Revelado possível marcador para microcefalia causada por zika

Cientistas do Instituto de Química da USP e da Fiocruz do Rio de Janeiro e da Bahia identificaram consideráveis alterações lipídicas no plasma de recém-nascidos com exposição pré-natal ao vírus da zika.

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.

Repositioning and investigational drugs for Zika virus infection treatment: a patent review.

INTRODUCTION: Zika virus (ZIKV) is transmitted to humans throughout bites of Aedes mosquitoes. ZIKV infection may be asymptomatic in most cases, but it may cause fever, headache, muscle pain, and rash. Guillain-Barré syndrome also may be associated with the infection. Furthermore, the Pan American Health Organization informed 3,715 cases of the congenital ZIKV syndrome (CZS) in the Americas from 2015 - 2017, which may include microcephaly and other craniofacial deformities. AREAS COVERED: This review identifies patent documents on repositioning for ZIKV infection treatment of already approved drugs or phases II/III investigated drugs for other diseases. Thirty-six patents were found reporting compounds with anti-ZIKV activity with application dates ranging from 2015 to 2019. EXPERT OPINION: The main drugs claimed in patents were ribavirin, sofosbuvir, and alpha interferons. Preventing CZS is one of the most significant challenges in ZIKV infection. Therefore, repositioning sofosbuvir and niclosamide, that pose no danger for pregnant women, is a particular issue to be considered for clinical tests involving ZIKV disease. Given the substantial costs and developing time of new a drug, repositioning of old drugs is becoming an attractive alternative for diseases with neglected treatments.

Preventive effects of folic acid on Zika virus-associated poor pregnancy outcomes in immunocompromised mice.

Zika virus (ZIKV) infection may lead to congenital microcephaly and pregnancy loss in pregnant women. In the context of pregnancy, folic acid (FA) supplementation may reduce the risk of abnormal pregnancy outcomes. Intriguingly, FA may have a beneficial effect on the adverse pregnancy outcomes associated with ZIKV infection. Here, we show that FA inhibits ZIKV replication in human umbilical vein endothelial cells (HUVECs) and a cell culture model of blood-placental barrier (BPB). The inhibitory effect of FA against ZIKV infection is associated with FRα-AMPK signaling. Furthermore, treatment with FA reduces pathological features in the placenta, number of fetal resorptions, and stillbirths in two mouse models of in utero ZIKV transmission. Mice with FA treatment showed lower viral burden and better prognostic profiles in the placenta including reduced inflammatory response, and enhanced integrity of BPB. Overall, our findings suggest the preventive role of FA supplementation in ZIKV-associated abnormal pregnancy and warrant nutritional surveillance to evaluate maternal FA status in areas with active ZIKV transmission.

Cost-effectiveness of Prophylactic Zika Virus Vaccine in the Americas.

Zika virus remains a major public health concern because of its association with microcephaly and other neurologic disorders in newborns. A prophylactic vaccine has the potential to reduce disease incidence and eliminate birth defects resulting from prenatal Zika virus infection in future outbreaks. We evaluated the cost-effectiveness of a Zika vaccine candidate, assuming a protection efficacy of 60%-90%, for 18 countries in the Americas affected by the 2015-2017 Zika virus outbreaks. Encapsulating the demographics of these countries in an agent-based model, our results show that vaccinating women of reproductive age would be very cost-effective for sufficiently low (<$16) vaccination costs per recipient, depending on the country-specific Zika attack rate. In all countries studied, the median reduction of microcephaly was >75% with vaccination. These findings indicate that targeted vaccination of women of reproductive age is a noteworthy preventive measure for mitigating the effects of Zika virus infection in future outbreaks.

CT Epidemiologia 21/03/16: Microcefalias: SES/PE

CT Epidemiologia 21/03/16: complicações neurológicas associadas as Arboviroses (Chikungunya e Zika)

Portaria interministerial n. 405, de 15 de marco de 2016

Institui no âmbito do Sistema Único de Saúde (sus) e do Sistema Único de Assistência Social (suas), a estratégia de ação rápida para o fortalecimento da atenção à saúde e da proteção social de crianças com microcefalia

Development of a fluorescence-based method for the rapid determination of Zika virus polymerase activity and the screening of antiviral drugs.

Zika virus (ZIKV) is an emerging pathogen that has been associated with large numbers of cases of severe neurologic disease, including Guillain-Barré syndrome and microcephaly. Despite its recent establishment as a serious global public health concern there are no licensed therapeutics to control this virus. Accordingly, there is an urgent need to develop methods for the high-throughput screening of antiviral agents. We describe here a fluorescence-based method to monitor the real-time polymerization activity of Zika virus RNA-dependent RNA polymerase (RdRp). By using homopolymeric RNA template molecules, de novo RNA synthesis can be detected with a fluorescent dye, which permits the specific quantification and kinetics of double-strand RNA formation. ZIKV RdRp activity detected using this fluorescence-based assay positively correlated with traditional assays measuring the incorporation of radiolabeled nucleotides. We also validated this method as a suitable assay for the identification of ZIKV inhibitors targeting the viral polymerase using known broad-spectrum inhibitors. The assay was also successfully adapted to detect RNA polymerization activity by different RdRps, illustrated here using purified RdRps from hepatitis C virus and foot-and-mouth disease virus. The potential of fluorescence-based approaches for the enzymatic characterization of viral polymerases, as well as for high-throughput screening of antiviral drugs, are discussed.

Developing animal models of Zika virus infection for novel drug discovery.

INTRODUCTION: Just before the Brazilian outbreak, Zika virus was related to a mild infection, causing fever and skin rash. Congenital Zika Syndrome was first described in Brazil, causing microcephaly and malformations in newborns. Three years after the outbreak, the mechanisms of Zika pathogenesis are still not completely elucidated. Moreover, as of today, there is still no approved vaccine that can be administered to the susceptible population. Considering the unmet clinical need, animal models represent an unprecedented opportunity to study Zika pathophysiology and test drugs for the treatment and prevention of vertical transmission. Areas covered: The authors explore the current knowledge about Zika through animal models and advancements in drug discovery by highlighting drugs with the greatest potential to treat ZIKV infection and block vertical transmission. Expert opinion: Some drugs used to treat other infections have been repurposed to treat Zika infection, reducing the cost and time for clinical application. One promising example is Sofosbuvir, which protected mice models against Zika pathogenesis by preventing vertical transmission. Importantly, there is a lack on exploration on the long-term effects of Zika Congenital Syndrome, as well as the possible ways to treat its sequelae.

Evaluation of alternative endpoints for ZIKV vaccine efficacy trials.

Zika virus (ZIKV) infection during pregnancy is associated with microcephaly and other birth defects, collectively termed Congenital Zika Syndrome (CZS). During the epidemic in 2015-16, ZIKV spread through the Americas and quickly joined the list of other known teratogenic pathogens, TORCH. Multiple ZIKV vaccines have been developed for protection of pregnant women and women of childbearing age. However, ZIKV infection incidence has since waned substantially, and adverse birth outcomes are rare outcomes of infection. Studying a vaccine's protective efficacy against CZS in a large phase III clinical trial may be infeasible in such times of low incidence. Should trials be initiated, researchers may resort to alternative clinical endpoints. In this study, we simulate a variety of vaccine clinical trial scenarios to evaluate the feasibility of the CZS endpoint in vaccine studies and compare CZS to other potential outcomes: ZIKV infection detected through weekly, biweekly, or monthly testing and laboratory-confirmed, symptomatic Zika Virus Disease. We compare the sample size required for 80% statistical power to detect vaccine efficacy and trial duration for each scenario. Our results show the feasibility of CZS clinical endpoints depends on the timing of simulated clinical trials in the course of a seasonal epidemic, due to CZS risk varying with trimester of infection. This result highlights additional considerations needed when designing vaccine efficacy trials of protection against teratogenic pathogens.

Using social media to estimate Zika's impact on tourism: #babymoon, 2014-2017.

Zika virus infection during pregnancy can cause microcephaly and other birth defects. We hypothesized that the Latin America Zika epidemic resulted in pregnant women and their partners adopting behavioral changes to limit risk, leading them to forego travel to Zika-affected locations. We evaluated this hypothesis by studying travelers' intent and behavior through Twitter data related to babymoon: a holiday taken by parents-to-be before their baby is born. We found the odds of mentioning representative Zika-affected locations in #babymoon tweets dropped significantly (Odds ratio: 0.29, 95% CI: 0.20-0.40) after the Zika-microcephaly association became well-known. This result was further corroborated through a content analysis of #babymoon tweets mentioning Zika-affected locations, which identified if the Twitter user was physically present in the Zika-affected locations. Conversely, we found a small but statistically insignificant increase in the odds of mentioning Zika-free locations from #babymoon tweets (Odds Ratio: 1.11, 95% CI: 0.97-1.27) after the Zika-microcephaly association became well-known.

A Biomimetic Nanodecoy Traps Zika Virus To Prevent Viral Infection and Fetal Microcephaly Development.

Zika virus (ZIKV) has emerged as a global health threat due to its unexpected causal link to devastating neurological disorders such as fetal microcephaly; however, to date, no approved vaccine or specific treatment is available for ZIKV infection. Here we develop a biomimetic nanodecoy (ND) that can trap ZIKV, divert ZIKV away from its intended targets, and inhibit ZIKV infection. The ND, which is composed of a gelatin nanoparticle core camouflaged by mosquito medium host cell membranes, effectively adsorbs ZIKV and inhibits ZIKV replication in ZIKV-susceptible cells. Using a mouse model, we demonstrate that NDs significantly attenuate the ZIKV-induced inflammatory responses and degenerative changes and thus improve the survival rate of ZIKV-challenged mice. Moreover, by trapping ZIKV, NDs successfully prevent ZIKV from passing through physiologic barriers into the fetal brain and thereby mitigate ZIKV-induced fetal microcephaly in pregnant mice. We anticipate that this study will provide new insights into the development of safe and effective protection against ZIKV and various other viruses that threaten public health.

Ethical Issues during Zika Epidemic in Puerto Rico and the Americas.

The Zika virus epidemic and the possible devastating teratogenic effects of the virus represent a challenge. Health authorities have the responsibility to create programs that provide adequate preventive, medical and psychological services to the affected population. The estimated risk of microcephaly in infants of mothers infected with Zika virus is 1 to 13% when the infection occurs in the first trimester of pregnancy. There is insufficient data to estimate the risk of microcephaly when infection occurs in the second or third trimester. Pregnant women and those in reproductive age are advised to avoid traveling to places where there is local transmission of the Zika virus. Human rights advocates have requested, comprehensive sexual and reproductive health services that include expanded access to contraceptive methods including emergency contraception and safe abortion services. These strategies created a debate between the abortion rights and the right of the disabled. The discussion rests on the assumption that there are lives that are not worth living. Most people focus on the most severely affected patients, but few consider that the spectrum of disabilities associated with congenital Zika infection is broad. The rights of children with disabilities and their dignity as individuals should be respected.

E90 subunit vaccine protects mice from Zika virus infection and microcephaly.

Zika virus (ZIKV) became a global threat due to its unprecedented outbreak and its association with congenital malformations such as microcephaly in developing fetuses and neonates. There are currently no effective vaccines or drugs available for the prevention or treatment of ZIKV infection. Although multiple vaccine platforms have been established, their effectiveness in preventing congenital microcephaly has not been addressed. Herein, we tested a subunit vaccine containing the 450 amino acids at the N-terminus of the ZIKV envelope protein (E90) in mouse models for either in utero or neonatal ZIKV infection. In one model, embryos of vaccinated dams were challenged with a contemporary ZIKV strain at embryonic day 13.5. The other model infects neonatal mice from vaccinated dams by direct injection of ZIKV into the developing brains. The vaccine led to a substantial reduction of ZIKV-infected cells measured in the brains of fetal or suckling mice, and successfully prevented the onset of microcephaly compared to unvaccinated controls. Furthermore, E90 could protect mice from ZIKV infection even at 140 days post-immunization. This work directly demonstrates that immunization of pregnant mice protects the developing brains of offspring both in utero and in the neonatal period from subsequent ZIKV infection and microcephaly. It also supports the further development of the E90 subunit vaccine towards clinical trials.

Inhibition of Neurogenesis by Zika Virus Infection.

BACKGROUND & OBJECTIVE: The link between Zika Virus (ZIKV) epidemic and neurological disorder has raised an urgent global alarm. The current epidemic of ZIKV has triggered quick responses in the scientific world. The first case of ZIKV was reported in 2015 from Brazil and now has spread over 30 countries. Nearly four hundred cases of traveler associated ZIKV infection have also been reported in the United States. ZIKV is primarily transmitted by mosquito belonging to the genus Aedes that are widely distributed throughout the world. Additionally, the virus can also be transmitted from male to female by sexual contact. The epidemiological investigations during the current outbreak found a causal link between infection in pregnant women and the development of microcephaly (MCPH) in their unborn babies. This finding is a cause of grave concern since MCPH is a serious neural developmental disorder that can lead to significant post-natal developmental abnormalities and disabilities. Recently, published data indicates that ZIKV infection severely affects the growth of fetal neural progenitor cells and cerebral neurons resulting in malformation of cerebral cortex leading to MCPH. Recently, it has been reported that ZIKV infection deregulates the signaling pathway of neuronal cell and inhibits the neurogenesis. CONCLUSION: In this review, we discussed the information about cellular and molecular mechanisms of neurodegeneration of human neuronal cells and inhibition of neurogenesis. The provided information in this review will be very useful further not only in neuro-scientific research but also in the desig and development of management strategies for MCPH and other mosquito-borne diseases.

Zika and Public Health: Understanding the Epidemiology and Information Environment.

Because Zika is a newly emerging infectious disease with little previous information known about it, there are many epidemiologic and clinical questions. The complexity of providing care to those who are at risk for infection or are already infected with Zika in this evidence-scarce environment cannot be understated. In this article, we provide an overview of the Zika virus (ZIKV) in the context of public health and pediatric health care. A broad public health focus is used to provide relevant information for addressing important questions about the epidemic and to facilitate communication with patients, parents, and caregivers within the current information environment. We explore issues regarding the epidemiology of the virus (including why ZIKV outbreaks are occurring), what has changed since the sporadic case reports before the outbreaks, why the true incidence is difficult to estimate, why attack rates vary by population and geography, and why the association between Zika and congenital Zika syndrome and Guillain-Barré syndrome have only come to light recently. Additionally, challenges related to the current information environment, traditional and informal information sources about the ZIKV, and examples of Zika public health communication campaigns are discussed. Importantly, we review the existing findings regarding the US population's Zika-related knowledge, attitudes, beliefs, and behavior by highlighting variations and gaps. We conclude by identifying related research questions that remain critical.

Media coverage of the Zika crisis in Brazil: The construction of a 'war' frame that masked social and gender inequalities.

Between 2015 and 2016, Zika became an epidemic of global concern and the focus of intense media coverage. Using a hybrid model of frame and social representations theory, we examine how the Zika outbreak was reported in two major newspapers in Brazil: O Globo and Folha de São Paulo. The analysis of 186 articles published between December 2015 and May 2016 reveals a dominant 'war' frame supported by two sub-frames: one focused on eradicating the vector (mosquito) and another on controlling microcephaly, placing the burden of prevention on women. Scientific uncertainties about the virus and its relationship to microcephaly coupled with political uncertainties in Brazil increased the power of the war frame. This frame gave prominence and legitimacy to certain representations of disease management during the crisis, masking social and gender inequalities. We show how the cartography of the disease overlaps with that of poverty and regional inequality in Brazil to argue that addressing socio-economic aspects is essential, but normally neglected, in media communications during disease outbreaks like Zika.

What we know and what we don't know about perinatal Zika virus infection: a systematic review.

INTRODUCTION: Zika virus (ZIKV) infection has caused the most challenging worldwide infectious epidemic outbreak in recent months. ZIKV causes microcephaly and other congenital malformations. There is a need to perform updated systematic reviews on ZIKV infection periodically because this epidemic is bringing up new evidence with extraordinary speed. Areas covered: Evidence related to ZIKV infection in the gestational, perinatal, and early infant periods covering epidemiology, virology, pathogenesis, risk factors, time of infection during pregnancy, newborn symptoms, treatment, and vaccines. To this end, a search was performed using terms ['Zika'] AND ['Perinatal Infection'] OR ['Congenital Infection'] in the PubMed® international electronic database. Out of a total of 1,538 articles published until 30 November 2017, we finally assessed 106 articles articles that were relevant to the research areas included in this study. Expert commentary: ZIKV is a new teratogenic/neurotropic virus affecting fetuses. Many challenges are still far from being solved regarding the epidemiology, case definition, clinical and laboratory diagnosis, and preventive measures. An approach using 'omics' and new biomarkers for diagnosis, and a ZIKV-vaccine for treatment, might finally give us the tools to solve these challenges.

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

Accumulating evidence support a causal link between Zika virus (ZIKV) infection during gestation and congenital microcephaly. However, the mechanism of ZIKV-associated microcephaly remains unclear. We combined analyses of ZIKV-infected human fetuses, cultured human neural stem cells and mouse embryos to understand how ZIKV induces microcephaly. We show that ZIKV triggers endoplasmic reticulum stress and unfolded protein response in the cerebral cortex of infected postmortem human fetuses as well as in cultured human neural stem cells. After intracerebral and intraplacental inoculation of ZIKV in mouse embryos, we show that it triggers endoplasmic reticulum stress in embryonic brains in vivo. This perturbs a physiological unfolded protein response within cortical progenitors that controls neurogenesis. Thus, ZIKV-infected progenitors generate fewer projection neurons that eventually settle in the cerebral cortex, whereupon sustained endoplasmic reticulum stress leads to apoptosis. Furthermore, we demonstrate that administration of pharmacological inhibitors of unfolded protein response counteracts these pathophysiological mechanisms and prevents microcephaly in ZIKV-infected mouse embryos. Such defects are specific to ZIKV, as they are not observed upon intraplacental injection of other related flaviviruses in mice.