, b) the assumptions that the authors needed to make in the absence of good data for the proportion of women who were infected during pregnancy.

Risk of microcephaly after Zika virus infection in Brazil, 2015 to 2016

The key message from this study is that the large uncertainty around the risk estimate needs to be further investigated because of a) the possible existence of co-factors that are yet to be validated, b) the assumptions that the authors needed to make in the absence of good data for the proportion of women who were infected during pregnancy.

Funding available for the SPSAS in Arbovirology in Brazil

15th International Dengue Course and ZIKAlliance WP1 meeting to be held in Cuba next August

Substrate selectivity of Dengue and Zika virus NS5 polymerase towards 2'-modified nucleotide analogues

In addition to representing the first ZIKV full-length NS5 activity report at the molecular level, this study should help the design of pan-flavivirus drugs aiming at the control of many Flavivirus members of this large family of emerging arboviruses, as well as understand the basis of re-purposing drugs against emerging viral diseases.

Zika Virus Methyltransferase: Structure and Functions for Drug Design Perspectives

The results outlined in the article contribute to a better understanding of the ZIKVMTase, a central player in viral replication and host innate immune response, and lay the basis for the development of potential antiviral drugs.

Real-Time Assessment of Health-Care Requirements During the Zika Virus Epidemic in Martinique

This study showcases the contribution of modeling to inform local health-care planning during an outbreak. Timely studies that estimate the proportion of infected persons that seek care are needed to improve the predictive power of such approaches.

Aedes aegypti Control Through Modernized, Integrated Vector Management

Researchers demonstrate that strategically combining the suppression methods with Wolbachia can generate a sustained control while mitigating the risks of inadvertent exacerbation of the wild mosquito population.

Study of volunteer blood donors in Martinique provides new information about Zika virus infection

This pioneering study provides a precise follow-up of incident cases and seroprevalence in blood donors, and it also provides important insights into the management of blood donations during ZIKV outbreaks and into the natural history of ZIKV infection in adults. It suggests that the study of blood donors during outbreaks of emerging pathogens has become a key element of epidemiological surveillance.

Zika virus causes supernumerary foci with centriolar proteins and impaired spindle positioning

The article concludes that infection with Flaviviridae can increase centrosome numbers and impair spindle positioning, thus potentially contributing to microcephaly in the case of Zika.

Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses

A study performed by the Institut National de la Santé et de la Recherche Médicale (INSERM) team of Dr Ali Amara (U944, Paris, France) and published in Cell Reports sheds new light on the mechanisms allowing ZIKV to infect cells within the human nervous system. Amara et al. showed that the protein Axl is expressed in a number of brain glial cells and that the entry of ZIKV into these cells requires another protein, Gas6, to act as a bridge between the ZIKV particles and the glial cells.

African and Asian Zika virus strains differentially induce early antiviral responses in primary human astrocytes

This study describes for the first time the specific antiviral gene expression in infected primary human astrocytes, the major glial cells within the central nervous system.

Zika virus in asymptomatic blood donors in Martinique

This pioneering study suggests that the study of blood donors during outbreaks of emerging pathogens has become a key element of epidemiological surveillance.

Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses

A study performed by the Institut National de la Santé et de la Recherche Médicale (INSERM) team of Dr Ali Amara (U944, Paris, France) and published in Cell Reports sheds new light on the mechanisms allowing ZIKV to infect cells within the human nervous system. Amara et al. showed that the protein Axl is expressed in a number of brain glial cells and that the entry of ZIKV into these cells requires another protein, Gas6, to act as a bridge between the ZIKV particles and the glial cells.

Simple reverse genetics systems for Asian and African Zika viruses

By using the bacterium-free ‘Infectious Subgenomic Amplicons’ (ISA) method, this study provides the scientific community with two simple and performing reverse genetics systems for ZIKV.

ZIKAlliance Kick-off Meeting in Brazil

Hosted by University Sao Paulo Medical School at the Centro de Convenções Rebouças ZIKAlliance, the multinational and multidisciplinary consortium coordinated by Inserm, the French National Institute of Health and Medical Research, and  created in response to a Horizon 2020 funding call by the European Commission’s Directorate-General Research and Innovation, has officially started its activities with the kick-off meeting held in Brazil over the 4^th and 5^th December 2016.

Zika and Other Emerging Viruses: Aiming at the Right Target

The article argues that the off-label use of drugs that may protect against Zika virus-induced brain damage has to be balanced with their risk during pregnancy.

How Did Zika Virus Emerge in the Pacific Islands and Latin America?

Based on comparative ZIKV complete genome phylogenetic analyses and temporal estimates, the authors identify amino acid substitutions that may be associated with increased viral epidemicity, CZVS, and GBS. Reverse genetics, vector competence, and seroepidemiological studies will test the hypothesis that these amino acid substitutions are determinants of epidemic and neurotropic ZIKV emergence.

From the Wellcome Trust: Zika: Why now and what next?

The Zika virus appears to have emerged from nowhere, causing widespread health concerns throughout the world after decades of relative silence.

CDC Video about Zika virus

The Zika virus is another wild card dealt to us by nature. It was first discovered in 1947.