Earlier this week, all eyes were fixed on media images of Kent Brantly, a 33-year-old American doctor infected with the Ebola virus, walking from an ambulance into Atlanta’s Emory University Hospital wearing a white, full-body biocontainment suit. Brantly arrived on Sunday, followed two days later by 59-year-old Nancy Writebol, another Ebola-infected American aid worker airlifted from Liberia to Emory for medical care. They are being treated with ZMapp, an experimental drug developed by San Diego, Calif.-based Mapp Biopharmaceutical that has not previously been tested on humans or received regulatory approval.
The fears surrounding Ebola are those of the unknown, as a global effort is under way to better understand the virus, contain it and treat victims in the absence of an approved vaccine or drug. Beginning in March this year, Ebola has thus far claimed 867 lives in the four West African nations of Guinea, Liberia, Sierra Leone and Nigeria; another 1,603 people are suspected of, or have a confirmed, Ebola infection, according to latest updates from the U.S. Centers for Disease Control and Prevention (CDC). It is the worst Ebola outbreak since the virus was first discovered 38 years ago in Sudan and Congo.
The seriousness of Ebola has prompted governments, health care workers and other stakeholders worldwide to weigh the strategies they should pursue to contain it, spread awareness and create incentives for vaccine and drug development. They are also taking into account the lessons that can be learned from past epidemics like the 2003 SARS (severe acute respiratory syndrome) outbreak, the H1N1 (“swine flu”) epidemic of 2009-2010 and the experiences of other developing countries battling diseases.
The CDC describes Ebola as a hemorrhagic fever that is severe and often fatal in humans and nonhuman primates such as monkeys, gorillas and chimpanzees. “It’s basically [the] hemorrhage” that kills patients, says Harvey Rubin, professor of medicine at the University of Pennsylvania’s Perelman School of Medicine. “They bleed into their brain, their kidneys, liver and lungs. You can die very, very quickly, but it depends on the how bad the particular organ involved is.” That process can be “very painful,” but physicians usually put such patients in an induced coma to prevent them from feeling the pain, he adds.
What Are the Risks?
The Ebola management effort faces multiple challenges, but for starters, not everybody agrees on the risks of the spread of the disease. The U.S. has issued travel warnings to Americans, and the International Civil Aviation Organization and the International Air Transport Association (IATA) have been working to prevent its spread on flights. Sanjay Gupta, CNN’s chief medical correspondent, said that there should no longer be the expectation that the disease will remain confined to just a few rural areas in West Africa — today, people can fly from West Africa to anywhere in the world, he noted in a CNN report.
“Two and a half million kids a year die of vaccine-preventable deaths, because the cold chain doesn’t work in the most remote parts of the world where there is no power.” –Harvey Rubin
The CDC is not so alarmist. “It’s very unlikely that they would be able to spread the disease to fellow passengers,” Stephen Moore, deputy director of the CDC’s National Center for Emerging Zoonotic and Infectious Diseases, said in the same CNN report. (Incidentally, a CDC official told Time magazine on Tuesday that it had received “several dozen calls” from states and hospitals about people who are ill after traveling in Africa. But specimens from a half-dozen or so of those cases tested negative for Ebola, the CDC added.)
“This particular strain of Ebola appears to be very virulent with very high mortality,” Rubin notes. “Generally speaking, Ebola is transmitted only by close contact with infected bodily fluids — blood, saliva, stool, urine. There is an outside, very remote chance that it could spread by aerosol — with a direct sneeze or cough into somebody’s face.” He notes that the CDC has issued guidance that at-risk individuals traveling on airplanes are to be given masks.
Stephen Sammut, a lecturer in Wharton’s health care management department, says that quarantining travelers returning from Ebola zones is “not practical” and suggests rapid diagnostic assessments in such cases. “The average time between contracting the infection and the start of symptoms is eight to 10 days, but can occur between two and 21 days,” he notes. “A lot can happen in that interval in the way of travel and transmission, and an infected person can be anywhere in the world.” That situation is a potential hazard for a country that is home to a traveler who has been exposed to Ebola, he adds.
A crucial aspect of treating Ebola-infected patients is administering the correct supportive care, where they are given fluids to replenish what they lose from vomiting and diarrhea, and drugs to reduce fevers. If an Ebola victim’s kidney is failing, it is essential that trained experts administer their dialysis, says Rubin.
According to Sammut, public health and crisis intervention programs in the Ebola-affected countries should be provided by well-trained groups that local populations trust. Outsiders don’t always understand cultural death rituals and funerary practices, he adds. “[However,] having local capacity in place means a long-term investment by someone.”
Coordinating a Scaled Response
Erwann Michel-Kerjan, executive director of the Wharton Risk Management and Decision Processes Center, studied several crisis situations for a 2010 book he co-authored with Paul Slovic, titled, The Irrational Economist: Making Decisions in a Dangerous World. The first priority in a case like Ebola is coordination, he says. “Actions have to be coordinated across the globe among responsible bodies — the WHO (World Health Organization), IATA, the CDC and its equivalent in other countries. Coordination also has to happen between the public sphere and businesses whose employees travel all the time.”
Also key to containing the virus is “live tracking,” he says. “Knowledge about the virus has to be constantly updated, and tipping points looked after very seriously,” he explains. For example, if suddenly the number of victims rises exponentially in one place, or if new cases emerge in unexpected locations, those need to be integrated into a global action plan.
Robert Meyer, co-director Wharton’s Risk Management and Decision Processes Center and a marketing professor, doesn’t expect governments to be unprepared in dealing with Ebola. “This is extremely well-charted territory,” he says. “For example, the 2003 global SARS outbreak was a much larger event in scale.”
“Except for a few dedicated scientific teams, Ebola is a case of out of sight, out of mind.” –Stephen Sammut
According to Meyer, one of the big challenges in scaling a proper response to potential epidemics — like any hazard – “is that one has to undertake preventive action before the scale of the threat is realized, and getting the tuning right is hard.” Governments or other organizations may react disproportionately to health emergencies, he adds. “Draconian over-reactions insure that the impact is minimized, but they also risk false-alarm effects, whereby people are more skeptical when warnings are issued about future threats.” He recalls that in the immediate aftermath of the SARS outbreak, critics said the disease control offices in some countries overreacted, including the “ubiquitous wearing of face masks.” (SARS originated in Asia and later spread to more than two dozen countries across Europe and the Americas, infecting more than 8,000 people and claiming 774 lives, according to the CDC.) However, Meyer doesn’t see any overreaction to Ebola, and finds the CDC’s response “appropriately measured” with travel warnings and other precautions.
Determining the right measure of caution is “always a difficult balancing act,” says Michel-Kerjan. “While people want government agencies to protect them, many are not ready to give up their freedom to travel. They have made plans a long time ago or need to be at an important business meeting next week.”
Such an attitude may prove costly, warns Michel-Kerjan. “Crying wolf has always been the enemy of good crisis management, but if you don’t do it and then something bad happens, you are even more at fault,” he points out. Therefore, a slight overreaction on the part of the government may not be a bad thing. Businesses, too, have to worry about reputations as they decide on how best to react to disease outbreaks, he adds.“No CEO wants the name of his or her firm on the front page of the Wall Street Journal because several of their people are sick due to a lack of proper crisis management.”
‘Optimistic Bias’ at Work
Using laboratory simulations, Meyer and his colleagues have shown that failures of preparation often precede catastrophes such as hurricanes Katrina and Sandy, and such missteps are “consistent with a number of hard-wired biases in how people respond to risk.” In the case of Ebola, Meyer feels another such bias may be at work. “What is [worrisome] is what psychologists call the ‘optimistic bias’ — a tendency to underestimate the personal risk of a threat relative to that of the general population.”
Meyer explains how that optimistic bias plays out. A person traveling to Sierra Leone may believe that the odds are fair that the typical traveler could contract the disease. But he or she would consider their own odds of getting infected to be low. “They [believe they] will be more careful, and diseases are things that happen to other people,” he notes. “This was always one of the reasons that AIDS was difficult to get under control and [why] people don’t stop smoking. We have no problem believing that there are problems — we are not in denial — but we have a tendency to believe that we are more immune than the average person in the population.”
Trust, Fear and Suspicion
In coordinating an effective response to Ebola in western Africa, the primary issues have to do with “trust, fear and suspicion,” according to Sarah A. Tishkoff, professor of genetics at the Perelman School of Medicine at the University of Pennsylvania. Tishkoff’s research specialties include genetics research in Africa, and she is also principal investigator at Penn’s Tishkoff Lab, which studies disease risk in global populations, among others.
“Crying wolf has always been the enemy of good crisis management, but if you don’t do it and then something bad happens, you are even more at fault.” –Erwann Michel-Kerjan
“In many of the rural areas of Africa there is distrust of scientists who come into their community, unless time and care is taken to get to know the community and to explain what this disease is and how they can prevent it in a culturally sensitive manner,” she says. Things get difficult if preventive measures go against cultural norms of caring for the ill, Tishkoff adds. “Also, because they see that sick people go to the hospital and many never leave [because they have died,] they may associate hospitals with causing the disease rather than treating it, and therefore avoid bringing people in for treatment.”
In such circumstances, stopping the spread of this disease will require a massive public health outreach, says Tishkoff. The aid workers who go into the villages need to have some familiarity with local cultural aspects. They must also patiently and carefully explain the situation to the community, she adds. “My experience has been that nearly everyone can understand the broad issues and impact, even if they haven’t had a lot of formal education, as long as it’s properly explained and if the local leaders are on board and participating in community discussions.”
According to Rubin, relationships are important, such as those between villages and the health care teams that are trying to help them. Some societies may not take quarantines seriously enough if that concept is not part of their “cultural heritage or memory,” he adds.
Sammut underscores the importance of good communication in such cases. “The existence of a vaccine or other post-exposure intervention is only as effective as the local health systems and communication can deliver the information and products,” he says. Instead of “crisis intervention” only during outbreaks, West African governments must continuously track Ebola and educate the affected populations in good time, he notes.
A Call for Global Governance
According to Rubin, a “global governance system” for infectious diseases could be the solution in a case like Ebola. This would provide incentives for basic research and pharmaceutical R&D to develop new drugs and vaccines, and it would ensure that adequate surveillance and reporting is encouraged globally, he says.
In his capacity as director of Penn’s Institute for Strategic Threat Analysis and Response (ISTAR), which focuses on global threats including those from infectious diseases, Rubin is working to enlist the support of the U.S. government to create such a system. “Ebola is a perfect example of where global governance has failed,” he says. Although the current Ebola outbreak appears to be “relatively contained,” it could continue to take its toll in economic and development consequences for the four West African nations, he notes.
Creating a supportive environment for basic research and even developing new drugs and vaccines for infectious diseases are not enough, Rubin points out. Delivering those medicines to developing countries that don’t have uninterrupted power is an equally critical challenge. “Suppose you do get a vaccine for Ebola, which hopefully will happen in the next several years, how are you going to keep it cold when you try to deliver it to the most remote parts of the world?” he asks.
“What is [worrisome] is what psychologists call the ‘optimistic bias’ — a tendency to underestimate the personal risk of a threat relative to that of the general population.”— Robert Meyer
As it happens, Rubin and his colleagues came up with a solution to that problem a couple of years ago by setting up a nonprofit called Energize the Chain, which has installed vaccine refrigerators powered by cell phone towers at 110 sites in Zimbabwe. Work is underway to expand that with another 200 sites by 2015, and also into Lesotho and Burundi. Rubin thought up the idea of using cell phone towers in developing countries that are powered primarily with diesel generators in the wake of the 2010 Haiti earthquake. The trigger was a call from his actor friend and neighbor David Morse (whose credits include 1999’s The Green Mile and last year’s World War Z) about children dying in Haiti for want of vaccines.
“We can do more. We clearly have to do more,” says Rubin. “Two and a half million kids a year die of vaccine-preventable deaths, because the cold chain doesn’t work in [countries] where there is no power.”
Developing Treatments
One of the biggest challenges in a case like Ebola is to find ways to encourage the pharmaceutical industry to develop a treatment when the patient population is too small to justify investments. “The research community and the pharmaceutical community need to be incentivized to develop drugs and vaccines against this disease,” says Rubin. “Forget about Ebola, which affects a couple thousand people. Pharmaceutical companies don’t even make antibiotics [for diseases] which kill tens of thousands of people. So you have to find strategic, novel and innovative ways to get these things done.”
Ian MacMillan, Wharton management professor and director of the Sol C. Snider Entrepreneurial Research Center, notes that it is “tragic” that pharmaceutical companies may resist developing treatments for diseases like Ebola where the patient populations are not large. “The WHO might want to consider an innovative program to fund such research at major medical research schools in the advanced economies,” he says. That research agenda could include borrowing best practices from disaster management efforts in the private sector, he adds.
According to Rubin, a fair amount of research is already being done to find treatments for Ebola, despite the lack of market incentives. For now, the only potential Ebola treatment is ZMapp, which Rubin describes as an antibody used to jumpstart the body’s immune response to fight off the virus. “I applaud [Mapp] for taking on a problem that ordinarily doesn’t have much financial incentive,” he says.
Another approach to incentivize drug research that Rubin points to is a unique “evidence-based” plan designed by a scientific group he chairs called Health Impact Fund. In that plan, pharma companies would get payments based on the impact of their drugs rather than the conventional measure of the amount of drugs sold. Companies have to be willing to enter into development programs with the promise of a payment downstream on proof of impact, he notes.
Other ideas to encourage drug development have been around for a while. For example, Rubin cites “patent pools,” where multiple drug companies have a shared interest in developing medicines that may not make business sense for just one firm. Another is the so-called “advanced market agreement,” where governments would promise to pay pharmaceutical companies a certain amount of money if they develop medicines to treat specific diseases.
Sammut agrees that the market in West Africa for an Ebola vaccine is “small, sporadic and generally poor financially, so there is little incentive to invest in development of a vaccine.” Yet, he doesn’t blame drug companies that fail to act. “Ebola has become the poster child for neglected tropical diseases, but it would not be fair to find fault with the pharmaceutical industry [in this case]. We need a broader international approach for intervention in these diseases,” he says.
