Zika Virus Outbreak Research Articles

Zika virus in Brazil: an overview of public health policies

Objective: The purpose of this review was to discuss the effectiveness of public health policies in controlling Zika virus (ZIKV) in Brazil from 2015 to 2019 with an emphasis in the state of Pernambuco. Literature Review: Zika virus is an arbovirus primarily transmitted to humans by Aedes aegypti mosquitoes. Since 2015, the control of Aedes aegypti proliferation and diffusion has been a global subject of discussion due to its role in ZIKV transmission and the emergence of serious clinical symptoms resulting from this infection. In Brazil, the public policies established to control ZIKV outbreak were mostly based on vector control. Final Considerations: The coping model to manage the transmission vector of ZIKV is not showing to be effective. Furthermore, until the social factors that favor the development and maintenance of mosquito breeding sites are eradicated, Brazil will continue to be susceptible to new outbreaks of mosquito-driven arboviruses. Here, we discussed the effectiveness of public health policies for the control of ZIKV in Brazil from 2015 to 2019, with a primary focus on the state of Pernambuco (PE).

Ante La Duda, Pregunta: A Social Marketing Campaign to Improve Contraceptive Access during a Public Health Emergency

ABSTRACT During the 2016–2017 Zika virus outbreak, preventing unintended pregnancy was recognized as a primary strategy to reduce adverse Zika-related pregnancy and birth outcomes. To increase awareness and uptake of contraceptive services provided through the Zika Contraception Access Network (Z-CAN) in Puerto Rico, a multi-strategy campaign called Ante La Duda, Pregunta (ALDP) was developed. The principal aim was to increase awareness of Z-CAN services, which included same-day access to the full range of reversible contraceptives at no cost to women living in Puerto Rico who choose to delay or avoid pregnancy during the 2016–2017 Zika virus outbreak. Using diverse strategies, ALDP increased exposure to and engagement with the campaign in order to raise awareness of Z-CAN services in Puerto Rico. The ALDP social marketing campaign played an important role in the overall Z-CAN effort. Of all the strategies utilized, Facebook appears to have reached the most people. While the importance of a social marketing campaign communicating to raise awareness and create demand has long been known, through the ALDP campaign efforts, it was shown that an effective campaign, built on formative research, can be developed and implemented rapidly in an emergency response situation without compromising on content, quality, or reach.

Postnatal symptomatic Zika virus infections in children and adolescents: A systematic review.

BackgroundRecent Zika virus (ZIKV) outbreaks in the Pacific and the Americas have highlighted clinically significant congenital neurological abnormalities resulting from ZIKV infection in pregnancy. However, little is known about ZIKV infections in children and adolescents, a group that is potentially vulnerable to ZIKV neurovirulence.MethodsWe conducted a systematic review on the clinical presentation and complications of children and adolescents aged 0 to 18 years with a robust diagnosis of ZIKV infection. We searched PubMed, Web of Science, LILACs, and EMBASE until 13 February 2020 and screened reference lists of eligible articles. We assessed the studies’ risk of bias using pre-specified criteria.FindingsOur review collated the evidence from 2543 pediatric ZIKV cases representing 17 countries and territories, identified in 1 cohort study, 9 case series and 22 case reports. The most commonly observed signs and symptoms of ZIKV infection in children and adolescents were mild and included fever, rash, conjunctivitis and arthralgia. The frequency of neurological complications was reported only in the largest case series (identified in 1.0% of cases) and in an additional 14 children identified from hospital-based surveillance studies and case reports. ZIKV-related mortality was primarily accompanied by co-morbidity and was reported in one case series (<0.5% of cases) and three case reports. One death was attributed to complications of Guillain-Barré Syndrome secondary to ZIKV infection.Conclusions and relevanceBased on the current evidence, the clinical presentation of ZIKV infection in children and adolescents appears to be primarily mild and similar to the presentation in adults, with rare instances of severe complications and/or mortality. However, reliable estimation of the risks of ZIKV complications in these age groups is limited by the scarcity and quality of published data. Additional prospective studies are needed to improve understanding of the relative frequency of the signs, symptoms, and complications associated with pediatric ZIKV infections and to investigate any potential effects of early life ZIKV exposure on neurodevelopment.

Early Growth Parameters as Predictors of Developmental Delay Among Children Conceived During the 2015-2016 Zika Virus Outbreak in Northeastern Brazil.

Background: Identifying infants with congenital infection for early intervention will likely be challenging in future Zika virus outbreaks. We investigated indicators of risk for developmental delay among children born with and without obvious manifestations of congenital Zika virus infection. Methods: We evaluated 120 children conceived during the 2015−2016 Zika virus outbreak in Paraíba, Brazil. We analyzed data from children at birth; ages 1−7 months and approximately 24 months, using medical records (i.e., anthropometric measurements diagnoses), medical evaluation (i.e., Zika/other laboratory tests, dysmorphic features), and parent report (seizures, developmental delay). We used a Bayesian modeling approach to identify predictors of developmental delay. Results: Head circumference (HC) and length at birth and rates of growth for HC and length at follow-up were consistent across domains of developmental delay; (e.g., for every 1 cm per month decrease in HC growth rate; there was a corresponding decrease in the gross motor z-score). Modeling results indicated that HC and length at birth, and follow-up HC and length rates of growth, were predictive of developmental delay. Conclusion: These findings suggest that accurate measurement and frequent monitoring of HC and length, especially in the first few months of life, may be useful for identifying children possibly congenitally exposed to Zika virus who could benefit from early intervention services.

Clinical features and laboratory diagnosis of emerging arthropod-transmitted viruses: A Report from the Pan American Society for Clinical Virology Clinical Practice Committee.

Arthropod-borne viruses (arboviruses) are an increasing global threat due to their ability to cause human disease and their expanding geographical distribution. They circulate in nature between arthropod vectors and vertebrate hosts. Infection of susceptible human hosts leads to harmful developmental and neurological manifestations. Arboviruses have caused recent outbreaks with significant public health implications, such as the Zika virus outbreak in the western hemisphere which caused fetal abnormalities in some infected pregnant women, or Eastern Equine Encephalitis which caused 15 deaths in 2019. This review discusses several arboviral infections and their clinical manifestations while highlighting the importance of laboratory diagnostics to detect infections and current attempts at vaccine development. The ability to accurately diagnose an arbovirus infection is critical for initiating a timely response to infections in order to improve patient outcomes.

Two Genetic Differences between Closely Related Zika Virus Strains Determine Pathogenic Outcome in Mice.

Recent Zika virus (ZIKV) outbreaks and unexpected clinical manifestations of ZIKV infection have prompted an increase in ZIKV-related research. Here, we identify two strain-specific determinants of ZIKV virulence in mice. We found that strain H/PF/2013 caused 100% lethality in Ifnar1-/- mice, whereas PRVABC59 caused no lethality; both strains caused 100% lethality in Ifnar1-/-Ifngr1-/- double-knockout (DKO) mice. Deep sequencing revealed a high-frequency variant in PRVABC59 not present in H/PF/2013: a G-to-T change at nucleotide 1965 producing a Val-to-Leu substitution at position 330 of the viral envelope (E) protein. We show that the V330 variant is lethal on both virus strain backgrounds, whereas the L330 variant is attenuating only on the PRVABC59 background. These results identify a balanced polymorphism in the E protein that is sufficient to attenuate the PRVABC59 strain but not H/PF/2013. The consensus sequences of H/PF/2013 and PRVABC59 differ by 3 amino acids, but these were not responsible for the difference in virulence between the two strains. H/PF/2013 and PRVABC59 differ by an additional 31 noncoding or silent nucleotide changes. We made a panel of chimeric viruses with identical amino acid sequences but nucleotide sequences derived from H/PF/2013 or PRVABC59. We found that 6 nucleotide differences in the 3' quarter of the H/PF/2013 genome were sufficient to confer virulence in Ifnar1-/- mice. Altogether, our work identifies a large and previously unreported difference in virulence between two commonly used ZIKV strains, in two widely used mouse models of ZIKV pathogenesis (Ifnar1-/- and Ifnar1-/- Ifngr1-/- DKO mice).IMPORTANCE Contemporary ZIKV strains are closely related and often used interchangeably in laboratory research. Here, we identify two strain-specific determinants of ZIKV virulence that are evident in only Ifnar1-/- mice but not Ifnar1-/-Ifngr1-/- DKO mice. These results identify a balanced polymorphism in the E protein that is sufficient to attenuate the PRVABC59 strain but not H/PF/2013. We further identify a second virulence determinant in the H/PF/2013 strain, which is driven by the viral nucleotide sequence but not the amino acid sequence. Altogether, our work identifies a large and previously unreported difference in virulence between two commonly used ZIKV strains, in two widely used mouse models of ZIKV pathogenesis. Our results highlight that even very closely related virus strains can produce significantly different pathogenic phenotypes in common laboratory models.

Dengue and Zika Viruses: Epidemiological History, Potential Therapies, and Promising Vaccines.

Dengue virus (DENV), which can lead to fatal hemorrhagic fever, affects 390 million people worldwide. The closely related Zika virus (ZIKV) causes microcephaly in newborns and Guillain-Barré syndrome in adults. Both viruses are mostly transmitted by Aedes albopictus and Aedes aegypti mosquitoes, which, due to globalization of trade and travel alongside climate change, are spreading worldwide, paving the way to DENV and ZIKV transmission and the occurrence of new epidemics. Local outbreaks have already occurred in temperate climates, even in Europe. As there are no specific treatments, these viruses are an international public health concern. Here, we analyze and discuss DENV and ZIKV outbreaks history, clinical and pathogenesis features, and modes of transmission, supplementing with information on advances on potential therapies and restraining measures. Taking advantage of the knowledge of the structure and biological function of the capsid (C) protein, a relatively conserved protein among flaviviruses, within a genus that includes DENV and ZIKV, we designed and patented a new drug lead, pep14-23 (WO2008/028939A1). It was demonstrated that it inhibits the interaction of DENV C protein with the host lipid system, a process essential for viral replication. Such an approach can be used to develop new therapies for related viruses, such as ZIKV.

Castanospermine reduces Zika virus infection-associated seizure by inhibiting both the viral load and inflammation in mouse models

Zika virus (ZIKV) outbreaks have been reported worldwide, including a recent occurrence in Brazil where it spread rapidly, and an association with increased cases of microcephaly was observed in addition to neurological issues such as GBS that were reported during previous outbreaks. Following infection of neuronal tissues, ZIKV can cause inflammation, which may lead to neuronal abnormalities, including seizures and paralysis. Therefore, a drug containing both anti-viral and immunosuppressive properties would be of great importance in combating ZIKV related neurological abnormalities. Castanospermine (CST) is potentially a right candidate drug as it reduced viral load and brain inflammation with the resulting appearance of delayed neuronal disorders, including seizures and paralysis in an Ifnar1−/− mouse.

Mothers as facilitators for a parent group intervention for children with Congenital Zika Syndrome: Qualitative findings from a feasibility study in Brazil.

The Zika virus outbreak in Brazil (2015-2016) affected thousands of children who were born with Congenital Zika Syndrome (CZS). Families play an important role in their care of children with complex needs, yet their knowledge, experience and skills are rarely harnessed in existing interventions to best support these families. This study explores the use of mothers as facilitators for a community-based group intervention for children with CZS and their caregivers in Brazil. Four facilitators were trained to deliver the 10-week intervention called "Juntos". Two were mothers of a child with CZS ("expert mothers") and two were therapists (speech therapist and physiotherapist). The intervention was delivered to three groups, generally including 8-10 caregivers. Two researchers, who were psychologists, observed the groups and held focus group discussions at the end of each session. They undertook semi-structured interviews post intervention with a purposive sample of caregivers, and with the facilitators. Observation notes were collated and summarised. Transcripts were transcribed and thematically analysed using five elements to assess feasibility: acceptability, demand, implementation, practicality and adaptation. The use of expert mothers as facilitators was considered to be acceptable and there was demand for their role. Their experiential knowledge was viewed as important for sharing and learning, and supporting and encouraging the group. The intervention was delivered with fidelity by the expert mothers. The practicality of the intervention was facilitated by holding the group sessions in the community, providing transport costs to facilitators and participants, paying expert mothers and therapist facilitators equally and supporting the expert mothers through a mentorship programme. Equal payment with the therapist enabled the expert mothers to better facilitate the groups, through increased confidence in the value of their role. Adaptation of the intervention included development of video resources and mentoring guidelines. The use of expert mothers as facilitators of caregiver groups provides a unique approach to harness the knowledge, experience, and skills of families to provide care, and is likely to be feasible in similar contexts.

Zika virus seroprevalence in women who gave birth during Zika virus outbreak in Brazil - a prospective observational study

BackgroundThe recent Zika virus (ZIKV) outbreak in Brazil started in August 2015 and ended in May 2017 without effective public health measures for its control have been taken. The immunological status of a community may not only predict future outbreaks as well to answer questions regarding ZIKV not known yet. ObjectiveTo verify the seroprevalence of ZIKV in a group of women who were pregnant during the Zika virus outbreak in Recife, three to nine months after the delivery, and to evaluate the neurodevelopment of their children. MethodsA cross-sectional study enrolled participants of a cohort study held at Instituto de Medicina Integral Professor Fernando Figueira (IMIP) during the ZIKV outbreak in Recife. Mothers who gave birth between the last trimester of 2015 and the first semester of 2016, period of the peak of microcephaly outbreak in Recife, were invited. All participants had the serum tested by the anti-ZIKV IgG/IgM enzyme-liked immunosorbent assays, ELISA kit (Euroimmun, Lübeck, Germany). All children whose mothers presented positive serology for ZIKV performed the IgG/IgM ELISA test for ZIKV. These children were also evaluated by a neuropediatrician and the Denver II development screening test was applied. ResultsAmong the 132 studied pregnant women who gave birth at the peak of ZIKV outbreak in Recife, all were ZIKV IgM negative and 81 (61,3%) had ZIKV IgG positive. Mothers ZIKV IgG positive had more fever and rash during the pregnancy as compared with mothers negative for ZIKV; respectively 27/81 (33,3%) vs 6/51 (11,7%), p = 0.005 and 22/81 (27,2%) vs 4 (7,8%), p = 0.016. Only one child had IgG positive serology for ZIKV. No children had neurodevelopment defect for the age group and the Denver II normal scores. ConclusionsA high ZIKV IgG seroprevalence in pregnant women at the end of the ZIKV outbreak in Recife was found. This finding suggests that community protective immunity may have contributed to the end of ZIKV outbreak in Recife, Brazil.

Information-Accessing Behavior during Zika Virus Outbreak, United States, 2016.

We used latent class analysis to examine Zika virus–related information-accessing behavior of US residents during the 2016 international outbreak. We characterized 3 classes of information-accessing behavior patterns: universalists, media seekers, and passive recipients. Understanding these patterns is crucial to planning risk communication during an emerging health threat.

A model partnership for communication and dissemination of scientific recommendations for pregnant women during the emergency response to the Zika virus outbreak: MotherToBaby and the Centers for Disease Control and Prevention.

During the Zika virus (ZIKV) outbreak, an urgent need existed for strong partnerships to disseminate Zika-related information to pregnant women and women of child-bearing age. The Centers for Disease Control and Prevention (CDC) partnered with MotherToBaby, a national organization experienced in providing information about exposures during pregnancy to healthcare providers and the public, to disseminate accurate information about ZIKV infection during pregnancy. Partnership activities included regular information sharing, cross-linking information for the public, and promoting common messaging. Following the ZIKV outbreak, we reviewed common inquiries received as well as key strategies and lessons learned from the partnership. Between June 2016 and June 2019, MotherToBaby received 5,387 Zika-related inquiries from the public and health care providers. The majority (90%) of inquires came from preconception, pregnant, and breastfeeding women. Concerns about travel, pregnancy, sexual transmission, and preconception guidelines comprised the top information requests. Live chat was the preferred method of communication for Zika-related inquiries. Key strategies and lessons learned from this partnership included: capitalizing on existing nationwide infrastructure and expertise, prominently referring to partners as a resource, promoting shared messaging using online resources and social media, holding regular calls to share information, and collecting data to identify common questions and revise messaging. This examination of strategies, lessons learned, and metrics from MotherToBaby and CDC's partnership during the ZIKV outbreak can be applied to future partnerships to address emerging public health threats.

IL-22 hinders antiviral T cell responses and exacerbates ZIKV encephalitis in immunocompetent neonatal mice

BackgroundThe Zika virus (ZIKV) outbreak that occurred in multiple countries was linked to increased risk of nervous system injuries and congenital defects. However, host immunity- and immune-mediated pathogenesis in ZIKV infection are not well understood. Interleukin-22 (IL-22) is a crucial cytokine for regulating host immunity in infectious diseases. Whether IL-22 plays, a role in ZIKV infection is unknown.MethodsThe cellular source of IL-22 was identified in IFNAR-/- mice and wild-type (WT) neonatal mice during ZIKV infection. To determine the role of IL-22, we challenged 1-day-old WT and IL-22-/- mice with ZIKV and monitored clinical manifestations. Glial cell activation in the brain was assessed by confocal imaging. ZIKV-specific CD8+ T cell responses in both the spleen and brain were analyzed by flow cytometry. In addition, glial cells were cultured in vitro and infected with ZIKV in the presence of IL-22, followed by the evaluation of cell proliferation, cytokine expression, and viral loads.ResultsWe found that γδ T cells were the main source of IL-22 during ZIKV infection in both the spleen and brain. WT mice began to exhibit weight loss, staggered steps, bilateral hind limb paralysis, and weakness at 10 days post-infection (dpi) and ultimately succumbed to infection at 16–19 dpi. IL-22 deficiency lessened weight loss, moderated the systemic inflammatory response, and greatly improved clinical signs of neurological disease and mortality. ZIKV infection also induced the activation of microglia and astrocytes in vitro. Additional analysis demonstrated that the absence of IL-22 resulted in reduced activation of microglia and astrocytes in the cortex. Although IL-22 displayed a negligible effect on glial cells in vitro, IL-22-/- mice mounted more vigorous ZIKV-specific CD8+ T cell responses, which led to a more effective control of ZIKV in the brain.ConclusionsOur data revealed a pathogenic role of IL-22 in ZIKV encephalitis.

Strategies and safeguards to ensure access to long-acting reversible contraception removal after the Zika Contraception Access Network ended: A prospective analysis of patient reported complaints

ObjectiveThe Zika Contraception Access Network (Z-CAN) was a short-term emergency response intervention that used contraception to prevent unintended pregnancy to reduce Zika-related adverse birth outcomes during the 2016 2017 Zika virus outbreak in Puerto Rico. Strategies and safeguards were developed to ensure women who chose long-acting reversible contraception (LARC) had access to no-cost removal, if desired, after Z-CAN ended. Study DesignWe assessed the number of women who chose LARC at their initial Z-CAN visit who filed complaints regarding challenges with LARC removal within 30-months after the Z-CAN program ended. Complaints and program responses were categorized. ResultsOf the 29,221 women who received Z-CAN services, 20,381 chose a LARC method at their initial visit (IUD = 12,276 and implant = 8105). Between September 2017 and February 2020, 63 patient complaints were logged, mostly due to LARC removal charges (76.2%) which were generally (71.4%) determined to be inappropriate charges. All complaints filed were resolved allowing LARC removal within an average of 28 days. ConclusionSafeguards to ensure prompt LARC removal when desired are critical to ensure women s reproductive autonomy. ImplicationsStrategies and safeguards used by Z-CAN to ensure women have access to LARC removal might be used by other contraception programs to prevent reproductive coercion and promote reproductive autonomy to best meet the reproductive needs of women.

A Review of the Control of Aedes aegypti (Diptera: Culicidae) in the Continental United States.

Aedes aegypti (L) is an anthropophilic mosquito involved in the transmission of a variety of viral pathogens worldwide including dengue, chikungunya, yellow fever, and Zika viruses. This species, native to Africa, is well established in the continental U.S. (CONUS) and occasionally contributes to localized outbreaks of viral diseases. In the last seven decades, mosquito control programs in the CONUS have been focused on vectors of eastern equine encephalitis, St. Louis encephalitis, and West Nile viruses, as well as nuisance species. Aedes aegypti receives little control focus except during outbreak periods, which has led to a lack of information on appropriate and effective control options targeting Ae. aegypti in the CONUS. As such, in the event of an Ae. aegypti-borne arboviral outbreak in the CONUS, there are limited evidence-based control recommendations or protocols in place. Autochthonous outbreaks of Ae. aegypti-borne pathogens have occurred recently in the CONUS, including dengue outbreaks in 2010 and 2013, a chikungunya outbreak in 2014, and the 2016 outbreak of Zika virus. The increasing frequency of Ae. aegypti-borne outbreaks necessitates increased attention and research on control of this species to prevent and mitigate future outbreaks. This review consolidates and synthesizes the available literature on control of Ae. aegypti, specifically within the CONUS, focusing on data generated through operational applications as well as field and semifield experiments. The purpose of this review is to identify and highlight areas where additional research is needed. The review covers chemical control and insecticide resistance, biological control, source reduction, trapping, and alternative techniques.

Differentiation-dependent susceptibility of human muscle cells to Zika virus infection.

Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, that may be involved in the physiopathological course of the infection. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human primary myoblasts that can be differentiated into myotubes, we found that myoblasts can be productively infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection, suggesting a differentiation-dependent susceptibility. Infection was accompanied by a caspase-independent cytopathic effect, associated with paraptosis-like cytoplasmic vacuolization. Proteomic profiling was performed 24h and 48h post-infection in cells infected with two different isolates. Proteome changes indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, and differentiation-dependent restriction of infection from myoblasts to myotubes. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences in ZIKV infection pathogenesis.

Exploratory analysis of machine learning approaches for surveillance of Zika-associated birth defects.

In 2016, Centers for Disease Control and Prevention (CDC) established surveillance of pregnant women with Zika virus infection and their infants in the U.S. states, territories, and freely associated states. To identify cases of Zika-associated birth defects, subject matter experts review data reported from medical records of completed pregnancies to identify findings that meet surveillance case criteria (manual review). The volume of reported data increased over the course of the Zika virus outbreak in the Americas, challenging the resources of the surveillance system to conduct manual review. Machine learning was explored as a possible method for predicting case status. Ensemble models (using machine learning algorithms including support vector machines, logistic regression, random forests, k-nearest neighbors, gradient boosted trees, and decision trees) were developed and trained using data collected from January 2016-October 2017. Models were developed separately, on data from the U.S. states, non-Puerto Rico territories, and freely associated states (referred to as the U.S. Zika Pregnancy and Infant Registry [USZPIR]) and data from Puerto Rico (referred to as the Zika Active Pregnancy Surveillance System [ZAPSS]) due to differences in data collection and storage methods. The machine learning models demonstrated high sensitivity for identifying cases while potentially reducing volume of data for manual review (USZPIR: 96% sensitivity, 25% reduction in review volume; ZAPSS: 97% sensitivity, 50% reduction in review volume). Machine learning models show potential for identifying cases of Zika-associated birth defects and for reducing volume of data for manual review, a potential benefit in other public health emergency response settings.

Immuno-informatics-based Identification of Novel Potential B Cell and T Cell Epitopes to Fight Zika Virus Infections

Globally, the recent outbreak of Zika virus (ZIKV) in Brazil, Asia Pacific, and other countries highlighted the unmet medical needs. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. In this study, we aimed to design an epitope-based vaccine for ZIKV using an in silico approach to predict and analyze B- and T-cell epitopes. The prediction of the most antigenic epitopes has targeted the capsid and envelope proteins as well as non-structural proteins NS5 and NS3 using immune-informatics tools PROTPARAM, CFSSP, PSIPRED, and Vaxijen v2.0. B and T-cell epitopes were predicted using ABCpred, IEDB, TepiTool, and their toxicity was evaluated using ToxinPred. The 3-dimensional epitope structures were generated by PEP-FOLD. Energy minimization was performed using Swiss- Pdb Viewer, and molecular docking was conducted using PatchDock and FireDock server. As a result, we predicted 307 epitopes of MHCI (major histocompatibility complex class I) and 102 epitopes of MHCII (major histocompatibility complex class II). Based on immunogenicity and antigenicity scores, we identified the four most antigenic MHC I epitopes: MVLAILAFLR (HLA-A*68:01), ETLHGTVTV (HLA-A*68:02), DENHPYRTW (HLA-B*44:02), QEGVFH TMW (HLA-B*44:03) and TASGRVIEEW (HLA-B*58:01), and MHC II epitopes: IIKKFKKDLAAMLRI (HLA-DRB3*02:02), ENSKMMLELDPPFGD (HLA-DRB3*01:01), HAET WFFDENHPYRT (HLA-DRB3*01:01), TDGVYRVMTRRLLGS (HLA-DRB1*11:01), and DGCW YGMEIRPRKEP (HLA-DRB5*01:01). This study provides novel potential B cell and T cell epitopes to fight against Zika virus infections and may prompt further development of vaccines against ZIKV and other emerging infectious diseases. However, further investigations for protective immune response by in vitro and in vivo studies to ratify immunogenicity, the safety of the predicted structure, and ultimately for the vaccine properties to prevent ZIKV infections are warranted.

VIDHOP, viral host prediction with deep learning.

MotivationZoonosis, the natural transmission of infections from animals to humans, is a far-reaching global problem. The recent outbreaks of Zikavirus, Ebolavirus, and Coronavirus are examples of viral zoonosis, which occur more frequently due to globalization. In case of a virus outbreak, it is helpful to know which host organism was the original carrier of the virus to prevent further spreading of viral infection. Recent approaches aim to predict a viral host based on the viral genome, often in combination with the potential host genome and arbitrarily selected features. These methods are limited in the number of different hosts they can predict or the accuracy of the prediction.ResultsHere, we present a fast and accurate deep learning approach for viral host prediction, which is based on the viral genome sequence only. We tested our deep neural network (DNN) on three different virus species (influenza A virus, rabies lyssavirus, rotavirus A). We achieved for each virus species an AUC between 0.93 and 0.98, allowing highly accurate predictions while using only fractions (100-400 bp) of the viral genome sequences. We show that deep neural networks are suitable to predict the host of a virus, even with a limited amount of sequences and highly unbalanced available data. The trained DNNs are the core of our virus-host prediction tool VIDHOP (VIrus Deep learning HOst Prediction). VIDHOP also allows the user to train and use models for other viruses.AvailabilityVIDHOP is freely available under https://github.com/flomock/vidhopSupplementary informationAvailable at DOI 10.17605/OSF.IO/UXT7

Zika Virus Disease and Pregnancy Outcomes in Colombia

BackgroundIn 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes.MethodsWe collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase–polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period.ResultsOf 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak.ConclusionsIn pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.)