New tools could catch disease outbreaks earlier - or predict them
Every year, the villages which lie in the so-called ‘Nipah belt’— which stretches along the western border between Bangladesh and India, brace themselves for the latest outbreak. For since 1998, when Nipah virus—a form of hemorrhagic fever most common in Bangladesh—first spilled over into humans, it has been a grim annual visitor to the people of this region.
With a 70 percent fatality rate, no vaccine, and no known treatments, Nipah virus has been dubbed in the Western world as ‘the worst disease no one has ever heard of.’ Currently, outbreaks tend to be relatively contained because it is not very transmissible. The virus circulates throughout Asia in fruit eating bats, and only tends to be passed on to people who consume contaminated date palm sap, a sweet drink which is harvested across Bangladesh.
But as SARS-CoV-2 has shown the world, this can quickly change.
“Nipah virus is among what virologists call ‘the Big 10,’ along with things like Lassa fever and Crimean Congo hemorrhagic fever,” says Noam Ross, a disease ecologist at New York-based non-profit EcoHealth Alliance. “These are pretty dangerous viruses from a lethality perspective, which don’t currently have the capacity to spread into broader human populations. But that can evolve, and you could very well see a variant emerge that has human-human transmission capability.”
That’s not an overstatement. Surveys suggest that mammals harbour about 40,000 viruses, with roughly a quarter capable of infecting humans. The vast majority never get a chance to do so because we don’t encounter them, but climate change can alter that. Recent studies have found that as animals relocate to new habitats due to shifting environmental conditions, the coming decades will bring around 300,000 first encounters between species which normally don’t interact, especially in tropical Africa and southeast Asia. All these interactions will make it far more likely for hitherto unknown viruses to cross paths with humans.
That’s why for the last 16 years, EcoHealth Alliance has been conducting ongoing viral surveillance projects across Bangladesh. The goal is to understand why Nipah is so much more prevalent in the western part of the country, compared to the east, and keep a watchful eye out for new Nipah strains as well as other dangerous pathogens like Ebola.
"There are a lot of different infectious agents that are sensitive to climate change that don't have these sorts of software tools being developed for them," says Cat Lippi, medical geography researcher at the University of Florida.
Until very recently this kind of work has been hampered by the limitations of viral surveillance technology. The PREDICT project, a $200 million initiative funded by the United States Agency for International Development, which conducted surveillance across the Amazon Basin, Congo Basin and extensive parts of South and Southeast Asia, relied upon so-called nucleic acid assays which enabled scientists to search for the genetic material of viruses in animal samples.
However, the project came under criticism for being highly inefficient. “That approach requires a big sampling effort, because of the rarity of individual infections,” says Ross. “Any particular animal may be infected for a couple of weeks, maybe once or twice in its lifetime. So if you sample thousands and thousands of animals, you'll eventually get one that has an Ebola virus infection right now.”
Ross explains that there is now far more interest in serological sampling—the scientific term for the process of drawing blood for antibody testing. By searching for the presence of antibodies in the blood of humans and animals, scientists have a greater chance of detecting viruses which started circulating recently.
Despite the controversy surrounding EcoHealth Alliance’s involvement in so-called gain of function research—experiments that study whether viruses might mutate into deadlier strains—the organization’s separate efforts to stay one step ahead of pathogen evolution are key to stopping the next pandemic.
“Having really cheap and fast surveillance is really important,” says Ross. “Particularly in a place where there's persistent, low level, moderate infections that potentially have the ability to develop into more epidemic or pandemic situations. It means there’s a pathway that something more dangerous can come through."
Scientists are searching for the presence of antibodies in the blood of humans and animals in hopes to detect viruses that recently started circulating.
EcoHealth Alliance
In Bangladesh, EcoHealth Alliance is attempting to do this using a newer serological technology known as a multiplex Luminex assay, which tests samples against a panel of known antibodies against many different viruses. It collects what Ross describes as a ‘footprint of information,’ which allows scientists to tell whether the sample contains the presence of a known pathogen or something completely different and needs to be investigated further.
By using this technology to sample human and animal populations across the country, they hope to gain an idea of whether there are any novel Nipah virus variants or strains from the same family, as well as other deadly viral families like Ebola.
This is just one of several novel tools being used for viral discovery in surveillance projects around the globe. Multiple research groups are taking PREDICT’s approach of looking for novel viruses in animals in various hotspots. They collect environmental DNA—mucus, faeces or shed skin left behind in soil, sediment or water—which can then be genetically sequenced.
Five years ago, this would have been a painstaking work requiring bringing collected samples back to labs. Today, thanks to the vast amounts of money spent on new technologies during COVID-19, researchers now have portable sequencing tools they can take out into the field.
Christopher Jerde, a researcher at the UC Santa Barbara Marine Science Institute, points to the Oxford Nanopore MinION sequencer as one example. “I tried one of the early versions of it four years ago, and it was miserable,” he says. “But they’ve really improved, and what we’re going to be able to do in the next five to ten years will be amazing. Instead of having to carefully transport samples back to the lab, we're going to have cigar box-shaped sequencers that we take into the field, plug into a laptop, and do the whole sequencing of an organism.”
In the past, viral surveillance has had to be very targeted and focused on known families of viruses, potentially missing new, previously unknown zoonotic pathogens. Jerde says that the rise of portable sequencers will lead to what he describes as “true surveillance.”
“Before, this was just too complex,” he says. “It had to be very focused, for example, looking for SARS-type viruses. Now we’re able to say, ‘Tell us all the viruses that are here?’ And this will give us true surveillance – we’ll be able to see the diversity of all the pathogens which are in these spots and have an understanding of which ones are coming into the population and causing damage.”
But being able to discover more viruses also comes with certain challenges. Some scientists fear that the speed of viral discovery will soon outpace the human capacity to analyze them all and assess the threat that they pose to us.
“I think we're already there,” says Jason Ladner, assistant professor at Northern Arizona University’s Pathogen and Microbiome Institute. “If you look at all the papers on the expanding RNA virus sphere, there are all of these deposited partial or complete viral sequences in groups that we just don't know anything really about yet.” Bats, for example, carry a myriad of viruses, whose ability to infect human cells we understand very poorly.
Cultivating these viruses under laboratory conditions and testing them on organoids— miniature, simplified versions of organs created from stem cells—can help with these assessments, but it is a slow and painstaking work. One hope is that in the future, machine learning could help automate this process. The new SpillOver Viral Risk Ranking platform aims to assess the risk level of a given virus based on 31 different metrics, while other computer models have tried to do the same based on the similarity of a virus’s genomic sequence to known zoonotic threats.
However, Ladner says that these types of comparisons are still overly simplistic. For one thing, scientists are still only aware of a few hundred zoonotic viruses, which is a very limited data sample for accurately assessing a novel pathogen. Instead, he says that there is a need for virologists to develop models which can determine viral compatibility with human cells, based on genomic data.
“One thing which is really useful, but can be challenging to do, is understand the cell surface receptors that a given virus might use,” he says. “Understanding whether a virus is likely to be able to use proteins on the surface of human cells to gain entry can be very informative.”
As the Earth’s climate heats up, scientists also need to better model the so-called vector borne diseases such as dengue, Zika, chikungunya and yellow fever. Transmitted by the Aedes mosquito residing in humid climates, these blights currently disproportionally affect people in low-income nations. But predictions suggest that as the planet warms and the pests find new homes, an estimated one billion people who currently don’t encounter them might be threatened by their bites by 2080. “When it comes to mosquito-borne diseases we have to worry about shifts in suitable habitat,” says Cat Lippi, a medical geography researcher at the University of Florida. “As climate patterns change on these big scales, we expect to see shifts in where people will be at risk for contracting these diseases.”
Public health practitioners and government decision-makers need tools to make climate-informed decisions about the evolving threat of different infectious diseases. Some projects are already underway. An ongoing collaboration between the Catalan Institution for Research and Advanced Studies and researchers in Brazil and Peru is utilizing drones and weather stations to collect data on how mosquitoes change their breeding patterns in response to climate shifts. This information will then be fed into computer algorithms to predict the impact of mosquito-borne illnesses on different regions.
The team at the Catalan Institution for Research and Advanced Studies is using drones and weather stations to collect data on how mosquito breeding patterns change due to climate shifts.
Gabriel Carrasco
Lippi says that similar models are urgently needed to predict how changing climate patterns affect respiratory, foodborne, waterborne and soilborne illnesses. The UK-based Wellcome Trust has allocated significant assets to fund such projects, which should allow scientists to monitor the impact of climate on a much broader range of infections. “There are a lot of different infectious agents that are sensitive to climate change that don't have these sorts of software tools being developed for them,” she says.
COVID-19’s havoc boosted funding for infectious disease research, but as its threats begin to fade from policymakers’ focus, the money may dry up. Meanwhile, scientists warn that another major infectious disease outbreak is inevitable, potentially within the next decade, so combing the planet for pathogens is vital. “Surveillance is ultimately a really boring thing that a lot of people don't want to put money into, until we have a wide scale pandemic,” Jerde says, but that vigilance is key to thwarting the next deadly horror. “It takes a lot of patience and perseverance to keep looking.”
This article originally appeared in One Health/One Planet, a single-issue magazine that explores how climate change and other environmental shifts are increasing vulnerabilities to infectious diseases by land and by sea. The magazine probes how scientists are making progress with leaders in other fields toward solutions that embrace diverse perspectives and the interconnectedness of all lifeforms and the planet.
Patients voice hope and relief as FDA gives third-ever drug approval for ALS
At age 52, Glen Rouse suffered from arm weakness and a lot of muscle twitches. “I first thought something was wrong when I could not throw a 50-pound bag of dog food over the tailgate of my truck—something I use to do effortlessly,” said the 54-year-old resident of Anderson, California, about three hours north of San Francisco.
In August, Rouse retired as a forester for a private timber company, a job he had held for 31 years. The impetus: amyotrophic lateral sclerosis, or ALS, a progressive neuromuscular disease that is commonly known as Lou Gehrig’s disease, named after the New York Yankees’ first baseman who succumbed to it less than a month shy of his 38th birthday in 1941. ALS eventually robs an individual of the ability to talk, walk, chew, swallow and breathe.
Rouse is now dependent on ventilation through a nasal mask and uses a powerchair to get around. “I can no longer walk or use my arms very well,” he said. “I can still move my wrists and fingers. I can also transfer from my chair to the toilet if I have two of my friends help me.”
It’s “shocking” that modern medicine has very little to offer to people with this devastating condition, Rouse said. But there is hope on the horizon. Yesterday, the U.S. Food and Drug Administration approved Relyvrio, a drug made up of two parts, sodium phenylbutyrate and taurursodiol, to treat patients with ALS.
“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” said Billy Dunn, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a statement. “The FDA remains committed to facilitating the development of additional ALS treatments.”
Until this point, the FDA had approved only two other medications—Riluzole (rilutek) in 1995 and Radicava (edaravone) in 2017—to extend life in patients with ALS, which typically kills within two to five years after diagnosis. That’s why earlier this week, Rouse was optimistic about the FDA’s likely approval of a controversial new drug for ALS.
When Relyvrio is taken in addition to Riluzole, it appears to slow functional decline by an additional 25 percent and extend life by another 6 to 10 months, said Richard Bedlak, director of the Duke ALS Clinic. “It is not a cure, but it is definitely a step forward.”
“The whole ALS community is extremely excited about it,” he said the day before Relyvrio’s expected approval. “We are very hopeful. We’re on pins and needles.”
A study of 137 ALS patients did not result in “substantial evidence” that Relyvrio was effective, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee concluded in March. However, after some persuasion from FDA officials, patients and their families, the committee met again and decided to recommend approving the drug.
In January 2019, following an ALS diagnosis at age 58 in October the previous year, Jeff Sarnacki, of Chester, Maryland, was accepted into a trial for Relyvrio. “Because of the trial, we did experience hope and a greater sense of help than had we not had that opportunity,” said Juliet Taylor, his wife and caregiver. They both believed the drug “worked for him in giving him more time.”
In June 2019, Sarnacki chose an open-label extension, offered to patients by drug researchers after a study ends, and took the active drug until he died peacefully at home under hospice care in May 2020, five days after his 60th birthday. A retired agent with the federal Bureau of Alcohol, Tobacco, Firearms and Explosives who later worked as a security consultant, Sarnacki lived about 19 months after diagnosis, which is shorter than the typical prognosis.
His symptoms began with leg cramps in fall 2017 and foot drop in early 2018. A feeding tube was placed in 2019, as it became necessary early in his illness, Taylor said. He also took Radicava and Riluzole, the two previously approved drugs, for his ALS. “We were both incredulous that, so many years after Lou Gehrig’s own diagnosis, there were so few treatments available,” she said.
The dearth of successful treatments for ALS is “certainly not for lack of trying,” said Karen Raley Steffens, a registered nurse and ALS support services coordinator at the Les Turner ALS Foundation in Skokie, Ill. “There are thousands of researchers and scientists all over the world working tirelessly to try to develop treatments for ALS.”
Unfortunately, she added, research takes time and exorbitant amounts of funding, while bureaucratic challenges persist. The rare disease also manifests and progresses in many different ways, so many treatments are needed.
As of 2017, the Centers for Disease Control and Prevention estimated that more than 31,000 people in the U.S. live with ALS, and an average of 5,000 people are newly diagnosed every year. It is slightly more common in men than women. Most people are diagnosed between the ages of 55 and 75.
Most cases of ALS are sporadic, meaning that doctors don’t know the cause. There is about a one-year interval between symptom onset and an ALS diagnosis for most patients, so many motor neurons are lost by the time individuals can enroll in a clinical trial, said Richard Bedlack, professor of neurology and director of the Duke ALS Clinic in Durham, North Carolina.
Bedlack found the new drug, Relyvrio, to be “very promising,” which is why he testified to the FDA in favor of approval. (He’s a consultant and disease state speaker for multiple companies including Amylyx, manufacturer of Relyvrio.)
The “drug has different mechanisms of action than the currently approved treatments,” Bedlack said. He added that, when Relyvrio is taken in addition to Riluzole, it appears to slow functional decline by an additional 25 percent and extend life by another 6 to 10 months. “It is not a cure, but it is definitely a step forward.”
T. Scott Diesing, a neurohospitalist and director of general neurology at the University of Nebraska Medical Center in Omaha, said he hopes the drug is “as good as people anticipated it should be, because there are not too many options for these patients.”
"FDA went out on a limb in approving Relyvrio based on limited results from a small trial while a larger study remains in progress," said Florian P. Thomas, co-director of the ALS Center at Hackensack University Medical Center and Hackensack Meridian School of Medicine in New Jersey. "While it is definitely promising, clearly, the last word on this drug has not been spoken."
So far, Rouse's voice is holding up, but he knows the day will come when ALS will steal that and much more from him.
ALS is 100 percent fatal, with some patients dying as soon as a year after diagnosis. A few have lasted as long as 15 years, but those are the exceptions, Diesing said.
“If this drug can provide even months of additional life, or would maintain quality of life, that’s a big deal,” he noted, adding that “the patients are saying, ‘I know it’s not proven conclusively, but what do we have to lose?’ So, they would like to try it while additional studies are ongoing.” The drug has already been conditionally approved in Canada.
As his disease progresses, Rouse hopes to get a speech-to-text voice-generating computer that he can control with his eyes. So far, his voice is holding up, but he knows the day will come when ALS will steal that and much more from him. He works at I AM ALS, a patient-led community, and six of his friends have already died of the disease.
“Every time I lose a friend to ALS, I grieve and am sad but I resolve myself to keep working harder for them, myself and others,” Rouse said. “People living with ALS find great purpose in life advocating and trying to make a difference.”
Friday Five Podcast: New drug may slow the rate of Alzheimer's disease
The Friday Five covers important stories in health and science research that you may have missed - usually over the previous week, but today's episode is a lookback on important studies over the month of September.
Most recently, on September 27, pharmaceuticals Biogen and Eisai announced that a clinical trial showed their drug, lecanemab, can slow the rate of Alzheimer's disease. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend and the new month.
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This Friday Five episode covers the following studies published and announced over the past month:
- A new drug is shown to slow the rate of Alzheimer's disease
- The need for speed if you want to reduce your risk of dementia
- How to refreeze the north and south poles
- Ancient wisdom about Neti pots could pay off for Covid
- Two women, one man and a baby