2
A Wake-Up Call: The 2014
Ebola Outbreak Response
By the time Victor Dzau, president of the National Academy of Medicine, welcomed participants to the first day of the workshop on March 26, 2015, there were more than 24,000 reported cases of Ebola, and more than 10,000 reported deaths. While Liberia had only one new case the prior week and no new cases for 3 consecutive weeks before that, Sierra Leone and Guinea continued to face many new cases and challenges in controlling the outbreak. Following this workshop, Liberia had a reemergence of cases in July 2015, showing the world that help was still needed, and illustrating the lack of a vaccine or treatment, more than 1 year after the outbreak had begun.
Some experts believe the international response to EVD has failed miserably, Dzau stated. This chapter highlights what speakers described as critical gaps in preparedness and response across sectors. The multidisciplinary gaps include appreciating the threat level, achieving science preparedness, conducting disease surveillance, MCM development, relationship building, and accountability.
Gaps in Appreciation of the Threat and Consequences
According to Jeremy Farrar, director of the Wellcome Trust, the sense that the Ebola outbreak is coming to an end is misguided, and the “road to zero (cases)” is going to be bumpy and extraordinarily difficult. There was optimism in Guinea in August and September 2014, he said,
when the epidemic curve seemed to have peaked and the case count was decreasing. However, from August 2014 until March 2015, the curve has plateaued, and cases continue to be geographically dispersed, he explained. In contrast to epidemics like influenza, where population-level immunity develops, Ebola carries with it a difficult set of circumstances because the vast majority of people in the area remain susceptible to the virus.
If our efforts wane, if our interest dissipates, or we think it is done, … that will come back to haunt us.
— Jeremy Farrar, Director,
Wellcome Trust
Farrar expressed optimism about how the world is coming to regard emerging infectious diseases as priority areas with far-reaching consequences. As he stated, the Ebola outbreak not only has serious primary effects due to the direct outbreak itself, but also devastating secondary effects on health systems and society. In Guinea, Liberia, and Sierra Leone, he said, maternal and child health care, mental health care, diabetes management, and HIV care have all suffered during the EVD outbreak. As noted by Dzau, the three countries where Ebola has emerged already had preexisting fragile health systems, were emerging from a civil war, and/or lacked a sense of trust between the government and the governed. Still, the challenges of responding to epidemics are not limited to the developing world, nor are they limited to one nation or region, Farrar said. The United Kingdom, for example, had an intensive care occupancy rate of about 115 percent during the second wave of the H1N1 influenza epidemic in the winter of 2010. However, no intensive care units in the United Kingdom had spare ventilators. Additionally, urbanization is changing the nature of transmission of infections. Ebola is no longer a rural disease, and transmission occurs differently from previous outbreaks. In 1976, the average number of individuals in the Democratic Republic of the Congo associated with a single Ebola case was between 9 and 10. In 2014, the average number was 120 in Monrovia, Liberia. Individuals in urban centers travel more, have more contacts, and are often less willing to follow governing structures, he said. Most developing countries have fragile or fragmented health care systems, and there is not an appreciation of the benefits of public health, Farrar said. Health ministers in many countries are in relatively weak positions within executive body cabinets and are not empowered to be advocates for change within governments. In addition to strengthening the role of the health minister, it is also important to look beyond the health ministry
to the finance and other ministries to strengthen the focus on health, Farrar noted.
Gaps in Science Preparedness
In Western countries, clinicians now consider Ebola to be a survivable disease, but according to Assistant Secretary Lurie, this did not translate very well to the events in West Africa. In a step toward global science preparedness, new vaccines and therapies in development are being tested in both established research networks and new research networks in West Africa, many of which are being led locally by African partners. Despite these efforts to become more scientifically prepared, she lamented, there was no standardized case report form either for patients in West Africa or for medically evacuated patients. Currently, there are no published guidelines for treatment of Ebola patients in West Africa. Some treatment units, have published their protocols, but results vary across units, and there has not been sufficient analysis of what is successful. Similarly, for MERS-CoV, there is a case definition but no uniform case report form, and limited analysis of what treatment protocols are effective. This will be the case for the next infectious disease and the one after that, Lurie cautioned, unless a change is made now.
Sustainable Commitment
Development of MCM for Ebola has moved forward as the need is clearly understood, but this has not been the case for MERS-CoV, Chikungunya, or other emerging infectious diseases for which the need and commercial market is currently not well defined. The two prevalent MCM strategies for Ebola during this outbreak were new product development and repurposing of existing pharmaceuticals, Lurie explained. The repurposing of current drugs (e.g., favipiravir, brincidofovir, amidarone) has not been particularly successful, and she noted a lack of transparency existing around data and clinical trials. Intellectual property disputes, issues with technology transfer, and challenges with data and specimen sharing have also slowed down development. Lurie applauded companies around the world that committed their own funding to MCM development without any guarantee of financial return on that investment. Some vaccine and therapeutic candidate development has been done in other countries (e.g., Canada, China), but the level of
country investment around the world has not been comparable to that of the United States. This, she said, raises concerns about the ability to sustain such efforts. She also commended the speed and flexibility of the FDA with regard to MCM development and clinical trials, but noted concerns about the lack of global coordination of the trials being done in West Africa. Investigators and companies complicate coordination by seeking prestige and advantage in countries that are in a desperate situation, with inadequate infrastructure to sort out the overwhelming requests while trying to manage the epidemic response. Officials in one Ebola-stricken country told Lurie that they had been approached by 35 different companies and investigators wanting to set up clinical trials in their country. She suggested that opportunism has trumped scientific rationality in too many cases, making progress even more challenging.
Gaps in Data Collection and Surveillance
In West Africa, efforts to collect and transmit data were very limited until late in the epidemic because of the challenges of working in the “hot zone” itself, and because the humanitarian workers in those countries believe their primary mission to be caring for the very sick, not to perform scientific data collection and analysis, Assistant Secretary Lurie commented. Science preparedness1 was also hampered, she said, by global disagreements about study design, ethical standards, insufficient infrastructure to conduct clinical trials of any kind, and a perceived lack of urgency regarding how to move forward with experimental treatment therapies or potential vaccines.
Farrar stressed the importance of looking forward, adding that we tend to prepare for the previous epidemic when we need to prepare for the unknown disease in the next unexpected place. A greater understanding of the biology of epidemics is needed. For example, what drives the transmission route of a disease migrating from animal to human? What drives virulence in human-to-human transmission? Contemporary disease surveillance technology has uncovered an unprecedented number of circulating influenza viruses, but no one can predict which present the most risk in terms of developing into a global
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1ASPR defines “Science Preparedness” as a collaborative effort to establish and sustain a scientific research framework that can enable emergency planners, responders, and the whole community to better prepare for, respond to, and recover from major public health emergencies and disasters. For more information, see http://www.phe.gov/Preparedness/planning/science/Pages/overview.aspx (accessed August 11, 2015).
pandemic. Better and smarter global disease surveillance and the sharing of real-time data to inform decisions are critical, he added, and the capacity to respond should be associated with such surveillance efforts. He noted that there are also competing disincentives to sharing data and samples (e.g., some countries have said that if they share samples of pathogens from outbreaks, they will then be sold interventions at prices they cannot afford). He suggested the need for a dedicated epidemic surveillance and response unit within a global organization that is semi-autonomous from the WHO member states, and also has the mandate and the leadership to bring about the coordination that is needed.
Gaps in Sustainable MCM Development
Elements of sustainable MCM development include partner commitment, financial models to ensure long-term resources, infrastructure, trust, advocacy by and for the beneficiaries of MCM development, and building on existing strengths and progress. Scientifically, Lurie said, there has been tremendous progress, not just with new vaccines and therapies but also platforms for rapid development of diagnostics and for product manufacturing. However, we need better, more effective products, and we need them faster, she said. Also needed are better approaches to life cycle management for both targeted and broad-spectrum products. This includes longer-life-cycle products that can be stockpiled as well as dual-use products that have day-to-day applications and are readily accessible to health care delivery systems around the world.
Farrar expressed concern about partnerships not including industry at the table from the start. Industry wants to help, but it must be understood that it is there as a commercial enterprise. “We do not ask for a cheap battleship when working with defense budgets,” he said. “We ask for the best battleship and technology, and then we work out how we are going to afford it. Whereas with public health they ask for whatever can be bought with the least amount of money.” The dynamic of always asking for a cheap drug or affordable intervention for public health emergencies needs to change. “We will not have what we need unless we are willing to pay for it,” Farrar said. While some funding comes from philanthropy, governments often provide the majority of funding in a response. To make sure amounts are adequate, improved communication and true understanding of threats are needed.
Gaps in Relationship Building
A 21st-century public health response involves more than just public health measures (e.g., masks, isolation); it involves diagnostics, drugs, vaccines, information technology, logistics, and, where necessary, a military presence. The response needs to happen over days to weeks, not weeks to months or longer, Farrar emphasized. Getting there requires manufacturing capacity, regulations, ethics, design of studies, and other capacities that need to be developed in the interepidemic period. Farrar added that any activity not built on a trusting relationship between public health and communities will have limited success. Trust and mutual respect are built up over many years and involve local capacity building. They do not come from flying in with resources during a crisis and flying out when the event is over, he said.
Gaps in Accountability
The health infrastructure in developing countries, particularly where Ebola has recently emerged, is almost nonexistent despite decades of investment in health system strengthening by bilateral donors and national governments, said Rajeev Venkayya, president of the Global Vaccine Business Unit at Takeda Pharmaceuticals. This represents a colossal failure on the part of the global community, he said. Although substantial improvements have been made in maternal and child health, as well as immunization, there is not much more than well-functioning immunization programs in these countries. Venkayya considered improving the health infrastructure as a collective responsibility.
Many of these countries have resources, but they choose not to allocate sufficient resources to health, he said, illustrating Farrar’s previous statement about looking past the ministries of health to include other sectors and decision makers. Venkayya called for a need for accountability that ensures that donor funds complement government funding for health. In many cases, governments use donor funds to replace the funding that the national government had been investing in health (i.e., government money for health is reallocated elsewhere). Global response to a crisis needs to be overseen by an organization that has command and control over assets that are precommitted to the response. There need to be preidentified, appropriately trained personnel from multiple countries who are ready to step up and equipped to respond, he noted.
Venkayya said the White House can play an important role in bringing together federal agencies whose day-to-day activities may not be aligned—as the agencies and people in them are doing phenomenal work—but the overall response could be improved by coordination. Venkayya observed that, during some of the recent health crises, there was not an office inside the White House that had technical health experts who also understood policy and could bring the agencies together and hold them accountable for delivering results. This coordinating, overarching role, allowing the departments and agencies to focus on and execute their roles and responsibilities without overlap or duplication, could be very helpful.
