From PBS NOVA: “To predict the next infectious disease outbreak, ask a computer”

From PBS NOVA

October 15, 2019
Katherine J. Wu

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Lyle’s flying fox (Pteropus lylei), one of several bat species known to carry Nipah virus, which can cause serious illness in people. Animal health and human health go hand in hand, researchers say. Image Credit: asawinimages, iStock

On December 26, 2013, a two-year-old boy named Emile Ouamouno fell ill in the village of Meliandou in Guinea, West Africa. For two days, his tiny body was wracked with fever as he vomited and passed black stool. By December 28, he was dead.

Within weeks, his sister, mother, and grandmother were, too—the first casualties of what would eventually become thousands. The largest Ebola outbreak in history had begun.

It would be many months, however, before a team of researchers would pinpoint the probable source of the epidemic: a colony of Angolan free-tailed bats (Mops condylurus) that had roosted in a hollow cola tree less than 200 feet from Emile’s home. The locals called them lolibelo, or flying mice, for their distinctive smell and long tails. They were common targets for children at play, who would rouse them from sleep with sticks and roast them as snacks.

By the time ecologists and veterinarians arrived in Meliandou in April 2014, the tree in question had been burned and the bats were long gone. But the winged, mouse-sized mammals are still considered some of the likeliest candidates for Ebola’s so-called animal reservoirs, maintaining the virus in the wild before it makes each of its fateful hops into humans.

The disease’s devastating trajectory is a familiar one. Ebola, like SARS, Lyme disease, HIV, and most of the other infections known to plague people, got its start in another species. It’s in these creatures that pathogens can also hide between epidemics, biding time before they re-emerge.

By the time most reservoir species are identified, the pathogens in question have already spilled over into people. In the wake of an outbreak, that leaves just one course of action: mitigation—the frantic attempt to halt the collapse of a line of dominos after they’ve already begun to fall.

For Barbara Han, a disease ecologist at the Cary Institute, this reactive approach isn’t enough. “The fact is, you’ve already waited until people got sick,” she says. “You don’t want to hand out umbrellas after the rain falls. You want to forecast the rain before it starts.”

To get ahead of the curve, researchers need better tools that can predict these outbreaks before they happen, says David Redding, a disease ecologist at University College London. That means searching for the ecological and epidemiological patterns that precede spillovers—the harbingers of outbreaks that flicker to life in the wild, then trickle into humans.

Most of these warning signs aren’t readily discernible by human brains alone. So scientists like Han and Redding have turned to computational models that can scour gobs of ecological and demographic data in their stead, hunting for clues to where the next infectious leak might spring.

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The border between Guinea and Liberia, during the 2014 Ebola outbreak. Frequent boat travel, as well as other modes of transport, can help Ebola virus hop from one country to another. Image Credit: CDC Global, flickr

Into the wild, and back out again

Out in the wild, infection is a given—a reality Barbara Han, who got her scientific start in animal ecology, became intimately familiar with while tracking fungal pathogens [PLOS|ONE] in amphibians.

But the bugs that lurk in wildlife don’t always stay there.

Of the new and emerging infectious diseases documented by the Centers for Disease Control (CDC) over the past couple decades, 75 percent are zoonotic, or capable of spreading from animals to humans. And while scientists have amassed a good deal of data on animal reservoirs over the years, they’ve long struggled to uncover the crucial commonalities among them—the traits that make a species ideally suited to pass a pathogen to people.

That’s why Han has turned to a tool that could accomplish what human researchers can’t on their own. Several years ago, she and her team trained a computer model [PNAS] to pick out new rodent species with high disease-carrying potential, based on the traits they shared with 217 previously identified carriers of disease. Han compares the approach to Pandora’s strategy for recommending songs: An algorithm learns the trends that dictate musical taste or vulnerability to infection, then offers up a comparable band or animal that hasn’t been considered before. Using this tactic, Han’s model scanned through the 2,277 rodent species that exist worldwide and homed in on 58 not previously designated as reservoirs.

The list was diverse, spanning much of the rodent family tree. But its members did seem to have a couple things in common, like brief lifespans, early sexual maturity, and large numbers of offspring. “These rodents basically have a ‘live fast, die young’ approach to life,” Han says. It’s possible they prioritizing reproduction over other resource-heavy pursuits like, say, an ironclad immune system, she says. But unlike rats and mice, long-lived, slow-maturing humans have more to lose by ignoring infections.

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A northern grasshopper mouse (Onychomys leucogaster), one of several species pinpointed by a machine learning model trained to detect rodents at risk of carrying infectious diseases. Image Credit: Weber, iStock

Predictions aren’t guarantees. And it’s likely that many of these disease-carrying candidates will never harbor a problematic pathogen at all. But when done well, “modeling studies are great for hypothesis generation—they demonstrate what could happen,” says Inger Damon, Director of the CDC’s Division of High-Consequence Pathogens and Pathology.

And in certain instances, they seem spot on, Han says. While her team’s paper was being prepped for publication, two [Parasitology International] of the voles [PLOS] on their computer-generated list were confirmed to harbor parasites.

A similar story has played out in other animal groups, too. In 2016, Han and her colleagues published a list of bat species [PLOS] that could play host to filoviruses [Emerging Infectious Diseases], the group that includes Ebola. Less than a year later, a team of virus hunters uncovered filoviruses lurking in China’s fruit bats, including a couple species from Han’s paper.

Around the same time, a colleague at Columbia University phoned Han, bursting with excitement: He’d discovered a new ebolavirus [Nature Biotechnology] in Sierra Leone. It wasn’t yet clear if the virus could cause disease in humans, but it had been detected in two types of bats. One of them was the Angolan free-tailed bat—another species high on Han’s list of potential reservoirs. The same species suspected of infecting Emile Ouamouno years before.

Bridging the divide

Reservoirs aren’t reservoirs until they’re tapped. For a disease to jump into a human population, it needs access—a region where infected animals and people overlap.

At University College London, David Redding and ecologist Kate Jones have taken their own computational approach to uncover the dynamics of infection at these ports of entry. Their newest model, described in a paper published today in the journal Nature Communications, is what Redding calls a hybrid approach, borrowing from both ecology and epidemiology to predict areas at high risk of Ebola spillover and subsequent outbreak in Africa.

“We know where animal hosts are,” he says. (In Ebola’s case, that almost certainly means bats, and possibly great apes and duikers—a type of antelope—as well.) “And we also know where people are. Where you have both, you have likely contact, and risk of disease.”

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Workers in Guinea, West Africa, shortly after Ebola was confirmed to have hit the region. Image Credit: EU Civil Protection and Humanitarian Aid, flickr

That might sound simple enough. But a bevy of other variables make dynamics of a spillover far more complex, Redding says. Land use, for instance, can have a big impact on a reservoir’s range, and how much the members of different populations mix. On the human side, the size of an ensuing outbreak depends on connectivity—how easy it is for people to physically get around and mingle with others—and regional wealth, which often dictates the amount of money allocated to health care.

From the virus’ perspective, “the ideal situation would probably include a human population situated in a forested area with animal hosts, near a big transportation hub, near a big city,” Redding says. “That’s where you would expect large outbreaks to occur.”

While these are many of the critical variables that affect zoonotic disease, Damon says, there are always more variables to consider. Only some spillovers turn into outbreaks. And the likelihood of that transition can hinge on aspects of human behavior that Redding’s model didn’t capture, like the prevalence of funerary practices that may increase contact with infected bodies, she says.

By definition, computational modeling will always be a bit reductionist, says Sadie Ryan, a disease ecologist at the University of Florida. Programs have to accurately and efficiently capture the complexities of the real world with a limited set of data. That’s a huge challenge—and a high stakes one, she says. “If you’re doing massive spatial computational simulations without real information, you’re just making video games.”

But models like these, which take animals, humans, and their environments into account, effectively capture the “biological realism of these spillover events,” Ryan says.

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The largest Ebola outbreak in history may have begun when an Angolan free-tailed bat (Mops condylurus) passed the virus to a toddler in Meliandou, Guinea, West Africa in 2013. Children in the village often roused bats from tree hollows to play with cook eat them. Image Credit: Jakob Fahr, iNaturalist

In its current iteration, Redding’s model has proven powerful. With the data it was fed, it correctly identified several areas that had already experienced Ebola outbreaks, such as the Democratic Republic of Congo (DRC), Gabon, and regions in West Africa hit by the epidemic that began in Meliandou.

When the simulation originally ran in 2018, it also flagged several other regions—including Nigeria, Ghana, Rwanda, and Kenya—that, at the time, had been mostly untouched by the virus. In the months since, two of its outbreak predictions in the DRC have come true.

Cloudy with a chance of infection

West Africa’s Ebola epidemic ended in June of 2016. In the two and a half years after Emile Ouamouno fell ill in Meliandou, at least 28,646 people had been infected and at least 11,323 had died—more than all previous Ebola outbreaks combined.

The virus has since re-emerged. And with so many available hiding places in the wild, it’s likely to do so again, Redding says.

This is where outbreak predictions can be powerful, Han says. They can inform where health care resources are diverted next, or how ecologists and conservationists can protect and monitor (rather than villainize) reservoir species in their natural habitats, she says.

Acting on the numbers churned out by these models, however, is another issue entirely, Damon says. Predicting spillover isn’t the same as preventing it—a process that requires increased surveillance, or an infusion of resources that can quash outbreaks before they have a chance to grow.

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An infection control supervisor (left) demonstrates proper hand washing techniques during a field supervision visit to a small clinic in N’Zérékoré, Guinea. Image Credit: Lindsey Horton, CDC Global, flickr

These interventions will become increasingly complicated to execute in a rapidly changing world, Ryan says. As temperatures rise and habitats disappear, reservoir species—among many others—will be forced to uproot and adopt new behaviors, rejiggering their potential to transmit disease. “Climate change impacts literally everything,” says Han, who’s now collaborating with researchers at NASA to incorporate climate data into her team’s predictions.

In the case of Ebola, one trend may already be clear: The worse climate change gets, the more outbreaks we’ll have, Redding says. Projecting into the year 2070, his team’s simulations show that warmer, wetter conditions will raise the risk of spillovers across the African continent. Some of these effects can be mitigated by reducing carbon emissions and increasing sustainable development, Redding says—but only if the world takes action soon.

“This is about getting the concept of intervention out there ahead of time,” Ryan says. “If this is how the future is unfolding, let’s be there before it happens. And let’s be ready.”

See the full article here .

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From WIRED: “Ebola Is Now Curable. Here’s How the New Treatments Work”

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From WIRED

08.12.19
Megan Molteni

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A clinical trial in the Democratic Republic of Congo has been testing new Ebola drugs with dramatic results. For newly infected patients on one of the drugs, the mortality rate dropped to 6 percent.

Amid unrelenting chaos and violence, scientists and doctors in the Democratic Republic of Congo have been running a clinical trial of new drugs to try to combat a year-long Ebola outbreak. On Monday, the trial’s cosponsors at the World Health Organization and the National Institutes of Health announced that two of the experimental treatments appear to dramatically boost survival rates.

While an experimental vaccine previously had been shown to shield people from catching Ebola, the news marks a first for people who already have been infected. “From now on, we will no longer say that Ebola is incurable,” said Jean-Jacques Muyembe, director general of the Institut National de Recherche Biomedicale in the DRC, which has overseen the trial’s operations on the ground.

Starting last November, patients in four treatment centers in the country’s east, where the outbreak is at its worst, were randomly assigned to receive one of four investigational therapies—either an antiviral drug called remdesivir or one of three drugs that use monoclonal antibodies. Scientists concocted these big, Y-shaped proteins to recognize the specific shapes of invading bacteria and viruses and then recruit immune cells to attack those pathogens. One of these, a drug called ZMapp, is currently considered the standard of care during Ebola outbreaks. It had been tested and used during the devastating Ebola epidemic in West Africa in 2014, and the goal was to see if those other drugs could outperform it. But preliminary data from the first 681 patients (out of a planned 725) showed such strong results that the trial has now been stopped.

Patients receiving Zmapp in the four trial centers experienced an overall mortality rate of 49 percent, according to Anthony Fauci, director of the NIH’s National Institute of Allergy and Infectious Diseases. (Mortality rates are in excess of 75 percent for infected individuals who don’t seek any form of treatment.) The monoclonal antibody cocktail produced by a company called Regeneron Pharmaceuticals had the biggest impact on lowering death rates, down to 29 percent, while NIAID’s monoclonal antibody, called mAb114, had a mortality rate of 34 percent. The results were most striking for patients who received treatments soon after becoming sick, when their viral loads were still low—death rates dropped to 11 percent with mAb114 and just 6 percent with Regeneron’s drug, compared with 24 percent with ZMapp and 33 percent with Remdesivir.

Drugs based on monoclonal antibodies have become a mainstay of modern medicine—fending off a variety of diseases from cancer to lupus. But it takes many years of painstaking reverse-engineering to make them. Zmapp, for instance, was developed by infecting mice with Ebola and then collecting the antibodies the mice produced against the virus. Those antibodies then had to be further engineered to look more like a human antibody, so as not to provoke an immune reaction. Ebola infiltrates its victims’ cells using spiky proteins on the virus’s outer shell, so researchers screened the antibodies for the ones that did the best job of binding to those proteins. Block access, and the virus can’t replicate and spread. But compared with other viruses, Ebola is large and has the ability to change shape, making it difficult for any one antibody to block its infection. That’s why a cocktail approach has become favored, like the Regeneron product—a combination of three monoclonal antibodies generated first in mice.

An even better solution, some have posited, would be to mine the serum of Ebola survivors and harvest the DNA from the white blood cells that make antibodies. That would yield a set of genetic instructions for making antibodies with a proven track record against the Ebola virus. That’s what the NIH’s mAb114 is—an antibody isolated from the blood of a survivor of a 1995 outbreak in Kikwit, DRC. Scientists discovered it a few years ago—they had been circulating in his body for more than a decade.

With the WHO’s announcement a new trial will now kick off, directly comparing Regeneron to mAb114, which is being produced by a Florida-based company called Ridgeback Biotherapeutics. And all Ebola treatment units in the outbreak zone will now only administer the two most effective monoclonal antibody drugs, according to the WHO’s director of health emergencies, Mike Ryan.

“Today’s news puts us one more step to saving more lives,” said Ryan. “The success is clear. But there’s also a tragedy linked to the success. The tragedy is that not enough people are being treated. We are still seeing too many people staying away from treatment centers, people not being found in time to benefit from these therapies.”

Since the ongoing outbreak began last August in DRC’s North Kivu province, more than 2,800 people have become infected, with 1,794 confirmed deaths. It is the second-largest Ebola outbreak ever recorded. On July 17, the WHO declared it a “public health emergency of international concern,” after a case showed up in Goma, a large city bordering Rwanda. The risk of transmission across international borders remains high.

See the full article here .

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From CSIROscope: “Combatting Ebola through more than just outbreak response”

CSIRO bloc

From CSIROscope

9 August 2019
Professor S.S. Vasan

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An artificially coloured electron microscope image of the Ebola virus

The World Health Organization has declared Ebola a ‘Public Health Emergency of International Concern’ (PHEIC), for the second time in five years. So, how can the global public health community better support relief efforts in the Democratic Republic of Congo (DRC)?

Current situation with Ebola in the Democratic Republic of Congo

The last major African outbreak mainly affected Sierra Leone, Liberia and Guinea, with 28,646 cases and a 40 per cent mortality rate. This epidemic killed five times more people than all other known Ebola outbreaks combined. And a PHEIC was declared between 8 March 2014 and 29 March 2016.

After sporadic outbreaks in 2017 and 2018, the DRC is now experiencing the world’s second-largest recorded outbreak. As of 5 August 2019, 3150 people have infected with a 59 per cent mortality rate. Reports out of the region suggest that only half of the cases are being identified and reported. Most of them in the region of Kivu.

The disease has also spread to neighbouring Uganda and been reported in places close to the DRC’s border with Rwanda and South Sudan.

The decision to declare a PHEIC is a complex one. It involves weighing potential effects on travel and trade that could impede support to affected regions and hinder outbreak control, as argued by the World Health Organisation (WHO).

What can developed countries do?

The outbreak cannot be solved just with more funding and medical expertise that will arrive thanks to the PHEIC declaration.

First and foremost, we need to listen to the local leadership and ask them what they need for a community-led response. And not assume what they want.

The DRC Ministry of Health had asked for “more cohesion, more harmonization between the different interventions, [and] more alignment with the strategic plan of the Ministry of Health.” Lot of us want to help but are unsure how. So, we need more coordination to ensure each of us is focusing on our core competencies to address needs on the ground.

Secondly, we need to take on board the valuable and transferable lessons from the last outbreak. This includes dialogue and delicate compromise with the community to ensure safe burial practices.

Similar to the sustainable Resilient Zero program in Sierra Leone, we should strengthen their district health capacity, laboratory network and disease surveillance systems. We can then detect and respond effectively to not just Ebola, but also other infectious diseases.

Thirdly, vaccination alone cannot solve Ebola. This is due to a range of factors including lack of 100 per cent protection, adverse effects, clinical and other challenges around coverage, compliance and cost-effectiveness. That is why the global scientific community needs to accelerate the development of treatments that complement the two experimental Ebola vaccines currently in use.

Promising novel and repurposed drugs and treatments need to be evaluated in appropriate animal models in laboratories operating under the highest containment (‘Biosafety Level 4’). But such high secure facilities, like our own Australian Animal Health Laboratory (AAHL), are very few in number. So, we need greater coordination to ensure there is no duplication of efforts. Some mechanisms are already in place, such as the BSL4ZNet, an international network of laboratories like AAHL to protect against animal to human disease. And the fast track model agreement for rapid collaboration, which shares results for a global coordinated response.

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A CSIRO infectious disease researcher working in the CSIRO high containment lab

Looking long-term beyond outbreak response

Recently there has been a greater risk of infectious diseases being transmitted to people from wild and domesticated animals. This is due to growth and geographic expansion of human populations and the increase in agricultural practices. Increased global travel also means there is a greater likelihood that infectious agents, particularly airborne pathogens that can produce disease, can rapidly spread among the human population. Together, these factors have increased the risk of pandemics. It’s not so much a matter of if, but when. While the current list of known emerging infectious diseases is a major concern, it’s the unknown viruses, with a potential for efficient human-to-human transmission that pose the biggest threat.

Ebola and other haemorrhagic fever viruses are likely to re-emerge and pose a great threat to health and biosecurity. Especially in Africa and other developing nations. These settings have a relatively low health expenditure, high likelihood of such outbreaks, and an urgent need for rapid, safe, cheap and effective treatment options. Therefore, the typical 17 years’ ‘implementation gap’ in the health research translation process is simply not an option for Ebola and similar diseases.

Ebola has increased the ‘intersectionality’ of suffering among the 13 million people living in a complex humanitarian crisis in the DRC. This includes ongoing conflict and widening health, wealth and gender inequalities. To solve this, we need a strong and locally-led social science and humanitarian focus. This would help guide scientific research, development, evaluation and uptake of response strategies and promising medical countermeasures. For the long-term, we need to focus on planning, preparedness and resilience, not just outbreak response.

See the full article here .


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SKA/ASKAP radio telescope at the Murchison Radio-astronomy Observatory (MRO) in Mid West region of Western Australia

So what can we expect these new radio projects to discover? We have no idea, but history tells us that they are almost certain to deliver some major surprises.

Making these new discoveries may not be so simple. Gone are the days when astronomers could just notice something odd as they browse their tables and graphs.

Nowadays, astronomers are more likely to be distilling their answers from carefully-posed queries to databases containing petabytes of data. Human brains are just not up to the job of making unexpected discoveries in these circumstances, and instead we will need to develop “learning machines” to help us discover the unexpected.

With the right tools and careful insight, who knows what we might find.

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CSIRO, the Commonwealth Scientific and Industrial Research Organisation, is Australia’s national science agency and one of the largest and most diverse research agencies in the world.

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From UCLA Newsroom : “40 years after first Ebola outbreak, survivors show signs they can stave off new infection”


UCLA Newsroom

December 13, 2017
Enrique Rivero

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An Ebola researcher works out of a mobile laboratory set up in a mud hut in the Democratic Republic of the Congo.

Survivors of the first known Ebola outbreak, which occurred in the Democratic Republic of the Congo in 1976, may be key to development of vaccines and therapeutic drugs to treat future outbreaks, according to a new study led by researchers at the UCLA Fielding School of Public Health.

UCLA researchers located the 14 Ebola survivors of the 1976 outbreak who, in January 2016, were still living in the same small, remote villages in the forests of the Équateur Province of northwestern Democratic Republic of the Congo. The researchers obtained blood samples and health history reports from them. The data revealed evidence that these survivors’ immune systems are likely to provide some protection against future infection.

The study, published online in the Journal of Infectious Diseases, marks the first time that the effects of the virus have been studied four decades after infection and the first findings that indicate Ebola survivors may be able to stave off future infections.

The Ebola virus is often associated with high mortality rates in humans, ranging from 25 percent to 90 percent, and outbreaks have occurred with increased frequency since the first reported event in the Democratic Republic of the Congo in 1976 in which 318 cases were recorded, with a fatality rate of 88 percent. The Ebola virus disease is highly contagious and spreads through direct or indirect contact with bodily fluids. It initially causes fever, headache and muscle aches and can progress to vomiting, diarrhea, and sometimes internal and external bleeding. The 2014-2016 outbreak of Ebola in Western Africa was unprecedented in size and scope — there were an estimated 28,000 cases and more than 10,000 survivors.

“Unimaginable death tolls and devastation to families and communities have occurred as a result of Ebola,” said lead author Anne Rimoin, associate professor of epidemiology at the UCLA Fielding School of Public Health. “With the number and frequency of Ebola outbreaks increasing over time, the need to find effective measures to combat and prevent outbreaks is critical.”

Rimoin said researchers know there are more than 10,000 survivors of the West Africa epidemic, but they don’t know what long-term health effects those survivors may endure in the future. Their goal, she said, was to locate survivors of the initial 1976 outbreak to learn what happens 40 years after infection.

Since no online records of the 1976 outbreak investigation existed, the UCLA team collaborated with and gained access to handwritten notes from three scientists who investigated that outbreak — Dr. Peter Piot and Dr. David Heymann of the London School of Hygiene and Tropical Medicine, and Professor Jean Jacques Muyembe of the Institut National de Recherche Biomedical in Kinshasa.

The UCLA researchers traveled to small, remote villages in the forests of the Équateur Province to locate and meet the survivors, and gain access to data. They used a mobile laboratory that was set up in a mud hut to do their work.

The research was funded by the Bill and Melinda Gates Foundation, Faucett Catalyst Fund, the National Institute of Allergy and Infectious Diseases, a DFG fellowship, the Fogarty International Center of the National Institutes of Health and the University of California Global Health Institute.

Study co-authors include Matthew Bramble, Reena Doshi, Nicole Hoff, Vivian Alfonso, Christina Ramirez and Cyrus Sinai of the UCLA Fielding School of Public Health; Patrick Mukadi and Jean Jacques Muyembe-Tamfum of Institut National de Recherche Biomedicale in Kinshasa, Democratic Republic of the Congo; Emile Okitolonda Wemakoy of Kinshasa School of Public Health; and Benoit Kebela Illunga of Direction de la Lutte Contre les Maladies in the Democratic Republic of the Congo.

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From PNNL: “Unlocking the secrets of Ebola”

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PNNL Lab

November 16, 2017
Tom Rickey
tom.rickey@pnnl.gov
(509) 375-3732

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PNNL scientists and their collaborators have identified molecules in the blood that indicate which patients with Ebola virus are most likely to have a poor outcome. (Credit: Photo courtesy of PNNL)

Scientists have identified a set of biomarkers that indicate which patients infected with the Ebola virus are most at risk of dying from the disease.

The results come from scientists at the Department of Energy’s Pacific Northwest National Laboratory and their colleagues at the University of Wisconsin-Madison, Icahn School of Medicine at Mount Sinai, the University of Tokyo and the University of Sierra Leone. The results were published online Nov. 16 in the journal Cell Host & Microbe.

The findings could allow clinicians to prioritize the scarce treatment resources available and provide them to the sickest patients, said the senior author of the study, Yoshihiro Kawaoka, a virology professor at the UW-Madison School of Veterinary Medicine.

The focus of the study were blood samples from Ebola patients that were obtained during the outbreak in Sierra Leone in 2014. The Wisconsin team obtained 29 blood samples from 11 patients who ultimately survived and nine blood samples from nine patients who died from the virus. The Wisconsin team inactivated the virus according to approved protocols, developed in part at PNNL, and then shipped the samples to PNNL and other institutions for analysis.

The team looked at activity levels of genes and proteins as well as the amounts of lipids and byproducts of metabolism. The team found 11 biomarkers that distinguish fatal infections from non-fatal ones and two that, when screened for early upon symptom onset, accurately predict which patients are likely to die.

“Our team studied thousands of molecular clues in each of these samples, sifting through extensive data on the activity of genes, proteins, and other molecules to identify those of most interest,” said Katrina Waters, the leader of the PNNL team and a corresponding author of the paper. “This may be the most thorough analysis yet of blood samples of patients infected with the Ebola virus.”

The team found that survivors had higher levels of some immune-related molecules and lower levels of others compared to those who died. Plasma cytokines, which are involved in immunity and stress response, were higher in the blood of people who perished. Fatal cases had unique metabolic responses compared to survivors, higher levels of virus, changes to plasma lipids involved in processes like blood coagulation, and more pronounced activation of some types of immune cells.

Pancreatic enzymes also leaked into the blood of patients who died, suggesting that these enzymes contribute to the tissue damage characteristic of fatal Ebola virus disease.

The scientists found that levels of two biomarkers, known as L-threonine (an amino acid) and vitamin-D-binding-protein, may accurately predict which patients live and which die. Both were present at lower levels at the time of admission in the patients who ultimately perished.

The team found that many of the molecular signals present in the blood of sick, infected patients overlap with sepsis, a condition in which the body – in response to infection by bacteria or other pathogens – mounts a damaging inflammatory reaction.

Fifteen PNNL scientists contributed to the study. Among the corresponding authors of the study are three PNNL scientists: Waters, Thomas Metz and Richard D. Smith. Three additional PNNL scientists – Jason P. Wendler, Jennifer E. Kyle and Kristin E. Burnum-Johnson – are among six scientists who share “first author” honors.

Other PNNL authors include Jon Jacobs, Young-Mo Kim, Cameron Casey, Kelly Stratton, Bobbie-Jo Webb-Robertson, Marina Gritsenko, Matthew Monroe, Karl Weitz, and Anil Shukla.

Analyses of proteins, lipids and metabolites in the blood samples were performed at EMSL, the Environmental Molecular Sciences Laboratory, a DOE Office of Science User Facility at PNNL.

The study was funded by a Japanese Health and Labor Sciences Research Grant; by grants for Scientific Research on Innovative Areas from the Ministry of Education, Cultures, Sports, Science and Technology of Japan; by Emerging/Re-emerging Infectious Diseases Project of Japan; and by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Support was also provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai and by a grant from the National Institute of General Medicine.

See the full article here .

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Pacific Northwest National Laboratory (PNNL) is one of the United States Department of Energy National Laboratories, managed by the Department of Energy’s Office of Science. The main campus of the laboratory is in Richland, Washington.

PNNL scientists conduct basic and applied research and development to strengthen U.S. scientific foundations for fundamental research and innovation; prevent and counter acts of terrorism through applied research in information analysis, cyber security, and the nonproliferation of weapons of mass destruction; increase the U.S. energy capacity and reduce dependence on imported oil; and reduce the effects of human activity on the environment. PNNL has been operated by Battelle Memorial Institute since 1965.

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#applied-research-technology, #ebola, #medicine, #pnnl, #the-focus-of-the-study-were-blood-samples-from-ebola-patients-that-were-obtained-during-the-outbreak-in-sierra-leone-in-2014, #the-scientists-found-that-levels-of-two-biomarkers-known-as-l-threonine-an-amino-acid-and-vitamin-d-binding-protein-may-accurately-predict-which-patients-live-and-which-die, #the-team-found-that-survivors-had-higher-levels-of-some-immune-related-molecules-and-lower-levels-of-others-compared-to-those-who-died, #the-team-looked-at-activity-levels-of-genes-and-proteins-as-well-as-the-amounts-of-lipids-and-byproducts-of-metabolism

From NIH: “Antibodies from Ebola survivor could lead to treatments and vaccines”

National Institutes of Health

June 6, 2017
Harrison Wein, Ph.D.

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Colorized scanning electron micrograph of filamentous Ebola virus particles (green) attached to and budding from an infected cell (blue) (25,000x magnification).NIAID

The 2013-16 Ebola outbreak in West Africa highlighted the need for an effective treatment or vaccine. Researchers have been making progress on several fronts, but many scientific and logistical challenges loom.

Viruses from three of the five known ebolavirus species (Zaire, Sudan, and Bundibugyo) have caused large outbreaks in humans, and the other two (Reston and Tai Forest) cause severe disease in primates. The related Marburg and Ravn viruses also cause similar hemorrhagic fevers and serious outcomes in people. An ideal approach would target many, if not all, of the viruses in this family, called filoviruses.

Scientists have searched for insights from natural antibodies, molecules produced by the immune system that bind to a specific substance, such as an invading virus. Antibodies recognize small, often unique, portions of viruses. Researchers previously discovered an antibody from a mouse that recognizes a common region among multiple ebolavirus species. The antibody proved protective in mouse models of infection.

A team of academic, industry, and government scientists set out to find similar broadly protective human antibodies. The group was led by Dr. John M. Dye at the U.S. Army Medical Research Institute of Infectious Diseases, Dr. Kartik Chandran at Albert Einstein College of Medicine, and Dr. Zachary A. Bornholdt at Mapp Biopharmaceutical, Inc. Their work was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Results appeared in Cell on May 18, 2017.

The researchers surveyed 349 antibodies derived from the blood of one survivor of the West African Ebola outbreak, which was caused by the Zaire strain of ebolavirus. They searched for antibodies that could neutralize all five ebolavirus species. Two that they found of interest were called ADI-15878 and ADI-15742. Both protected human cells in the laboratory from becoming infected with the three ebolaviruses that cause outbreaks in humans. Neither, however, protected against the more distantly related filoviruses Lloviu or Marburg.

In animal models of ebolavirus infection, the antibodies protected mice from the Zaire and Sudan ebolaviruses and ferrets from Bundibugyo ebolavirus. However, in ferrets treated with ADI-15742, the researchers found that the virus had developed a mutation that enabled it to escape the antibody’s effects.

Further study showed that the antibodies recognize a section of a protein found on the surface of ebolaviruses called the GP fusion loop, which is critical for infection. The antibodies don’t prevent the viruses from being engulfed by cells. Rather, they are taken up along with the virus particles and neutralize the viruses as they are being processed within the cell.

“Since it’s impossible to predict which of these agents will cause the next epidemic, it would be ideal to develop a single therapy that could treat or prevent infection caused by any known ebolavirus,” Bornholdt says. While much work still needs to be done, the identification of this vulnerable shared region on the surface of ebolaviruses is an important step toward creating effective treatments or vaccines.

See the full article here .

You can Help Stamp Out EBOLA.

This WCG project runs at Scripps Institute


Scripps

Outsmart Ebola Together

Visit World Community Grid (WCG). Download and install the BOINC software on which it runs. Attach to the Outsmart Ebola Together project. This will allow WCG to use your computer’s free CPU cycles to process computational data for the project.


While you are at WCG and BOINC, check out the other very worthwhile projects running on this software. All project results are “open source”, free for the use of scientists world while to advance health and other issues of mankind.

MyBOINC

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The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency — making important discoveries that improve health and save lives.

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From NYT: “New Ebola Vaccine Gives 100 Percent Protection”

New York Times

The New York Times

DEC. 22, 2016
DONALD G. McNEIL Jr.

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Health workers in November 2015 with Mibemba Soumah, infected by Ebola, at a treatment center in Conakry, Guinea. Credit Samuel Aranda for The New York Times.

In a scientific triumph that will change the way the world fights a terrifying killer, an experimental Ebola vaccine tested on humans in the waning days of the West African epidemic has been shown to provide 100 percent protection against the lethal disease.

The vaccine has not yet been approved by any regulatory authority, but it is considered so effective that an emergency stockpile of 300,000 doses has already been created for use should an outbreak flare up again.

Since Ebola was discovered in the former Zaire in 1976, there have been many efforts to create a vaccine. All began with a sense of urgency but then petered out for lack of money. Although only about 1,600 people died of Ebola over those years, the grotesque nature their deaths — copious hemorrhaging from every orifice — has lent the disease a frightening reputation.

Ultimately, only the huge, explosive 2014 outbreak that took 11,000 lives in Africa and spread overseas, reaching a handful of people in Europe and the United States, provided the political and economic drive to make an effective vaccine.

The test results of the trial in Guinea were released Thursday in The Lancet.

The vaccine was not ready in time to stop the outbreak, which probably began in a hollow, bat-filled tree in Guinea and swept Liberia and Sierra Leone before being defeated. But the prospect of a vaccine stockpile now has brought optimism among public health experts.

“While these compelling results come too late for those who lost their lives during West Africa’s Ebola epidemic, they show that when the next outbreak hits, we will not be defenseless,” said Marie-Paule Kieny, the World Health Organization’s assistant director-general for health systems and innovation and the study’s lead author. “The world can’t afford the confusion and human disaster that came with the last epidemic.”

The vaccine opens up new, faster, more efficient ways to encircle and strangle the virus. The many small Ebola outbreaks that occurred between 1976 and 2014 were all stopped in remote villages by laborious methods: medical teams flew in, isolated the sick, and donned protective gear to treat them and bury the dead.

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A volunteer receiving the experimental Ebola vaccine at a clinic in Conakry, Guinea, in 2015. Credit Yann Libessart/Medicins Sans Frontieres, via European Pressphoto Agency

But that tactic failed in 2014 when the virus reached crowded capital cities, where it spread like wildfire and dead bodies piled up in the streets.

The new vaccine has some flaws, experts said. It appears to work only against one of the two most common strains of the Ebola virus, and it may not give long-lasting protection. Some of those who get it report side effects like joint pain and headaches.

“It’s certainly good news with regard to any new outbreak — and one will occur somewhere,” said Dr. Anthony S. Fauci, director of the National Institute for Allergy and Infectious Diseases, which makes many vaccines and did some early testing on this one. “But we still need to continue working on Ebola vaccines.”

The Lancet study was done in 11,841 residents of Guinea last year. Among the 5,837 people who got the vaccine, none came down with Ebola 10 or more days later. There were 23 Ebola cases among the thousands of others not immediately vaccinated.

(The 10-day window was important because the trial used the “ring vaccination” technique developed during the drive to eliminate smallpox. Once a confirmed case was found, researchers contacted everyone in the circle of family, friends, neighbors and caregivers around the victim. About half the “circles” were offered vaccine. No one who fell ill within the first nine days after vaccination was counted, however, because it was assumed that they had already been infected before vaccination.)

The Ebola trial was led by the World Health Organization, the Guinean Health Ministry, Norway’s Institute of Public Health and other institutions. The vaccine, known as rVSV-ZEBOV, was developed over a decade ago by the Public Health Agency of Canada and the United States Army and is now licensed to Merck.

Its genetic “spine” is that of a vesicular stomatitis virus, which sickens cattle but usually does not infect humans. Spliced into the spine is the gene coding for an Ebola virus surface protein that prompts the immune system to make antibodies.

Tests in monkeys showed that one shot protected all of them when it was given at least a week before they were given a high dose of Ebola. The shot even protected a few monkeys who received it a day after being infected with Ebola.

The Ebola virus has five known subtypes, the most common of which are Ebola-Zaire, the one that caused the West African outbreak, and Ebola-Sudan. Ebola is also related to Marburg virus, which is similarly lethal.

An ideal vaccine would protect against all Ebola strains and Marburg. However, Dr. Kieny said, it may not be possible to make a shot effective against several strains if it is t based on the VSV spine because VSV triggers a lot of side effects.

Risks that are acceptable in the midst of a deadly epidemic are not acceptable in a preventive vaccine given to healthy children and adults, several experts noted.

The new vaccine is “a step in the right direction but not the ultimate solution,” said Dr. Gary J. Nabel, chief scientific officer for global health research at the Sanofi pharmaceutical company, who designed a different Ebola vaccine in the 1990s when he worked at the National Institutes of Health.

A randomized clinical trial involving tens of thousands of subjects is the preferred way to test any vaccine, he noted. But by the time testing could start in mid-2015 in West Africa, isolation and treatment of the sick in tent hospitals had made Ebola cases so rare that researchers had to switch to ring vaccination around the few they could find.

A likely candidate for a routine Ebola vaccine is one now being developed by GSK, Dr. Nabel said. It uses two shots: the first has the Ebola surface protein attached to a chimpanzee adenovirus that can infect humans without harming them; the second uses a weakened pox virus similar to that used in smallpox vaccine.

Dr. Seth F. Berkley, chief executive of Gavi, the Vaccine Alliance, said his organization’s board voted in late 2014 to spend up to $390 million for 12 million doses of an Ebola vaccine. At the time, several companies had candidates but none had been fully tested in humans. “That was at a time when the epidemic was raging and we did not know if it could be controlled without a vaccine,” he said.

By early last year, when preliminary results suggested the Merck vaccine worked well, Gavi gave the company $5 million to make 300,000 doses as an emergency supply to be used if Ebola-Zaire exploded again.

It is not yet clear how big a stockpile will eventually be created. Merck is now required to seek approval of its vaccine from the World Health Organization, which itself requires licensing by a major regulatory agency like the United States Food and Drug Administration or the European Medicines Agency.

See the full article here .

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