The U.S. Is Sitting on Promising Ebola Vaccines
August 7, 2014
Zoë Schlanger and Elijah Wolfson* [caption id="attachment_10852" align="alignleft" width="300"] Locals watch workers with Doctors Without Borders at a private clinic working to combat the spread of the Ebola virus in Teldou, Guinea, July 10, 2014. Samuel Aranda/The New York Times/Redux[/caption]
Ebola was once thought to be a intermittent scourge limited to the bush of Central Africa. The virus would jump from its animal hosts to a nearby community eating those animals, but these outbreaks flared up and quickly “burned out,” killing about 1,600 people over the nearly four decades since the first case was identified in a Sudanese factory worker in 1976.
But now, with easier travel and more permeable borders, an Ebola outbreak has spread from rural villages to populous hubs where it has never been before, like Guinea’s coastal capital of Conakry, a city of some 2 million, where it is likely to become endemic. “Before this outbreak, Ebola was not known to be present in Sierra Leone, in Liberia, in Conakry. But it is now present there,” says Stephen Morrison, the director of the Global Health Policy Center at the Center for Strategic and International Studies. “If it recedes, it does not mean it is not present. You will see more outbreaks. It will be recurrent.”
It’s spreading faster and farther than ever before. One American who contracted the virus, Patrick Sawyer, 40, would have boarded a plane to Minnesota had he not died in Lagos. He had flown from Liberia to Ghana to Togo before arriving at Nigeria’s largest city. That’s five countries in one trip, with countless new pathways to infection along the route. Modern borders are as porous as the number of flights, goods and people that cross them, which is to say they are extremely permeable. Viruses are along for the ride, spreading farther than they ever have.On August 2, an American infected with the virus was flown to the U.S. His transport was delicate—staff covered head to toe in nonporous hazmat suits placed the patient in an isolation pod for the flight. From the airport, he was transferred to Emory University in Atlanta, which has one of the country’s four specially equipped isolation wards and staff specifically trained to handle highly infectious disease. A second American patient is expected to be similarly flown from Africa to Atlanta on August 5.
The two Americans, Dr. Kent Brantly and Nancy Writebol, were both health care workers who had been volunteering in Africa. Somehow, despite wearing full hazmat suits while working with Ebola patients, they contracted the disease that, as of this writing, has killed a suspected 826 people in four countries over the past six months in the most deadly Ebola outbreak in history.
And yet, despite much hyperventilating on network news and social media about the transport of these Ebola victims, Brantly and Writebol will almost certainly not bring this deadly plague to America. And even if they did, the consequences would be minor. “If [Ebola] were to appear in the U.S., it would stop very rapidly in its tracks. The whole dynamic of transmission of this virus doesn’t exist here,” says Ian Lipkin, the epidemiologist and Columbia University professor credited for identifying West Nile virus as the cause of a 1999 encephalitis epidemic in New York City.
Unlike H1N1 swine flu, which killed as many as 575,400 people across 74 countries during a 2009 pandemic, Ebola is not airborne. It is spread only by bodily fluids. By the time people become contagious, they are extremely ill and would quickly come under medical care (at least in the U.S.). Also, with a “good culture of infection control, blood and bodily fluids would be handled in the correct manner,” says Dr. Amesh Adalja, an infectious disease physician at the University of Pittsburgh who analyzes threats and response plans for hospitals. Ebola would be contained like Lassa fever, another virally transmitted hemorrhagic fever, which has reached the U.K. eight times since 1980 and has been snuffed out without anyone becoming infected or the public even paying much mind.
News about the spread of Ebola, on the other hand, could never be buried. Nightmarish images of blood-spewing people dying horrible deaths while their internal organs are destroyed have been seared into our brains. We already have a picture of what an outbreak in the U.S. would look like: The 1995 film Outbreak imagined a monkey-hosted, Ebola-like virus spreading from a lab in California and prompting martial law. Plus, as we learned from Richard Preston’s 1994 best-selling nonfiction thriller The Hot Zone, a simple headache could be the first symptom of something much graver, and deadlier, like Ebola. Mass paranoia and gore-panic can be ignited at the mere mention of the disease.
One reason Ebola inspires so much public fear is that it is, right now, essentially untreatable. And yet a vaccine could be ready in as little as two years, according to Heinz Feldmann of the U.S. National Institute of Allergy and Infectious Diseases, a branch of the National Institutes of Health. If only the disease could generate as much funding and political will as it does panic.
Today, several vaccines and drugs are on the edge of becoming useful—they have shown promise in animal studies, and some are so far along that human clinical trials could probably have begun at any time in the past several years, Feldmann says. One promising vaccine he helped develop was shown in lab tests to fully protect rhesus macaques against contracting Ebola-Zaire, the strain now tearing through Central and West Africa. It even worked as a treatment—it saved four out of eight animals infected with the virus. For an infection that can sometimes reach a kill rate in humans of around 90 percent, those are excellent results.
“What is frustrating is that we have another outbreak where potentially none of these treatment options are being used,” Feldmann says. “The thinking has to change now. We can’t just wait and wait and wait. Some of these vaccines have been stuck in this position for 10 years.”
The lack of funding is largely due to a lack of interest shown by pharmaceutical companies, for whom a rural, relatively low-kill African disease presents no lucrative market. Ebola research did gain some financial footing after anthrax attacks sent through the mail killed five and put the country on a bioterror alert in 2001. Ebola looked like a prime candidate for a future attack: Some strains have killed 90 percent of the people infected. While it can be transmitted only via bodily fluids, “once it hits, there are a lot of bodily fluids,” says Morrison. The virus causes hemorrhagic fever, which makes the blood unable to clot wherever the virus’s minute infectious agents, called virons, tear through tissue. In the worst cases, blood gushes from all orifices, which is part of why the U.S. Centers for Disease Control and Prevention (CDC) notes that the disease would likely prompt “public panic and social disruption.”
The U.S. has classified Ebola a “Category A” potential bioterror agent, listed at the highest priority level. Millions of federal dollars were put toward developing countermeasures should the virus be used as a bioterrorism agent. (In 2013, the National Institute of Allergy and Infectious Diseases reported spending $42.49 million on Ebola research.) But that hasn’t proved enough to bring even a single promising vaccine to the market. Feldmann frets that after this outbreak, the sense of threat and urgency surrounding Ebola will fade, as will the prospects for advancing Ebola pharmaceuticals. “My biggest worry is that after this outbreak is over, that everyone will go back to normal. We have to make sure that doesn’t happen.”
Were it not for a lack of funding, the death toll of this Ebola outbreak could have been much lower. “The notion that we should sit by idly while thousands die in other parts of the world is unconscionable,” Lipkin says.
nto the Wild
But what may be even more important than finding a cure for Ebola—both for the countries where it is endemic and those outside of Africa—is developing a way to prevent the next, currently unknown infectious disease from emerging from the wild. And that would take a truly global approach.
Public health experts know Ebola outbreaks begin in wild animals and jump to humans who eat them or come into contact with their feces, urine or saliva. Ebola doesn’t harm every animal host in infects; it thrives in certain animals—the “reservoir” species—for years between human outbreaks. Though no one knows for sure, bats are considered the most likely reservoir species for the Ebola virus. Bats are eaten in the West African regions where Ebola has recently erupted, as are chimpanzees, which may come into contact with fruit eaten by the bats, or bat waste.
Ebola may not pose as great a trans-Atlantic threat as H1N1, SARS or MERS, but all of them share similar zoonotic origins: They all jumped from animals to humans. SARS, it turns out, made the leap from bats as well. The 2003 SARS pandemic, which killed 774 and infected 8,098 people worldwide, emerged in China, where wildlife species were brought to urban live animal markets from regions all over the country. Scientists discovered that bats were the likely source of SARS and were transmitting it to civets (a small, farmed mammal sometimes eaten) in live animal markets in southern China.
Butchering and handling the meat in those crowded markets spread the pathogen further. Soon the government banned the sale of civets. Bats technically should not have been present in the markets anyway, based on wildlife protection laws enacted in 1989, but because there is a big demand for wildlife species in the area, there was (and still are) underground wildlife markets in various parts of China. The ongoing MERS outbreak had similar bat-related origins in the Middle East.
The link between wildlife spillover and the threat posed by major global pandemics are a growing field of inquiry, and the United States Agency for International Development (USAID) has established a dedicated Emerging Pandemic Threats (EPT) consortium of experts designed to establish an early-warning system for those connections. “We wanted to find a way to get ahead of the curve—to get beyond the traditional model of waiting until there’s an outbreak, and trying to respond, contain and trace it back to its source,” says Jonathan Epstein, an epidemiologist with the nonprofit EcoHealth Alliance, which is part of the USAID consortium. EPT works with local governments to identify viruses in wildlife hosts that have the potential to cause pandemics, as well as to conduct surveillance in high-risk activities, like wildlife markets, that bring people or livestock in closer contact with wildlife and increase the risk of viral spillover.
This work, though, is complicated by the same forces that make it a pressing need. When researchers from developed countries like the U.S. and nations in Western Europe enter the places where emerging infectious diseases are endemic, they face the uncomfortable reality that the most effective means of keeping the people of Africa, Southeast Asia and parts of Latin America safe from disease requires changing their culture. Communities in close contact with their animals rely on hunting bushmeat to feed their families, and they consider physical closeness a key component of family values. Those factors negate the traditional public health approaches.
Epstein says that when researchers move in, they start small. “Hand washing can be a very simple and effective strategy for reducing the risk of infection, but even so, it’s still not such an easily adopted behavior,“ he says. But more radical changes are less likely to take hold. “Experience has shown that outright bans on behavior typically don’t work,” he adds. Imposing Western sensibilities of what people should eat, or how they should behave, invariably backfires. “We’re dealing with deeply ingrained cultural practices. Rather than trying to stop these activities, which is unrealistic and culturally insensitive, we make a big effort to work with government and local partners in countries to adapt behavior such that the risk is reduced.”
For example, in the mid-2000s in Bangladesh an illness caused by Nipah virus infection spread among locals by way of date palm sap that had been contaminated by infected bats. The date palm sap was an essential component of the local culture, trade and diet. Every night, sap salesmen would tap the date palm trees and allow the sap to collect in a pot overnight; in the morning, they would collect it and then sell it door to door. Instead of putting an end to the practice, anthropologists and health officials from the Bangladesh-based International Centre for Diarrhoeal Disease Research worked with the locals to develop an affordable bamboo skirt that could be placed above the pot, to keep bats from getting into the sap. (EPT helped promote their use.) It also kept out bugs, dirt and other contaminants, and the result was a better product the locals could sell for more money —and one that would keep their communities free of the Nipah virus.
These nuanced programs require time and money, neither of which are in great supply. The World Health Organization recently moved much of their funds away from communicable disease work amid stifling budgetary restrictions. The U.S. CDC and the NIH have been similarly squeezed.
Earlier this year, the Obama administration pledged $85 million over two years to help 10 nations build their capacity to identify and contain infectious disease outbreaks. “That’s just scratching the surface,” says Morrison. “We know that [infectious disease management] has to be driven by external dollars, and this has to be a long-term plan. It shouldn’t be something that the U.S. alone is out doing… [But] there is no free-standing dedicated budgetary line for this in the U.S. budgets.” He says that’s a dangerous mistake.
David Quammen, the author of Spillover, an ominous chronicle of the evolution of human epidemics, says agencies that monitor and prevent outbreaks are of the utmost national importance. “We should look at this outbreak in West Africa and if we find it scary, then next time the budget comes around and Congress is talking about cutting funds for the CDC, the public should rise up and say no.”
While global air travel is making disease perilously easy to spread, climate change, which is rearranging and in some cases expanding habitats for carrier animals, is poised to make future outbreaks of Ebola, H1N1, TB, and a host of other diseases worse. As humans encroach further into previously wild domain, exposure patterns will change. The possibility that a disease could mutate into a stronger version of itself, or a previously animal-only pathogen could make the leap into humans, is not science fiction.
“The question is not whether there will be a Next Big One, but which virus it will be, and how bad it’ll be, and how big it’ll be,” Quammen says. “More of these things are going to happen.”
UPDATE, Aug. 4, 2014 2:05 PM: The two Americans stricken with Ebola, Dr. Kent Brantly and Nancy Writebol, have been given an experimental treatment for the virus, reports CNN. The treatment is called ZMapp, and was developed by the biotech from Mapp Biopharmaceutical Inc. According to CNN, the patents were “told that this treatment had never been tried before in a human being, but had shown promuise in small experiments with monkeys.” Reportedly within an hour of receiving the medication, Brantly’s symptoms improved dramatically. Writebol’s first dose did not have immediate effect, but the second dose resulted in “significant improvement.” Five days ago, the Defense Threat Reduction Agency awarded additional funding to Mapp Biopharmaceutical for the “promising results” the ZMapp treatment had shown.
Nkemnji Global Tech
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