TSRI scientists reveal workings of key 'relief-valve' in cells

A team led by scientists at The Scripps Research Institute (TSRI) has solved a long-standing mystery in cell biology by showing essentially how a key “relief-valve” in cells does its job.

The relief valve, known as VRAC (volume-regulated anion channel), normally keeps cells from taking in too much water and swelling excessively. But VRAC’s importance to cellular health is just beginning to be understood—already it has been tentatively linked to stroke-induced brain damage, diabetes, immune deficiency and even cancer treatment resistance.

In a study published in Cell on January 28, 2016, the scientists showed that VRAC is a complex structure with five different protein subunits—the precise mix of which determines its relief-valve properties. The team also determined that VRAC’s relief-valve function is activated not by the physical swelling of a cell per se, but by a closely linked event: the low concentration of dissolved ions that results from a sudden flow of water into a cell.

“Knowing how VRAC is assembled and how it works is important not only because it is a fundamental regulatory mechanism in cells, but also because it seems to have relevance for a variety of diseases and conditions,” said principal investigator Ardem Patapoutian, a professor at TSRI and a Howard Hughes Medical Institute (HHMI) Investigator.

Sorting Through the Molecular Soup

Scientists discovered VRAC’s existence decades ago, but only recently began to identify its components. In early 2014, Patapoutian’s laboratory and a separate group in Germany discovered independently that one VRAC subunit is a protein called LRRC8A (SWELL1), which is necessary for VRAC to function properly. It was apparent at the time, however, that VRAC has other subunits.

In the new study, Patapoutian and his team sought a more complete understanding of how VRAC is put together and how it senses volume changes.

Knowing that LRRC8A is always present in VRAC, co-first author Zhaozhu Qiu, a postdoctoral fellow in the Patapoutian lab and at the Genomics Institute of the Novartis Research Foundation (GNF), created test cells that produce LRRC8A with a special protein tag attached. The tagged LRRC8A were used as a handle to pull the full VRAC complex out of the molecular soup contained in cells.

Co-first author Ruhma Syeda, also a postdoctoral fellow in the Patapoutian lab, led the effort to put purified VRAC complexes into model cell membranes (lipid bilayers) to measure the conductance of charged ions. The results were startling. Although an ion channel typically has a sharply defined single channel conductance, measurements of VRAC suggested a broad range of conductances.

Prior research had suggested that the VRAC structure can include other members of the LRRC8 family besides LRRC8A, namely LRRC8B, LRRC8C, LRRC8D and/or LRRC8E. Qiu and Stuart Cahalan, another postdoctoral fellow, therefore created a set of cell lines in which genes for one or more of the LRRC8 proteins were deleted. With this and other methods, the team established that VRAC is in fact a diverse family of ion channels, each of which has approximately six protein subunits. At least one subunit of any VRAC structure is LRRC8A, but the other subunits appear to be a variable mix of LRRC8B-E proteins. That variability of composition leads to different charge-flow properties when channel complexes were measured in the minimalistic bilayer system. Swetha Murthy, a postdoctoral fellow, and Adrienne Dubin, an assistant professor of neuroscience (and co-corresponding author), determined that charge-flow properties of single VRAC channels on intact swollen cells were also dictated by the subunit combination.

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“We speculate that different cell types need different forms of VRAC to cope with their different environments—that’s an idea we’re keen to test,” said Qiu.

“This finding also suggests that subtle variations in VRAC’s composition can have profound effects on how it works in cells and potentially contributes to disease,” said Patapoutian.

How to Sense a Swelling Cell

Perhaps the biggest unanswered question about VRAC has been: how does it sense the swelling of a cell?

“People have scratched their heads over this for decades, because it’s hard to imagine how a cell could directly measure an increase in its volume,” Patapoutian said.

One possibility has been that VRAC senses a volume increase indirectly, by detecting the stretching of the cell membrane, as some sensory ion channels do. However, examining VRAC complexes in the simplified environment of lipid bilayers, the team found that they were not activated by membrane stretching. They were, however, readily activated when the usual concentration of dissolved ions was reduced.

That made sense. “Local decrease in the ionic strength is an inevitable result when the water rushes in and the cell swells,” Syeda said.

Further studies of VRAC will be aimed at determining its precise physical structure, how variations in that structure alter its ion-conducting properties, how VRAC varies in different cell types, and how VRAC variants or mutants contribute to disease. VRAC is thought to worsen stroke-related brain damage and heart-attack damage, for example, by allowing abnormal, harmful flows of signaling molecules in the low-oxygen condition following arterial blockage. VRAC may also be linked to immune system development: a 2003 study found that a mutation of LRRC8A, now known to be VRAC’s chief subunit, prevents antibody-producing B cells from developing normally. A more recent study implicated VRAC in the clinical response to the cancer drugs cisplatin and carboplatin—the drug molecules use VRACs as portals into tumor cells.

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The Scripps Research Institute (TSRI)

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Immune signaling molecule in infected mothers linked to behavioral abnormalities in offspring

In 2010, a large study in Denmark found that women who suffered an infection severe enough to require hospitalization while pregnant were much more likely to have a child with autism (even though the overall risk of delivering a child with autism remained low).

Now research from MIT, the University of Massachusetts Medical School, the University of Colorado, and New York University Langone Medical Center reveals a possible mechanism for how this occurs. In a study of mice, the researchers found that immune cells activated in the mother during severe inflammation produce an immune effector molecule called IL-17 that appears to interfere with brain development.

The researchers also found that blocking this signal could restore normal behavior and brain structure.

“In the mice, we could treat the mother with antibodies that block IL-17 after inflammation had set in, and that could ameliorate some of the behavioral symptoms that were observed in the offspring. However, we don’t know yet how much of that could be translated into humans,” says Gloria Choi, an assistant professor of brain and cognitive sciences, a member of MIT’s McGovern Institute for Brain Research, and the lead author of the study, which appears in the Jan. 28 online edition of Science.

Finding the link

In the 2010 study, which included all children born in Denmark between 1980 and 2005, severe infections (requiring hospitalization) that correlated with autism risk included influenza, viral gastroenteritis, and urinary tract infections. Severe viral infections during the first trimester translated to a threefold risk for autism, and serious bacterial infections during the second trimester were linked with a 1.5-fold increase in risk.

Choi and her husband, Jun Huh, were graduate students at Caltech when they first heard about this study during a lecture by Caltech professor emeritus Paul Patterson, who had discovered that an immune signaling molecule called IL-6 plays a role in the link between infection and autism-like behaviors in rodents.

Huh, now an assistant professor at the University of Massachusetts Medical School and one of the paper’s senior authors, was studying immune cells called Th17 cells, which are well known for contributing to autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases, and rheumatoid arthritis. He knew that Th17 cells are activated by IL-6, so he wondered if these cells might also be involved in cases of animal models of autism associated with maternal infection.

“We wanted to find the link,” Choi says. “How do you go all the way from the immune system in the mother to the child’s brain?”

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Choi and Huh launched the study as postdocs at New York University School of Medicine, working with Dan Littman, a professor of molecular immunology at NYU and one of the paper’s senior authors. They began by injecting pregnant mice with a synthetic analog of double-stranded RNA, which activates the immune system in a similar way to viruses.

Confirming the results of previous studies in mice, the researchers found behavioral abnormalities in the offspring of the infected mothers, including deficits in sociability, repetitive behaviors, and abnormal communication. They then disabled Th17 cells in the mothers before inducing inflammation and found that the offspring mice did not show those behavioral abnormalities. The abnormalities also disappeared when the researchers gave the infected mothers an antibody that blocks IL-17, which is produced by Th17 cells.

The researchers next asked how IL-17 might affect the developing fetus. They found that brain cells in the fetuses of mothers experiencing inflammation express receptors for IL-17, and they believe that exposure to the chemical provokes cells to produce even more receptors for IL-17, amplifying its effects.

In the developing mice, the researchers found irregularities in the normally well-defined layers of cells in the brain’s cortex, where most cognition and sensory processing take place. These patches of irregular structure appeared in approximately the same cortical regions in all of the affected offspring, but they did not occur when the mothers’ Th17 cells were blocked.

Disorganized cortical layers have also been found in studies of human patients with autism.

Preventing autism

The researchers are now investigating whether and how these cortical patches produce the behavioral abnormalities seen in the offspring.

“We’ve shown correlation between these cortical patches and behavioral abnormalities, but we don’t know whether the cortical patches actually are responsible for the behavioral abnormalities,” Choi says. “And if it is responsible, what is being dysregulated within this patch to produce this behavior?”

The researchers hope their work may lead to a way to reduce the chances of autism developing in the children of women who experience severe infections during pregnancy. They also plan to investigate whether genetic makeup influences mice’s susceptibility to maternal inflammation, because autism is known to have a very strong genetic component.

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Massachusetts Institute of Technology

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Immune signaling molecule in infected mothers linked to behavioral abnormalities in offspring

In 2010, a large study in Denmark found that women who suffered an infection severe enough to require hospitalization while pregnant were much more likely to have a child with autism (even though the overall risk of delivering a child with autism remained low).

Now research from MIT, the University of Massachusetts Medical School, the University of Colorado, and New York University Langone Medical Center reveals a possible mechanism for how this occurs. In a study of mice, the researchers found that immune cells activated in the mother during severe inflammation produce an immune effector molecule called IL-17 that appears to interfere with brain development.

The researchers also found that blocking this signal could restore normal behavior and brain structure.

“In the mice, we could treat the mother with antibodies that block IL-17 after inflammation had set in, and that could ameliorate some of the behavioral symptoms that were observed in the offspring. However, we don’t know yet how much of that could be translated into humans,” says Gloria Choi, an assistant professor of brain and cognitive sciences, a member of MIT’s McGovern Institute for Brain Research, and the lead author of the study, which appears in the Jan. 28 online edition of Science.

Finding the link

In the 2010 study, which included all children born in Denmark between 1980 and 2005, severe infections (requiring hospitalization) that correlated with autism risk included influenza, viral gastroenteritis, and urinary tract infections. Severe viral infections during the first trimester translated to a threefold risk for autism, and serious bacterial infections during the second trimester were linked with a 1.5-fold increase in risk.

Choi and her husband, Jun Huh, were graduate students at Caltech when they first heard about this study during a lecture by Caltech professor emeritus Paul Patterson, who had discovered that an immune signaling molecule called IL-6 plays a role in the link between infection and autism-like behaviors in rodents.

Huh, now an assistant professor at the University of Massachusetts Medical School and one of the paper’s senior authors, was studying immune cells called Th17 cells, which are well known for contributing to autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases, and rheumatoid arthritis. He knew that Th17 cells are activated by IL-6, so he wondered if these cells might also be involved in cases of animal models of autism associated with maternal infection.

“We wanted to find the link,” Choi says. “How do you go all the way from the immune system in the mother to the child’s brain?”

Related Stories

Choi and Huh launched the study as postdocs at New York University School of Medicine, working with Dan Littman, a professor of molecular immunology at NYU and one of the paper’s senior authors. They began by injecting pregnant mice with a synthetic analog of double-stranded RNA, which activates the immune system in a similar way to viruses.

Confirming the results of previous studies in mice, the researchers found behavioral abnormalities in the offspring of the infected mothers, including deficits in sociability, repetitive behaviors, and abnormal communication. They then disabled Th17 cells in the mothers before inducing inflammation and found that the offspring mice did not show those behavioral abnormalities. The abnormalities also disappeared when the researchers gave the infected mothers an antibody that blocks IL-17, which is produced by Th17 cells.

The researchers next asked how IL-17 might affect the developing fetus. They found that brain cells in the fetuses of mothers experiencing inflammation express receptors for IL-17, and they believe that exposure to the chemical provokes cells to produce even more receptors for IL-17, amplifying its effects.

In the developing mice, the researchers found irregularities in the normally well-defined layers of cells in the brain’s cortex, where most cognition and sensory processing take place. These patches of irregular structure appeared in approximately the same cortical regions in all of the affected offspring, but they did not occur when the mothers’ Th17 cells were blocked.

Disorganized cortical layers have also been found in studies of human patients with autism.

Preventing autism

The researchers are now investigating whether and how these cortical patches produce the behavioral abnormalities seen in the offspring.

“We’ve shown correlation between these cortical patches and behavioral abnormalities, but we don’t know whether the cortical patches actually are responsible for the behavioral abnormalities,” Choi says. “And if it is responsible, what is being dysregulated within this patch to produce this behavior?”

The researchers hope their work may lead to a way to reduce the chances of autism developing in the children of women who experience severe infections during pregnancy. They also plan to investigate whether genetic makeup influences mice’s susceptibility to maternal inflammation, because autism is known to have a very strong genetic component.

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Massachusetts Institute of Technology

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A&Es struggle after 'surge' in demand

A&Es struggle after ‘sharp rise’ in demand

By Nick Triggle
Health correspondent
  • 29 January 2016
  • From the section Health

Doctors and nursesImage copyright
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A “sharp rise” in demand in A&E units is causing real problems for hospitals, NHS bosses are warning.

The BBC has learnt some NHS trusts have even had to take extreme measures to cope with the “exceptional” pressures.

One hospital had to cancel all its routine operations, while another considered setting up a temporary treatment area in a tent.

Over the past fortnight there have been 45 temporary closures of A&E units – up 50% on the same period last year.

This is considered an extreme step in which ambulances are sent to other hospitals and is ordered when wards are full and waiting times increasing rapidly.

The number of patients visiting A&Es in England jumped by 20,000 last week to nearly 340,000 – well above the average for winter.

As well as a rise in visits to A&E, hospitals bosses are also reporting problems discharging patients.

NHS England warned the pressures would last to the spring.

Among the problems reported were:

  • Coventry University Hospital cancelling all its routine operations on Wednesday and for part of Thursday because of “exceptional” circumstances.
  • GPs in north London being told to try to avoid referring patients to emergency departments in Ealing and Northwick Park because of “very high pressure”
  • A double-sized ambulance having to be parked outside Leicester Royal Infirmary last weekend as A&E staff were struggling to cope with the numbers of patients being brought in. Bosses even discussed setting up a temporary treatment area in a tent.
  • Royal Cornwall Hospital spending a week on black alert – a sign of extreme pressure – which led to routine operations being cancelled each day to free up resources. The black alert status was lifted only on Thursday.
  • Portsmouth Hospitals NHS Trust also spending time on black alert this week after “exceptional numbers of very sick, frail and elderly patients” needed care.
  • Last weekend NHS 111 seeing a “huge rise” in calls – up by more than a quarter on the same weekend the year before
  • A snapshot poll of major UK A&E units by the Royal College of Emergency Medicine suggesting during the first three weeks of January between 80% to 85% of patients were seen in four hours – well below the 95% target

The NHS in winter: Want to know more?

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Special report page: For the latest news, analysis and video

Winter across the UK: A guide to how the NHS is coping

Video: Why hospitals are under so much pressure

Video: How a hospital can grind to a halt


Coventry University Hospital’s chief executive, Andy Hardy, said this week had been “incredibly difficult”.

“I would like to apologise to any patients who have been affected.”

The pressures built during Tuesday when more than 500 patients turned up at A&E, leading to the unprecedented step of cancelling all the routine operations, such as knee and hip replacements, that had been planned for Wednesday and Thursday.

Mr Hardy said the trust had large numbers of patients in the hospital who did not need to be there but could not be discharged because there were “no spaces” in the community.

Leicester’s clinical director for emergency medicine Dr Ian Lawrence said the numbers coming in had “rocketed” since the start of January.

“Almost every bed in our three hospitals is being used and many staff members have voluntarily done extra shifts to help out,” he added.

Dr Cliff Mann, president of the Royal College of Emergency Medicine, said the NHS was reaching a “critical point” in winter.

“We were beginning to think this winter would not be as bad as last winter, but the problems we are beginning to see suggest it could end up being worse.

“We have virtually no flu or norovirus [a vomiting bug which leads to mass ward closures] – if there was to be an outbreak of either we could see the whole system tip over.”

NHS England’s Richard Barker said the recent bad weather was likely to have contributed to the “sharp rise” in A&E visits.

“The pressures remain very real. We don’t expect those to abate in the run-up to spring,” he added.

Elsewhere in the UK significant problems have been reported – last week doctors in Wales warned A&E was “on the edge”.

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UK 'world's worst' at breastfeeding

UK ‘world’s worst’ at breastfeeding

By James Gallagher
Health editor, BBC News website
  • 29 January 2016
  • From the section Health

BreastfeedingImage copyright
Thinkstock

Rates of breastfeeding in the UK are the lowest in the world, an international study shows.

The data, published in the Lancet, shows that only one in 200 women – or 0.5% – is still doing any degree of breastfeeding after a year.

That compares with 23% in Germany, 56% in Brazil and 99% in Senegal.

The researchers said it was a “widespread misconception” that breastfeeding was beneficial only in poor countries.

In the UK, 81% of mothers had tried breastfeeding at some point, but only 34% were breastfeeding at six months and 0.5% at 12 months.

In the US, 79% started, 49% were still going after six months and 27% after a year.

It is the worst record in the world. Breastfeeding is far more common in developing countries, but the UK figures are behind even similar countries in Europe.

Women in the UK are advised to feed their baby exclusively on breast milk for the first six months and then a combination of breast milk and other foods, however, it does not give a recommend end-point.

Life saver

Breastfeeding is good for the health of the baby and lowers the risk of breast and ovarian cancer.

Prof Cesar Victora, report author from the Federal University of Pelotas in Brazil, said: “There is a widespread misconception that the benefits of breastfeeding only relate to poor countries.

“Nothing could be further from the truth, our work clearly shows that breastfeeding saves lives and money in all countries, rich and poor alike.”

The Lancet report said breastfeeding in developed countries reduced the risk of sudden infant deaths by more than a third.

And in poorer countries, half of cases of diarrhoea and a third of respiratory infections could be avoided by breastfeeding.

Bottom five countries after 12 months Top five countries after 12 months
UK (0.5%) Senegal (99.4%)
Saudi Arabia (2%) The Gambia (98.7)
Denmark (3%) Malawi (98.3%)
Greece (6%) Guinea-Bissau (97.8%)
Canada and France (both 9%) Ethiopia (97.3%)

Overall, the report’s authors said that near-universal breastfeeding could save over 800,000 children’s lives a year.

A commentary, signed by Save the Children UK and the World Health Organization, was critical of formula milk being promoted at the expense of breastfeeding.

It said: “The active and aggressive promotion of breast milk substitutes by their manufacturers and distributors continues to be a substantial global barrier to breastfeeding.

“Promotion and marketing have turned infant formula, which should be seen as a specialised food that is vitally important for those babies who cannot be breastfed, into a normal food for any infant.”

Commenting on the findings, Sarah Redshaw, from the BabyCentre website, said: “It is crucial to bear in mind the various barriers and challenges faced by mums when it comes to breastfeeding.

“Generally mums are aware that breastfeeding is best for their baby but often don’t get the right support if they encounter problems in the early weeks – which many, many do.

“As a result, significant numbers give up on breastfeeding.”

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UK 'world's worst' at breastfeeding

UK ‘world’s worst’ at breastfeeding

By James Gallagher
Health editor, BBC News website
  • 29 January 2016
  • From the section Health

BreastfeedingImage copyright
Thinkstock

Rates of breastfeeding in the UK are the lowest in the world, an international study shows.

The data, published in the Lancet, shows that only one in 200 women – or 0.5% – is still doing any degree of breastfeeding after a year.

That compares with 23% in Germany, 56% in Brazil and 99% in Senegal.

The researchers said it was a “widespread misconception” that breastfeeding was beneficial only in poor countries.

In the UK, 81% of mothers had tried breastfeeding at some point, but only 34% were breastfeeding at six months and 0.5% at 12 months.

In the US, 79% started, 49% were still going after six months and 27% after a year.

It is the worst record in the world. Breastfeeding is far more common in developing countries, but the UK figures are behind even similar countries in Europe.

Women in the UK are advised to feed their baby exclusively on breast milk for the first six months and then a combination of breast milk and other foods, however, it does not give a recommend end-point.

Life saver

Breastfeeding is good for the health of the baby and lowers the risk of breast and ovarian cancer.

Prof Cesar Victora, report author from the Federal University of Pelotas in Brazil, said: “There is a widespread misconception that the benefits of breastfeeding only relate to poor countries.

“Nothing could be further from the truth, our work clearly shows that breastfeeding saves lives and money in all countries, rich and poor alike.”

The Lancet report said breastfeeding in developed countries reduced the risk of sudden infant deaths by more than a third.

And in poorer countries, half of cases of diarrhoea and a third of respiratory infections could be avoided by breastfeeding.

Bottom five countries after 12 months Top five countries after 12 months
UK (0.5%) Senegal (99.4%)
Saudi Arabia (2%) The Gambia (98.7)
Denmark (3%) Malawi (98.3%)
Greece (6%) Guinea-Bissau (97.8%)
Canada and France (both 9%) Ethiopia (97.3%)

Overall, the report’s authors said that near-universal breastfeeding could save over 800,000 children’s lives a year.

A commentary, signed by Save the Children UK and the World Health Organization, was critical of formula milk being promoted at the expense of breastfeeding.

It said: “The active and aggressive promotion of breast milk substitutes by their manufacturers and distributors continues to be a substantial global barrier to breastfeeding.

“Promotion and marketing have turned infant formula, which should be seen as a specialised food that is vitally important for those babies who cannot be breastfed, into a normal food for any infant.”

Commenting on the findings, Sarah Redshaw, from the BabyCentre website, said: “It is crucial to bear in mind the various barriers and challenges faced by mums when it comes to breastfeeding.

“Generally mums are aware that breastfeeding is best for their baby but often don’t get the right support if they encounter problems in the early weeks – which many, many do.

“As a result, significant numbers give up on breastfeeding.”

Follow James on Twitter.

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Peru reports first patient carrying the Zika virus


A model of a mosquito is exhibited during a campaign to raise awareness of preventing the entry of the Zika virus into the country, at the Health Ministry in Lima, Peru January 27, 2016.   REUTERS/Mariana Bazo


A model of a mosquito is exhibited during a campaign to raise awareness of preventing the entry of the Zika virus into the country, at the Health Ministry in Lima, Peru January 27, 2016.



Reuters/Mariana Bazo


Peru said Friday a Venezuelan man in Lima, who recently traveled through Colombia, had contracted the mosquito-borne virus Zika, in the Andean country’s first confirmed case of the disease that is rapidly spreading across the Americas.

Health Minister Anibal Velasquez said he expected other cases of people who had been infected with Zika abroad to appear in Peru in the coming days.

Peru shares borders with Colombia, Ecuador and Brazil, where President Dilma Rousseff called for war on the virus that has caused severe birth defects in thousands of babies.Zika is also spreading in Colombia and Ecuador.

“It was inevitable that cases of imported Zika would arrive to Peru,” Velasquez said at a news conference. “The patient is isolated and we’re taking steps to prevent its spread.”

The Venezuelan man passed through the northern coastal city of Tumbes before coming to the capital, and health authorities there are bolstering efforts to eradicate mosquitoes, Velasquez said.

Zika is linked to severe birth defects and is “spreading explosively” in the Americas, according to the World Health Organization.

Venezuela has reported some 4,700 cases of potential infection.

(Reporting by Mitra Taj; Editing by Bernadette Baum)


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Peru reports first patient carrying the Zika virus


A model of a mosquito is exhibited during a campaign to raise awareness of preventing the entry of the Zika virus into the country, at the Health Ministry in Lima, Peru January 27, 2016.   REUTERS/Mariana Bazo


A model of a mosquito is exhibited during a campaign to raise awareness of preventing the entry of the Zika virus into the country, at the Health Ministry in Lima, Peru January 27, 2016.



Reuters/Mariana Bazo


Peru said Friday a Venezuelan man in Lima, who recently traveled through Colombia, had contracted the mosquito-borne virus Zika, in the Andean country’s first confirmed case of the disease that is rapidly spreading across the Americas.

Health Minister Anibal Velasquez said he expected other cases of people who had been infected with Zika abroad to appear in Peru in the coming days.

Peru shares borders with Colombia, Ecuador and Brazil, where President Dilma Rousseff called for war on the virus that has caused severe birth defects in thousands of babies.Zika is also spreading in Colombia and Ecuador.

“It was inevitable that cases of imported Zika would arrive to Peru,” Velasquez said at a news conference. “The patient is isolated and we’re taking steps to prevent its spread.”

The Venezuelan man passed through the northern coastal city of Tumbes before coming to the capital, and health authorities there are bolstering efforts to eradicate mosquitoes, Velasquez said.

Zika is linked to severe birth defects and is “spreading explosively” in the Americas, according to the World Health Organization.

Venezuela has reported some 4,700 cases of potential infection.

(Reporting by Mitra Taj; Editing by Bernadette Baum)


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WHO says Zika virus spreads explosively, four million cases forecast


The Zika virus, linked to severe birth defects in thousands of babies in Brazil, is “spreading explosively” and could infect as many as 4 million people in the Americas, the World Health Organization (WHO) said on Thursday.

Director-General Margaret Chan told members of the U.N. health agency’s executive board the spread of the mosquito-borne disease had gone from a mild threat to one of alarming proportions. The WHO would convene an emergency meeting on Monday to help determine its response, she said.

“The level of alarm is extremely high,” Chan told the Geneva gathering.

“Last year, the virus was detected in the Americas, where it is now spreading explosively. As of today, cases have been reported in 23 countries and territories in the region,” Chan said, promising quick action from the WHO.

The agency was criticized last year for reacting too slowly to West Africa’s Ebola epidemic, which killed more than 10,000 people, and it promised to cut its response time.

“We are not going to wait for the science to tell us there is a link (with birth defects). We need to take actions now,” Chan said, referring to the condition called microcephaly in which babies are born with abnormally small heads and brains that have not developed properly.

There is no vaccine or treatment for Zika, which is like dengue and causes mild fever, rash and red eyes. An estimated 80 percent of people infected have no symptoms. Much of the effort against the illness focuses on protecting people from mosquitoes and reducing mosquito populations.

Developing a safe and effective vaccine could take a year, WHO Assistant Director Bruce Aylward said, and it would take six to nine months just to confirm whether Zika is the actual cause of the birth defects, or if the two are just associated.

“In the area of vaccines, I do know that there has been some work done by some groups looking at the feasibility of a Zika virus vaccine. Now something like that, as people know, is going to be a 12-month-plus time frame,” he said.

U.S. health officials said the United States has two potential candidates for a Zika vaccine and may begin human clinical trials by the end of this year, but there will not be a widely available vaccine for several years.

Marcos Espinal, head of communicable diseases at the Pan American Health Organization, the WHO’s Americas arm, forecast 3 to 4 million Zika cases in the Americas.

As the virus spreads from Brazil, other countries in the Americas are likely to see cases of babies with Zika-linked birth defects, according to Carissa Etienne, regional director for the Pan American Health Organization.

Brazil has reported around 4,000 suspected cases of microcephaly, vastly more than in an average year and equivalent to 1 to 2 percent of all newborns in the state of Pernambuco, one of the worst-hit areas.

The WHO’s Chan said that while a direct causal relationship between Zika virus infection and birth malformations has not yet been established, it is strongly suspected.

“The possible links, only recently suspected, have rapidly changed the risk profile of Zika from a mild threat to one of alarming proportions,” she said.

Health and law expert Lawrence Gostin of Georgetown University in Washington, who had urged the WHO to act, welcomed Chan’s decision to convene an expert meeting, calling it “a critical first step in recognizing the seriousness of an emerging epidemic.”

OLYMPICS CONCERNS

With Rio de Janeiro set to host the Olympics from Aug. 5 to Aug. 21, International Olympic Committee President Thomas Bach said the IOC will issue guidelines this week concerning Zika.

“We will do everything to ensure the health of the athletes and all the visitors,” Bach told reporters in Athens.

Dr. Anne Schuchat of the U.S. Centers for Disease Control and Prevention, said there have been 31 cases of Zika infection among U.S. citizens who traveled to areas affected by the virus.

“It’s possible and even likely that we will see limited outbreaks in the United States,” Schuchat said.

In Washington, U.S. Senator Edward Markey of Massachusetts called on the WHO and the U.S. Department of Health and Human Services to explain how they were tackling the virus because many Americans visit the affected region and more are expected to attend the Olympics.

White House spokesman Josh Earnest said President Barack Obama’s administration’s concern was focused mostly on pregnant women or women who could become pregnant, given the link to microcephaly.

Lufthansa (LHAG.DE), British Airways (ICAG.L) and JetBlue (JBLU.O) became the latest international carriers to offer rebookings or refunds for tickets to areas impacted by the virus.

Lufthansa and British Airways said they would offer pregnant women the opportunity to change their reservations to another destination or delay travel. They stopped short of offering complete refunds as several U.S. airlines have.

(Additional reporting by Kate Kelland in London; Additional reporting by Susan Heavey in Washington and Julie Steenhuysen in Chicago; Writing by Kate Kelland and Will Dunham; Editing by Mark Heinrich and
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WHO says Zika virus spreads explosively, four million cases forecast


The Zika virus, linked to severe birth defects in thousands of babies in Brazil, is “spreading explosively” and could infect as many as 4 million people in the Americas, the World Health Organization (WHO) said on Thursday.

Director-General Margaret Chan told members of the U.N. health agency’s executive board the spread of the mosquito-borne disease had gone from a mild threat to one of alarming proportions. The WHO would convene an emergency meeting on Monday to help determine its response, she said.

“The level of alarm is extremely high,” Chan told the Geneva gathering.

“Last year, the virus was detected in the Americas, where it is now spreading explosively. As of today, cases have been reported in 23 countries and territories in the region,” Chan said, promising quick action from the WHO.

The agency was criticized last year for reacting too slowly to West Africa’s Ebola epidemic, which killed more than 10,000 people, and it promised to cut its response time.

“We are not going to wait for the science to tell us there is a link (with birth defects). We need to take actions now,” Chan said, referring to the condition called microcephaly in which babies are born with abnormally small heads and brains that have not developed properly.

There is no vaccine or treatment for Zika, which is like dengue and causes mild fever, rash and red eyes. An estimated 80 percent of people infected have no symptoms. Much of the effort against the illness focuses on protecting people from mosquitoes and reducing mosquito populations.

Developing a safe and effective vaccine could take a year, WHO Assistant Director Bruce Aylward said, and it would take six to nine months just to confirm whether Zika is the actual cause of the birth defects, or if the two are just associated.

“In the area of vaccines, I do know that there has been some work done by some groups looking at the feasibility of a Zika virus vaccine. Now something like that, as people know, is going to be a 12-month-plus time frame,” he said.

U.S. health officials said the United States has two potential candidates for a Zika vaccine and may begin human clinical trials by the end of this year, but there will not be a widely available vaccine for several years.

Marcos Espinal, head of communicable diseases at the Pan American Health Organization, the WHO’s Americas arm, forecast 3 to 4 million Zika cases in the Americas.

As the virus spreads from Brazil, other countries in the Americas are likely to see cases of babies with Zika-linked birth defects, according to Carissa Etienne, regional director for the Pan American Health Organization.

Brazil has reported around 4,000 suspected cases of microcephaly, vastly more than in an average year and equivalent to 1 to 2 percent of all newborns in the state of Pernambuco, one of the worst-hit areas.

The WHO’s Chan said that while a direct causal relationship between Zika virus infection and birth malformations has not yet been established, it is strongly suspected.

“The possible links, only recently suspected, have rapidly changed the risk profile of Zika from a mild threat to one of alarming proportions,” she said.

Health and law expert Lawrence Gostin of Georgetown University in Washington, who had urged the WHO to act, welcomed Chan’s decision to convene an expert meeting, calling it “a critical first step in recognizing the seriousness of an emerging epidemic.”

OLYMPICS CONCERNS

With Rio de Janeiro set to host the Olympics from Aug. 5 to Aug. 21, International Olympic Committee President Thomas Bach said the IOC will issue guidelines this week concerning Zika.

“We will do everything to ensure the health of the athletes and all the visitors,” Bach told reporters in Athens.

Dr. Anne Schuchat of the U.S. Centers for Disease Control and Prevention, said there have been 31 cases of Zika infection among U.S. citizens who traveled to areas affected by the virus.

“It’s possible and even likely that we will see limited outbreaks in the United States,” Schuchat said.

In Washington, U.S. Senator Edward Markey of Massachusetts called on the WHO and the U.S. Department of Health and Human Services to explain how they were tackling the virus because many Americans visit the affected region and more are expected to attend the Olympics.

White House spokesman Josh Earnest said President Barack Obama’s administration’s concern was focused mostly on pregnant women or women who could become pregnant, given the link to microcephaly.

Lufthansa (LHAG.DE), British Airways (ICAG.L) and JetBlue (JBLU.O) became the latest international carriers to offer rebookings or refunds for tickets to areas impacted by the virus.

Lufthansa and British Airways said they would offer pregnant women the opportunity to change their reservations to another destination or delay travel. They stopped short of offering complete refunds as several U.S. airlines have.

(Additional reporting by Kate Kelland in London; Additional reporting by Susan Heavey in Washington and Julie Steenhuysen in Chicago; Writing by Kate Kelland and Will Dunham; Editing by Mark Heinrich and
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