Zika Virus

Bill Gates-Funded Company Releases Genetically Modified Mosquitoes in US

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Genetically modified mosquitoes have been released for the first time in the United States as part of an experiment to combat insect-borne diseases such as Dengue fever, yellow fever, and the Zika virus.

UK-based biotechnology firm Oxitec, which is funded by the Bill and Melinda Gates Foundation, said it released the mosquitoes in six locations in Monroe County’s Florida Keys: two on Cudjoe Key, one on Ramrod Key, and three on Vaca Key.

It’s part of an effort to help tackle a disease-transmitting invasive mosquito population—the Aedes aegypti mosquito species—that’s responsible for “virtually all mosquito-borne diseases transmitted to humans,” according to the company.

These mosquitoes make up about 4 percent of the mosquito population in the Keys, and transmit dengue, Zika, yellow fever, and other human diseases, as well as heartworm and other potentially deadly diseases to pets and other animals.

The experiment is in collaboration with the Florida Keys Mosquito Control District (FKMCD), and was approved by the U.S. Environmental Protection Agency (EPA), the Florida Department of Agriculture and Consumer Services (FDACS), the U.S. Centers for Disease Control and Prevention, and an independent advisory board.

Over the next 12 weeks, fewer than 12,000 mosquitoes are expected to emerge each week, for approximately 12 weeks. Untreated comparison sites will be monitored with mosquito traps on Key Colony Beach, Little Torch Key, and Summerland Key.

If successful, some 20 million additional genetically modified mosquitoes will be released later in the year.

“We really started looking at this about a decade ago, because we were in the middle of a dengue fever outbreak here in the Florida Keys,” FKMCD Executive Director Andrea Leal said during a video news conference. “So we’re just very excited to move forward with this partnership, working both with Oxitec and members of the community.”

The insects released by the biotechnology firm are all male, so they don’t bite. They’re expected to mate with the local biting female mosquitoes, and in doing so, they will pass on a lethal gene that will ensure their female offspring die before reaching maturity.

According to Quartz, areas including Malaysia, Brazil, the Cayman Islands, and Panama, where similar experiments have been carried out, have seen mosquito populations drop by as much as 90 percent.

The project has faced backlash from residents, who say their consent was not sought for the experiment.

Outcomes After Zika Virus Infection in Pregnant Women

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A lower rate of possible Zika-related deficits was found in offspring of women in French territories in the Americas than has been reported in Brazil.

During the past year, Latin American countries and the U.S have reported on the outcomes of pregnancies of women infected with Zika virus. Reports, primarily from Brazil, demonstrate teratogenic effects, mainly on the ocular and central nervous systems. Now, researchers report on the outcomes of pregnancies of Zika-infected women in the French territories in the Americas (French Guiana, Guadeloupe, and Martinique). The investigators prospectively examined pregnant women with suspected Zika virus infection and enrolled 546 women in any stage of pregnancy who had laboratory-confirmed Zika virus infection on the basis of a positive result on a reverse-transcriptase polymerase chain reaction assay on blood, urine, or both.

The pregnancies included 555 fetuses and resulted in 11 miscarriages (2.0%), 32 cases of microcephaly of any degree (defined as greater than 2 standard deviations below the mean for sex and gestational age; 5.8%), and 28 other cases of central nervous system defects (5.0%). Overall, 7% of fetuses or infants had either neurologic or ocular defects possibly associated with Zika. The rate of neurologic or ocular defects was highest when Zika virus infection occurred during the first trimester of pregnancy (12.7%) versus the second or third trimester (3.6% and 5.3%, respectively).

Comment

The proportion of ocular and nervous system birth defects reported in this population is similar to a report from the U.S. (6%) but much lower than in a report from Brazil (42%). This difference is largely unexplained except if the predominant Zika strain differs among different countries. As the authors note, some defects may not be evident until these offspring are followed for a longer period.

1 in 7 babies exposed to Zika in the womb have health problems, CDC reports

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A mosquito net covers a baby stroller where 2-month-old twins are sleeping during a visit for regular vaccinations at a primary health clinic in Loiza, Puerto Rico. 

As the Zika outbreak that erupted in 2016 ebbed, health authorities warned that birth defects seen then might just be the tip of all the problems the virus caused when it infected fetuses.

Now, as children exposed to the virus during pregnancy start to get older, researchers have started to tease out how common these secondary neurodevelopmental problems may be — and how they can occur even if babies appeared fine at birth.

In a study published Tuesday, researchers from the Centers for Disease Control and Prevention and colleagues reported that 9 percent of 1,450 children examined had at least one neurodevelopmental abnormality possibly tied to Zika, including seizures, hearing problems, difficulties swallowing, and cerebral-palsy-like movement issues. They also found that 6 percent had a Zika-related birth defect and 1 percent had both defects and neurodevelopmental problems.

Taken together, the study reports that 14 percent of babies exposed to the virus in utero — about 1 in 7 — appear to have been harmed in some way.

“By continuing to follow these babies as they age and grow, we will learn more about Zika and remain alert to the problems that develop over time,” CDC Director Robert Redfield said on a call with reporters.

The study focused on cases in the U.S. territories, including Puerto Rico, and looked at children likely exposed to the Zika virus during pregnancy who were at least 1 year old. It’s possible that additional neurodevelopmental problems could emerge as the children grow up.

In an interview, Peggy Honein, director of the CDC’s Division of Congenital and Developmental Disorders, said that officials don’t have baseline rates of these neurodevelopmental abnormalities for babies at 1 year old, so it is difficult to know whether Zika is causing all of the problems seen in the children in the sample. But many of the health problems are consistent with what’s known about the Zika virus — that it zeroes in on brain cells and can destroy the tissue. Other viruses that can pass from mother to fetus also lead to neurodevelopmental problems that crop up after birth. And scientists previously reported that Zika-affected babies in other countries have been missing developmental milestones.

The study’s birth defect rate of 6 percent fits with past studies that have found between 5 and 10 percent of affected fetuses are born with defects.

Birth defects caused by Zika include brain damage, eye problems, and, most notoriously, microcephaly — when the brain doesn’t develop fully and the head doesn’t grow properly. But microcephaly can also arise as children age, and about 1 percent of babies in the new report showed signs of so-called postnatal-onset microcephaly.

“Many of these looked healthy at birth,” Honein told STAT. “Their head didn’t grow the way it was supposed to, which is an indication that their brain is not developing properly.”

In January 2016, the CDC issued recommendations for how to evaluate infants possibly exposed to Zika during pregnancy, even if they appear healthy at birth. But the new report showed that not all of these children are getting the advised tests: 60 percent had brain imaging, about half had hearing screens, and just over a third had an ophthalmologic evaluation.

The study included only babies that had some follow-up care reported to the U.S. Zika registry, and there were almost 700 other Zika-exposed babies in U.S. territories who had turned 1 but had not had their care reported.

It’s possible that some babies’ exams weren’t reported, but, Honein said, “We still think there are opportunities for improvement here.”

Identifying neurodevelopmental problems is important because early intervention can improve cognitive and behavioral function, experts say.

Zika is primarily spread by mosquitoes, but it can also be transmitted through sex. And on Tuesday in a separate report, the CDC revised its recommendations for how long men who might have contracted Zika should wait to have unprotected sex to avoid spreading the virus. It is now three months from either symptom onset or the last possible exposure to the virus, which is down from six months and is the result of additional research that painted a clearer picture of how long the virus can linger in a person.

The second report also noted that studies conducted in mice and monkeys indicate that sexual transmission of Zika might be more damaging to fetuses than mosquito-borne transmission, a finding officials flagged to highlight the importance of preventing sexual passage of the virus.

Although it has faded from the headlines, Zika is still circulating at low levels in places around the world, and the CDC continues to emphasize that its travel recommendations for pregnant women, their partners, and others remain in place.

“It’s still a risk to pregnant women and their babies,” Honein said. “The Zika story is not over, particularly for the children who have been affected by congenital infection.”

OpenZika Researchers Continue Calculations and Prepare for Next Stage

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Summary
The OpenZika researchers are continuing to screen millions of chemical compounds as they look for potential treatments for the Zika virus. In this update, they report on the status of their calculations and their continuing work to spread the word about the project.

While the Zika virus may not be getting the continuous press coverage that it received in 2015 and 2016, it is still a threat to the health of people across the globe. New infections continue to be reported in both South America and North America, and medical workers are just beginning to assess the effects of the virus on young children whose mothers were infected while pregnant.Project Background

The search for effective treatments is crucial to stemming the tide of the virus. In addition to the OpenZika project, several other labs are doing cell-based screens with drugs already approved by the US Food and Drug Administration (FDA) agency, but few to none of the “hit” compounds that have been identified thus far are both potent enough against Zika virus and also safe for pregnant women.

Also, there are a number of efforts underway to develop a vaccine against the Zika virus. However, vaccines do not help people who already have the infection. It will be several years before they are proven effective and safe, and before enough doses can be mass produced and distributed. And even after approved vaccines are available and distributed to the public, not all people will be vaccinated. Consequently, in the meantime and in the future, cures for Zika infections are needed.

Progress on choosing compounds for lab testing

ZIKV NS3 helicase bound to RNA with the predicted binding modes of five approved drugs (from our second set of candidates) selected by virtual screening. These candidates are shown as surfaces with different shades of green. The identification of these candidates and the video were made by Dr. Alexander L. Perryman.

We began the analysis phase of the project by focusing on the results against the apo NS3 helicase crystal structure (apo means that the protein was not bound to anything else, such as a cofactor, inhibitor, or nucleic acid) to select our first set of candidates, which are currently being assayed by our collaborator at University of California San Diego, Dr. Jair L. Siqueira-Neto, using cell-based assays. The NS3 helicase is a component of the Zika virus that is required for it to replicate itself.

In the second set of screening results that we recently examined, we used the new crystal structure of NS3 helicase bound to RNA as the target (see the images / animation above). Similar to the first set of candidates, we docked approximately 7,600 compounds in a composite library composed of the US Food and Drug Administration-approved drugs, the drugs approved in the European Union, and the US National Institutes of Health clinical collection library against the new RNA-bound structure of the helicase. Below are the results of this second screening:

  • 232 compounds passed the larger collection of different energetic and interaction-based docking filters, and their predicted binding modes were inspected and measured in detail.
  • Of the compounds that were inspected in detail, 19 unique compounds passed this visual inspection stage of their docked modes.
  • From the compounds that passed the visual inspection, 9 passed subsequent medicinal chemistry-based inspection and will be ordered soon.

Status of the calculations

In total, we have submitted 2.56 billion docking jobs, which involved the virtual screening of 6 million compounds versus 427 different target sites. We have already received approximately 1.9 billion of these results on our server. (There is some lag time between when the calculations are performed on your volunteered machines and when we get the results, since all of the results per “package” of approximately 10,000 different docking jobs need to be returned to World Community Grid, re-organized, and then compressed before sending them to our server.)

Except for a few stragglers, we have received all of the results for our experiments that involve docking 6 million compounds versus the proteins NS1, NS3 helicase (both the RNA binding site and the ATP site), and NS5 (both the RNA polymerase and the methyltransferase domains).  We are currently receiving the results from our most recent experiments against the NS2B / NS3 protease.

A new stage of the project

We just finished preparing and testing the docking input files that will be used for the second stage of this project. Instead of docking 6 million compounds, we will soon be able to start screening 30.2 million compounds against these targets. This new, massive library was originally obtained in a different type of format from the ZINC15 server. It represents almost all of “commercially available chemical space” (that is, almost all of the “small molecule” drug-like and hit-like compounds that can be purchased from reputable chemical vendors).

The ZINC15 server provided these files as “multi-molecule mol2” files (that is, many different compounds were contained in each “mol2” formatted file). These files had to be re-formatted (we used the Raccoon program from Dr. Stefano Forli, who is part of the FightAIDS@Home team) by splitting them into individual mol2 files (1 compound per file) and then converting them into the “pdbqt” docking input format.

We then ran a quick quality control test to make sure that the software used for the project, called AutoDock Vina, could properly use each pdbqt file as an input. Many compounds had to be rejected, because they had types of atoms that cause Vina to crash (such as silicon or boron), and we obviously don’t want to waste the computer time that you donate by submitting calculations that will crash.

By splitting, reformatting, and testing hundreds of thousands of compounds per day, day after day, after approximately six months this massive new library of compounds is ready to be used in our OpenZika calculations. Without the tremendous resources that World Community Grid volunteers provide for this project, we would not even dream of trying to dock over 30 million compounds against many different targets from the Zika virus. Thank you all very much!!!

For more information about these experiments, please visit our website.

Publications and Collaborations

Our PLoS Neglected Tropical Diseases paper, “OpenZika: An IBM World Community Grid Project to Accelerate Zika Virus Drug Discovery,” was published on October 20, and it has already been viewed over 4,000 times. Anyone can access and read this paper for free. Another research paper “Illustrating and homology modeling the proteins of the Zika virus” has been accepted by F1000Research and viewed > 3800 times.

A group from Brazil, coordinated by Prof. Glaucius Oliva, has contacted us because of our PLoS Neglected Tropical Diseases paper to discuss a new collaboration to test the selected candidate compounds directly on enzymatic assays with the NS5 protein of Zika virus. They have solved two high-resolution crystal structures of ZIKV NS5, which have been recently released on the PDB (Protein Data Bank) (PDB ID: 5TIT and 5U04).

Our paper entitled “Molecular Dynamics simulations of Zika Virus NS3 helicase: Insights into RNA binding site activity” was just accepted for publication in a special issue on Flaviviruses for the journal Biochemical and Biophysical Research Communications. This study of the NS3 helicase system helped us learn more about this promising target for blocking Zika replication. The results will help guide how we analyze the virtual screens that we already performed against NS3 helicase, and the molecular dynamics simulations generated new conformations of this protein that we will use as input targets in new virtual screens that we perform as part of OpenZika.

These articles are helping to bring additional attention to the project and to encourage the formation of new collaborations.

Additional News

We have applied and been accepted to present “OpenZika: Opening the Discovery of New Antiviral candidates against Zika Virus and Insights into Dynamic behavior of NS3 Helicase” to the 46th World Chemistry Congress. The conference will be held in Sao Paulo, Brazil, on July 7-14.

Dr. Sean Ekins has hired a postdoc and a master level scientist who will get involved with the OpenZika project. We have also started to collate literature inhibitors from Zika papers.

Also, Drs. Sean Ekins and Carolina Andrade have offered to buy some of the candidate compounds that we identified in the virtual screens from OpenZika, so that they can be assayed in the next round of tests.

Fundraising

Dr. Alex Perryman models an OpenZika shirt. Profits from the sale of OpenZika merchandise go to purchasing compounds for lab testing. (Photo by Keith Bratcher, courtesy of Rutgers University)

Thank you to anyone who has visited our store on Zazzle to check out OpenZika merchandise such as T-shirts, polo shirts, mugs, buttons, mouse pads, and phone cases. All profits from the sale of this merchandise will go toward buying compounds for lab testing. Drs. Alex Perryman and Sean Ekins have bought OpenZika shirts for themselves. Alex likes the polo style version the best, and he recommends getting the white or gray shirts. But avoid the red shirts, since the OpenZika logo does not stand out as well, especially after it is washed (Alex learned this the hard way).

The OpenZika team is working on grants from the National Institutes of Health, CNPq (a Brazilian funding agency), and other organizations to try raise funds for purchasing and testing compounds.

Outreach

We have been working hard to promote the project, and we continue to look for additional opportunities. Below is a list of our most recent outreach efforts.

  • Dr. Carolina Horta Andrade gave one invited lecture at the 27th annual Institute of Biology Week, at Federal University of Goias, Brazil, to biology and pharmacy students and to the general public regarding the “Design and discovery of new drug candidates for the Zika and Dengue Viruses and OpenZika” (November, 2016).
  • Dr. Carolina Horta Andrade has been elected as an Affiliated Member of the Brazilian Academy of Sciences. She also gave a talk at the Federal University of Minas Gerais, Brazil, to researchers from many different fields of science and to authorities, in which she discussed OpenZika (October 2016).
  • Dr. Melina Mottin, one of the OpenZika team members, presented a poster and gave an oral presentation, titled “OpenZika: an open science collaboration project to discover drug candidates against Zika virus,” at the 8th Brazilian Symposium on Medicinal Chemistry, held in Búzios, Rio de Janeiro, Brazil, from November 27-30, 2016.
  • Dr. Melina Mottin also gave an invited lecture at the Federal University of Rio Grande do Sul, Brazil, at the Post-Graduation Program in Chemistry, to chemistry and pharmacy Ph.D. students and to the general public regarding “Identification of Drug Candidates for Zika virus using Virtual Screening and Molecular Dynamics Simulations,” in which she discussed the OpenZika project (December 2016).
  • Dr. Sean Ekins attended the National Institutes of Health (NIH) “Rare disease day” (February 27, 2017) and also the Gordon Research Conference on Tropical Infectious Diseases (March 12-17 2017).

 

We are very grateful for all of the volunteers who are donating their unused computing time to this project!  Thank you very much!!

Source:https://www.worldcommunitygrid.org

Zika virus may cause men’s testicles to SHRINK by up to 90 per cent.

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  • ZIKA infection could cause lasting infertility in men, experts in the US warn
  • Doctors found infection in mice caused their testicles to shrink by 90%
  • If findings apply to humans, it could spark an infertility epidemic caused be the disease, experts say

ZIKA infection could cause lasting infertility and lead to men’s testicles shrinking, medical researchers warn.

Doctors warn that if the ‘dramatic’ findings, in mice, apply to humans it could lead to an epidemic of infertility caused by the disease.

It is not yet known whether the 90 per cent shrinkage in mice would apply to humans – but doctors believe at the very least the virus is likely to reduce sperm counts and testosterone levels in affected men.

ZIKA infection could cause lasting infertility and lead to men's testicles shrinking, medical researchers warn (stock image)

ZIKA infection could cause lasting infertility and lead to men’s testicles shrinking, medical researchers warn (stock image)

The virus is already known to leads to shrunken heads in babies whose mothers catch the infection, which is carried in tropical countries and has recently been found in the tourist hotspot of Florida.

The virus has the unusual ability to cross the barrier that separates the male reproductive organs from the blood stream.

Michael Diamond, of Washington University School of Medicine said: ‘We undertook this study to understand the consequences of Zika virus infection in males.

‘While our study was in mice -and with the caveat that we don’t yet know whether Zika has the same effect in men – it does suggest that men might face low testosterone levels and low sperm counts after Zika infection, affecting their infertility.’

The virus was already known to persist in semen for months – but it was not known what impact this could have on an infected man.

Research published in Nature Genetics, Professor Diamond and colleagues infected mice with Zika.

After two weeks the testicles had shrunken significantly, their ‘internal structure collapsing’ with many dead or dying cells, the researchers said.

And after three weeks, the mices’ testicles had shrunk to a tenth of their normal size.

Their testicles did not heal even after six weeks, when the virus had cleared from their bodies.

Researchers hailed the study as 'proof of principle that Zika virus during pregnancy is treatable'. Tested on pregnant mice, it reduced levels of the virus in mothers, and protected pups. 

 Doctors warn that if the ‘dramatic’ findings, in mice, apply to humans it could lead to an epidemic of infertility caused by the disease

Professor Diamond said: ‘We don’t know for certain if the damage is irreversible, but I expect so, because the cells that hold the internal structure in place have been infected and destroyed.’

The Zika virus was found to attack Sertoli cells, which do not regenerate, and which nourish growing sperm cells.

Infected mice were four times less likely to get a female mouse pregnant, their sperm numbers fell tenfold, and their testosterone levels were very low.

Co-author Kelle Moley said: ‘This is the only virus I know of that causes such severe symptoms of infertility. There are very few microbes that can cross the barrier that seprates the testes from the bloodstream to infect the testes directly.

Because the study of Zika is relatively new, no studies have been published linking infertility to men with Zika.

‘People often don’t find out they’re infertile until they try to have children, and that could be years or decades after infection.

‘I think it is more likely doctors will start seeing men with symptoms of low testosterone, and they will work backward to make the connection to Zika.’

It is not yet known whether the 90 per cent shrinkage in mice would apply to humans – but doctors believe at the very least the virus will reduce sperm counts and testosterone levels in affected men (file picture)

It is not yet known whether the 90 per cent shrinkage in mice would apply to humans – but doctors believe at the very least the virus will reduce sperm counts and testosterone levels in affected men (file picture)

The effects of low testosterone, which can be diagnosed with a simple blood test, include low sex drive, erectile dysfunction, fatigue and loss of body hair and muscle.

‘If testosterone levels drop in men like they did in the mice, I think we’ll start to see men coming forward saying, ‘I don’t feel like myself,’ and we’ll find out about it that way.

‘You might also ask ‘Wouldn’t a man notice if his testicles shrank?’ Well, probably.

But we don’t really know how the severity in men might compare with the severity in mice. I assume that something is happening to the testes of men, but whether it’s as dramatic as in the mice is hard to say.’

As of 26 October 2016, there have been 244 diagnosed cases of Zika caught by travellers returning home to the UK since 2015.

British experts not involved in the research said the findings may mean humans could be affected.

Dr Peter Barlow, British Society for Immunology spokesperson and Reader in Immunology & Infection at Edinburgh Napier University said: ‘While it is currently unclear if Zika virus infection would cause reduced testes size and fertility in man, this study does raise concerns that Zika virus could potentially have direct effects on male fertility. Therefore, more work is needed to determine if these observations in mice would translate to men.’

Dr Derek Gatherer, Lecturer in the Division of Biomedical and Life Sciences, Lancaster University, said: ‘It’s been known for a while that Zika virus in men can find its way into the reproductive organs and may then go on to be sexually transmitted, but this study in mice is the first suggestion that this passage through the reproductive tract may actually be damaging.’

Prof Richard Sharpe, Honorary Professor, MRC Centre for Reproductive Health, and expert in male reproductive health, University of Edinburgh, said there were already anecdotal reports of testicular and groin pain in infected men, but some virus effects could be ‘species specific’.

But he said: ‘the reality is that we do not know yet if effects shown here in the mouse can or will occur in humans.’

 

 

 

South Carolina just obliterated millions of bees by accident

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Reports out of South Carolina have indicated that when officials approved the spraying of local farmlands with insecticide to prevent the spread of Zika-carrying mosquitos, it accidentally wiped out millions of bees too.

The insecticide in question, called Naled, is known to be “highly toxic” to bees, and these vital pollinators appear to be the latest collateral damage in the fight against Zika.

In response to the ensuing outcry from local farmers after last Sunday’s bout of aerial spraying in Dorchester County, the local administrator’s office announcedthat the state health department had reported four travel-related cases of Zika virus in the Summerville area of Dorchester County on Friday 26 August.

While the health department reported that no one has been infected from a local mosquito bite to date, Dorchester County officials justified the accidental bee cull on the grounds that the mosquito population remained a threat.

“Dorchester County is concerned about the safety of its citizens,” a statement from the County Administrator’s Office reads. “This includes protecting citizens from insect bites from pests such as mosquitoes that carry viruses including West Nile and Zika.”

The spraying commenced at 6:30am last Sunday morning, and the effects on bees were reportedly instant.

“Stressed insects tried to flee their nests, only to surrender in little clumps at hive entrances,” Ben Guarino reports for The Washington Post. “The pattern matched acute pesticide poisoning. By one estimate, at a single apiary – Flowertown Bee Farm and Supply, in Summerville – 46 hives died on the spot, totalling about 2.5 million bees.”

The decision to conduct aerial spraying with Naled – something that’s never been done in South Carolina before – is of course highly controversial, but what’s perhaps even more contentious is the fact that local officials claim to have warned farmers ahead of Sunday.

 

Zika Virus Can Persist for Months in Newborns, Case Study Suggests

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With prolonged infection may come more tissue damage.

An infant born with microcephaly, but with an otherwise normal physical examination at birth, had evidence of the Zika virus in serum, saliva, and urine nearly 2 months after birth, a case report from Brazil found.

The mother of the male infant was potentially infected during her third trimester of pregnancy, and the baby was born at term (40 weeks) with microcephaly. Laboratory testing found evidence of Zika virus in the infant up through 2 months of age, and he began displaying neurological symptoms at 6 months of age, Danielle B.L. Oliveira, PhD, of Universidade de São Paulo in Brazil, and colleagues, reported in a research letter in theNew England Journal of Medicine.

The authors said that despite being born with microcephaly, the infant had a normal vision and hearing test, and analysis of cerebrospinal fluid was normal at birth, with no abnormalities detected during an initial physical examination. In fact, the infant showed “no obvious illness or evidence of any immunocompromising condition” on day 54 of life.

“If Zika is shown to persist as a threat to infected newborns long after in utero exposure, there are serious implications for monitoring and managing exposed babies, even if there are no clinical manifestations noted at birth,” Irwin Redlener, MD, of Columbia University Mailman School of Public Health in New York City, who was not involved with the research, told MedPage Today via email.

But similar to the findings in a recent study, brain imaging revealed that the infant had reduced brain volume in the frontal and parietal lobes, with calcifications in subcortical areas. A polymerase chain reaction test was positive for Zika in serum, urine, and saliva at day 54 of life and positive for serum on day 67. The test was negative on day 216, although the authors noted that Zika-specific IgG titers were higher than in the first and second samples — potentially indicating that the infant had mounted an immune response to the virus.

“Prolonged viral shedding in the infant … may have had a role in the damage the virus was able to incite,” said Amesh Adalja, MD, a spokesperson for the Infectious Diseases Society of America. “It will be important to conduct more research in this vein in order to determine how common prolonged shedding is and if it is associated with a worsened clinical course,” he told MedPage Today via email.

At 6 months of age, the infant showed evidence of neuropsychomotor developmental delay, with global hypertonia, or spasticity, and spastic hemiplegia — a constant state of contraction of muscles on one side of the body, often associated with cerebral palsy. This is also consistent with recent research showing a delayed onset of symptoms in some infants with congenital Zika virus infection.

 The other interesting detail about this case was that not only did the mother appear to contract Zika virus later in her pregnancy, but she may have done so through “suspected” sexual transmission from the father. The authors reported that the mother stayed in São Paulo for the duration of her pregnancy, but the father traveled to northeastern Brazil. The father then had symptoms of Zika virus infection when the mother was 23 weeks pregnant, but she did not show symptoms until 26 weeks.

“This report provides evidence that a third trimester infection with Zika, which has been generally considered to be lower risk than earlier periods in a pregnancy, is not always benign and can lead to microcephaly,” added Adalja.

New report details pre- and postnatal brain defects from Zika virus

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microcephaly
Surface reconstruction postnatal CT image one week after delivery at 38 weeks of gestation in the case of a woman pregnant with twins, with characteristic rash at nine weeks of pregnancy and confirmed Zika virus infection.

The journal Radiology has published a special report, detailing the spectrum of imaging findings in babies and fetuses infected with the Zika virus.

“Imaging is essential for identifying the presence and the severity of the structural changes induced by the infection, especially in the central nervous system,” said the report’s lead author, Fernanda Tovar-Moll, MD, PhD, vice president of the D’Or Institute for Research and Education and professor at the Federal University of Rio de Janeiro, in Rio de Janeiro, Brazil. “Microcephaly is just one of several radiological features.”

Zika appears to be most dangerous when transmitted from a pregnant mother to her fetus during the first trimester of pregnancy, increasing the likelihood of severe brain defects in the baby, including microcephaly. In cases of microcephaly, the baby’s head is exceptionally small, due to an underdeveloped brain. Zika has also been linked to eye defects, hearing impairment and stunted growth in babies.

“The first trimester is the time where infection seems to be riskiest for the pregnancy,” said study coauthor Deborah Levine, MD, director of Obstetric & Gynecologic Ultrasound at Beth Israel Deaconess Medical Center and professor of radiology at Harvard Medical School in Boston. “From an imaging standpoint, the abnormalities in the brain are very severe when compared to other congenital infections.”

Though much of the concern in the media regarding the toxic effects of Zika virus has focused on brain findings of microcephaly, the researchers noted that there are a variety of brain abnormalities that can be found in fetuses exposed to the virus, including gray and white matter volume loss, brainstem abnormalities, calcifications, and a condition called ventriculomegaly, where the ventricles, or fluid filled spaces in the brain, are enlarged. Some babies infected by Zika may not have a small head size if the ventricles remain excessively enlarged.

The researchers performed a retrospective review of imaging and autopsy findings associated with congenital Zika virus infection found in the Instituto de Pesquisa in Campina Grande state Paraiba (IPESQ) in northeastern Brazil, where the infection has been severe.

From June 2015 to May 2016, 438 patients were referred to the IPESQ due to rash during pregnancy or suspected central nervous system abnormality. From this group, the researchers identified 17 fetuses or neonates of women who had imaging at IPESQ, as well as documented Zika infection in fluid or tissue (“confirmed cohort”), and 28 fetuses or neonates with brain findings suspicious for Zika infection with intracranial calcifications (“presumed cohort”). Imaging exams included fetal MRI, postnatal brain CT, postnatal brain MRI and, in some cases, longitudinal prenatal ultrasound.

The brain abnormalities seen in confirmed and presumed Zika groups were very similar. Nearly all of the babies in each group had ventriculomegaly. Although most fetuses had at least one exam showing abnormally small head circumference, the researchers discovered that head circumference was normal in three fetuses with severe ventriculomegaly.

Ninety-four percent of the confirmed Zika group and 79 percent of the presumed Zika group had abnormalities of the corpus callosum, which is a large nerve fiber bundle that allows communication between the left and right hemispheres of the brain. All but one had cortical migrational abnormalities, meaning the neurons did not travel to their proper destination in the brain.

Intracranial calcifications were present in almost all of the neonates, most commonly found at the gray-white junction of the brain. All of the babies exhibited reduced tissue volume in their brains. All patients showed varying abnormalities in cortical development.

“The severity of the cortical malformation and associated tissue changes, and the localization of the calcifications at the grey-white matter junction were the most surprising findings in our research,” Dr. Tovar-Moll said.

The babies’ skulls frequently had a collapsed appearance with overlapping sutures and redundant skin folds. The researchers believe the unusual appearance of the skull is due to a combination of the small brain as it develops, but also a result of what at some point was likely a larger head size–due to ventriculomegaly–that then decompresses, and/or brain atrophy, giving the skull the collapsed shape.

Dr. Levine noted that ultrasound in pregnancy can show the abnormalities associated with congenital Zika infection, but it may take time before these changes are obvious.

“More than one ultrasound or MRI scan in pregnancy may be needed to assess the growth and development abnormalities of the brain,” she said.

Zika is mainly spread to humans via the bite of an infected mosquito. Symptoms may include fever, rash, joint or muscle pain, headache, and bloodshot eyes. However, many people infected with Zika have no symptoms at all. Although the current Zika outbreak is centered in Brazil, it has spread to countries and territories around the world, including the United States.

Pregnant women and women who are considering becoming pregnant should avoid visiting areas where infected mosquitos are known to be present. However, if women live in areas where the mosquitos are present, the recommendation of the Centers for Disease Control and Prevention (CDC) is to wear clothes that protect from mosquito bites, use mosquito repellent and get appropriate testing, including routine prenatal care and an ultrasound at 18 to 20 weeks. Pregnant women who are worried that they may have contracted the virus should speak with their obstetrician to initiate testing.

Dr. Tovar-Moll noted that the researchers are continuing to investigate the central nervous system changes induced by congenital Zika virus infection to better understand the spectrum of the changes they have seen.

“We are also interested in investigating how congenital Zika virus infection can interfere with not only prenatal, but also postnatal gray and white brain maturation,” she added.

The Lethal Suspects for Microcephaly in Brazil, With Zika Virus at the Bottom of the List

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We often hear that correlation is not causation, so why are world renowned scientists treating the Zika virus as the sole cause of microcephaly in Brazil when there are so many other factors? 

Since the virus Zika was blamed for a cluster of cases in northeastern Brazil of the devastating birth defect microcephaly, the mainstream media have been dominated by fear of a Zika pandemic. Meanwhile, the real culprit(s) behind the surge in microcephaly in that corner of Brazil have been ignored, with the exception of a few scientists, and even fewer journalists.

This story started on Feb. 1, 2016, when the World Health Organization (WHO) announced a pandemic emergency with the Zika virus, a much milder cousin of Dengue fever. The WHO blamed Zika alone for the sharp uptick inmicrocephaly (shrunken heads, resulting in shrunken and undeveloped brains, with a wide range of symptoms and disabilities possible, depending on the severity of the case) in babies born in impoverished areas of northeast Brazil.

Politics and an unscientific approach ensued, with the Centers for Disease Control (CDC) and National Institutes of Health (NIH) joining forces with the WHO. The twin U.S. health care agencies launched a propaganda campaign of fear to justify a money grab from U.S. taxpayers. But for a change, Congress developed a backbone and denied the pleas of President Obama, CDC Director Tom Frieden, and NIH Director Anthony Fauci, who were seeking $1.9 billion for Zika vaccine R&D.

On June 28, the “Zika Bill” was blocked by Senate Democrats, due to issues over the “provisions of the bill,” but apparently not the lower price tag of $1.1 billion.

Missing CSI Investigation

Whether it’s a failed structure or a broken marriage, it often isn’t one item alone that causes the collapse, but a series of them in a cascade of negative events that does the final damage.

Instead of announcing the Zika pandemic, the three international health agencies should have launched a CSI-type investigation in that quarter of Brazil examining all of the environmental triggers and toxins that might be contributing to the surge in microcephaly. But that didn’t happen.

“The increase in microcephaly in that part of the world is unique to Brazil. You don’t see rate increases anywhere else,” Dr. James Lyons-Weiler said in a telephone interview on the likely suspects causing the rise in deformed fetuses and babies.

He explained that the “interactions between two or more of the potential causal factors are rarely ever studied by CDC’s scientists. They are not very good with studying interactions,” which might be the underlying cause of an infectious disease or spread of a virus.

Author and research scientist Lyons-Weiler’s early problem solving skills in recognizing the utility in information in DNA-hybridization led him into deeper research on the evolution of diseases, cancer, and mammals.

In 2015, Dr. Lyons-Weiler launched the Institute for Pure and Applied Knowledge (IPAK), a non-profit organization that since its inception has been challenging half-baked science taken as gospel.

In a co-authored paper that Lyons-Weiler led, his scientific team identified nine likely suspects for the rise in microcephaly. The unpublished paper to date, “Areas of Research and Preliminary Evidence on Microcephaly,Guillain-Barré Syndrome and Zika Virus Infection in the Western Hemisphere,” outlined the suspects.

They range from “Direct Zika-related microcephaly through unspecified mechanisms” and “molecular mimicry” in two types of vaccines given to pregnant women, to “Glyphosate toxicity in bovine products” leaching into those vaccines, and the unintended outcome of genetically modified (GM) mosquitoes, whose world pilot program was launched in 2012 in that same northeast corner of Brazil by the British concern Oxitec.

“The Zika virus has a protein that matches a human protein within 96 percent. Zika also has an element in its genomic sequence similar to one in other flaviviruses, too, like West Nile to Dengue fever. That means Zikacould enter the placenta and blood brain barrier of infants. Yet since there is no increase in acute microcephaly outside of Brazil, if it’s Zika, there may be a missing molecular or chemical co-factor,” Lyons-Weiler explained.

The ability of viruses to produce specific disease symptoms is often known to be modified by co-factors.  “Something is different in Brazil,” said Lyons-Weiler.

Overlooked Glyphosate

On June 1, 2015, Denmark, a farming country, banned the sale and use of Monsanto’s ubiquitous weed killer Roundup, as a result of the Danish Environment Authority declaring glyphosate as a carcinogen. Earlier that year, the WHO classified glyphosate as “probably carcinogenic to humans.”

The ban and the statement had little effect on removing the sale ofglyphosate-containing products in the United States and South America. And that has bugged MIT Senior Research Scientist Stephanie Seneff, Ph.D., who conducts research at the MIT Computer Science and Artificial Intelligence Laboratory.

At this year’s Autism One Conference in Chicago, Dr. Seneff presented a 66-slide deck, “Glyphosate, Folic Acid, Neural Tube Defects and Autism,” highlighting potential associations between chemicals, biology, and children susceptible to autism. In mid-June, Seneff presented at a U.S. Congressional hearing on glyphosate, in Washington, D.C.

In an email, Stephanie Seneff wrote: “It is ridiculous that the only thing the research community seems to be focused on with respect to themicrocephaly epidemic in NE Brazil is the Zika virus. While the virus may be a factor in the epidemic, there are many other potential factors that deserve at least equal attention. These include:

(1) “Simultaneous exposure to two herbicides—glufosinate and glyphosate—due to the recent introduction of GMO glufosinate-resistant soybeans on top of the glyphosate-resistant soybeans (glufosinate substitution for glutamine during protein synthesis is a direct path to microcephaly via disruption of asparagine synthase);

(2) “The addition of larvicides directly to the drinking water;

(3) “The introduction of the GM mosquitoes from larvae that were likely fedglyphosate-contaminated sugar and glyphosate-contaminated blood following maturation;

(4) “The heavy use of ethanol as a fuel in the trucks driving through the region (derived from GM Roundup-ready sugar beets or sugar cane sprayed with Roundup just before harvest), and;

(5) “The recent implementation of policies that encourage vaccination of pregnant women with Tdap, flu vaccine, and possibly MMR vaccine. All of these potential contributors should be thoroughly investigated before concluding that Zika is the entire story with the epidemic.”

What do all of these potential triggers mean? Even if they are not the direct cause of microcephaly, they are contributing to both polluting the land and thus plant, animal, and human life. That should give governments around the world pause.

To date, it has not worked out that way yet.

Where there is big opportunity for billions of dollars in profits, there is Big Industry—Big Pharma, Big Agriculture, Big you name it—led by multinational corporations that seek home run-like profits. There are also big governments that either look the other way or are fine with raking in some of those profits, too.

“The timing is wrong for Zika” said Lyons-Weiler, who pointed to a study showing an increase in microcephaly in Brazil two years before Zika made it to Brazil.

“What is clear is the experimentation with whole-cell pertussis vaccination in the slums is ongoing, because the population cannot afford the fee for the clinic, where the safer acellular vaccine is available. The increase inmicrocephaly began one year after Brazil adopted a mandatory prenatal care program, which includes vaccinations during pregnancy,” he concluded.

Zika is not about science. It’s about money and profit at the expense of the people, domestic and foreign.

Zika Infects Adult Neural Progenitors Too

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A mouse study shows that the virus has tropism for adult proliferative neural progenitor cells and immature neurons.

Zika virus exposure in a mouse model can infect adult neural stem cells in the brain, leading to cell death and reduced proliferation.CELL STEM CELL, H. LI ET AL.Microcephaly and associated birth defects in babies born to mothers infected with the virus during pregnancy is considered the most serious consequence of the ongoing Zika outbreak. However, the increasing incidence of Guillain-Barré syndrome and other neuropathologies linked to the mosquito-borne and sexually transmissible pathogen indicate that Zika virus infection represents a risk to adults, as well.

A number of recent studies have investigated how Zika virus infects fetal brain cells. Working in mice, scientists at Rockefeller University in New York City and their colleagues elsewhere have now examined how Zika virus infection impacts adult brain cells. As it turns out, as it has for fetal neural progenitor cells, Zika virus has tropism for adult proliferative neural progenitor cells and immature neurons. The team’s results were published today (August 18) in Cell Stem Cell.

Zika virus infection can also induce apoptosis of adult neural progenitor cells in the anterior subventricular and subgranular zones of the mouse brain, the researchers reported.

The results of this mouse study show, “for the first time, that [Zika virus] can affect adult neurogenesis by increasing cell death in both adult neurogenic niches,” the anterior subventricular and subgranular zones,”Patricia Garcez, who studies neuoroplasticity at Brazil’s Federal University of Rio de Janeiro and was not involved in the work, wrote in an email to The Scientist. “Humans produce more than 700 neurons a day in adult hippocampus. . . . If the [neural] stem cells are depleted the effect would be long-lasting.”

While the findings “suggest that the virus has the potential to infect and destroy adult neural progenitor cells in . . . the adult mouse brain,” wrote Arnold Kriegstein, director of the University of California, San Francisco, School of Medicine’s developmental and stem cell biology program, they “do not shed light onhow the virus infects the adult cells.” This mechanism has yet to be uncovered.

The researchers worked with six-week-old mice triply deficient in interferon regulatory factor, which were infected by a single strain of Zika virus, and examined only once post-infection. “We limited our results to just this once strain of mice, this one strain of virus, and this one endpoint in order to have robust and quantitative results,” study coauthor Joseph Gleeson of Rockefeller University wrote in an email to The Scientist. “We used one of the strains of Zika that is known to cause human disease,” he added, “so the work is relevant to the current outbreak.”

As to whether the results in mice might translate to humans, Gleeson noted that “future research would require analysis of the stem cell populations as well as neurocognitive outcomes in adults following Zika infection.” Still, he wrote, it stands to reason that “some immunocompromised or even some healthy individuals might have reactions to Zika like we show in mice.”

Overall, said Kriegstein, who was not involved in the work, “this paper highlights the potential risk that Zika virus infection of adults might have unsuspected consequences—in at least some patients—that could affect brain function and behavior.”