More Evidence for Zika as a Causal Agent Of Guillain-Barré Syndrome

MedicalResearch.com Interview with:

Emilio Dirlikov, PhD Epidemic Intelligence Service Officer CDC 

Dr. Dirlikov

Emilio Dirlikov, PhD
Epidemic Intelligence Service Officer
CDC 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In December 2015, Puerto Rico Department of Health (PRDH) reported its first confirmed locally acquired case of Zika virus disease. In February 2016, PRDH reported the first person diagnosed with Guillain-Barré syndrome (GBS) who also had evidence of Zika virus infection. At the time, scientific evidence of the potential association between Zika virus infection and GBS was lacking, and rigorous studies were needed.

Through a collaboration between PRDH, CDC, and the University of Puerto Rico (UPR), we conducted a case-control study to determine risk factors for GBS during the 2016 Zika virus epidemic. By prospectively enrolling case-patients, we shortened the time to enrollment, increasing the likelihood of detecting Zika virus nucleic acids to confirm Zika virus infection.

As a result, we found that an acute Zika virus infection confirmed by laboratory testing is a risk factor for developing Guillain-Barré syndrome. This is the first case-control study to find laboratory evidence showing this given the difficulty of confirming Zika virus infection among people diagnosed with GBS.

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Can Zika Be Used To Fight Glioblastoma Brain Tumors?

MedicalResearch.com Interview with:

Milan G. Chheda, MD Assistant Professor  Department of Medicine  Oncology Division  Molecular Oncology  Department of Neurology Washington University School of Medicine in St. Louis

Dr. Chheda

Milan G. Chheda, MD
Assistant Professor
Department of Medicine
Oncology Division
Molecular Oncology
Department of Neurology
Washington University School of Medicine in St. Louis

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Glioblastoma is an extremely aggressive brain tumor. Most patients die in less than two years. A longstanding challenge has been killing tumor cells that are inherently resistant to our current therapies (radiation and chemotherapy). These cells, called cancer stem cells, are extremely hardy. A longstanding dream of oncologists has been to devise a way to find them and kill them. The public health epidemic in 2015 made Zhe Zhu, post-doctoral fellow in Jeremy Rich’s lab, wonder whether Zika virus could work on cancer stem cells, that share properties with stem cells in fetal brain. Zika virus doesn’t cause significant problems in adults.

We took a lesson from nature and tested Zika virus.

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Potential Drug-Binding Site Against Zika Virus Identified

MedicalResearch.com Interview with:

Dr. Jikui Song PhD Assistant professor of biochemistry University of California, Riverside.

Dr. Jikui Song

Dr. Jikui Song PhD
Assistant professor of biochemistry
University of California, Riverside.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recent outbreak of Zika virus (ZIKV) has become a wordwide health concern. However, no vaccines or antiviral drugs against ZIKV are currently available. To explore potential druggable sites for ZIKV, we set out to determine the crystal structure of full-length ZIKV NS5, the molecular machinery responsible for the genomic replication of ZIKV.

The major findings of our study include the identification of a conserved domain conformation within flavivirus NS5 family, which may be important for functional regulation of flavivirus NS5. Furthermore, our structural analysis revealed a potential drug-binding site of ZIKV NS5, providing basis for future development of novel antivirals against ZIKV.

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Comparison Zika Outbreaks in French Polynesia, Colombia and the State of Bahia in Brazil

MedicalResearch.com Interview with:

Daihai He PhD Department of Applied Mathematics The Hong Kong Polytechnic University Hung Hom, Kowloon Hong Kong (SAR), China

Dr. Daihai He

Daihai He PhD
Department of Applied Mathematics
The Hong Kong Polytechnic University
Hung Hom, Kowloon
Hong Kong (SAR), China

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika virus disease has large outbreaks in many Pacific and American countries in 2016, and the outbreaks are still on-going. Our work is conducted against this background. We compared data from three localities: French Polynesia in 2013-2014, Colombia and Brazil in 2016. We found that in French Polynesia the infection attack rate (i.e. the proportion of the population who got infected) is about 3/4, which matched previous serological studies. We then make estimation for the other two place. We found that the infection attack rate in Colombia in 2016 was most likely less than 50%. For Bahia province of Brazil, we did not arrive at a very accurate estimation, as the confidence interval is wide, and our best estimate is 30%. The relatively low infection attack rate in Colombia and Brazil implies that future outbreaks of Zika virus diseases are still possible. Thus control and surveillance efforts should be continued.

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Human Placenta May Be Most Vulnerable To Zika In First Trimester

MedicalResearch.com Interview with:

R. Michael Roberts

Dr. R. Michael Roberts

R. Michael Roberts PhD
Curators’ Distinguished Professor
240b Bond Life Sciences Center
Columbia, Missouri 65211-7310

MedicalResearch.com: What is the background for this study?

Response: My background in placental biology and in communication between the embryo and the mother in early pregnancy made me curious about how the zika virus (ZIKV) crossed the placenta in early pregnancy to cause microcephaly. My group had been working on a laboratory model for placental trophoblast for over 10 years. We generate trophoblast from human pluripotent cells (embryonic stem cells and induced pluripotent stem cells) by exposing them to the growth factor BMP4 and two pharmaceuticals that inhibit the signaling pathways necessary to maintain pluripotency. I was curious to determine whether or not ZIKV could infect these cells, replicate, and release infectious virus, because work from my collaborator Yoel Sadovsky at the University of Pittsburgh indicated that the mature placenta was likely to be resistant to infection.

MedicalResearch.com: What are the main findings?

Response: There are, I believe two striking outcomes from this work.

One is that the results indicate that the human placenta is likely most vulnerable to infection by Zika during the first trimester. We also suggest that women whose fetus is affected from an infection occurring later in pregnancy likely had a past dengue infection. The second striking result is that the African strain of Zika may have greater virulence towards early placenta than the Asian strains, such as the ones that have spread in the New World.

The work with the virus only began when we realized that term trophoblasts lacked expression of the genes that encode the protein factors that promote flavivirus infection (ZIKV is a flavivirus, like dengue, West Nile virus), e.g. TYRO3, AXL, MERTK, and also had a poised innate immune system that would counteract virus replication. Conversely, the trophoblasts we create from embryonic stem cells had the factors that would promote virus uptake, but seemed ill-prepared to counteract virus replication once infection occurred. In other words, the early placental trophoblasts were potentially more susceptible to infection. We confirmed this hypothesis with two strains of ZIKV (an Asian strain related to the one encountered in Brazil, and an African strain often considered to be relatively benign). What was unexpected was the African strain appeared to be more virulent than the Asian strain.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Whether the early placenta could be protected by some sort of immune therapy or by prior vaccination of the mother is clearly uncertain at present. Vaccination programs have not been altogether successful when used to protect against Dengue, which is a virus related to ZIKV.

There is evidence that the early placenta is also permissive to other viruses, such as Rubella. Also there is a very interesting paper in the Journal of the American medical Association by Honein et al. that was published on December 15, 2016. In this study, the overall risk for microcephaly and other brain abnormalities in infants born to a large cohort of U.S. women exposed to ZIKV while traveling (n = 442) was 5.9 % (18), and, of these, there were no cases noted among the women known to have been infected during their second or third trimesters. In Brazil, women appear to be at risk for fetal infections by ZIKV throughout their pregnancies but this may be because they had experienced an earlier infection by Dengue. I have discussed this puzzle in the paper.

I have no disclosures to make, nor conflicts of interest regarding the research or this response to your queries.

Citation:

PNAS Plus – Biological Sciences – Applied Biological Sciences:
Megan A. Sheridan, Dinar Yunusov, Velmurugan Balaraman, Andrei P. Alexenko, Shinichiro Yabe, Sergio Verjovski-Almeida, Danny J. Schust, Alexander W. Franz, Yoel Sadovsky, Toshihiko Ezashi, and R. Michael Roberts
Vulnerability of primitive human placental trophoblast to Zika virus PNAS 2017 114 (9) E1587-E1596; published ahead of print February 13, 2017, doi:10.1073/pnas.1616097114

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Human Genetics Contributes To Zika-Induced Brain Damage

MedicalResearch.com Interview with:

Ping Wu, MD, PhD John S. Dunn Distinguished Chair in Neurological Recovery Professor, Department of Neuroscience & Cell Biology University of Texas Medical Branch Galveston, TX 77555-0620

Dr. Ping Wu

Ping Wu, MD, PhD
John S. Dunn Distinguished Chair in Neurological Recovery
Professor, Department of Neuroscience & Cell Biology
University of Texas Medical Branch
Galveston, TX 77555-0620

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika viral infection poses a major global public health threat, evidenced by recent outbreaks in America with many cases of microcephaly in newborns and other neurological impairments. A critical knowledge gap in our understanding is the role of host determinants of Zika-mediated fetal malformation. For example, not all infants born to Zika-infected women develop microcephaly, and there is a wide range of Zika-induced brain damage. To begin to fill the gap, we infected brain stem cells that were derived from three human donors, and found that only two of them exhibited severer deficits in nerve cell production along with aberrant alterations in gene expression.

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Persistence of Zika Virus in Body Fluids — Preliminary Report

MedicalResearch.com Interview with:
Gabriela Paz-Bailey MD PhD

Senior Epidemiologist
Centers for Disease Control and Prevention 

MedicalResearch.com: What is the background for this study?

Response: Zika virus is recognized as a cause of microcephaly and other severe birth defects when a woman is infected during pregnancy. Additionally, it has been associated with potentially fatal complications, such as Guillain-Barré syndrome. It is not well understood how often Zika virus particles can be detected in semen and other body fluids and for how long they remain detectable. Existing evidence is based on case reports and cross-sectional observations, primarily from returning travelers. A more comprehensive description of the dynamics of the early stages of Zika virus infection, observed within infected people over time, is needed to inform diagnostic testing as well as prevention recommendations and interventions.
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Zika Virus Infection in Pregnant Women in Rio de Janeiro

MedicalResearch.com Interview with:

Karin Nielsen, MD, MPH Professor of Clinical Pediatrics Division of Pediatric Infectious Diseases David Geffen School of Medicine at UCLA Director, Center for Brazilian Studies

Karin Nielsen

Karin Nielsen, MD, MPH
Professor of Clinical Pediatrics
Division of Pediatric Infectious Diseases
David Geffen School of Medicine at UCLA
Director, Center for Brazilian Studies

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our research was a prospective study in which pregnant women in Rio de Janeiro who developed a rash in the last 5 days between the end of 2015 to mid 2016 were screened for possible infection with Zika virus by a special molecular test (PCR) which looked for the virus in blood or urine. Women who were found to have Zika virus in either blood, urine or both were followed throughout time to look for pregnancy and infant outcomes. We also followed women who had a negative PCR test for Zika as a comparison group. By July 2016, we had outcomes known for 125 Zika affected pregnancies, of these 58 had abnormal outcomes, with 9 fetal losses and 49 babies who had abnormal findings on physical exam or brain imaging, all consistent with neurologic abnormalities. This meant 46% of the pregnant women in our study had an abnormal pregnancy outcome, and 42% of live birth infants were found to have an abnormality in the first few months of life.

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OCT of Retinal Lesions in Infants with Congenital Zika Syndrome

MedicalResearch.com Interview with:
Camila Ventura MD
Pediatric Retina Research Fellow at Bascom Palmer Eye Institute (BPEI), USA
PhD student at Federal University of São Paulo (Unifesp)
Medical Retina, Ocular Oncology, and Uveitis Department at Altino Ventura Foundation Brazil

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Brazilian outbreak of Zika virus (ZIKV) began in April 2015 and since then, we have not been able to stop its rapid spread throughout the Americas. Not only has ZIKV been disseminating very rapidly, patients affected by the ZIKV have also been presenting with some findings never before reported in the literature. Until recently, ZIKV infection was only associated with mild symptoms such as headache, rash, arthralgia, and conjunctivitis. However, in October 2015, a twenty-fold increase in the prevalence of newborns with microcephaly was reported that was later confirmed to be associated to ZIKV infection during pregnancy.

Although microcephaly and other central nervous system findings were the first abnormalities reported, recent publications have described other malformations associated with ZIKV congenital infection including hearing loss, limb anomalies and ocular findings. Due to all of these systemic findings, this new clinical condition has been named Congenital Zika Syndrome (CZS).

In January 2016, our group published the first report on the ocular findings of infants with microcephaly and presumed congenital ZIKV infection, followed by another manuscript describing 10 additional cases. We have also contributed with an article published in JAMA Ophthalmology reporting the risk factors associated to the ocular findings in babies with CZS. Other authors such as De Paula Freitas et al and Miranda 2nd et al, have also contributed to the literature by describing similar ocular findings in these infants with CZS.

In the present case series, we describe the Ocular Coherence Tomography (OCT) findings in ten eyes of eight infants with CZS.

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Zika Can Cause Multiple Other Brain Abnormalities Other Than Microcephaly

MedicalResearch.com Interview with:

Fernanda Tovar Moll, MD, PhD Vice president of the D'Or Institute for Research and Education Professor,Federal University of Rio de Janeiro Rio de Janeiro, Brazil

Dr. Fernanda Tovar-Moll

Fernanda Tovar Moll, MD, PhD
Vice president of the D’Or Institute for Research and Education
Professor,Federal University of Rio de Janeiro
Rio de Janeiro, Brazil

MedicalResearch.com: What is the background for this study?

Response: The consequences of congenital zika virus infection are still under investigation. Recent studies suggest microcephaly as one of the consequences, but we wanted to go deeper in investigating what other kinds of neurological changes could happen in the developing central nervous system.

Based on that, we performed a cohort study with multimodal images exams and longitudinal follow up (pre and post natal analyses) of some cases.

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CDC Reports Zika Has Spread to the Bahamas

Local mosquito transmission of Zika virus infection (Zika) has been reported on the island of New Providence in The Bahamas (which includes the city of Nassau). Local mosquito transmission means that mosquitoes in the area are infected with Zika virus and are spreading it to people……

Please read rest of CDC report HERE

CDC Urges Wider Availability of Contraceptives In Regions Affected by Zika

MedicalResearch.com Interview with:

Charlan D. Kroelinger, PhD Division of Reproductive Health National Center for Chronic Disease Prevention and Health Promotion CDC

Dr. Charlan Kroelinger

Charlan D. Kroelinger, PhD
Division of Reproductive Health
National Center for Chronic Disease Prevention and Health Promotion
CDC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika virus infection during pregnancy can cause microcephaly and other severe fetal brain defects. Doctors have also found other problems in pregnancies and among infants infected with Zika virus before birth, such as absent or poorly developed brain structures, defects of the eye, hearing deficits, and impaired growth. Nearly half of all pregnancies in the United States are unintended. Increased access to birth control may lead to reductions in unintended pregnancies, which may result in fewer adverse pregnancy and birth outcomes in the context of a Zika virus outbreak.

A new report from CDC estimates that use of highly effective, reversible forms of birth control, called long-acting reversible contraception (LARC), which includes intrauterine devices (IUDs) and implants, remains lower than use of moderate or less effective methods such as oral contraceptive pills and condoms, although contraception use varied across states and by age group and race/ethnicity.

CDC scientists used data from four state-based surveillance systems to estimate contraception use for non-pregnant and postpartum women at risk for unintended pregnancy and sexually active female high school students who live in states with the potential for local Zika virus transmission. Less than one in four sexually active women of reproductive age and fewer than one in 10 sexually active female high school students reported using LARC. A higher percentage of postpartum women reported LARC use. Moderately effective and less effective contraceptive methods, including pills, patches, rings, injections, condoms and other barrier methods, were used more frequently than highly effective methods. These estimates are of concern because the most commonly used methods of contraception are not as effective at preventing unintended pregnancy.

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CDC Gives Recommendations For Limiting Zika Spread After RIO Olympics

MedicalResearch.com Interview with:

Dr. Martin Cetron, MD Director of the CDC’s Division of Global Migration and Quarantine

Dr. Martin Cetron

Dr. Martin Cetron, MD
Director of the CDC’s Division of Global Migration and Quarantine

MedicalResearch.com: What is the background for this study?

Response: According to the Brazilian Tourism Board, approximately 350,000 – 500,000 international visitors and athletes from 207 countries are expected to travel to Rio de Janeiro, Brazil for the 2016 Olympic and Paralympic Games. This travel volume represents a very small fraction – less than 0.25% – of the total estimated 2015 travel volume to Zika-affected countries.

CDC conducted a risk analysis to predict those countries at risk for Zika virus importation exclusively attributable to the Games.

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Two New Vaccines Provide Protection Against Zika in Mice

MedicalResearch.com Interview with:

Dan Barouch, M.D., Ph.D. Professor of Medicine Harvard Medical School Ragon Institute of MGH, MIT, and Harvard Director, Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center

Dr. Dan Barouch

Dan Barouch, M.D., Ph.D.
Professor of Medicine
Harvard Medical School
Ragon Institute of MGH, MIT, and Harvard
Director, Center for Virology and Vaccine Research
Beth Israel Deaconess Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We showed that two vaccines, a DNA vaccine and a purified inactivated virus vaccine, both provided complete protection against Zika virus challenge in mice. To the best of our knowledge, this is the first demonstration of Zika vaccine protection in any animal model.

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Requests for Abortions in South American Rise Dramatically Since Zika, Especially in Brazil

MedicalResearch.com Interview with:

Abigail R.A. Aiken, MD, MPH, PhD Assistant Professor LBJ School of Public Affairs University of Texas at Austin Austin, TX, 78713

Dr. Abigail Aiken

Abigail R.A. Aiken, MD, MPH, PhD
Assistant Professor
LBJ School of Public Affairs
University of Texas at Austin
Austin, TX, 78713

MedicalResearch.com: What is the background for this study?

Response: As Zika began to emerge as an epidemic in Latin America and its links with microcephaly began to be realized, we were aware that women in the region who were already pregnant or who would become pregnant would have a very limited set of reproductive options. Research and media attention about the possible biological effects of Zika in pregnancy began to appear rapidly. But much less attention was been paid to the impacts of Zika on women. We followed the responses of governments and health organizations and when they began to issue advisories warning women to avoid pregnancy, we knew it would be important to investigate the impacts of those advisories. A country-wide policy that is impossible to follow if you are pregnant or cannot avoid pregnancy is an unusual and important public issue. Accurate data on abortion are very difficult to obtain in Latin America because in most countries, abortion is highly restricted. We wanted to provide a window on the issue of how women were responding to the risks of Zika and its associated advisories, so we worked with Women on Web (WoW), an online non-profit telemedicine initiative that provides safe medical abortion to women in countries where safe, legal abortion is not universally available.

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Inflammation Caused By Mosquito Bites Helps Viral Infections Spread

MedicalResearch.com Interview with:
Clive McKimmie PhD
Research Fellow,
Virus Host Interaction Team (VHIT),
University of Leeds
St James’ University Hospital
Leeds UK

MedicalResearch.com: What is the background for this study?

Response: With the rapid spread of Zika in the Americas, attention has been drawn to this group of neglected mosquito-borne viral infections. The Zika virus is not alone in causing problems, others such as dengue and chikungunya viruses are infecting millions of people each year. Yet there’s little doctors can do to help people who get sick.
When mosquitoes bite you they can transmit these disease causing viruses. We don’t understand what happens during the early stages of infection very well. However, it is known that the mosquito bite itself somehow helps the virus to infect your body.

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CDC Recommends Urine Testing of Patients Suspected of Acute Zika Infection

MedicalResearch.com Interview with:
Andrea M. Bingham, PhD
Vector-Borne Disease Surveillance Coordinator
Florida Department of Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Bingham: Since its introduction to Brazil in 2015, Zika virus has spread throughout the Caribbean and South and Central America. We are constantly learning new things about Zika virus, including its potential for sexual transmission and its ability to cause certain birth defects such as microcephaly. Because many states, including Florida, have mosquito vectors that can potentially be infected with Zika virus, being able to identify infected people is important to ensure proper response and control measures are put in place to prevent local introductions. Improving testing capacity helps ensure that we have the ability to rapidly detect local Zika virus introductions if they occur.

On the basis of previous small Zika fever case studies that reported positive testing of patient urine and/or saliva samples, the Florida Department of Health made the decision to collect multiple specimen types from persons with suspected acute travel-related Zika fever in order to determine the most sensitive and efficient testing algorithm. Testing performed at our state public health laboratories in Tampa and Jacksonville suggested that urine was the most useful specimen for identifying acute Zika fever infections. Zika virus real time reverse-transcriptase polymerase chain reaction (RT-PCR) testing conducted on urine and serum samples collected the same day from 66 travel-associated Zika fever patients, detected Zika virus in nearly twice as many urine samples (61) as serum samples (31). Viral RNA was also detectable in urine longer than in serum. Although a high percentage of saliva samples also tested positive, no additional cases were identified through saliva testing alone. Based on these results and those of the small case studies, CDC updated their guidance to include urine as a recommended specimen type for testing of patients with suspected acute Zika fever.

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Clinical Findings and Brain Calcifications of Zika Babies Described

MedicalResearch.com Interview with:

Team of Doctors Brazil - Article BJM - Zika -  Ana van Der Linden, Alessandra Brainer, Maria de Fatima Aragao, Vanessa va Der Linden e Arthur Cesário.jpg

Team of Doctors:  Ana van Der Linden, Alessandra Brainer, Maria de Fatima Aragao, Vanessa va Der Linden e Arthur Cesário

Maria de Fatima Vasco Aragao MD, PhD
Radiologist and Neuroradiologist
Professor of Radiology, Mauricio de Nassau University, Recife, Brazil
Scientific Director of Multimagem Radiology Clinic, Recife – PE, Brazil
President of Pernambuco Radiology Society

MedicalResearch.com: What is the background for this study?

Response: The new Zika virus epidemic in Brazil was recognized as starting in the first half of 2015 and the microcephaly epidemic was detected in the second half of that same year.

This is a transmission electron micrograph (TEM) of Zika virus, which is a member of the family Flaviviridae. Virus particles are 40 nm in diameter, with an outer envelope, and an inner dense core.

This is a transmission electron micrograph (TEM) of Zika virus, which is a member of the family Flaviviridae. Virus particles are 40 nm in diameter, with an outer envelope, and an inner dense core.

MedicalResearch.com: What are the main findings?

  • Response:  In our study of the 23 mothers, only one did not report rash during pregnancy (rash is a sign that can happen in Zika virus infection). However, Zika virus infection can be asymptomatic in three of every four infected patients. All of the 23 babies had the same clinical and epidemiological characteristics and other congenital infection diseases had been excluded. Of these 23 babies, six were tested for IgM antibodies, specific to Zika virus and all six proved positive. So, by deduction, the other 17 babies on whom it was not possible to make the IgM test, were considered as also having presumed congenital infection related to the Zika virus, after other congenital infections being excluded.
  • All the babies showed malformations of cortical development and sulcation.  The most frequent cortical malformation were: Microcephaly with a simplified cortical gyral pattern and areas of thick cortex of polymicrogyria or pachygyria which were located predominantly in the frontal lobes.
  • Abnormalities of the corpus callósum (hypogenesis and hypoplasia) were common.
  • Decreased brain volume was a common finding. Ventriculomegaly was present in all the babies, with a predominant enlargement of the posterior portions of the lateral ventricles,
  • Delayed myelination were also common. The cisterna magna was enlarged in most of the cases, with or without cerebellar hypoplasia.
  • Some of the babies showed a symmetrical enlargement of the anterior subarachnoid space of the supratentorial compartment, associated with severe ventriculomegaly.

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Scientists Consider Using Bacteria To Deliver Lethal RNA to Zika Spreading Mosquitoes

MedicalResearch.com Interview with:

Prof Paul Dyson Institute of Life Science Swansea University Medical School Singleton Park Swansea UK

Prof. Paul Dyson

Prof Paul Dyson
Institute of Life Science
Swansea University Medical School
Singleton Park
Swansea UK

Medical Research: What is the background for this study? What are the main findings?

Prof. Dyson: The spread of insect-vectored viruses such as Dengue and, more recently, Zika, underline the urgent necessity to develop new technologies to control insect disease vectors that, due to human activity, are spreading globally. The concept of using RNAi in insects is not new and is widely used as a research tool in the model organism Drosophila melanogaster. However, adapting RNAi for use in non-model insects has been slow, almost entirely due to the problem of delivering interfering RNA to the insect. Manual injection is a less than optimal means of delivery for larger insects, while including interfering RNA in a food source can be effective in smaller insects in the laboratory. But neither delivery system is suited for field applications of RNAi as a biocide. Faced with this challenge, we (myself and Dr Miranda Whitten) conceived the concept of symbiont-mediated RNAi and have advanced it with support from the UK BBSRC and the Gates Foundation, establishing it as a viable mechanism of delivery of RNAi in

(a) a tropical disease vector, Rhodnius prolixus, a vector of Chagas disease, exemplified by targeting insect fertility, and

(b) a globally invasive vector of plant disease, Western Flower Thrips, targeting larval growth. Interfering RNA is actively produced by symbiotic insect bacteria that multiply within the host.

Critical to the technology is to ensure the stability of RNA synthesis by these bacteria. The interfering RNA is then released by the bacteria, absorbed and systemically circulated within the host, thereby causing knock-down of gene expression in specific tissues. We have exploited this technology to severely impair fertility of Rhodnius prolixus, and to cause mortality of developing larvae of Western Flower Thrips. As a biocide, the technology offers exquisite specificity due to the co-evolution and co-dependencies of the symbiont and its insect host, combined with the sequence-specificity of the RNAi. Moreover, development of resistance is highly improbable.

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Link Between Zika Virus, Microcephaly, Stillbirths and Miscarriages

MedicalResearch.com Interview with:
Nancy Dirubbo, DNP, FNP, FAANP
, Certificate in Travel Health, American Association of Nurse Practitioners (AANP) Fellow
Cindy Cooke, DNP, FNP-C, FAANP, American Association of Nurse Practitioners (AANP) President of the Board

Medical Research: Can you provide some background on what is the Zika virus?

Response: Zika virus was first found in monkeys in the Zika Forest of Uganda in 1947 during a research project on mosquito borne viral diseases. From Africa, it spread to India, Indonesia and South East Asia over the next 20-30 years. Not much attention was paid to this illness, as it is often asymptomatic (perhaps as much as 80% of all cases). It causes few symptoms in adults (mild rash, conjunctivitis and headache) and so is often underdiagnosed or misdiagnosed as other self-limiting, viral diseases. Then fast forward to 2015, when a sudden increase in infants born in Brazil with microcephaly occurred and a connection was made with a sharp increase in Zika viral infections, even though the direct mechanism for causing this birth defect is not known. In 2014, there were less than 150 cases of microcephaly in Brazil, and by October 2015, there were 4,700 cases reported.

Medical Research: What is the concern regarding pregnant women and their babies?

Response: The concern for pregnant women is that there appears to be a link between Zika virus and microcephaly, still birth and miscarriages. Children who do survive have severe intellectual disabilities. The virus is most often transmitted by mosquitos, but may also be sexually transmitted. According to the CDC, “Sexual transmission of Zika virus is possible, and is of particular concern during pregnancy. Current information about possible sexual transmission of Zika is based on reports of three cases.” The CDC also recommends, “Men who reside in or have traveled to an area of active Zika virus transmission who have a pregnant partner should abstain from sexual activity or consistently and correctly use condoms during sex (i.e., vaginal intercourse, anal intercourse or fellatio) for the duration of the pregnancy.” It has yet to be determined if Zika virus can be transmitted in other ways, including blood transfusions.

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Incidence of Guillain-Barré Syndrome Rising As Zika Spreads

MedicalResearch.com Interview with:

Dr. Kenneth C. Gorson, MD President Elect GBS|CIDP Foundation International Global Medical Advisory Board

Dr. Ken Gorson

Dr. Kenneth C. Gorson, MD
President Elect GBS|CIDP Foundation International Global Medical Advisory Board
Guillain-Barre syndrome (GBS)
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Medical Research: What is Guillain-Barré Syndrome? What are the main symptoms?

Dr. Gorson: Guillain-Barré Syndrome (GBS) is an immune mediated disorder affecting the peripheral motor and sensory nerves and nerve roots, and is the most common cause of rapidly progressive generalized paralysis in western countries. It is characterized by acute or subacute, progressive, symmetrical limb weakness with distal numbness or tingling in the arms and legs, and reduced or absent deep tendon reflexes in previously healthy patients. Patients notice the sudden onset of difficulty walking, climbing stairs, carrying objects and impaired fine motor skills. Balance is impaired due to sensory loss or weakness and a minority of patients develop facial weakness, trouble speaking and swallowing, and double vision. Severely affected patients may require ventilator support due to respiratory muscle weakness. Symptoms worsen over days to weeks, and most patients reach a maximum deficit (nadir) by 4 weeks, followed by a plateau phase for weeks to months, and then a recovery phase over additional weeks to months. Approximately 80 percent of patients recover to walk with minimal or no residual symptoms or functional disability. Maximal improvement usually occurs by one year, but more severely affected patients may continue to observe subtle improvements for several years after symptom onset.

In approximately two thirds of affected patients there is some preceding triggering event, classically a viral syndrome manifest as a transient upper respiratory or gastrointestinal illness with fever that resolves uneventfully prior to the onset of the neuropathy. Current evidence indicates the pathophysiology of GBS is related to molecular mimicry, where the patient’s antibody response to the preceding infection interacts with a variety of antigens on peripheral nerve myelin or axons producing a generalized but multifocal inflammatory demyelinating process and associated axonal loss in some instances.

The diagnosis is established with nerve conduction studies and electromyography, which shows features indicative of a demyelinating neuropathy affecting multiple motor nerves in the arms and legs. The cerebrospinal fluid protein level is elevated without a cellular response (cyto-albuminological dissociation) in up to 80 percent of patients when performed in the first week of the illness.

Treatment is directed toward the immune response, and several large randomized controlled trials have demonstrated that intravenous immunoglobulin and plasma exchange hasten recovery, and both treatments have similar efficacy.

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Clip-on OFF! Can Kill Zika-Carrying Mosquitos

MedicalResearch.com Interview with:

Christopher Bibbs Anastasia Mosquito Control District Florida

Christopher Bibbs

Christopher Bibbs
Anastasia Mosquito Control District
Florida

Medical Research: What is the background for this report?

Mr. Bibbs: In vector management, the uphill battle is always against the mosquito. And of those, the anthropophilic Yellow Fever mosquito, Aedes aegypti, has become established world-wide as a vector of several emergent diseases. Historically, these mosquitoes carried Yellow Fever and to this day still carry Dengue. Chikungunya, a newly established virus in the Caribbean, has joined the western hemisphere since 2014. And most recently, Zika virus made its way to Brazil and others in South America during 2015. This mosquito thrives in the United States as well, and should a traveler visit a country suffering from these disease and return home sick they risk passing it along to the representative mosquito in your home country.

In order to manage these risks, vector management programs employ an integrated approach using multiple techniques and surveillance tools. But oft-neglected are what is available over-the-counter to consumers wanting relief. One such tool is called “spatial repellents.” By vaporizing a minute amount of chemical into the air, it creates a flight barrier to the mosquito. The mosquito, upon encountering this vapor, will become disoriented and leave the area, thusly reducing bite contact. But as yet these tools are exclusively considered as repellent. But is that all they do?   Continue reading

No Treatment for Zika Infections So Prevention is Key

MedicalResearch.com Interview with:

Mary E. Wilson, MD Visiting Professor of Epidemiology and Biostatistics School of Medicine, University of California San Francisco Adjunct Professor of Global Health and Population Harvard T.H. Chan School of Public Health Boston, Massachusetts

Dr. Mary Wilson

Mary E. Wilson, MD
Visiting Professor of Epidemiology and Biostatistics
School of Medicine, University of California
San Francisco
Adjunct Professor of Global Health and Population
Harvard T.H. Chan School of Public Health
Boston, Massachusetts 

Medical Research: What is the background for this study?
Response: Zika virus infections are spreading explosively in the Americas. This flavivirus infection, spread by Aedes mosquitoes, is new to the Americas, so the majority clinicians have little knowledge of the infection and its potential complications. The country most affected so far is Brazil, where more than a million infections have been reported in less than a year. Infection has also spread to at least 20 other countries in the Americas (the Caribbean, Mexico, Central and South America). Prior to 2007 Zika virus was known to cause infections only in Africa and Asia. Since then, it has spread and caused epidemics in Micronesia, French Polynesia, Easter Island, and since 2015 in Brazil. Most of the movement of the virus from one region to another is via travelers who are infected and then are bitten by mosquitoes in a new region.

In Brazil an increase in cases of infants born with microcephaly (small head) has been noted coincident with the Zika epidemic, and the virus has been recovered from amniotic fluid and from fetal tissue, suggesting that Zika infection during pregnancy may cause microcephaly in the developing fetus. An increase in cases of Guillain-Barre syndrome has also been observed during this and previous outbreaks. Studies are underway to determine if Zika virus is the cause of microcephaly and Guillain-Barre syndrome.In Brazil an increase in cases of infants born with microcephaly (small head) has been noted coincident with the Zika epidemic, and the virus has been recovered from amniotic fluid and from fetal tissue, suggesting that Zika infection during pregnancy may cause microcephaly in the developing fetus. An increase in cases of Guillain-Barre syndrome has also been observed during this and previous outbreaks. Studies are underway to determine if Zika virus is the cause of microcephaly and Guillain-Barre syndrome.

Most countries in the Americas, including the United States, are infested with types of mosquitoes that are competent to transmit the virus, but weather conditions also have to be warm enough to permit the virus to disseminate in the mosquito so that it can be transmitted to another person.

The symptoms of Zika virus infection are typically mild and self-limited  – fever, aches, rash, and conjunctivitis. In fact, the majority of those infected have no symptoms. Because the virus can enter the bloodstream even in asymptomatic infected persons, there is concern that the virus could be spread by blood transfusion, if a person donates blood during the short period (probably a few days at most) when virus is in the blood.

Other reasons for the paper are to highlight what is known about some of the insect repellents and to point out important gaps in our knowledge of their use and urgent research needs.

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