How two effective vaccines on the market make it so much harder to quickly test any competing vaccines.

This article was published on Tuesday, January 5, 2021 in Kaiser Health News.

By Arthur Allen

As I prepared to get my shot in mid-December as part of a covid vaccine trial run by Janssen Pharmaceuticals, I considered the escape routes. Bailing out of the trial was a very real consideration since two other vaccines, made by Moderna and Pfizer-BioNTech, had been deemed safe and effective for emergency approval.

Leaving the trial would be a perfectly sane decision for me or anyone who had volunteered for an ongoing covid experiment. Why risk getting covid-19 if I was given a placebo, a shot with no vaccine in it? The way tests are designed, I might not be told whether I received the vaccine until the clinical trial is over, months from now.

Dropping the placebo arm could also be ethically sound from the company's point of view. Researchers frequently halt trials when they have a product that works — or manifestly doesn't. And the two approved vaccines are 95% effective.

That very real choice for thousands of people offering to join or remain in the ongoing vaccine tests creates a conundrum for science and for society. If trials can't go forward, that could very well have an impact on the world's supply of covid vaccines and eventually on vaccine prices, especially if booster shots are needed in years to come. In markets where there are only two competing drugs, prices can shoot sky-high. If there are four or five on the market, competition usually kicks in to control costs.

In short, the welcome arrival of two covid vaccines deemed safe has uncovered a series of ethical and logistical challenges. And it has governments, companies and scientists scrambling for solutions.

"The world's vaccine experts are saying the longer we can carry out a placebo-controlled trial the better," Matthew Hepburn, who runs the vaccine development arm of Operation Warp Speed, the multibillion-dollar federal program to fight covid-19, told me. "But as a volunteer in the Janssen trial, you can always drop out."

As for the best way to resolve broader problems, "it's a debate in real time," he said.

Generally, there are two aspects to the debate. First, what should be done with placebo recipients of the Moderna and Pfizer trials now that it's clear both shots prevent the disease and appear safe? Second, how can the scores of companies in the United States and overseas that are still testing covid vaccines adapt when there are apparently reliable products already on the market?

The FDA's advisory committee debated the first question during two meetings in December. They heard Stanford University statistician Steven Goodman argue in favor of a "double-blind crossover" modification of the Pfizer and Moderna trials. Everyone who got placebo shots in the trials would now get two doses of the real vaccine, and vice versa. That way everyone would be protected but still "blind" as to when they were properly vaccinated.

Such a rejigger of the current trial would provide more data on the vaccine's safety and durability of protection, although the longer-term comparison of vaccine versus placebo would be lost. It's a marvelous idea in principle, the panelists agreed, but pretty hard to carry out. Neither Moderna nor Pfizer has agreed to it.

Pfizer wants to "unblind" placebo recipients of its vaccine — to reveal they got the saline solution and give them the real thing — once their risk group gets its turn in line for the vaccine. It has already started vaccinating healthcare workers who got the placebo.

Moderna, which has thousands of soon-to-expire leftover doses from its trial, said it intends to unblind its trial and vaccinate all the placebo recipients. In doing so, it would be recognizing the altruistic service the test subjects made to science and society by joining the trial.

Another proposal would split the placebo recipients in the trial into two groups. In one group, everyone would get a single dose of the vaccine. In the other, each would get two doses. This would be a way of testing evidence that emerged during the Pfizer and Moderna trials that a single dose might provide sufficient protection. If that were true, vaccination of the country could happen nearly twice as fast, because there would be twice as many doses of vaccine to go around.

No one knows to what extent the Food and Drug Administration could force the hands of the two companies, which still expect to get full licensure for their vaccines this year. Moderna is considered more amenable to the suggestion since, unlike Pfizer, it got nearly $1 billion in federal funding to develop its vaccine.

Other vaccine developers — including Operation Warp Speed participants Janssen (owned by Johnson & Johnson), AstraZeneca, Novavax, Sanofi and Merck & Co. — are closely watching to see which path is taken.

They are in a race against time — a race that may not end well for those running late in getting their vaccine out. And halting those efforts could hurt billions of people elsewhere in the world whose lives and livelihoods will depend on the arrival of plentiful, cheap vaccines.

One problem is finding willing test subjects. As increasing numbers of Americans are vaccinated, and the virus recedes from our shores, "the fewer the number of people eligible to participate in trials," said Susan Ellenberg, professor of biostatistics at the University of Pennsylvania.

For now, AstraZeneca and Janssen appear well situated. Both have closed enrollment in their U.S. trials and are likely to file within a few months for emergency use authorizations, like those that have allowed Moderna and Pfizer to start vaccinating the public.

Novavax officials last week started their late-stage trial in the U.S. and predict they can get full enrollment before the majority of the U.S. population is vaccinated.

Sanofi and Merck, whose timetables are more drawn out, are more likely to conduct most of their trials overseas.

In theory, drug companies could overcome these hurdles by testing multiple vaccines against one another and against approved vaccines. Dr. Steven Joffe, a University of Pennsylvania bioethicist, proposed in a recent JAMA article that Operation Warp Speed pay for such a trial.

Scientists and policymakers batted around the idea of a single U.S. trial, with multiple vaccine candidates competing against one another and a single placebo arm, during initial discussions last spring about the creation of Operation Warp Speed.

The idea went nowhere in the United States. It was taken up by World Health Organization officials and major biomedical research groups, which have tried to create such a vaccine trial in the rest of the world — with little success thus far.

So, for now, future vaccine trials are somewhat up in the air.

"There's this tension created by getting the first vaccines out there so quickly," said David Wendler, a senior researcher in bioethics at the National Institutes of Health's Clinical Center. "For public health it's good, but it has the potential to undermine our ability to keep going on the research side and really knock out the virus."

Companies, governments and outside funders need to quickly develop consensus on appropriate trial designs and regulatory processes for additional covid vaccines, added Mark Feinberg, president and CEO of the International AIDS Vaccine Initiative.

As for me, I decided I would stay in the Janssen trial. However, the day before I was scheduled to get my injection — real or fake — the research organization running the inoculations called to say I failed to make the cut: J&J had stopped its trial enrollment.

So, I'll buy some new masks and get in line for my vaccine with everyone else.

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Healthcare Foundation.

Arthur Allen: ArthurA@kff.org, @ArthurAllen202

Those disparities extend to the medical workers who have intubated  COVID patients, cleaned their bedsheets and held their hands in their final days.

This article was published on Tuesday, January 5, 2021 in Kaiser Health News.

By Danielle Renwick, The Guardian

Last spring, New Jersey emergency room nurse Maritza Beniquez saw "wave after wave" of sick patients, each wearing a look of fear that grew increasingly familiar as the weeks wore on.

Soon, it was her colleagues at Newark's University Hospital — the nurses, techs and doctors with whom she had been working side by side — who turned up in the ER, themselves struggling to breathe. "So many of our own co-workers got sick, especially toward the beginning; it literally decimated our staff," she said.

By the end of June, 11 of Beniquez's colleagues were dead. Like the patients they had been treating, most were Black and Latino.

"We were disproportionately affected because of the way that Blacks and Latinos in this country have been disproportionately affected across every [part of] our lives — from schools to jobs to homes," she said.

Now Beniquez feels like a vanguard of another kind. On Dec. 14, she became the first person in New Jersey to receive the coronavirus vaccine — and was one of many medical workers of color featured prominently next to headlines heralding the vaccine's arrival at U.S. hospitals.

It was a joyous occasion, one that kindled the possibility of again seeing her parents and her 96-year-old grandmother, who live in Puerto Rico. But those nationally broadcast images were also a reminder of those for whom the vaccine came too late.

Covid-19 has taken an outsize toll on Black and Hispanic Americans. And those disparities extend to the medical workers who have intubated them, cleaned their bedsheets and held their hands in their final days, a KHN/Guardian investigation has found. People of color account for about 65% of fatalities in cases in which there is race and ethnicity data.

One recent study found healthcare workers of color were more than twice as likely as their white counterparts to test positive for the virus. They were more likely to treat patients diagnosed with covid, more likely to work in nursing homes — major coronavirus hotbeds — and more likely to cite an inadequate supply of personal protective equipment, according to the report.

In a national sample of 100 cases gathered by KHN/The Guardian in which a healthcare worker expressed concerns over insufficient PPE before they died of covid, three-quarters of the victims were identified as Black, Hispanic, Native American or Asian.

"Black healthcare workers are more likely to want to go into public-sector care where they know that they will disproportionately treat communities of color," said Adia Wingfield, a sociologist at Washington University in St. Louis who has studied racial inequality in the healthcare industry. "But they also are more likely to be attuned to the particular needs and challenges that communities of color may have," she said.

Not only do many Black healthcare staffers work in lower-resourced health centers, she said, they are also more likely to suffer from many of the same co-morbidities found in the general Black population, a legacy of systemic inequities.

And they may fall victim to lower standards of care. Dr. Susan Moore, a 52-year-old Black pediatrician in Indiana, was hospitalized with covid in November and, according to a video posted to her Facebook account, had to ask repeatedly for tests, remdesivir and pain medication. She said her white doctor dismissed her complaints of pain and she was discharged, only to be admitted to another hospital 12 hours later.

Numerous studies have found Black Americans often receive worse medical care than their white counterparts: In March, a Boston biotech firm published an analysis showing physicians were less likely to refer symptomatic Black patients for coronavirus tests than symptomatic whites. Doctors are also less likely to prescribe painkillers to Black patients.

"If I was white, I wouldn't have to go through that," Moore said in the video posted from her hospital bed. "This is how Black people get killed, when you send them home, and they don't know how to fight for themselves." She died on Dec. 20 of covid complications, her son Henry Muhammad told news outlets.

Along with people of color, immigrant health workers have suffered disproportionate losses to covid-19. More than one-third of healthcare workers to die of covid in the U.S. were born abroad, from the Philippines to Haiti, Nigeria and Mexico, according to a KHN/Guardian analysis of cases for which there is data. They account for 20% of healthcare workers in the U.S. overall.

Dr. Ramon Tallaj, a physician and chairman of Somos, a nonprofit network of healthcare providers in New York, said immigrant doctors and nurses often see patients from their own communities — and many working-class, immigrant communities have been devastated by covid.

"Our community is essential workers. They had to go to work at the beginning of the pandemic, and when they got sick, they would come and see the doctor in the community," he said. Twelve doctors and nurses in the Somos network have died of covid, he said.

Dr. Eriberto Lozada was an 83-year-old family physician in Long Island, New York. He was still seeing patients out of his practice when cases began to climb last spring. Originally from the Philippines, a country with a history of sending skilled medical workers to the United States, he was proud to be a doctor and "proud to have been an immigrant who made good," his son James Lozada said.

Lozada's family members remember him as strict and strong-willed — they affectionately called him "the king." He instilled in his children the importance of a good education. He died in April.

Two of his four sons, John and James Lozada, are doctors. Both were vaccinated last month. Considering all they had been through, John said, it was a "bittersweet" occasion. But he thought it was important for another reason — to set an example for his patients.

The inequities in covid infections and deaths risk fueling distrust in the vaccine. In a recent Pew study, around 42% of Black respondents said they would "definitely or probably" get the vaccine compared with 60% of the general population.

This makes sense to Patricia Gardner, a Black, Jamaican-born nursing manager at Hackensack University Medical Center in New Jersey who has been infected with the coronavirus along with family members and colleagues. "A lot of what I hear is, 'How is it that we weren't the first to get the care, but now we're the first to get vaccinated?'" she said.

Like Beniquez, the nurse in Newark, she was vaccinated on Dec. 14. "For me to step up to say, 'I want to be in the first group' — I'm hoping that sends a message," she said.

Beniquez said she felt the weight of that responsibility when she signed on to be the first person in her state to receive the vaccine. Many of her patients have expressed skepticism over the vaccine, fueled, she said, by a health system that has failed them for years.

"We remember the Tuskegee trials. We remember the 'appendectomies'" — reports that women were forcibly sterilized in a U.S. Immigration and Customs Enforcement detention center in Georgia. "These are things that have happened to this community to the Black and Latino communities over the last century. As a healthcare worker, I have to recognize that their fears are legitimate and explain 'This is not that,'" she said.

Beniquez said her joy and relief over receiving the vaccine are tempered by the reality of rising cases in the ER. The adrenaline she and her colleagues felt last spring is gone, replaced by fatigue and wariness of the months ahead.

Her hospital placed 11 trees in the lobby, one for each employee who has died of covid; they have been adorned with remembrances and gifts from their colleagues.

There is one for Kim King-Smith, 53, the friendly EKG technician, who visited friends of friends or family whenever they ended up in the hospital.

One for Danilo Bolima, 54, the nurse from the Philippines who became a professor and was the head of patient care services.

One for Obinna Chibueze Eke, 42, the Nigerian nursing assistant, who asked friends and family to pray for him when he was hospitalized with covid.

"Each day, we remember our fallen colleagues and friends as the heroes who helped keep us going throughout this pandemic and beyond," hospital president and CEO Dr. Shereef Elnahal said in a statement. "We can never forget their contributions and their collective passion for this community, and each other."

Just outside the building, stands a 12th tree. "It's going to be for whoever else we lose in this battle," Beniquez said.

This story is part of "Lost on the Frontline," an ongoing project from The Guardian and Kaiser Health News that aims to document the lives of healthcare workers in the U.S. who die from COVID-19, and to investigate why so many are victims of the disease. If you have a colleague or loved one we should include, please share their story.

The affordability problem is worsened by soaring list prices for many specialty drugs used to treat cancer and other serious diseases.

This article was published on Monday, January 4, 2021 in Kaiser Health News.

By Harris Meyer

Sharon Clark is able to get her life-sustaining cancer drug, Pomalyst — priced at more than $18,000 for a 28-day supply — only because of the generosity of patient assistance foundations.

Clark, 57, a former insurance agent who lives in Bixby, Oklahoma, had to stop working in 2015 and go on Social Security disability and Medicare after being diagnosed with multiple myeloma, a blood cancer. Without the foundation grants, mostly financed by the drugmakers, she couldn't afford the nearly $1,000 a month it would cost her for the drug, since her Medicare Part D drug plan requires her to pay 5% of the list price.

Every year, however, Clark has to find new grants to cover her expensive cancer drug.

"It's shameful that people should have to scramble to find funding for medical care," she said. "I count my blessings, because other patients have stories that are a lot worse than mine."

Many Americans with cancer or other serious medical conditions face similar prescription drug ordeals. It's often worse, however, for Medicare patients. Unlike private health insurance, Part D drug plans have no cap on patients' 5% coinsurance costs once they hit $6,550 in drug spending this year (rising from $6,350 in 2020), except for very low-income beneficiaries.

President-elect Joe Biden favors a cap, and Democrats and Republicans in Congress have proposed annual limits ranging from $2,000 to $3,100. But there's disagreement about how to pay for that cost cap. Drug companies and insurers, which support the concept, want someone else to bear the financial burden.

That forces patients to rely on the financial assistance programs. These arrangements, however, do nothing to reduce prices. In fact, they help drive up America's uniquely high drug spending by encouraging doctors and patients to use the priciest medications when cheaper alternatives may be available.

Growing Expense of Specialty, Cancer Medicines

Nearly 70% of seniors want Congress to pass an annual limit on out-of-pocket drug spending for Medicare beneficiaries, according to a KFF survey in 2019. (KHN is an editorially independent program of KFF.)

The affordability problem is worsened by soaring list prices for many specialty drugs used to treat cancer and other serious diseases. The out-of-pocket cost for Medicare and private insurance patients is often set as a percentage of the list price, as opposed to the lower rate negotiated by insurers.

For instance, prices for 54 orally administered cancer drugs shot up 40% from 2010 to 2018, averaging $167,904 for one year of treatment, according to a 2019 JAMA study. Bristol Myers Squibb, the manufacturer of Clark's drug, Pomalyst, has raised the price 75% since it was approved in 2013, to about $237,000 a year. The company believes "pricing should be put in the context of the value, or benefit, the medicine delivers to patients, healthcare systems and society overall," a spokesperson for Bristol Myers Squibb said via email.

As a result of rising prices, 1 million of the 46.5 million Part D drug plan enrollees spend above the program's catastrophic coverage threshold and face $3,200 in average annual out-of-pocket costs, according to KFF. The hit is particularly heavy on cancer patients. In 2019, Part D enrollees' average out-of-pocket cost for 11 orally administered cancer drugs was $10,470, according to the JAMA study.

The median annual income for Medicare beneficiaries is $26,000.

Medicare patients face modest out-of-pocket costs if their drugs are administered in the hospital or a doctor's office and they have a Medigap or Medicare Advantage plan, which caps those expenses.

But during the past several years, dozens of effective drugs for cancer and other serious conditions have become available in oral form at the pharmacy. That means Medicare patients increasingly pay the Part D out-of-pocket costs with no set maximum.

"With the high cost of drugs today, that 5% can be a third or more of a patient's Social Security check," said Brian Connell, federal affairs director for the Leukemia & Lymphoma Society.

This has forced some older Americans to keep working, rather than retiring and going on Medicare, because their employer plan covers more of their drug costs. That way, they also can keep receiving financial help directly from drugmakers to pay for the costs not covered by their private plan, which isn't allowed by Medicare.

'This Is a Little Nuts'

All this has caused financial and emotional turmoil for people who face a life-threatening disease.

Marilyn Rose, who was diagnosed with chronic myeloid leukemia three years ago, until recently was paying nothing out-of-pocket for her cancer drug, Sprycel, which has a list price of $176,500 a year. That's because Bristol Myers Squibb, the manufacturer, paid her insurance deductible and copays for the drug.

But the self-employed artist and designer, who lives in West Caldwell, New Jersey, recently turned 65 and went on Medicare. The Part D plan offering the best deal on Sprycel charges more than $10,000 a year in coinsurance for the drug.

Rose asked her oncologist if she could switch to an alternative medication, Gleevec, for which she'd pay just $445 a year. But she ultimately decided to stick with Sprycel, which her doctor said is a longer-lasting treatment. She hopes to qualify for financial aid from a foundation to cover the coinsurance but won't know until sometime this month.

"It's just strange you have to make a decision about your treatment based on your finances rather than what's the right drug for you," she said. "I always thought that when I get to Medicare age I'll be able to breathe a sigh of relief. This is a little nuts."

Given the sticker shock, many other patients choose not to fill a needed prescription, or delay filling it. Nearly half of patients who face a price of $2,000 or more for a cancer drug walk away from the pharmacy without it, according to a 2017 study. Fewer than half of Medicare patients with blood cancer received treatment within 90 days of their diagnosis, according to a 2019 study commissioned by the Leukemia & Lymphoma Society.

"If I didn't do really well at scrounging free drugs and getting copay foundations to work with us, my patients wouldn't get the drug, which is awful," said Dr. Barbara McAneny, an oncologist in Albuquerque, New Mexico, and past president of the American Medical Association. "Patients would just say, 'I can't afford it. I'll just die.'"

The high drug prices and coverage gaps have forced many patients to rely on complicated financial assistance programs offered by drug companies and foundations. Under federal rules, the foundations can help Medicare patients as long as they pay for drugs made by all manufacturers, not just by the company funding the foundation.

But Daniel Klein, CEO of the PAN Foundation, which provides drug copay assistance to more than 100,000 people a year, said there are more patients in need than his foundation and others like it can help.

"If you are a normal consumer, you don't know much about any of this until you get sick and all of a sudden you find out you can't afford your medication," he said. Patients are lucky, he added, if their doctor knows how to navigate the charitable assistance maze.

Yet many don't. Daniel Sherman, who trains hospital staff members to navigate financial issues for patients, estimates that fewer than 5% of U.S. cancer centers have experts on staff to help patients with problems paying for their care.

Sharon Clark, who struggles to cover her cancer drugs, works with the Leukemia & Lymphoma Society counseling other patients on how to access helping resources. "People tell me they haven't started treatment because they don't have money to pay," she said. "No one in this country should have to choose between housing, food or medicine. It should never be that way, never."

This article is part of a series on the impact of high prescription drug costs on consumers made possible through the 2020 West Health and Families USA Media Fellowship.

With the world's attention gripped by the spread of the coronavirus, infectious disease experts are redoubling their efforts to show the robust connection between the health of nature, wildlife and humans.

This article was published on Monday, January 4, 2021 in Kaiser Health News.

By Jim Robbins

As the covid-19 pandemic heads for a showdown with vaccines it's expected to lose, many experts in the field of emerging infectious diseases are already focused on preventing the next one.

They fear another virus will leap from wildlife into humans, one that is far more lethal but spreads as easily as SARS-CoV-2, the strain of coronavirus that causes covid-19. A virus like that could change the trajectory of life on the planet, experts say.

"What keeps me up at night is that another coronavirus like MERS, which has a much, much higher mortality rate, becomes as transmissible as covid," said Christian Walzer, executive director of health at the Wildlife Conservation Society. "The logistics and the psychological trauma of that would be unbearable."

SARS-CoV-2 has an average mortality rate of less than 1%, while the mortality rate for Middle East respiratory syndrome, or MERS — which spread from camels into humans — is 35%. Other viruses that have leapt the species barrier to humans, such as bat-borne Nipah, have a mortality rate as high as 75%.

"There is a huge diversity of viruses in nature, and there is the possibility that one has the Goldilocks characteristics of pre-symptomatic transmission with a high fatality rate," said Raina Plowright, a virus researcher at the Bozeman Disease Ecology Lab in Montana. (Covid-19 is highly transmissible before the onset of symptoms but fortunately is far less lethal than several other known viruses.) "It would change civilization."

That's why in November the German Federal Foreign Office and the Wildlife Conservation Society held a virtual conference called One Planet, One Health, One Future, aimed at heading off the next pandemic by helping world leaders understand that killer viruses like SARS-CoV-2 — and many other less deadly pathogens — are unleashed on the world by the destruction of nature.

With the world's attention gripped by the spread of the coronavirus, infectious disease experts are redoubling their efforts to show the robust connection between the health of nature, wildlife and humans. It is a concept known as One Health.

While the idea is widely accepted by health officials, many governments have not factored it into policies. So the conference was timed to coincide with the meeting of the world's economic superpowers, the G20, to urge them to recognize the threat that wildlife-borne pandemics pose, not only to people but also to the global economy.

The Wildlife Conservation Society — America's oldest conservation organization, founded in 1895 — has joined with 20 other leading conservation groups to ask government leaders "to prioritize protection of highly intact forests and other ecosystems, and work in particular to end commercial wildlife trade and markets for human consumption as well as all illegal and unsustainable wildlife trade," they said in a recent press release.

Experts predict it would cost about $700 billion to institute these and other measures, according to the Wildlife Conservation Society. On the other hand, it's estimated that covid-19 has cost $26 trillion in economic damage. Moreover, the solution offered by those campaigning for One Health goals would also mitigate the effects of climate change and the loss of biodiversity.

The growing invasion of natural environments as the global population soars makes another deadly pandemic a matter of when, not if, experts say — and it could be far worse than covid. The spillover of animal, or zoonotic, viruses into humans causes some 75% of emerging infectious diseases.

But multitudes of unknown viruses, some possibly highly pathogenic, dwell in wildlife around the world. Infectious disease experts estimate there are 1.67 million viruses in nature; only about 4,000 have been identified.

SARS-CoV-2 likely originated in horseshoe bats in China and then passed to humans, perhaps through an intermediary host, such as the pangolin — a scaly animal that is widely hunted and eaten.

While the source of SARS-CoV-2 is uncertain, the animal-to-human pathway for other viral epidemics, including Ebola, Nipah and MERS, is known. Viruses that have been circulating among and mutating in wildlife, especially bats, which are numerous around the world and highly mobile, jump into humans, where they find a receptive immune system and spark a deadly infectious disease outbreak.

"We've penetrated deeper into eco-zones we've not occupied before," said Dennis Carroll, a veteran emerging infectious disease expert with the U.S. Agency for International Development. He is setting up the Global Virome Project to catalog viruses in wildlife in order to predict which ones might ignite the next pandemic. "The poster child for that is the extractive industry — oil and gas and minerals, and the expansion of agriculture, especially cattle. That's the biggest predictor of where you'll see spillover."

When these things happened a century ago, he said, the person who contracted the disease likely died there. "Now an infected person can be on a plane to Paris or New York before they know they have it," he said.

Meat consumption is also growing, and that has meant either more domestic livestock raised in cleared forest or "bush meat" — wild animals. Both can lead to spillover. The AIDS virus, it's believed, came from wild chimpanzees in central Africa that were hunted for food.

One case study for how viruses emerge from nature to become an epidemic is the Nipah virus.

Nipah is named after the village in Malaysia where it was first identified in the late 1990s. The symptoms are brain swelling, headaches, a stiff neck, vomiting, dizziness and coma. It is extremely deadly, with as much as a 75% mortality rate in humans, compared with less than 1% for SARS-CoV-2. Because the virus never became highly transmissible among humans, it has killed just 300 people in some 60 outbreaks.

One critical characteristic kept Nipah from becoming widespread. "The viral load of Nipah, the amount of virus someone has in their body, increases over time" and is most infectious at the time of death, said the Bozeman lab's Plowright, who has studied Nipah and Hendra. (They are not coronaviruses, but henipaviruses.) "With SARS-CoV-2, your viral load peaks before you develop symptoms, so you are going to work and interacting with your family before you know you are sick."

If an unknown virus as deadly as Nipah but as transmissible as SARS-CoV-2 before an infection was known were to leap from an animal into humans, the results would be devastating.

Plowright has also studied the physiology and immunology of viruses in bats and the causes of spillover. "We see spillover events because of stresses placed on the bats from loss of habitat and climatic change," she said. "That's when they get drawn into human areas." In the case of Nipah, fruit bats drawn to orchards near pig farms passed the virus on to the pigs and then humans.

"It's associated with a lack of food," she said. "If bats were feeding in native forests and able to nomadically move across the landscape to source the foods they need, away from humans, we wouldn't see spillover."

A growing understanding of ecological changes as the source of many illnesses is behind the campaign to raise awareness of One Health.

One Health policies are expanding in places where there are likely human pathogens in wildlife or domestic animals. Doctors, veterinarians, anthropologists, wildlife biologists and others are being trained and training others to provide sentinel capabilities to recognize these diseases if they emerge.

The scale of preventive efforts is far smaller than the threat posed by these pathogens, though, experts say. They need buy-in from governments to recognize the problem and to factor the cost of possible epidemics or pandemics into development.

"A road will facilitate a transport of goods and people and create economic incentive," said Walzer, of the Wildlife Conservation Society. "But it will also provide an interface where people interact and there's a higher chance of spillover. These kinds of costs have never been considered in the past. And that needs to change."

The One Health approach also advocates for the large-scale protection of nature in areas of high biodiversity where spillover is a risk.

Joshua Rosenthal, an expert in global health with the Fogarty International Center at the National Institutes of Health, said that while these ideas are conceptually sound, it is an extremely difficult task. "These things are all managed by different agencies and ministries in different countries with different interests, and getting them on the same page is challenging," he said.

Researchers say the clock is ticking. "We have high human population densities, high livestock densities, high rates of deforestation — and these things are bringing bats and people into closer contact," Plowright said. "We are rolling the dice faster and faster and more and more often. It's really quite simple."