Zika Virus Outbreak In Brazil Research Articles

Recent advances in the study of zika virus structure, drug targets, and inhibitors.

Zika Virus (ZIKV) is a positive-strand RNA virus that can lead to Guillain-Barré syndrome or encephalitis in some individuals and hence presents a serious public health risk. Since the first outbreak of ZIKV in Brazil in 2015, no effective clinical inhibitors have been developed, making the development of effective ZIKV drugs an urgent issue that needs to be addressed. ZIKV belongs to the Flaviviridae family, and its structure includes three structural proteins, namely, capsular (C), premembrane (prM), and envelope (E) proteins, as well as seven nonstructural proteins, namely, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. To provide a reference for the development of future ZIKV drugs, this paper reviews the structure of the ZIKV based on recent literature reports, analyzes the potential therapeutic targets of various proteins, and proposes feasible drug design strategies. Additionally, this paper reviews and classifies the latest research progress on several protease inhibitors, such as E protein inhibitors, NS2B-NS3 inhibitors, and NS5 inhibitors, so that researchers can quickly understand the current status of development and the interconnections among these inhibitors.

Zika Virus 101: A Mini Review

Zika virus is a mosquito-borne Flavivirus that is the focus of an ongoing pandemic and public health emergency. The Zika virus outbreak in Brazil in 2015, previously limited to sporadic cases in Africa and Asia, heralded a rapid spread across the Americas. Although most Zika virus infections are characterized by subclinical or mild flu-like illness, severe manifestations have been reported, including Guillain-Barre syndrome in adults and microcephaly in children born to infected mothers. There is no effective treatment or vaccine for the Zika virus; therefore, the public health response is primarily focused on preventing infections, especially in pregnant women. Despite the growing knowledge of this virus, questions remain regarding the vectors and reservoirs of the virus, pathogenesis, genetic diversity, and potential synergistic effects of coinfection with other circulating viruses. These questions highlight the need for research to optimize surveillance, patient management, and public health interventions in the current Zika virus epidemic .Zika virus (ZIKV) is an emerging arthropod-borne Flavivirus that leads to teratogenic effects and neurological disorders after infection. ZIKV infections are a serious global public health problem, leading scientists to increase research into antiviral and vaccines against the virus. These efforts are still ongoing, as the pathogenesis and immune evasion mechanisms of ZIKV are not yet fully understood. There are currently no specific vaccines or drugs approved for ZIKV; however, some are undergoing clinical trials. Notably, several strategies have been used to develop antiviral, including drugs that target viral and host proteins. In addition, drug reuse is preferred because it is cheaper and less timeconsuming than other strategies because the drugs used have already been approved for human use. Similarly, various platforms for vaccine design have been evaluated, including DNA, mRNA, peptide, protein, viral vectors, virus-like particles (VLPS), inactivated viruses, and live attenuated virus vaccines. These vaccines have been shown to induce specific humoral and cellular immune responses and reduce viremia and viral RNA in vitro and in vivo. Importantly, most of these vaccines have entered clinical trials. Understanding the mechanism of viral disease will provide better strategies for the development of therapeutic agents against ZIKV. This review provides a comprehensive summary of the viral pathogenesis of ZIKV and current progress in the development of vaccines and drugs against this virus.

Sustainable drainage to address Zika and lack of drainage in favelas, Brazil: community perspectives

The 2015 Zika virus outbreak in Brazil established that neonate microcephaly was related to maternal infection by the virus during pregnancy, the highest densities of which occurred in the northeast and southeast of Brazil, the country’s most populated areas. These areas are typically associated with informal settlements or favelas which lack effective water management, sanitation and drainage, hence providing suitable breeding environments for the Aedes aegypti mosquito, the Zika virus vector. This paper reports on a novel study of community perceptions around the potential for Sustainable Drainage Systems to provide a means of reducing areas for the mosquito to breed, and hence reduce Zika infections in favelas. Interviews were carried out with key external stakeholders working with favelas and members of the favela community. Poor management of water supply, drainage and solid waste were clearly emphasised by participants illustrating gaps in current research connecting these areas. Participants proposed that only a holistic approach could address sanitation issues, hence the distribution of Zika-carrying mosquitos, subsequent infections and microcephaly. An approach was therefore needed taking account of the environment as a whole, increasing public awareness of sanitation and environmental health, improving sanitation infrastructure and providing adequate systems for solid waste management.

Would Zika virus Infection in Pregnancy Be a Sentence of Poor Neurological Prognosis for Exposed Children? Neurodevelopmental Outcomes in a Cohort from Brazilian Amazon.

Infections with Flavivirus in pregnant women are not associated with vertical transmission. However, in 2015, severe cases of congenital infection were reported during the Zika virus outbreak in Brazil. More subtle infections in children born to mothers with ZIKV still remain uncertain and the spectrum of this new congenital syndrome is still under construction. This study describes outcomes regarding neurodevelopment and neurological examination in the first years of life, of a cohort of 77 children born to pregnant women with ZIKV infection in Manaus, Brazil, from 2017 to 2020. In the group of normocephalic children (92.2%), most showed satisfactory performance in neuropsychomotor development, with a delay in 29.6% and changes in neurological examination in 27.1%, with two children showing muscle-strength deficits. All microcephalic children (5.2%) evolved with severe neuropsychomotor-development delay, spastic tetraparesis, and alterations in the imaging exam. In this cohort, 10.5% of the children had macrocephaly at birth, but only 2.6% remained in this classification. Although microcephaly has been considered as the main marker of congenital-Zika-virus syndrome in previous studies, its absence does not exclude the possibility of the syndrome. This highlights the importance of clinical follow-up, regardless of the classification of head circumference at birth.

Development of a neutralizing antibody targeting linear epitope of the envelope protein domain III of ZIKV

Zika virus (ZIKV) infection represents an emerging infectious disease that poses an increasing threat to human health, especially after the ZIKV outbreak in Brazil in 2015. Unfortunately, there continues to be a lack of highly effective antiviral drugs or vaccines against ZIKV. In this study, we expressed the ZIKV envelope protein domain III (ZIKV EDIII) in E. coli strain BL21. The purified recombinant protein was used to immunize mice to produce monoclonal antibodies (mAbs). After 6 screening and 5 subcloning cycles, 10 monoclonal cell lines that stably produced antibodies, termed 2F5, 5B8, 6G6, 7E12, 8B6, 17E6, 19E7, 20F4, 26G6, and 37E6, were identified. The mAb 8B6 could neutralize ZIKV and recognize the ZIKV EDIII epitope (GRLITANPVITESTE). Another 9 mAbs did not exhibit neutralizing activity; however, they could specifically recognize the ZIKV EDIII and ZIKV lysate, suggesting their potential use in the diagnosis of ZIKV.

An update on preclinical pregnancy models of Zika virus infection for drug and vaccine discovery

ABSTRACT Introduction Congenital Zika syndrome is caused by Zika virus (ZIKV) infection during pregnancy and can culminate in structural and neurological defects in the fetus, including a spectrum of symptoms such as brain calcifications, hydrocephalus, holoprosencephaly, lissencephaly, ventriculomegaly, and microcephaly. Using animal models to study ZIKV infection during pregnancy represents a critical tool for understanding ZIKV pathophysiology, drug testing, vaccine development, and prevention of vertical transmission. Areas covered In this review, the authors cover state-of-the-art preclinical pregnancy models of ZIKV infection for drug discovery and vaccine development to prevent vertical transmission. Expert opinion The discovery of drugs against ZIKV infection represents an urgent necessity, and until now, no effective drug that can prevent the effects of vertical transmission has been tested in humans. Even after six years of the ZIKV outbreak in Brazil, no drugs or vaccines have been approved for use in humans. In part, this failure could be related to the lack of translatability from available preclinical models to humans.

Zika virus outbreak in Brazil under current and future climate

IntroductionZika virus (ZIKV) is primarily transmitted byAedes aegypti and Aedes albopictus mosquitoes between humans and non-human primates. Climate change may enhance virus reproduction in Aedes spp. mosquito populations, resulting in intensified ZIKV outbreaks. The study objective was to explore how an outbreak similar to the 2016 ZIKV outbreak in Brazil might unfold with projected climate change. MethodsA compartmental infectious disease model that included compartments for humans and mosquitoes was developed to fit the 2016 ZIKV outbreak data from Brazil using least squares optimization. To explore the impact of climate change, published polynomial relationships between temperature and temperature-sensitive mosquito population and virus transmission parameters (mosquito mortality, development rate, and ZIKV extrinsic incubation period) were used. Projections for future outbreaks were obtained by simulating transmission with effects of projected average monthly temperatures on temperature-sensitive model parameters at each of three future time periods: 2011–2040, 2041–2070, and 2071–2100. The projected future climate was obtained from an ensemble of regional climate models (RCMs) obtained from the Co-Ordinated Regional Downscaling Experiment (CORDEX) that used Representative Concentration Pathways (RCP) with two radiative forcing values, RCP4.5 and RCP8.5. A sensitivity analysis was performed to explore the impact of temperature-dependent parameters on the model outcomes. ResultsClimate change scenarios impacted the model outcomes, including the peak clinical case incidence, cumulative clinical case incidence, time to peak incidence, and the duration of the ZIKV outbreak. Comparing 2070–2100 to 2016, using RCP4.5, the peak incidence was 22,030 compared to 10,473; the time to epidemic peak was 12 compared to 9 weeks, and the outbreak duration was 52 compared to 41 weeks. Comparing 2070–2100 to 2016, using RCP8.5, the peak incidence was 21,786 compared to 10,473; the time to epidemic peak was 11 compared to 9 weeks, and the outbreak duration was 50 compared to 41weeks. The increases are due to optimal climate conditions for mosquitoes, with the mean temperature reaching 28 °C in the warmest months. Under a high emission scenario (RCP8.5), mean temperatures extend above optimal for mosquito survival in the warmest months. ConclusionOutbreaks of ZIKV in locations similar to Brazil are expected to be more intense with a warming climate. As climate change impacts are becoming increasingly apparent on human health, it is important to quantify the effect and use this knowledge to inform decisions on prevention and control strategies.

Zika virus outbreak in Brazil-Lessons learned and perspectives for a safe and effective vaccine.

Zika virus (ZIKV) is an emerging pathogen of public health concern, associated with a dramatic burden in places where the virus caused outbreaks between 2015 and 2017. In the Americas, the ZIKV was first reported in Brazil and rapidly spread through the Americas. Since its first report, a number of studies have been published as we continue to learn, not only about modes of transmission, but also clinical manifestations, risk of congenital anomalies, including microcephaly and neurological malformations in fetuses born from mothers infected during pregnancy. Interventions to reduce the burden of ZIKV infection are restricted to mosquito control, and for Aedes spp mosquitoes the strategies implemented to that end proved to be unsuccessful so far. Hence the lessons we can learn following the ZIKV epidemics become of paramount importance in the development of drug treatments and in search for a vaccine.

Juntos: A Support Program for Families Impacted by Congenital Zika Syndrome in Brazil.

The 2015-2016 Zika virus outbreak in Brazil was unprecedented and resulted in the birth of more than 3,000 children with congenital Zika syndrome (CZS). These children experience multiple complex health conditions and have limited services to support them and their family's needs. An existing family support program for children with cerebral palsy (Getting to Know Cerebral Palsy) was adapted to the Zika context in Brazil through expert consultation. The program was pilot tested at 2 sites among 6 groups of caregivers (total of 48 families) from August 2017 to June 2018. Group observation and focus group discussions with facilitators and participants at the end of each session informed fast-track learning, which was used to tailor the program for future groups. Fast-track learning-adjusting the intervention in real time based on gathered feedback-was found to be a helpful process to inform and hone the program from its initial concept. The intervention, Juntos, is a facilitated participatory group program for caregivers of children who have CZS. The group sessions are cofacilitated by a parent of a child who has CZS and an allied health professional. The group meets for 10 sessions that last 4 hours. Each session includes an icebreaker, activities, and group discussions. Content covers practical information on caring for a child with a developmental disability including that caused by Zika. Psychosocial support forms an important component, and families are guided from the first week to define and develop their own communities of support. Six pilot groups were successfully run in Rio de Janeiro and Greater Salvador, Bahia. The groups gave positive feedback on acceptability and demand. The program has the potential to be an important tool for community health and social support services in South America in response to Zika. The program can also be applied to children with neurodevelopmental disabilities other than those caused by the Zika virus, which could be important in ensuring families of children with CZS are less isolated.

How congenital Zika virus impacted my child’s functioning and disability: a Brazilian qualitative study guided by the ICF

IntroductionThe Zika virus outbreak in Brazil has had devasting social, medical and financial consequences for families. Both researchers and clinicians are measuring longer-term outcomes to understand the impact of the...

Can Zika Virus Infection in High Risk Pregnant Women Be Differentiated on the Basis of Symptoms?

Zika virus (ZIKV) infection in pregnancy is associated with congenital neurological abnormalities. Our understanding of the full clinical spectrum of ZIKV infection is incomplete. Using data from this prospective cohort study consisting of 650 women attending a high-risk pregnancy clinic during the Zika virus outbreak in Brazil, we investigated the extent to which specific symptoms can be utilized to differentiate ZIKV-infected pregnant women from those with other pregnancy-related problems. All were tested for ZIKV in urine by RT–qPCR. Demographic and clinical data including physical symptoms during follow-up were recorded and analyzed with respect to Zika virus exposure status. Forty-eight (7.4%) women were positive for ZIKV by RT–qPCR. The majority (70.8%) were asymptomatic, and only four ZIKV-positive women (8.3%) reported symptoms during pregnancy that met the WHO case definition. Zika-positive and -negative women reported similar frequencies of ZIKV-like symptoms (as per the WHO definition): fever (16.7% vs. 13.6%), arthralgia/arthritis (10.4% vs. 11.3%), rash (4.2% vs. 5.3%), and conjunctivitis (2.1% vs. 3.2%). Most pregnant women positive for ZIKV in urine are asymptomatic and do not deliver a baby with microcephaly. Physical symptoms alone did not differentiate between high-risk pregnant women positive or negative for ZIKV.

Governance of interorganizational health emergency networks: Facing the Zika pandemic

AbstractGlobal health is on the threshold of a new era, facing major threats such as infections, non‐communicable diseases, and the challenges of globalization itself (the effects of climate change, trade policies on health), in a multifaceted global context of diverse societies, norms, values, interests, and inequalities.However, facing the challenges presented by health crises requires high volumes of financial and human resources, and cooperation efforts between different actors, which makes the challenge even more complex for developing countries. In this context, the formation of interorganizational networks, involving individuals and public and private organizations, is fundamental to face various outbreaks.This study, based on the case of the Zika virus outbreak in Brazil in 2015, aims to analyze the governance of an interorganizational health emergency network. The results point out new perspectives to identify and deal with these interorganizational networks’ challenges, such as the coordination of institutional and individual actors, conflicts, issues related to the network's leadership, learning and mobilization regarding health emergencies – particularly in situations where there is little knowledge and evidence about the risks and effects of viruses and other pathogens, which makes the act of declaring emergency politically controversial.

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.

Zika virus infection in pregnancy and adverse fetal outcomes in S\xe3o Paulo State, Brazil: a prospective cohort study

Robust epidemiological and biological evidence supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. However, it remains uncertain if ZIKV infection in pregnancy also increases the risk for other adverse fetal and birth outcomes. In a prospective cohort study we investigated the influence of ZIKV on the prevalence of prematurity, low birth weight, small-for-gestational-age, and fetal death as well as microcephaly (i.e., overall and disproportionate) in the offspring of women attending a high-risk pregnancy clinic during the recent ZIKV outbreak in Brazil. During the recruitment period (01 March 2016–23 August 2017), urine samples were tested for ZIKV by RT-PCR from all women attending the high-risk pregnancy clinic at Jundiaí University Hospital and from the neonates after delivery. Of the 574 women evaluated, 44 (7.7%) were ZIKV RT-PCR positive during pregnancy. Of the 409 neonates tested, 19 (4.6%) were ZIKV RT-PCR positive in the first 10 days of life. In this cohort, maternal ZIKV exposure was not associated with increased risks of prematurity, low birth weight, small-for-gestational-age, or fetal death. However, relative to ZIKV-negative neonates, ZIKV-positive infants had a five-fold increased risk of microcephaly overall (RR 5.1, 95% CI 1.2–22.5) and a ten-fold increased risk of disproportionate microcephaly (RR 10.3, 95% CI 2.0–52.6). Our findings provide new evidence that, in a high-risk pregnancy cohort, ZIKV RT-PCR positivity in the neonate at birth is strongly associated with microcephaly. However, ZIKV infection during pregnancy does not appear to influence the risks of prematurity, low birth weight, small-for-gestational-age or fetal death in women who already have gestational comorbidities. The results suggest disproportion between neonatal head circumference and weight may be a useful screening indicator for the detection of congenital microcephaly associated with ZIKV infection.

Recombination between African and Asian lineages of Zika virus in vitro and its consequences for viral phenotype

Recombination is a process of extensive genetic exchange that is known to contribute to virus evolution and has been frequently observed in positive-sense RNA viruses. Zika virus (ZIKV) is an emerging arbovirus of the family Flaviviridae with two distinct lineages – African and Asian. While some phylogenetic evidence suggests that recombination in the envelope-encoding region of the ZIKV genome has occurred during evolution, there has been no experimental evidence for ZIKV recombination to date. We conducted co-infections of mammalian and insect cells, using the prototype African ZIKV strain (MR766) and an Asian isolate from the 2015-16 ZIKV outbreak in Brazil (BeH819015), and used a recombinant-specific PCR assay to detect recombinant sequences from total cell RNA extracts. In brief, a 564bp fragment spanning the boundary between the structural and the non-structural genes of the viral genome was amplified using a primer pair consisting of an Asian-specific and an African-specific primer. A total of 24 individual sequences were screened. All were in-frame recombinants and they formed 10 unique junctions. Several of the detected recombinant sequences were chosen for construction of full-length infectious clones to test the viability and phenotype of the recombinant viruses. This study represents the first isolation of recombinant ZIKV sequences from co-infected cultured cells and demonstrates the capacity of ZIKV to recombine in an experimental system. Further investigation is required to better understand the evolutionary potential of this mechanism and its putative role in the emergence of ZIKV.

Adapting the Ages and Stages Questionnaire to Identify and Quantify Development Among Children With Evidence of Zika Infection.

This article describes novel methods of applying the Ages and Stages Questionnaire-3rd edition (ASQ-3) to assess and quantify developmental delay among children following the 2015-2016 Zika virus outbreak in Brazil. Many of the children with Zika virus infection were expected to have severe developmental delay. However, administering the ASQ-3 to caregivers of these children according to standard protocol would have screened for the overall presence of delay but not the severity of delay. We adopted an amended protocol for administration of the ASQ-3 to quantify the developmental functioning of children severely affected by Zika virus infection in this investigation. Protocols for administering the ASQ-3 among this population were drafted in consultation with developmental measurement experts and are presented here. Specific developmental estimates are discussed, including developmental age equivalents, developmental quotients, and developmental quotient z scores. The calculations of these estimates are presented with examples in the context of the 2015-2016 Zika virus outbreak and associated microcephaly among prenatally infected children from 2 states in northeastern Brazil. Potential applications of these methods for estimating developmental ability among similar pediatric populations are discussed.

Human Vaginal Epithelial Cells are Susceptible to the Zika Virus: Implications for Zika Vaginal Transmission

The Zika Virus (ZIKV) is an emerging RNA virus that cause congenital birth defects and neurological compilations among infected individuals. Since the 2015 ZIKV outbreak in Brazil, the Centers for Disease Control, and Prevention (CDC) reports over 35,000 cases ZIKV disease cases within the United States (US) and US territories. Although ZIKV is primarily transmitted through an infected Aedes mosquito, recent studies demonstrate this pathogenic virus can be transmitted via sexual contact with an infected partner. CDC confirmed multiple clinical cases of infected patients acquired ZIKV through sexual transmission within the US. Additionally, mounting evidence from animal and cell studies demonstrate that the female reproductive tract supports ZIKV replication following intravaginal exposure. Despite the growing evidence associating ZIKV to sexual transmission, the underlying molecular mechanism involving vaginal transmission remains elusive. The overarching goal is to examine the role of the vaginal tract in ZIKV sexual transmission on a molecular level. The vaginal tract has multiple layers of epithelial cells that constitutes as the first line of defense against foreign pathogens. Given the capacity of sexual intercourse, we hypothesize that the initial event for ZIKV vaginal transmission is most likely through direct viral uptake at the outermost epithelial layer of the vaginal tract. We aim to test our hypothesis by (1) characterizing the replication kinetics of ZIKV in human vaginal epithelial cells (hVECs) in vitro and (2) determining the functional role of the putative ZIKV entry receptor, AXL, in hVECs. Our recent findings indicate hVECs is a permissive cell target for local ZIKV replication and production. Vaginal infection resulted in de novo replication of the ZIKV RNA genome, active production of the viral envelope protein, and steady release of infectious viral particles. Cell viability studies further indicate that hVECs do not exhibit significant cytopathic effect following ZIKV exposure. Additional studies show that the flaviviral entry receptor AXL is endogenously expressed in hVECs on a protein, mRNA level, and surface level. When expression patterns were compared between Vero and 293T cell lines, our results show similar protein levels of endogenous AXL in both Vero and VK2E6E7 cell lines, which may suggest that ZIKV entry via AXL‐mediated pathway and the dynamics of viral growth act independently of one another during sexual transmission. Our AXL knockdown and overexpression studies validate that this tyrosine receptor kinase is involved in ZIKV vaginal entry. In the future, kinase inhibitory studies will be performed to further validate whether downstream signaling contributes to ZIKV replication and production in hVECs. The outcome of this research will provide further insight into host‐virus interactions on a molecular level, which can lead to devising therapeutic agents aimed at interfering with the pathology caused by the virus.Support or Funding Information• T32 Grant: NIH National Heart, Lung, and Blood Institute, Research Training in Cardiovascular Biology at Meharry

Depressive Symptoms and Care Demands Among Primary Caregivers of Young Children with Evidence of Congenital Zika Virus Infection in Brazil.

Evidence suggests that caring for a child with special health care needs can affect many domains of family life, including caregiver mental health. However, few studies have examined these outcomes among families impacted by the Zika virus (ZIKV). This study examines depressive symptom severity and care demands among primary caregivers of children, aged 15 to 26 months, with evidence of congenital Zika virus infection (ZVI). A sample of primary caregivers of children with evidence of congenital ZVI in northeastern Brazil (n = 150) reported on depressive symptoms, care demands, and their children's development. Children were categorized into groups according to their developmental delay status. Bivariate analyses were run to test for differences between groups. A path analysis model was used to examine the indirect effects of developmental delay on depressive symptoms through economic challenges and time spent providing health care at home and whether these associations varied by child care support. Compared to primary caregivers of children without developmental delay, primary caregivers of children with developmental delay had higher depression scores (p = 0.002), reported more economic (p < 0.001) and child care (p < 0.001) challenges, and spent more time providing health care at home (p < 0.001). Among primary caregivers who did not have child care support, developmental delay had a significant indirect effect on depressive symptoms through economic challenges but not through time spent providing health care at home. For families impacted by the ZIKV outbreak in Brazil, economic and child care challenges may be associated with primary caregiver mental health.

Development and assessment of the feasibility of a Zika family support programme: a study protocol

The Zika virus outbreak in Brazil in 2015 affected thousands of people. Zika is now known to cause congenital malformations leading to impairments and developmental delays in affected children, including Congenital Zika Syndrome (CZS). Children with CZS have complex care needs. Caregivers require significant levels of support to meet these needs, and there are large gaps in healthcare services. This study aims to develop, pilot and assess the feasibility and scalability of a community-based Family Support Programme for caregivers of children with CZS. The programme is adapted from the Getting to Know Cerebral Palsy (GTKCP) programme for the context of CZS in Brazil. GTKCP is a 10-session programme held with 6-10 caregivers in the local community. It includes practical, educational, peer-support and psychosocial aspects, which aim to improve confidence and capacity to care for a child with CP, and quality of life and empowerment of caregivers. The research project contains four components: Ascertaining need for the caregiver programme: a mixed-methods approach that included two literature reviews, interviews with key stakeholders in country, and incorporation of findings from the Social and Economic Impact of Zika study.Adapting GTKCP for the context of CZS and Brazil: undertaken with guidance from technical experts.Pilot testing the intervention: deliver the 10-session programme to one group of caregivers of children with CZS in Rio de Janeiro and another in Greater Salvador.Update the manual through fast-track learning from participant and facilitator feedback. Assessing the feasibility of the intervention for scale up: deliver the updated programme to two groups each in Rio de Janeiro and Greater Salvador, and evaluate the acceptability, demand, implementation, practicality, adaptation, integration, expansion, and limited efficacy, through questionnaires, direct observation, semi-structured interviews and cost calculation. The project has ethics approval in both the UK and Brazil.