scientificamerican--2020-08-25--Two Strains of Polio Down, One to Go

Two Strains of Polio Down, One to Go

Editor ’ s Note ( 8/25/20 ) : This article is being republished today in light of the news that Africa is expected to be declared free of wild polio .
The achievement comes after decades of vaccination drives succeeded in driving the virus out from its last foothold in Nigeria .
In January 2014 an American public health worker was visiting northern Nigeria to observe a polio prevention campaign by local health workers .
It was a big , festive event with a marching band to bring out parents and children for their immunizations .
But the American visitor @ @ @ @ @ @ @ themselves being drawn away from the action , down deserted streets to an area still under construction .
They were being led by a young girl .
“ And what was happening was that she was bringing us to her house , ” recalls John Vertefeuille , now chief of the polio eradication branch at the U.S. Centers for Disease Control and Prevention .
“ She had a baby brother born the night before , and the father brought out the baby , and we were able to vaccinate him .
She was @ @ @ @ @ @ @ her new brother that gift .
She probably didn ’ t comprehend it , but she had given that child the possibility of a life without polio .
What an incredible thing it will be when we can do that for every child , from here until the end of time.
” The international effort to achieve this goal passed a major milestone this week with the worldwide eradication of wild poliovirus type 3 .
The announcement , due Thursday from the Global Commission for the Certification of the Eradication of Poliomyelitis comes @ @ @ @ @ @ @ poliovirus type 2 .
It leaves only a single strain , wild poliovirus type 1 , on the loose .
Type 1 is now holed up in the smallest area in the history of the disease—though that area comprises politically and geographically fraught regions of Pakistan and Afghanistan .
The current target for worldwide eradication is 2023 , according to the Global Polio Eradication Initiative ( GPEI ) , a multinational partnership that has been pursuing this goal since 1988 .
Polio would be only the second human disease to be wiped out @ @ @ @ @ @ @ The 2023 target is ambitious .
It would mean seeing the world ’ s last cases of wild poliovirus sometime next year—down from 88 cases so far in 2019—followed by a minimum of three years of intensive monitoring to certify eradication .
But the antipolio effort has a recent history of success against long odds .
India , where polio was paralyzing 500 to 1,000 children per day in the 1990s , eliminated the disease in 2014 .
The wrenching spectacle of child polio victims begging in that nation ’ s streets , @ @ @ @ @ @ @ , is now history .
Nigeria , where antigovernment gunmen assassinated nine women polio vaccinators in 2013 , has now gone three years without any evidence of wild poliovirus—and seven years without type 3—largely through the heroic persistence of community health workers .
Success there , says Carol Pandak of Rotary International , means the entire African continent could be certified free of all three strains of wild poliovirus sometime next year .
As the last two countries reporting wild poliovirus , Pakistan and Afghanistan are now feeling “ tremendous global pressure to @ @ @ @ @ @ @ says .
The Taliban had suspended the vaccination campaign early this year in parts of Afghanistan under its control , but last month it reversed itself and allowed polio immunizations to resume in clinics—though not in mosques or door-to-door .
In neighboring Pakistan the government of Prime Minister Imran Khan recently made eradication its top priority , with Khan to assume leadership of the campaign starting next month .
But GPEI , led by the World Health Organization , the CDC , the United Nations Children ’ s Fund , Rotary International and @ @ @ @ @ @ @ also faces daunting obstacles .
The most alarming of them is the emergence and spread of vaccine-derived type 2 poliovirus , mainly in Africa .
Public health workers have recognized the problem since 2000 , according to Walter Orenstein , an infectious disease and polio specialist at the Emory University School of Medicine .
The live but attenuated , or weakened , virus used in the Sabin oral vaccine ( which is the mainstay of eradication campaigns ) can sometimes spread from a vaccinated child to someone who is still susceptible to polio @ @ @ @ @ @ @ Orenstein says , when a vaccine recipient is shedding the weakened virus in feces and inadvertently passes it to a susceptible person via interpersonal contact or a drinking-water source .
In the subsequent chain of infection from person to person , the virus may mutate in the human body into more virulent and transmissible forms—and begin to circulate like a wild poliovirus among unvaccinated children .
Last year vaccine-derived poliovirus outbreaks caused 105 cases of paralysis in children , according to GPEI .
So far , though , there has not been any @ @ @ @ @ @ @ in eradication efforts , Orenstein says .
The inactivated vaccine administered by injection is highly effective at protecting individuals by inducing humoral immunity ( in the blood and other bodily fluids ) , he says , but it is not so good at inducing intestinal immunity .
That makes it less useful in areas with poor sanitation , where accidentally ingesting fecal matter from drinking water is a hazard .
The oral vaccine is not only easier and less costly to use in large-scale door-to-door campaigns ; it also confers stronger intestinal immunity @ @ @ @ @ @ @ cases , helps protect the community by reducing the amount of the virus shed in human waste .
Researchers have now identified the key points on the oral vaccine ’ s genome where mutations can cause it to revert to a more virulent form .
That achievement has made it possible to introduce genetic modifications at those points to prevent reversion , says Jay Wenger of the Gates Foundation , which has funded the effort .
Two new oral vaccine candidates with these modifications have advanced to testing for emergency-use regulatory approval by @ @ @ @ @ @ @ countries , and they could be available as early as June .
That timeline still leaves a critical eight-month window , however , in which a vaccine-derived outbreak could occur .
Another potential obstacle is fatigue at the international donor level .
“ We know that the last mile has proved to be the toughest phase of eradication , ” says Michel Zaffran , director of polio eradication for the World Health Organization .
People tend to become complacent as the success of a vaccine leads them to forget just how dreadful the @ @ @ @ @ @ @ seeking $ 3.27 billion for its next four years of work , with a donor “ pledging moment ” scheduled for November 19 in Abu Dhabi .
“ It ’ s always a challenge to ask for more money—especially for a disease that , for many people , no longer exists , ” Zaffran says .
“ People ask , ‘ Why is it costing so much to eradicate polio when you have so few cases left ?
’ But eradicating polio and stopping these outbreaks means we have to vaccinate 400 million @ @ @ @ @ @ @ to vaccinate children for at least another 10 years— “ to ensure there is no reemergence of the disease.
” It also requires a sophisticated network to check samples from individual patients , sewage systems and open water bodies for any sign of the virus .
Fatigue at the levels of the community and individual parents could be an even greater challenge .
In areas with poor sanitation , children sometimes need eight to 10 doses of vaccine to achieve immunity .
Polio vaccinators have continued working to reach those children , despite @ @ @ @ @ @ @ naturally wonder why public health workers keep coming back to them with polio vaccine when families still lack clean water , basic sanitation or access to general health care .
That situation has required the polio eradication effort to broaden its focus to other community needs and to persuade local political and religious figures to become leaders of the campaign .
Would it be more practical just to back off from the difficult goal of eradication and instead focus on merely controlling the spread of the disease ?
Zaffran cites a 2007 study @ @ @ @ @ @ @ control would cost $ 3.5 billion annually—and result in 200,000 cases of polio every year .
“ If we stop , ” he says , “ the disease will come back .
It will rapidly spread into the Middle East , into Africa and maybe even into Europe and the United States , as we have seen with measles .
I truly believe that now is the time to finish the job—and we have all the tools to do it .
”

Editor’s Note (8/25/20): This article is being republished today in light of the news that Africa is expected to be declared free of wild polio. The achievement comes after decades of vaccination drives succeeded in driving the virus out from its last foothold in Nigeria.
In January 2014 an American public health worker was visiting northern Nigeria to observe a polio prevention campaign by local health workers. It was a big, festive event with a marching band to bring out parents and children for their immunizations. But the American visitor and the local program manager soon found themselves being drawn away from the action, down deserted streets to an area still under construction. They were being led by a young girl.
“And what was happening was that she was bringing us to her house,” recalls John Vertefeuille, now chief of the polio eradication branch at the U.S. Centers for Disease Control and Prevention. “She had a baby brother born the night before, and the father brought out the baby, and we were able to vaccinate him. She was so excited to be able to give her new brother that gift. She probably didn’t comprehend it, but she had given that child the possibility of a life without polio. What an incredible thing it will be when we can do that for every child, from here until the end of time.”
The international effort to achieve this goal passed a major milestone this week with the worldwide eradication of wild poliovirus type 3. The announcement, due Thursday from the Global Commission for the Certification of the Eradication of Poliomyelitis comes just four years after eradication of wild poliovirus type 2. It leaves only a single strain, wild poliovirus type 1, on the loose. Type 1 is now holed up in the smallest area in the history of the disease—though that area comprises politically and geographically fraught regions of Pakistan and Afghanistan.
The current target for worldwide eradication is 2023, according to the Global Polio Eradication Initiative (GPEI), a multinational partnership that has been pursuing this goal since 1988. Polio would be only the second human disease to be wiped out globally, after smallpox in 1980.
The 2023 target is ambitious. It would mean seeing the world’s last cases of wild poliovirus sometime next year—down from 88 cases so far in 2019—followed by a minimum of three years of intensive monitoring to certify eradication. But the antipolio effort has a recent history of success against long odds. India, where polio was paralyzing 500 to 1,000 children per day in the 1990s, eliminated the disease in 2014. The wrenching spectacle of child polio victims begging in that nation’s streets, with their twiglike legs folded beneath them, is now history.
Nigeria, where antigovernment gunmen assassinated nine women polio vaccinators in 2013, has now gone three years without any evidence of wild poliovirus—and seven years without type 3—largely through the heroic persistence of community health workers. Success there, says Carol Pandak of Rotary International, means the entire African continent could be certified free of all three strains of wild poliovirus sometime next year.
As the last two countries reporting wild poliovirus, Pakistan and Afghanistan are now feeling “tremendous global pressure to get the job done,” Pandak says. The Taliban had suspended the vaccination campaign early this year in parts of Afghanistan under its control, but last month it reversed itself and allowed polio immunizations to resume in clinics—though not in mosques or door-to-door. In neighboring Pakistan the government of Prime Minister Imran Khan recently made eradication its top priority, with Khan to assume leadership of the campaign starting next month.
But GPEI, led by the World Health Organization, the CDC, the United Nations Children’s Fund, Rotary International and the Bill & Melinda Gates Foundation, also faces daunting obstacles. The most alarming of them is the emergence and spread of vaccine-derived type 2 poliovirus, mainly in Africa. Public health workers have recognized the problem since 2000, according to Walter Orenstein, an infectious disease and polio specialist at the Emory University School of Medicine. The live but attenuated, or weakened, virus used in the Sabin oral vaccine (which is the mainstay of eradication campaigns) can sometimes spread from a vaccinated child to someone who is still susceptible to polio.
This transmission most commonly happens, Orenstein says, when a vaccine recipient is shedding the weakened virus in feces and inadvertently passes it to a susceptible person via interpersonal contact or a drinking-water source. In the subsequent chain of infection from person to person, the virus may mutate in the human body into more virulent and transmissible forms—and begin to circulate like a wild poliovirus among unvaccinated children. Last year vaccine-derived poliovirus outbreaks caused 105 cases of paralysis in children, according to GPEI.
So far, though, there has not been any way around reliance on the oral vaccine in eradication efforts, Orenstein says. The inactivated vaccine administered by injection is highly effective at protecting individuals by inducing humoral immunity (in the blood and other bodily fluids), he says, but it is not so good at inducing intestinal immunity. That makes it less useful in areas with poor sanitation, where accidentally ingesting fecal matter from drinking water is a hazard. The oral vaccine is not only easier and less costly to use in large-scale door-to-door campaigns; it also confers stronger intestinal immunity and, in the vast majority of cases, helps protect the community by reducing the amount of the virus shed in human waste.
Researchers have now identified the key points on the oral vaccine’s genome where mutations can cause it to revert to a more virulent form. That achievement has made it possible to introduce genetic modifications at those points to prevent reversion, says Jay Wenger of the Gates Foundation, which has funded the effort. Two new oral vaccine candidates with these modifications have advanced to testing for emergency-use regulatory approval by the World Health Organization and the affected countries, and they could be available as early as June. That timeline still leaves a critical eight-month window, however, in which a vaccine-derived outbreak could occur.
Another potential obstacle is fatigue at the international donor level. “We know that the last mile has proved to be the toughest phase of eradication,” says Michel Zaffran, director of polio eradication for the World Health Organization. People tend to become complacent as the success of a vaccine leads them to forget just how dreadful the disease can be. GPEI is now seeking $3.27 billion for its next four years of work, with a donor “pledging moment” scheduled for November 19 in Abu Dhabi.
“It’s always a challenge to ask for more money—especially for a disease that, for many people, no longer exists,” Zaffran says. “People ask, ‘Why is it costing so much to eradicate polio when you have so few cases left?’ But eradicating polio and stopping these outbreaks means we have to vaccinate 400 million children every year”—and then continue to vaccinate children for at least another 10 years—“to ensure there is no reemergence of the disease.” It also requires a sophisticated network to check samples from individual patients, sewage systems and open water bodies for any sign of the virus.
Fatigue at the levels of the community and individual parents could be an even greater challenge. In areas with poor sanitation, children sometimes need eight to 10 doses of vaccine to achieve immunity. Polio vaccinators have continued working to reach those children, despite recent assassinations in Pakistan. But parents naturally wonder why public health workers keep coming back to them with polio vaccine when families still lack clean water, basic sanitation or access to general health care. That situation has required the polio eradication effort to broaden its focus to other community needs and to persuade local political and religious figures to become leaders of the campaign.
Would it be more practical just to back off from the difficult goal of eradication and instead focus on merely controlling the spread of the disease? Zaffran cites a 2007 study calculating that the switch from eradication to control would cost $3.5 billion annually—and result in 200,000 cases of polio every year. “If we stop,” he says, “the disease will come back. It will rapidly spread into the Middle East, into Africa and maybe even into Europe and the United States, as we have seen with measles. I truly believe that now is the time to finish the job—and we have all the tools to do it.”


scientificamerican--2020-08-25--Why Do Some People Weather Coronavirus Infection Unscathed?

One of the reasons Covid-19 has spread so swiftly around the globe is that for the first days after infection , people feel healthy .
Instead of staying home in bed , they may be out and about , unknowingly passing the virus along .
But in addition to these pre-symptomatic patients , the relentless silent spread of this pandemic is also facilitated by a more mysterious group of people : the so-called asymptomatics .
According to various estimates , between 20 and 45 percent of the people who get Covid-19—and possibly more , according to a recent study from @ @ @ @ @ @ @ through a coronavirus infection without realizing they ever had it .
No fever or chills .
No loss of smell or taste .
No breathing difficulties .
They don ’ t feel a thing .
Asymptomatic cases are not unique to Covid-19 .
They occur with the regular flu , and probably also featured in the 1918 pandemic , according to epidemiologist Neil Ferguson of Imperial College London .
But scientists aren ’ t sure why certain people weather Covid-19 unscathed .
“ That is a tremendous mystery at this point , ” @ @ @ @ @ @ @ expert at Boston University ’ s School of Public Health .
The prevailing theory is that their immune systems fight off the virus so efficiently that they never get sick .
But some scientists are confident that the immune system ’ s aggressive response , the churning out of antibodies and other molecules to eliminate an infection , is only part of the story .
These experts are learning that the human body may not always wage an all-out war on viruses and other pathogens .
It may also be capable of accommodating @ @ @ @ @ @ @ no symptoms emerge .
This phenomenon , known as disease tolerance , is well-known in plants but has only been documented in animals within the last 15 years .
Disease tolerance is the ability of an individual , due to a genetic predisposition or some aspect of behavior or lifestyle , to thrive despite being infected with an amount of pathogen that sickens others .
Tolerance takes different forms , depending on the infection .
For example , when infected with cholera , which causes watery diarrhea that can quickly kill through dehydration @ @ @ @ @ @ @ maintain fluid and electrolyte balance .
During other infections , the body might tweak metabolism or activate gut microbes—whatever internal adjustment is needed to prevent or repair tissue damage or to make a germ less vicious .
Researchers who study these processes rely on invasive experiments that can not be done in people .
Nevertheless , they view asymptomatic infections as evidence that disease tolerance occurs in humans .
At least 90 percent of those infected with the tuberculosis bacterium don ’ t get sick .
The same is true for many of @ @ @ @ @ @ @ live with parasitic worms called helminths in their intestines .
“ Despite the fact that these worms are very large organisms and they basically migrate through your tissues and cause damage , many people are asymptomatic .
They don ’ t even know they ’ re infected , ” says Irah King , a professor of immunology at McGill University .
“ And so then the question becomes , what does the body do to tolerate these types of invasive infections ?
” While scientists have observed the physiological processes that minimize tissue @ @ @ @ @ @ @ , it ’ s only more recently that they ’ ve begun to think about them in terms of disease tolerance .
For example , King and colleagues have identified specific immune cells in mice that increase the resilience of blood vessels during a helminth infection , leading to less intestinal bleeding , even when the same number of worms are present .
“ This has been demonstrated in plants , bacteria , other mammalian species , ” King says .
“ Why would we think that humans would not have developed these @ @ @ @ @ @ @ our health in the face of infection ?
” he adds .
In a recent Frontiers in Immunology editorial , King and his McGill colleague Maziar Divangahi describe their long-term hopes for the field : A deeper understanding of disease tolerance , they write , could lead to “ a new golden age of infectious disease research and discovery.
” Scientists have traditionally viewed germs as the enemy , an approach that has generated invaluable antibiotics and vaccines .
But more recently , researchers have come to understand that the human body is @ @ @ @ @ @ @ essential to optimal health , and that the relationship between humans and germs is more nuanced .
Meddlesome viruses and bacteria have been around since life began , so it makes sense that animals evolved ways to manage as well as fight them .
Attacking a pathogen can be effective , but it can also backfire .
For one thing , infectious agents find ways to evade the immune system .
Moreover , the immune response itself , if unchecked , can turn lethal , applying its destructive force to the body ’ @ @ @ @ @ @ @ like Covid , I think it ’ s going to be very parallel to TB , where you have this Goldilocks situation , ” says Andrew Olive , an immunologist at Michigan State University , “ where you need that perfect amount of inflammation to control the virus and not damage the lungs.
” Some of the key disease tolerance mechanisms scientists have identified aim to keep inflammation within that narrow window .
For example , immune cells called alveolar macrophages in the lung suppress inflammation once the threat posed by the pathogen @ @ @ @ @ @ @ why there is such a wide range of responses to Covid-19 , from asymptomatic to mildly sick to out of commission for weeks at home to full-on organ failure .
“ It ’ s very , very early days here , ” says Andrew Read , an infectious disease expert at Pennsylvania State University who helped identify disease tolerance in animals .
Read believes disease tolerance may at least partially explain why some infected people have mild symptoms or none at all .
This may be because they ’ re better at scavenging @ @ @ @ @ @ @ or replenishing their lung tissues at faster rates , those sorts of things.
” The mainstream scientific view of asymptomatics is that their immune systems are especially well-tuned .
This could explain why children and young adults make up the majority of people without symptoms because the immune system naturally deteriorates with age .
It ’ s also possible that the immune systems of asymptomatics have been primed by a previous infection with a milder coronavirus , like those that cause the common cold .
Asymptomatic cases don ’ t get much attention @ @ @ @ @ @ @ these people do n't go to the doctor and thus are tough to track down .
But Janelle Ayres , a physiologist and infectious disease expert at the Salk Institute For Biological Studies who has been a leader in disease tolerance research , studies precisely the mice that do n't get sick .
The staple of this research is something called the “ lethal dose 50 ” test , which consists of giving a group of mice enough pathogen to kill half .
By comparing the mice that live with those that die @ @ @ @ @ @ @ their physiology that enable them to survive the infection .
She has performed this experiment scores of times using a variety of pathogens .
The goal is to figure out how to activate health-sustaining responses in all animals .
A hallmark of these experiments—and something that surprised her at first—is that the half that survive the lethal dose are perky .
They are completely unruffled by the same quantity of pathogen that kills their counterparts .
“ I thought going into this … that all would get sick , that half would live @ @ @ @ @ @ @ isn ’ t what I found , ” Ayres says .
“ I found that half got sick and died , and the other half never got sick and lived.
” Ayres sees something similar happening in the Covid-19 pandemic .
Like her mice , asymptomatics seem to have similar amounts of the virus in their bodies as the people who fall ill , yet for some reason they stay healthy .
Studies show that their lungs often display damage on CT scans , yet they are not struggling for breath ( though @ @ @ @ @ @ @ will fully escape long-term impacts ) .
Moreover , a small recent study suggests that asymptomatics mount a weaker immune response than the people who get sick—suggesting that mechanisms are at work that have nothing to do with fighting infection .
“ Why , if they have these abnormalities , are they healthy ?
” asks Ayres .
“ Potentially because they have disease tolerance mechanisms engaged .
These are the people we need to study.
” The goal of disease tolerance research is to decipher the mechanisms that keep infected people healthy @ @ @ @ @ @ @ everyone .
“ You want to have a drought-tolerant plant , for obvious reasons , so why wouldn ’ t we want to have a virus-tolerant person ?
” Read asks .
A 2018 experiment in Ayres ’ lab offered proof of concept for that goal .
The team gave a diarrhea-causing infection to mice in a lethal dose 50 trial , then compared tissue from the mice that died with those that survived , looking for differences .
They discovered that the asymptomatic mice had utilized their iron stores to route extra @ @ @ @ @ @ @ that the pacified germs no longer posed a threat .
The team subsequently turned this observation into a treatment .
In further experiments , they administered iron supplements to the mice and all the animals survived , even when the pathogen dose was upped a thousandfold .
When the pandemic hit , Ayres was already studying mice with pneumonia and the signature malady of Covid-19 , acute respiratory distress syndrome , which can be triggered by various infections .
Her lab has identified markers that may inform candidate pathways to target for treatment @ @ @ @ @ @ @ people who progressed to severe stages of Covid-19 with asymptomatics to see whether markers emerge that resemble the ones she ’ s found in mice .
If a medicine is developed , it would work differently from anything that ’ s currently on the market because it would be lung-specific , not disease-specific , and would ease respiratory distress regardless of which pathogen is responsible .
But intriguing as this prospect is , most experts caution that disease tolerance is a new field and tangible benefits are likely many years off .
The @ @ @ @ @ @ @ the levels of a pathogen in the body , which means killing an animal and searching all of its tissues .
“ You can ’ t really do controlled biological experiments in humans , ” Olive says .
In addition , there are countless disease tolerance pathways .
“ Every time we figure one out , we find we have 10 more things we don ’ t understand , ” King says .
Things will differ with each disease , he adds , “ so that becomes a bit overwhelming.
” Nevertheless , @ @ @ @ @ @ @ disease tolerance research could have profound implications for treating infectious disease in the future .
Microbiology and infectious disease research has “ all been focused on the pathogen as an invader that has to be eliminated some way , ” says virologist Jeremy Luban of the University of Massachusetts Medical School .
And as Ayres makes clear , he says , “ what we really should be thinking about is how do we keep the person from getting sick.
” This article was originally published on Undark .
Read the original article .

One of the reasons Covid-19 has spread so swiftly around the globe is that for the first days after infection, people feel healthy. Instead of staying home in bed, they may be out and about, unknowingly passing the virus along. But in addition to these pre-symptomatic patients, the relentless silent spread of this pandemic is also facilitated by a more mysterious group of people: the so-called asymptomatics.
According to various estimates, between 20 and 45 percent of the people who get Covid-19—and possibly more, according to a recent study from the Centers for Disease Control and Prevention—sail through a coronavirus infection without realizing they ever had it. No fever or chills. No loss of smell or taste. No breathing difficulties. They don’t feel a thing.
Asymptomatic cases are not unique to Covid-19. They occur with the regular flu, and probably also featured in the 1918 pandemic, according to epidemiologist Neil Ferguson of Imperial College London. But scientists aren’t sure why certain people weather Covid-19 unscathed. “That is a tremendous mystery at this point,” says Donald Thea, an infectious disease expert at Boston University’s School of Public Health.
The prevailing theory is that their immune systems fight off the virus so efficiently that they never get sick. But some scientists are confident that the immune system’s aggressive response, the churning out of antibodies and other molecules to eliminate an infection, is only part of the story.
These experts are learning that the human body may not always wage an all-out war on viruses and other pathogens. It may also be capable of accommodating an infection, sometimes so seamlessly that no symptoms emerge. This phenomenon, known as disease tolerance, is well-known in plants but has only been documented in animals within the last 15 years.
Disease tolerance is the ability of an individual, due to a genetic predisposition or some aspect of behavior or lifestyle, to thrive despite being infected with an amount of pathogen that sickens others. Tolerance takes different forms, depending on the infection. For example, when infected with cholera, which causes watery diarrhea that can quickly kill through dehydration, the body might mobilize mechanisms that maintain fluid and electrolyte balance. During other infections, the body might tweak metabolism or activate gut microbes—whatever internal adjustment is needed to prevent or repair tissue damage or to make a germ less vicious.
Researchers who study these processes rely on invasive experiments that cannot be done in people. Nevertheless, they view asymptomatic infections as evidence that disease tolerance occurs in humans. At least 90 percent of those infected with the tuberculosis bacterium don’t get sick. The same is true for many of the 1.5 billion of people globally who live with parasitic worms called helminths in their intestines. “Despite the fact that these worms are very large organisms and they basically migrate through your tissues and cause damage, many people are asymptomatic. They don’t even know they’re infected,” says Irah King, a professor of immunology at McGill University. “And so then the question becomes, what does the body do to tolerate these types of invasive infections?”
While scientists have observed the physiological processes that minimize tissue damage during infections in animals for decades, it’s only more recently that they’ve begun to think about them in terms of disease tolerance. For example, King and colleagues have identified specific immune cells in mice that increase the resilience of blood vessels during a helminth infection, leading to less intestinal bleeding, even when the same number of worms are present.
“This has been demonstrated in plants, bacteria, other mammalian species,” King says.
“Why would we think that humans would not have developed these types of mechanisms to promote and maintain our health in the face of infection?” he adds.
In a recent Frontiers in Immunology editorial, King and his McGill colleague Maziar Divangahi describe their long-term hopes for the field: A deeper understanding of disease tolerance, they write, could lead to “a new golden age of infectious disease research and discovery.”
Scientists have traditionally viewed germs as the enemy, an approach that has generated invaluable antibiotics and vaccines. But more recently, researchers have come to understand that the human body is colonized by trillions of microbes that are essential to optimal health, and that the relationship between humans and germs is more nuanced.
Meddlesome viruses and bacteria have been around since life began, so it makes sense that animals evolved ways to manage as well as fight them. Attacking a pathogen can be effective, but it can also backfire. For one thing, infectious agents find ways to evade the immune system. Moreover, the immune response itself, if unchecked, can turn lethal, applying its destructive force to the body’s own organs.
“With things like Covid, I think it’s going to be very parallel to TB, where you have this Goldilocks situation,” says Andrew Olive, an immunologist at Michigan State University, “where you need that perfect amount of inflammation to control the virus and not damage the lungs.”
Some of the key disease tolerance mechanisms scientists have identified aim to keep inflammation within that narrow window. For example, immune cells called alveolar macrophages in the lung suppress inflammation once the threat posed by the pathogen diminishes.
Much is still unknown about why there is such a wide range of responses to Covid-19, from asymptomatic to mildly sick to out of commission for weeks at home to full-on organ failure. “It’s very, very early days here,” says Andrew Read, an infectious disease expert at Pennsylvania State University who helped identify disease tolerance in animals. Read believes disease tolerance may at least partially explain why some infected people have mild symptoms or none at all. This may be because they’re better at scavenging toxic byproducts, he says, “or replenishing their lung tissues at faster rates, those sorts of things.”
The mainstream scientific view of asymptomatics is that their immune systems are especially well-tuned. This could explain why children and young adults make up the majority of people without symptoms because the immune system naturally deteriorates with age. It’s also possible that the immune systems of asymptomatics have been primed by a previous infection with a milder coronavirus, like those that cause the common cold.
Asymptomatic cases don’t get much attention from medical researchers, in part because these people don't go to the doctor and thus are tough to track down. But Janelle Ayres, a physiologist and infectious disease expert at the Salk Institute For Biological Studies who has been a leader in disease tolerance research, studies precisely the mice that don't get sick.
The staple of this research is something called the “lethal dose 50” test, which consists of giving a group of mice enough pathogen to kill half. By comparing the mice that live with those that die, she pinpoints the specific aspects of their physiology that enable them to survive the infection. She has performed this experiment scores of times using a variety of pathogens. The goal is to figure out how to activate health-sustaining responses in all animals.
A hallmark of these experiments—and something that surprised her at first—is that the half that survive the lethal dose are perky. They are completely unruffled by the same quantity of pathogen that kills their counterparts. “I thought going into this … that all would get sick, that half would live and half would die, but that isn’t what I found,” Ayres says. “I found that half got sick and died, and the other half never got sick and lived.”
Ayres sees something similar happening in the Covid-19 pandemic. Like her mice, asymptomatics seem to have similar amounts of the virus in their bodies as the people who fall ill, yet for some reason they stay healthy. Studies show that their lungs often display damage on CT scans, yet they are not struggling for breath (though it remains to be seen whether they will fully escape long-term impacts). Moreover, a small recent study suggests that asymptomatics mount a weaker immune response than the people who get sick—suggesting that mechanisms are at work that have nothing to do with fighting infection.
“Why, if they have these abnormalities, are they healthy?” asks Ayres. “Potentially because they have disease tolerance mechanisms engaged. These are the people we need to study.”
The goal of disease tolerance research is to decipher the mechanisms that keep infected people healthy and turn them into therapies that benefit everyone. “You want to have a drought-tolerant plant, for obvious reasons, so why wouldn’t we want to have a virus-tolerant person?” Read asks.
A 2018 experiment in Ayres’ lab offered proof of concept for that goal. The team gave a diarrhea-causing infection to mice in a lethal dose 50 trial, then compared tissue from the mice that died with those that survived, looking for differences. They discovered that the asymptomatic mice had utilized their iron stores to route extra glucose to the hungry bacteria, and that the pacified germs no longer posed a threat. The team subsequently turned this observation into a treatment. In further experiments, they administered iron supplements to the mice and all the animals survived, even when the pathogen dose was upped a thousandfold.
When the pandemic hit, Ayres was already studying mice with pneumonia and the signature malady of Covid-19, acute respiratory distress syndrome, which can be triggered by various infections. Her lab has identified markers that may inform candidate pathways to target for treatment. The next step is to compare people who progressed to severe stages of Covid-19 with asymptomatics to see whether markers emerge that resemble the ones she’s found in mice.
If a medicine is developed, it would work differently from anything that’s currently on the market because it would be lung-specific, not disease-specific, and would ease respiratory distress regardless of which pathogen is responsible.
But intriguing as this prospect is, most experts caution that disease tolerance is a new field and tangible benefits are likely many years off. The work involves measuring not only symptoms but the levels of a pathogen in the body, which means killing an animal and searching all of its tissues. “You can’t really do controlled biological experiments in humans,” Olive says.
In addition, there are countless disease tolerance pathways. “Every time we figure one out, we find we have 10 more things we don’t understand,” King says. Things will differ with each disease, he adds, “so that becomes a bit overwhelming.”
Nevertheless, a growing number of experts agree that disease tolerance research could have profound implications for treating infectious disease in the future. Microbiology and infectious disease research has “all been focused on the pathogen as an invader that has to be eliminated some way,” says virologist Jeremy Luban of the University of Massachusetts Medical School. And as Ayres makes clear, he says, “what we really should be thinking about is how do we keep the person from getting sick.”
This article was originally published on Undark. Read the original article.


scientificamerican--2020-08-25--India Is in Denial about the COVID-19 Crisis

The Indian monsoon season is in full swing , drenching the streets of Mumbai and flooding the plains of Bihar .
But dark clouds of another kind—disease , hunger and death—are also gathering fast .
India is now ahead of all other countries in terms of the number of new recorded COVID-19 cases per day—close to 70,000 in mid-August .
That ’ s about one fourth of world-wide new cases .
Only two countries are anywhere close : Brazil and the United States ; and India has lagged behind those two countries in achieving a reduction in daily cases .
@ @ @ @ @ @ @ likely to be a small fraction of all COVID-19 infections .
That could be true in many countries , but the ratio of infections to recorded cases seems particularly large in India—at least 20:1 , judging from two recent serological surveys , in Delhi and Mumbai respectively .
This would mean that India already had more than 50 million COVID-19 infections , compared with a recorded figure of 2.5 million .
The silver lining is that , for reasons that are as yet unclear , COVID-19 mortality in India seems relatively low .
@ @ @ @ @ @ @ rate ( IFR ) may be as low as one per thousand .
If so , India may not be heading towards a major mortality crisis , or rather a major crisis of COVID-19 mortality , at least relative to normal levels of mortality .
COVID-19 deaths so far add up to less than 1 percent of annual deaths from all causes in India .
Per million population , there have been just 38 so far , compared with more than 500 in the US .
Overall mortality may spike , however , @ @ @ @ @ @ @ health services have been massively displaced by COVID-19 .
So far , COVID-19 infections were heavily concentrated in large cities located in India ’ s more prosperous states : Delhi , Mumbai , Chennai , among others .
The preparedness of the health system is much higher there than elsewhere .
But recorded cases are now rising fast in India ’ s poorer states , where health services are very fragile .
As the COVID-19 crisis absorbs their meager resources , many public health centers have stopped providing routine services .
Even child @ @ @ @ @ @ @ many states .
Consider the state of Bihar .
If Bihar were a separate country , it would be one of the very poorest countries in the world , with a population of more than 100 million .
About half of all children in Bihar are stunted .
COVID-19 was late to reach Bihar , but recorded cases have recently crossed 100,000 and are now rising at 3 to 4 percent per day .
The state has fewer than 40 doctors per 100,000 population , compared with 90 in India and more than @ @ @ @ @ @ @ of life in Bihar ’ s public hospitals paint a grim picture of missing doctors , unattended patients , broken equipment and stray dogs .
Where are people with routine health problems supposed to go ?
The other reason for a possible mortality spike is that India ’ s prolonged national lockdown ( from late March until unlock phases began in June ) has destroyed millions of people ’ s livelihoods .
Local lockdowns continue in many states and are likely to persist off and on for months .
Unlike affluent countries , @ @ @ @ @ @ @ way of a social security system , except for food subsidies and some relief work under the National Rural Employment Guarantee Act .
The employment crisis has already hit poor households really hard : recent surveys by Dalberg , Azim Premji University , the Center for the Study of Developing Societies ( CSDS ) and others reveal extreme food insecurity during and after the lockdown .
Just to cite one , 78 percent of the 25,000 respondents in the nationwide CSDS survey said that they had found it “ quite difficult ” or @ @ @ @ @ @ @ families during the lockdown .
Acute food insecurity is very likely to translate into higher mortality .
For children , it also means lasting damage from malnutrition .
To invoke Bihar again , more than half of the workforce there consists of casual laborers who live on the margin of subsistence at the best of times .
A recent survey of some 20,000 returning migrant workers found that 60 percent were unable to ensure two square meals for all members of the family .
With the local economy in the doldrums , except @ @ @ @ @ @ @ for a prolonged period of underemployment and hunger .
For good measure , Bihar is affected by devastating floods , as often happens at this time of the year .
Yet the state government seems more preoccupied with the coming assembly elections than with these multiple crises .
The situation is not much better in other poverty-stricken states of India such as Jharkhand , Uttar Pradesh and West Bengal .
With tax revenue a fraction of normal levels , state governments are finding it difficult to provide more than symbolic relief .
Alas @ @ @ @ @ @ @ to help them .
It did launch some limited relief measures during the national lockdown , such as free food-grain rations of five kilograms per person per month for two thirds of India ’ s population .
But now it seems to have lost interest and left it to the state governments to handle the crisis .
In this as in other domains , the Indian government seems more focused on public relations than enlightened action .
For a long time , it forcefully denied any “ community transmission ” of COVID-19 , @ @ @ @ @ @ @ millions .
When an early analysis of official data exposed the disruption of routine health services , the central government retracted the data .
Doctors and nurses critical of the government ’ s crisis response have been muzzled or harassed , as have many journalists .
Muddled statistics are routinely invoked to reassure the public that all is well : the Ministry of Health recently boasted , for instance , that COVID-19 recoveries had “ crossed the historic peak of 1.5 million ” —a meaningless achievement since COVID-19 has a recovery rate of @ @ @ @ @ @ @ In its hurry to turn India into a viswaguru ( world leader ) , the Modi government seems to have little patience for a humanitarian crisis .
Yet denying a crisis is the surest way to make it worse .

The Indian monsoon season is in full swing, drenching the streets of Mumbai and flooding the plains of Bihar. But dark clouds of another kind—disease, hunger and death—are also gathering fast.
India is now ahead of all other countries in terms of the number of new recorded COVID-19 cases per day—close to 70,000 in mid-August. That’s about one fourth of world-wide new cases. Only two countries are anywhere close: Brazil and the United States; and India has lagged behind those two countries in achieving a reduction in daily cases.
Further, recorded cases in India are likely to be a small fraction of all COVID-19 infections. That could be true in many countries, but the ratio of infections to recorded cases seems particularly large in India—at least 20:1, judging from two recent serological surveys, in Delhi and Mumbai respectively. This would mean that India already had more than 50 million COVID-19 infections, compared with a recorded figure of 2.5 million.
The silver lining is that, for reasons that are as yet unclear, COVID-19 mortality in India seems relatively low. The same surveys suggest that the infection-fatality rate (IFR) may be as low as one per thousand. If so, India may not be heading towards a major mortality crisis, or rather a major crisis of COVID-19 mortality, at least relative to normal levels of mortality. COVID-19 deaths so far add up to less than 1 percent of annual deaths from all causes in India. Per million population, there have been just 38 so far, compared with more than 500 in the US.
Overall mortality may spike, however, for two reasons. First, routine health services have been massively displaced by COVID-19. So far, COVID-19 infections were heavily concentrated in large cities located in India’s more prosperous states: Delhi, Mumbai, Chennai, among others. The preparedness of the health system is much higher there than elsewhere. But recorded cases are now rising fast in India’s poorer states, where health services are very fragile. As the COVID-19 crisis absorbs their meager resources, many public health centers have stopped providing routine services. Even child immunization has been discontinued for months in many states.
Consider the state of Bihar. If Bihar were a separate country, it would be one of the very poorest countries in the world, with a population of more than 100 million. About half of all children in Bihar are stunted. COVID-19 was late to reach Bihar, but recorded cases have recently crossed 100,000 and are now rising at 3 to 4 percent per day. The state has fewer than 40 doctors per 100,000 population, compared with 90 in India and more than 250 in the US. Firsthand accounts of life in Bihar’s public hospitals paint a grim picture of missing doctors, unattended patients, broken equipment and stray dogs. Where are people with routine health problems supposed to go?
The other reason for a possible mortality spike is that India’s prolonged national lockdown (from late March until unlock phases began in June) has destroyed millions of people’s livelihoods. Local lockdowns continue in many states and are likely to persist off and on for months. Unlike affluent countries, India has very little to show by way of a social security system, except for food subsidies and some relief work under the National Rural Employment Guarantee Act. The employment crisis has already hit poor households really hard: recent surveys by Dalberg, Azim Premji University, the Center for the Study of Developing Societies (CSDS) and others reveal extreme food insecurity during and after the lockdown. Just to cite one, 78 percent of the 25,000 respondents in the nationwide CSDS survey said that they had found it “quite difficult” or “very difficult” to feed their families during the lockdown. Acute food insecurity is very likely to translate into higher mortality. For children, it also means lasting damage from malnutrition.
To invoke Bihar again, more than half of the workforce there consists of casual laborers who live on the margin of subsistence at the best of times. A recent survey of some 20,000 returning migrant workers found that 60 percent were unable to ensure two square meals for all members of the family. With the local economy in the doldrums, except for farming, casual workers are heading for a prolonged period of underemployment and hunger. For good measure, Bihar is affected by devastating floods, as often happens at this time of the year. Yet the state government seems more preoccupied with the coming assembly elections than with these multiple crises.
The situation is not much better in other poverty-stricken states of India such as Jharkhand, Uttar Pradesh and West Bengal. With tax revenue a fraction of normal levels, state governments are finding it difficult to provide more than symbolic relief. Alas, the central government is doing little to help them. It did launch some limited relief measures during the national lockdown, such as free food-grain rations of five kilograms per person per month for two thirds of India’s population. But now it seems to have lost interest and left it to the state governments to handle the crisis.
In this as in other domains, the Indian government seems more focused on public relations than enlightened action. For a long time, it forcefully denied any “community transmission” of COVID-19, even as recorded cases were counted in millions. When an early analysis of official data exposed the disruption of routine health services, the central government retracted the data. Doctors and nurses critical of the government’s crisis response have been muzzled or harassed, as have many journalists. Muddled statistics are routinely invoked to reassure the public that all is well: the Ministry of Health recently boasted, for instance, that COVID-19 recoveries had “crossed the historic peak of 1.5 million”—a meaningless achievement since COVID-19 has a recovery rate of more than 99 percent in India.
In its hurry to turn India into a viswaguru (world leader), the Modi government seems to have little patience for a humanitarian crisis. Yet denying a crisis is the surest way to make it worse.


scientificamerican--2020-08-24--Evidence for Convalescent Plasma Coronavirus Treatment Lags behind Excitement

Update August 24 : The US Food and Drug Administration issued an emergency-use authorization on August 23 to treat COVID-19 with convalescent plasma .
US President Donald Trump has called on COVID-19 survivors to donate their blood plasma as a treatment for the disease , saying that “ it ’ s had tremendous response so far ” .
Meanwhile , rumours have been swirling that US drug regulators are grappling with whether to give the plasma to more people by authorizing it as an emergency therapy .
But researchers and clinicians around the world are concerned that a push to @ @ @ @ @ @ @ trials needed to determine whether it actually works against COVID-19 .
Although some US hospitals already offer the treatment in special cases , an emergency-use authorization from the Food and Drug Administration ( FDA ) would make it easier to obtain and administer convalescent plasma — the yellow liquid that remains after cells are removed from blood .
But so far , there ’ s little evidence that plasma actually helps patients , and the decision could confound efforts to study its effects , says former FDA commissioner Robert Califf , who now @ @ @ @ @ @ @ and Google Health in South San Francisco , California .
The antiviral drug remdesivir and the anti-inflammatory medicine dexamethasone are the only treatments that have been shown to combat COVID-19 in rigorous clinical trials .
Convalescent plasma has been tested only in small trials without the statistical power to provide firm conclusions .
The FDA did n't respond to queries from Nature about where things stand with its decision to authorize convalescent plasma .
But if the FDA issues an authorization , experts say , people with COVID-19 might choose to access the @ @ @ @ @ @ @ for a clinical trial and risk being assigned to a control group that does not receive plasma .
“ It ’ s a potential therapy that could work , and I don ’ t think it ’ s out of bounds to make it available ” with an authorization , says Califf .
“ But we ought to be really emphasizing in public-service announcements that participation in randomized trials is a first priority.
” For more than a century , doctors have used the convalescent plasma of donors recovering from infections to treat @ @ @ @ @ @ @ Ebola and Middle East respiratory syndrome ( MERS ) , which is also caused by a coronavirus .
The idea is that plasma contains antibodies and proteins involved in regulating immune responses .
And some of these antibodies might have helped the donor to recover from their infection — so giving it to infected people could kick-start their recovery .
Although there have been few data on whether convalescent plasma definitely improves outcomes for people with other diseases , it was logical to test the treatment against COVID-19 when the outbreak began .
@ @ @ @ @ @ @ its effectiveness in the middle of the pandemic , says Michael Joyner , an anaesthesiologist at Mayo Clinic in Rochester , Minnesota .
For one thing , convalescent plasma from different people varies widely in antibody concentration , making it challenging to study .
At first , researchers had no way to measure and standardize the level of antibodies in each batch .
Even now , researchers in some parts of the world are not able to test whether plasma contains powerful ‘ neutralizing antibodies ’ , which can prevent viral replication , @ @ @ @ @ @ @ certain containment procedures , says infectious-disease specialist Fazle Chowdhury at the Bangabandhu Sheikh Mujib Medical University in Dhaka .
Collecting rigorous clinical-trial data has also been difficult because doctors have been administering convalescent plasma to severely ill people on a ‘ compassionate use ’ basis .
In the United States , a special programme funded by the Biomedical Advanced Research and Development Authority ( BARDA ) has provided convalescent plasma on this basis to more than 66,000 people — without running any control groups .
The programme ’ s investigators — including Joyner @ @ @ @ @ @ @ published results from 5,000 people with severe COVID-19 , suggesting that the therapy is broadly safe .
“ We really don ’ t know what is happening when you use it on a compassionate basis , ” says Chowdhury .
“ If we use convalescent plasma , it should be under clinical trial.
” US researchers have complained that the BARDA-funded project has siphoned away potential participants and plasma donors from randomized clinical trials that would produce more rigorous data .
In the absence of a control group , Joyner and his colleagues @ @ @ @ @ @ @ the concentration of SARS-CoV-2 antibodies was not standardized .
The team looked at more than 35,000 plasma recipients , and compared results from those who received plasma with relatively low levels of antibodies with findings from people who got plasma with higher levels .
The study , published on the medRxiv preprint server before peer review , found that participants who received transfusions soon after their diagnosis and got high concentrations of antibodies showed more improvement and were less likely to die in the study period than were those who received later transfusions @ @ @ @ @ @ @ was an extremely important finding , ” says Cassandra Josephson , a paediatrician at Emory University in Atlanta , Georgia , who has been treating children who have COVID-19 .
But the lack of randomization makes it difficult to draw a firm conclusion from the study , cautions Anthony Gordon , an anaesthetist at Imperial College London .
For example , patients who received the treatment soon after diagnosis may have been treated at medical centres that provided better health care , he says , raising their chance of a better outcome .
@ @ @ @ @ @ @ association , ” he says .
“ We ’ re not seeing cause and effect.
” In lieu of conventional large clinical trials with statistical power , some researchers are trying to piece together evidence from smaller tests .
Another not-yet peer-reviewed preprint by Joyner and his colleagues , published on medRxiv on 30 July , compiles data from more than 800 participants across a dozen studies — in the hope of boosting statistical power .
The team found that the treatment cut mortality from 26 % to 13 % .
But it @ @ @ @ @ @ @ conclusion from data combined from disparate studies , cautions Josephson .
The trials treated people with varying disease severity , using different doses of plasma and tracking a range of measures of success .
“ There are a lot of things to pick apart ” about the analysis , says Josephson .
At the same time , it ’ s not without value .
“ We had nothing before except for safety data.
” And there are still data to come .
In the United Kingdom , epidemiologist Martin Landray and infectious-disease researcher @ @ @ @ @ @ @ of Oxford , are leading the large RECOVERY trial , which is testing several therapies , including convalescent plasma , in people hospitalized with COVID-19 .
And Gordon and his colleagues are testing convalescent plasma in people in intensive care , in an international trial called REMAP-CAP .
But the first surge of the pandemic in the United Kingdom has largely passed , so Landray says that he does not expect to have results until later in the year , when some epidemiological models predict COVID-19 cases will rise again .
In the @ @ @ @ @ @ @ team is stockpiling plasma from donors , to deploy rapidly if that surge arrives .
Landray cautions against assuming that convalescent plasma works until the data are in .
“ We have seen in this epidemic just how wrong well-meaning scientific hypotheses can be , ” he says , pointing to hydroxychloroquine as an example .
The malaria drug showed promise against COVID-19 in small , early trials and laboratory studies , but was eventually shown not to have an effect on the disease .
“ There is good science behind convalescent plasma @ @ @ @ @ @ @ it may turn out to be an effective treatment , ” Landray says .
“ But the bottom line is that we don ’ t have enough data to know.
” This article is reproduced with permission and was first published on August 19 , 2020 .
Read more about the coronavirus outbreak from Scientific American here .
And read coverage from our international network of magazines here .

Update August 24: The US Food and Drug Administration issued an emergency-use authorization on August 23 to treat COVID-19 with convalescent plasma.
US President Donald Trump has called on COVID-19 survivors to donate their blood plasma as a treatment for the disease, saying that “it’s had tremendous response so far”. Meanwhile, rumours have been swirling that US drug regulators are grappling with whether to give the plasma to more people by authorizing it as an emergency therapy. But researchers and clinicians around the world are concerned that a push to distribute blood plasma could undermine the clinical trials needed to determine whether it actually works against COVID-19.
Although some US hospitals already offer the treatment in special cases, an emergency-use authorization from the Food and Drug Administration (FDA) would make it easier to obtain and administer convalescent plasma — the yellow liquid that remains after cells are removed from blood.
But so far, there’s little evidence that plasma actually helps patients, and the decision could confound efforts to study its effects, says former FDA commissioner Robert Califf, who now heads clinical policy and strategy at Verily and Google Health in South San Francisco, California. The antiviral drug remdesivir and the anti-inflammatory medicine dexamethasone are the only treatments that have been shown to combat COVID-19 in rigorous clinical trials.
Convalescent plasma has been tested only in small trials without the statistical power to provide firm conclusions. The FDA didn't respond to queries from Nature about where things stand with its decision to authorize convalescent plasma. But if the FDA issues an authorization, experts say, people with COVID-19 might choose to access the treatment directly, rather than sign up for a clinical trial and risk being assigned to a control group that does not receive plasma.
“It’s a potential therapy that could work, and I don’t think it’s out of bounds to make it available” with an authorization, says Califf. “But we ought to be really emphasizing in public-service announcements that participation in randomized trials is a first priority.”
Data shortage
For more than a century, doctors have used the convalescent plasma of donors recovering from infections to treat others with the same disease, including Ebola and Middle East respiratory syndrome (MERS), which is also caused by a coronavirus. The idea is that plasma contains antibodies and proteins involved in regulating immune responses. And some of these antibodies might have helped the donor to recover from their infection — so giving it to infected people could kick-start their recovery. Although there have been few data on whether convalescent plasma definitely improves outcomes for people with other diseases, it was logical to test the treatment against COVID-19 when the outbreak began. But researchers have struggled to nail down its effectiveness in the middle of the pandemic, says Michael Joyner, an anaesthesiologist at Mayo Clinic in Rochester, Minnesota.
For one thing, convalescent plasma from different people varies widely in antibody concentration, making it challenging to study. At first, researchers had no way to measure and standardize the level of antibodies in each batch. Even now, researchers in some parts of the world are not able to test whether plasma contains powerful ‘neutralizing antibodies’, which can prevent viral replication, because the assay is expensive and requires certain containment procedures, says infectious-disease specialist Fazle Chowdhury at the Bangabandhu Sheikh Mujib Medical University in Dhaka.
Collecting rigorous clinical-trial data has also been difficult because doctors have been administering convalescent plasma to severely ill people on a ‘compassionate use’ basis. In the United States, a special programme funded by the Biomedical Advanced Research and Development Authority (BARDA) has provided convalescent plasma on this basis to more than 66,000 people — without running any control groups. The programme’s investigators — including Joyner — have been gathering data and have published results from 5,000 people with severe COVID-19, suggesting that the therapy is broadly safe.
“We really don’t know what is happening when you use it on a compassionate basis,” says Chowdhury. “If we use convalescent plasma, it should be under clinical trial.” US researchers have complained that the BARDA-funded project has siphoned away potential participants and plasma donors from randomized clinical trials that would produce more rigorous data.
In the absence of a control group, Joyner and his colleagues have taken advantage of the fact that the concentration of SARS-CoV-2 antibodies was not standardized. The team looked at more than 35,000 plasma recipients, and compared results from those who received plasma with relatively low levels of antibodies with findings from people who got plasma with higher levels. The study, published on the medRxiv preprint server before peer review, found that participants who received transfusions soon after their diagnosis and got high concentrations of antibodies showed more improvement and were less likely to die in the study period than were those who received later transfusions with lower antibody concentrations. “This was an extremely important finding,” says Cassandra Josephson, a paediatrician at Emory University in Atlanta, Georgia, who has been treating children who have COVID-19.
But the lack of randomization makes it difficult to draw a firm conclusion from the study, cautions Anthony Gordon, an anaesthetist at Imperial College London. For example, patients who received the treatment soon after diagnosis may have been treated at medical centres that provided better health care, he says, raising their chance of a better outcome. “We’re just seeing an association,” he says. “We’re not seeing cause and effect.”
Filling in the gaps
In lieu of conventional large clinical trials with statistical power, some researchers are trying to piece together evidence from smaller tests. Another not-yet peer-reviewed preprint by Joyner and his colleagues, published on medRxiv on 30 July, compiles data from more than 800 participants across a dozen studies — in the hope of boosting statistical power. The team found that the treatment cut mortality from 26% to 13%.
But it’s difficult to draw a firm conclusion from data combined from disparate studies, cautions Josephson. The trials treated people with varying disease severity, using different doses of plasma and tracking a range of measures of success. “There are a lot of things to pick apart” about the analysis, says Josephson. At the same time, it’s not without value. “We had nothing before except for safety data.”
And there are still data to come. In the United Kingdom, epidemiologist Martin Landray and infectious-disease researcher Peter Horby, both at the University of Oxford, are leading the large RECOVERY trial, which is testing several therapies, including convalescent plasma, in people hospitalized with COVID-19. And Gordon and his colleagues are testing convalescent plasma in people in intensive care, in an international trial called REMAP-CAP. But the first surge of the pandemic in the United Kingdom has largely passed, so Landray says that he does not expect to have results until later in the year, when some epidemiological models predict COVID-19 cases will rise again. In the meantime, he says, the RECOVERY team is stockpiling plasma from donors, to deploy rapidly if that surge arrives.
Landray cautions against assuming that convalescent plasma works until the data are in. “We have seen in this epidemic just how wrong well-meaning scientific hypotheses can be,” he says, pointing to hydroxychloroquine as an example. The malaria drug showed promise against COVID-19 in small, early trials and laboratory studies, but was eventually shown not to have an effect on the disease.
“There is good science behind convalescent plasma and a good reason for thinking that it may turn out to be an effective treatment,” Landray says. “But the bottom line is that we don’t have enough data to know.”
This article is reproduced with permission and was first published on August 19, 2020.
Read more about the coronavirus outbreak from Scientific American here. And read coverage from our international network of magazines here.


scientificamerican--2020-08-28--Cells Solve an English Hedge Maze with the Same Skills They Use to Traverse the Body

From the embryonic stages to late life , cells often make incredible journeys , sometimes even traversing an entire organism .
They reach their destination by chemotaxis , following signals that lead them to the goal like a chemical yellow brick road .
The catch is that different levels , or gradients , of a chemical drawing cells to a target only work over short distances .
What guides them over the hills and valleys of a longer journey through the body has been unclear .
Findings reported on August 27 in Science show how two kinds of cells—one a @ @ @ @ @ @ @ cancer cell line—manage these seemingly impossible journeys .
The key is that the cells do not work along a preexisting gradient but create one themselves by breaking down the chemical lure as they encounter it .
Like gathering string while finding one ’ s way out of a labyrinth , the chemical-free path they leave behind keeps them binding to—and following—the guide in front of them .
Take melanoma cells , which are among the most avidly metastasizing tumor cells .
Once they have broken down a chemoattractant called lysophosphatidic acid locally in @ @ @ @ @ @ @ levels of the molecule away from the tumor .
The cells forge a path into the bloodstream , where lysophosphatidic acid is relatively uniformly distributed .
The melanoma cells break the chemical down as they go , leaving a high concentration of it in front of them that they follow and consume , Pac-Man-like , whereas low levels remain behind .
The research team confirmed the use of this tactic in both an amoeba and a mammalian cell line , suggesting a commonality among cells engaged in long-distance orienteering .
That outcome “ @ @ @ @ @ @ @ gradients are a universal mechanism for steering directional migration of groups of cells for long distances , ” says Pablo Sáez , a professor and group leader in the department of biochemistry and molecular cell biology at the University Medical Center Hamburg–Eppendorf in Germany , who was not involved in the work .
He adds that the result highlights the usefulness of some of the techniques the researchers used , including mathematical modeling to predict how the cells might behave and employing mazes to test those predictions .
In navigating real mazes , @ @ @ @ @ @ @ purple ) , creating a gradient that left more of it ahead and less of it behind .
This high-to-low gradient drew the Pac-Man-like cells forward .
Credit : Luke Tweedy , Michele Zagnoni and Cancer Research UK .
In fact , Luke Tweedy , a postdoctoral research associate at the Beatson Institute for Cancer Research in Scotland and his colleagues reasoned that following a winding path through the complex topography of an organism might be a lot like navigating a labyrinth .
To test their idea , they used two kinds of @ @ @ @ @ @ @ or “ Dicty ” for short , and mouse pancreatic cancer cells .
Dicty cells were especially of interest because of their tendency to break down the chemical yellow brick road as they travel it so that the right path is always before them .
With this tendency to “ gather string ” as it moves along , Dicty was an exemplary candidate for maze solving—a “ chemotactic prodigy , ” as Tweedy puts it .
Tweedy and his colleagues found that Dicty lived up to its reputation , rapidly solving a complex @ @ @ @ @ @ @ the tortoiselike pancreatic cancer cells several days .
The researchers tested the cells in a lot of different mazes , some with shorter versus longer dead ends and different forks .
When cells faced a choice between a dead end and a true path , a few wayward ones would dispatch all of the chemoattractant trapped in the cul-de-sac , and the rest of them would orient to the other fork that was still flowing with the alluring molecules .
The most memorable test the investigators used was the one they modeled on @ @ @ @ @ @ @ near London .
They chose it , Tweedy says , for the “ razzle-dazzle ” and to “ capture the imagination.
” Dicty , the prodigy protist , not only solved this maze but also managed to use its self-generating gradient skills to find a shortcut .
Using math to predict cell behavior could have implications for human conditions that involve migrating cells .
An example is human cancer cells that have something in common with amoebas , Tweedy says—whether that connection involves the normal migration of immune cells or the pathological journey @ @ @ @ @ @ @ the same fundamental mechanism of migration , [ in which ] receptors detect attractants and guide the cytoskeleton to move the cell.
” In fact , the similarities are strong enough that Tweedy sees many ways to bridge the amoeba-human-cell gap , including applying maze-solving ideas to predicting the path that the cancer cells of glioblastoma follow .
The results could also offer a rare window into some early processes in mammalian embryos .
The cells that eventually set up shop in the gonads start far away from their target early in an @ @ @ @ @ @ @ germ cells have to move over embryonic hill and dale to get to the appropriate destination .
If the behavior of Dicty or the much slower pancreatic cancer cells is universal , then these germ cells may use a similar tactic to get to the future gonads and avoid taking a wrong turn toward , say , the gut .
The implication is that building complex organisms sometimes means that cells only get where they are going by making their own way .

From the embryonic stages to late life, cells often make incredible journeys, sometimes even traversing an entire organism. They reach their destination by chemotaxis, following signals that lead them to the goal like a chemical yellow brick road. The catch is that different levels, or gradients, of a chemical drawing cells to a target only work over short distances. What guides them over the hills and valleys of a longer journey through the body has been unclear.
Findings reported on August 27 in Science show how two kinds of cells—one a dirt-dwelling amoeba and the other a mouse cancer cell line—manage these seemingly impossible journeys. The key is that the cells do not work along a preexisting gradient but create one themselves by breaking down the chemical lure as they encounter it. Like gathering string while finding one’s way out of a labyrinth, the chemical-free path they leave behind keeps them binding to—and following—the guide in front of them.
Take melanoma cells, which are among the most avidly metastasizing tumor cells. Once they have broken down a chemoattractant called lysophosphatidic acid locally in the tumor, they move toward higher levels of the molecule away from the tumor. The cells forge a path into the bloodstream, where lysophosphatidic acid is relatively uniformly distributed. The melanoma cells break the chemical down as they go, leaving a high concentration of it in front of them that they follow and consume, Pac-Man-like, whereas low levels remain behind.
The research team confirmed the use of this tactic in both an amoeba and a mammalian cell line, suggesting a commonality among cells engaged in long-distance orienteering. That outcome “is really interesting and demonstrates that self-generated gradients are a universal mechanism for steering directional migration of groups of cells for long distances,” says Pablo Sáez, a professor and group leader in the department of biochemistry and molecular cell biology at the University Medical Center Hamburg–Eppendorf in Germany, who was not involved in the work. He adds that the result highlights the usefulness of some of the techniques the researchers used, including mathematical modeling to predict how the cells might behave and employing mazes to test those predictions.
In fact, Luke Tweedy, a postdoctoral research associate at the Beatson Institute for Cancer Research in Scotland and his colleagues reasoned that following a winding path through the complex topography of an organism might be a lot like navigating a labyrinth. To test their idea, they used two kinds of cells: the amoeba Dictyostelium discoideum, or “Dicty” for short, and mouse pancreatic cancer cells. Dicty cells were especially of interest because of their proficiency at breaking down the chemical yellow brick road as they travel it so that the right path is always before them. With this tendency to “gather string” as it moves along, Dicty was an exemplary candidate for maze solving—a “chemotactic prodigy,” as Tweedy puts it.
Tweedy and his colleagues found that Dicty lived up to its reputation, rapidly solving a complex maze in an hour that could take the tortoiselike pancreatic cancer cells several days. The researchers tested the cells in a lot of different mazes, some with shorter versus longer dead ends and different forks. When cells faced a choice between a dead end and a true path, a few wayward ones would dispatch all of the chemoattractant trapped in the cul-de-sac, and the rest of them would orient to the other fork that was still flowing with the alluring molecules.
The most memorable test the investigators used was the one they modeled on the famous maze at Hampton Court Palace near London. They chose it, Tweedy says, for the “razzle-dazzle” and to “capture the imagination.” Dicty, the prodigy protist, not only solved this maze but also managed to use its self-generating gradient skills to find a shortcut.
Researchers also brought in computational models to predict cell behavior, which could have implications for human conditions that involve migrating cells. An example is human cancer cells that have something in common with amoebas—whether that connection involves the normal migration of immune cells or the pathological journey of metastatic cancer cells “They use the same fundamental mechanism of migration, [in which] receptors detect attractants and guide the cytoskeleton to move the cell.”
In fact, the similarities are strong enough that Tweedy sees many ways to bridge the amoeba-human-cell gap, including applying maze-solving ideas to predicting the path that the cancer cells of glioblastoma follow.
The results could also offer a rare window into some early processes in mammalian embryos. The cells that eventually set up shop in the gonads start far away from their target early in an embryo’s development. These so-called germ cells have to move over embryonic hill and dale to get to the appropriate destination. If the behavior of Dicty or the much slower pancreatic cancer cells is universal, then these germ cells may use a similar tactic to get to the future gonads and avoid taking a wrong turn toward, say, the gut. The implication is that building complex organisms sometimes means that cells only get where they are going by making their own way.
A version of this article with the title “Cells in a Maze” was adapted for inclusion in the November 2020 issue of Scientific American.


scientificamerican--2020-08-28--The Problem with Implicit Bias Training

The Problem with Implicit Bias Training

While the nation roils with ongoing protests against police violence and persistent societal racism , many organizations have released statements promising to do better .
These promises often include improvements to hiring practices ; a priority on retaining and promoting people of color ; and pledges to better serve those people as customers and clients .
As these organizations work to make good on their declarations , implicit bias training is often at the top of the list .
As the thinking goes , these nonconscious prejudices and stereotypes are spontaneously and automatically activated and may inadvertently affect how white @ @ @ @ @ @ @ other people of color .
The hope is that , with proper training , people can learn to recognize and correct this damaging form of bias .
In the health care industry , implicit bias is among the likely culprits in many persistent racial and ethnic disparities , like infant and maternal mortality , chronic diseases such as diabetes , and more recently , COVID-19 .
Black Americans are about 2.5 times more likely to die from COVID-19 relative to whites , and emerging data indicate that Native Americans are also disproportionately suffering @ @ @ @ @ @ @ impact the ways in which clinicians and other health care professionals diagnose and treat people of color , leading to worse outcomes .
In response to these disparities , Michigan and California have mandated implicit bias training for some health professionals .
There ’ s just one problem .
We just don ’ t have the evidence yet that implicit bias training actually works .
To be sure , finding ways to counter unfair treatment is critical .
The evidence is clear that implicit prejudice , an affective component of implicit bias ( @ @ @ @ @ @ @ among health care providers with respect to Black and/or Latinx patients , as well as to dark-skinned patients not in those categories .
In turn , these biases lower the quality of patient-provider communication and result in lower satisfaction with the healthcare encounter .
But while implicit bias trainings are multiplying , few rigorous evaluations of these programs exist .
There are exceptions ; some implicit bias interventions have been conducted empirically among health care professionals and college students .
These interventions have been proven to lower scores on the Implicit Association Test @ @ @ @ @ @ @ used implicit measure of prejudice and stereotyping .
But to date , none of these interventions has been shown to result in permanent , long-term reductions of implicit bias scores or , more importantly , sustained and meaningful changes in behavior ( i.e.
, narrowing of racial/ethnic clinical treatment disparities ) .
Even worse , there is consistent evidence that bias training done the “ wrong way ” ( think lukewarm diversity training ) can actually have the opposite impact , inducing anger and frustration among white employees .
What this all means @ @ @ @ @ @ @ for implicit bias training , it will likely be ineffective at best ; at worst , it ’ s a poor use of limited resources that could cause more damage and exacerbate the very issues it is trying to solve .
So , what should we do ?
The first thing is to realize that racism is not just an individual problem requiring an individual intervention , but a structural and organizational problem that will require a lot of work to change .
It ’ s much easier for organizations to offer an @ @ @ @ @ @ @ long , hard look and overhaul the way they operate .
The reality is , even if we could reliably reduce individual-level bias , various forms of institutional racism embedded in health care ( and other organizations ) would likely make these improvements hard to maintain .
Explicit , uncritical racial stereotyping in medicine is one good example .
We have known for many years that race is a social construct rather than a proxy for genetic or biological differences .
Even so , recent work has identified numerous cases of race-adjusted clinical @ @ @ @ @ @ @ for example , race adjustments that make it appear as if Black patients have better kidney function than they actually do can potentially lead to worse outcomes such as delays in referral for needed specialist care or kidney transplantation .
Other more insidious stereotyping characterizes Native Americans and African Americans as more likely to be “ noncompliant ” with diet and lifestyle advice .
These characterizations of noncompliance as a function of attitudes and practices completely ignore structural factors such as poverty , segregation and marketing—factors that create health inequities in the first @ @ @ @ @ @ @ and institutional levels takes longer than a few days of implicit bias training .
But there are encouraging examples of individuals who have fought successfully for structural change within their health care organizations .
For example , medical students at the University of Washington successfully lobbied for race to be removed as a criterion for determining kidney function—a process that took many years .
Their success may have important implications for closing gaps in disparities among patients with renal disease .
And innovative new programs like the Mid-Ohio Farmacy have linked health care @ @ @ @ @ @ @ providers address food insecurity among their low-income patients—an issue that disproportionately impacts people of color .
( Doctors can write a “ food prescription ” that allows their patients to purchase fresh produce . )
None of this , of course , means that we should give up on trying to understand implicit bias or developing evidence-based training that successfully reduces discriminatory behaviors at the individual level .
What it does mean is that we need to lean into the hard work of auditing long-standing practices that unfairly stigmatize people of color and @ @ @ @ @ @ @ inequities evolve .
Creating organizations that value equity and ultimately produce better outcomes for people of color will be long , hard work , but it ’ s necessary and it ’ s been a long time coming .

While the nation roils with ongoing protests against police violence and persistent societal racism, many organizations have released statements promising to do better. These promises often include improvements to hiring practices; a priority on retaining and promoting people of color; and pledges to better serve those people as customers and clients.
As these organizations work to make good on their declarations, implicit bias training is often at the top of the list. As the thinking goes, these nonconscious prejudices and stereotypes are spontaneously and automatically activated and may inadvertently affect how white Americans see and treat Black people and other people of color. The hope is that, with proper training, people can learn to recognize and correct this damaging form of bias.
In the health care industry, implicit bias is among the likely culprits in many persistent racial and ethnic disparities, like infant and maternal mortality, chronic diseases such as diabetes, and more recently, COVID-19. Black Americans are about 2.5 times more likely to die from COVID-19 relative to whites, and emerging data indicate that Native Americans are also disproportionately suffering from the pandemic. Implicit biases may impact the ways in which clinicians and other health care professionals diagnose and treat people of color, leading to worse outcomes. In response to these disparities, Michigan and California have mandated implicit bias training for some health professionals.
There’s just one problem. We just don’t have the evidence yet that implicit bias training actually works.
To be sure, finding ways to counter unfair treatment is critical. The evidence is clear that implicit prejudice, an affective component of implicit bias (i.e., feeling or emotion) exists among health care providers with respect to Black and/or Latinx patients, as well as to dark-skinned patients not in those categories. In turn, these biases lower the quality of patient-provider communication and result in lower satisfaction with the healthcare encounter.
But while implicit bias trainings are multiplying, few rigorous evaluations of these programs exist. There are exceptions; some implicit bias interventions have been conducted empirically among health care professionals and college students. These interventions have been proven to lower scores on the Implicit Association Test (IAT), the most commonly used implicit measure of prejudice and stereotyping. But to date, none of these interventions has been shown to result in permanent, long-term reductions of implicit bias scores or, more importantly, sustained and meaningful changes in behavior (i.e., narrowing of racial/ethnic clinical treatment disparities).
Even worse, there is consistent evidence that bias training done the “wrong way” (think lukewarm diversity training) can actually have the opposite impact, inducing anger and frustration among white employees. What this all means is that, despite the widespread calls for implicit bias training, it will likely be ineffective at best; at worst, it’s a poor use of limited resources that could cause more damage and exacerbate the very issues it is trying to solve.
So, what should we do? The first thing is to realize that racism is not just an individual problem requiring an individual intervention, but a structural and organizational problem that will require a lot of work to change. It’s much easier for organizations to offer an implicit bias training than to take a long, hard look and overhaul the way they operate. The reality is, even if we could reliably reduce individual-level bias, various forms of institutional racism embedded in health care (and other organizations) would likely make these improvements hard to maintain.
Explicit, uncritical racial stereotyping in medicine is one good example. We have known for many years that race is a social construct rather than a proxy for genetic or biological differences. Even so, recent work has identified numerous cases of race-adjusted clinical algorithms in medicine. In nephrology, for example, race adjustments that make it appear as if Black patients have better kidney function than they actually do can potentially lead to worse outcomes such as delays in referral for needed specialist care or kidney transplantation. Other more insidious stereotyping characterizes Native Americans and African Americans as more likely to be “noncompliant” with diet and lifestyle advice. These characterizations of noncompliance as a function of attitudes and practices completely ignore structural factors such as poverty, segregation and marketing—factors that create health inequities in the first place.
Meaningful progress at the structural and institutional levels takes longer than a few days of implicit bias training. But there are encouraging examples of individuals who have fought successfully for structural change within their health care organizations. For example, medical students at the University of Washington successfully lobbied for race to be removed as a criterion for determining kidney function—a process that took many years. Their success may have important implications for closing gaps in disparities among patients with renal disease. And innovative new programs like the Mid-Ohio Farmacy have linked health care providers with community-based organizations, and help providers address food insecurity among their low-income patients—an issue that disproportionately impacts people of color. (Doctors can write a “food prescription” that allows their patients to purchase fresh produce.)
None of this, of course, means that we should give up on trying to understand implicit bias or developing evidence-based training that successfully reduces discriminatory behaviors at the individual level. What it does mean is that we need to lean into the hard work of auditing long-standing practices that unfairly stigmatize people of color and fail to take into account how health inequities evolve. Creating organizations that value equity and ultimately produce better outcomes for people of color will be long, hard work, but it’s necessary and it’s been a long time coming.


scientificamerican--2020-08-28--Cheap, Self-Powered Fire Sensor Could Sound an Early Alarm

Wildfires have recently devastated regions across the world , and their severity is increasing .
Hoping to reduce harm , researchers led by Yapei Wang , a chemist at Renmin University of China , say they have developed an inexpensive sensor to detect such blazes earlier and with less effort .
Current detection methods rely heavily on human watchfulness , which can delay an effective response .
Most wildfires are reported by the general public , and other alerts come from routine foot patrols and watchtower observers .
Passing planes and satellites also occasionally spot something , but “ the @ @ @ @ @ @ @ ground , ” Wang says .
“ When [ you see ] the fire from the sky … it is too late.
” The team says its new sensor can be placed near tree trunks ' bases and send a wireless signal to a nearby receiver if there is a dramatic temperature increase .
That heat also powers the sensor itself , eliminating the need to replace batteries .
The key is molten salts called ionic liquids : an abrupt temperature change causes electrons to migrate within the liquids , creating electrical energy @ @ @ @ @ @ @ .
The team printed the substances onto ordinary paper to create a sensor for just $ 0.40 , as described in June in ACS Applied Materials & Interfaces .
Jessica McCarty , a geographer at Miami University in Ohio , who was not involved in the study , says places such as San Diego—where wildland and city meet—could potentially benefit from sensors like this .
When a fire breaks out in a canyon that extends to someone 's property , she says , with such a device , “ you know that as @ @ @ @ @ @ @ have detected it.
” But improving coordination among the different agencies involved in firefighting is even more crucial to address , says Graham Kent , a seismologist at the University of Nevada , Reno , who was also not part of the study .
Kent is director of ALERTWildfire , a network that uses cameras and crowdsourcing to watch for fires in California , Nevada and Oregon .
“ The whole way that you respond to a fire until it 's put out is like a ballet , ” he says .
“ @ @ @ @ @ @ @ so , ” with resources allocated at precisely the right time and place from detection to confirmation to dispatch to extinguishing .
“ Fire detection is just step one ; if you blow steps two through 98 , all that technology … just does n't matter.
” Wang says his team 's next steps are to extend the device 's signal range beyond the current 100 meters , which can limit practical use , and to develop a protective shield for it .
The transmitter 's effectiveness , McCarty notes , will also @ @ @ @ @ @ @ .

Wildfires have recently devastated regions across the world, and their severity is increasing. Hoping to reduce harm, researchers led by Yapei Wang, a chemist at Renmin University of China, say they have developed an inexpensive sensor to detect such blazes earlier and with less effort.
Current detection methods rely heavily on human watchfulness, which can delay an effective response. Most wildfires are reported by the general public, and other alerts come from routine foot patrols and watchtower observers. Passing planes and satellites also occasionally spot something, but “the fire [first] appears on the ground,” Wang says. “When [you see] the fire from the sky … it is too late.”
The team says its new sensor can be placed near tree trunks' bases and send a wireless signal to a nearby receiver if there is a dramatic temperature increase. That heat also powers the sensor itself, eliminating the need to replace batteries. The key is molten salts called ionic liquids: an abrupt temperature change causes electrons to migrate within the liquids, creating electrical energy that triggers electrodes to send the signal. The team printed the substances onto ordinary paper to create a sensor for just $0.40, as described in June in ACS Applied Materials & Interfaces.
Jessica McCarty, a geographer at Miami University in Ohio, who was not involved in the study, says places such as San Diego—where wildland and city meet—could potentially benefit from sensors like this. When a fire breaks out in a canyon that extends to someone's property, she says, with such a device, “you know that as a homeowner before the fire agency may have detected it.”
But improving coordination among the different agencies involved in firefighting is even more crucial to address, says Graham Kent, a seismologist at the University of Nevada, Reno, who was also not part of the study. Kent is director of ALERTWildfire, a network that uses cameras and crowdsourcing to watch for fires in California, Nevada and Oregon. “The whole way that you respond to a fire until it's put out is like a ballet,” he says. “You'd have to choreograph it just so,” with resources allocated at precisely the right time and place from detection to confirmation to dispatch to extinguishing. “Fire detection is just step one; if you blow steps two through 98, all that technology … just doesn't matter.”
Wang says his team's next steps are to extend the device's signal range beyond the current 100 meters, which can limit practical use, and to develop a protective shield for it. The transmitter's effectiveness, McCarty notes, will also need to be tested in the field.