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The Response to Ebola—Looking Back and Looking Ahead

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JAMA

The 2015 Lasker-Bloomberg Public Service Award

2015

The 2015 Lasker-Bloomberg Public Service Award is given to Médecins Sans Frontières/Doctors Without Borders (MSF) for its bold response and leadership in fighting the Ebola outbreak in Africa. This Viewpoint describes the challenges involved in responding to this outbreak and the importance of ongoing research and preparedness efforts.

The 2014-2015 West Africa Ebola outbreak is a stark reminder that a health crisis in one place can quickly spiral into a major regional humanitarian emergency or even a global challenge. As of mid-August 2015, there have been nearly 28 000 Ebola cases (including confirmed, probable, and suspected cases) and more than 11 000 deaths1 (although these numbers likely underestimate the true disease burden). Much of this toll could have been prevented by an early, robust international response. Thus it stands as a grim reflection of failures—of collective political will, of global emergency response systems, and of the research and development (R&D) systems that, prior to this outbreak, failed to produce an effective vaccine, drug, or rapid diagnostic test since the first identification of Ebola in 1976.

The medical humanitarian organization Médecins Sans Frontières/Doctors Without Borders (MSF) has responded to many Ebola outbreaks over the past 20 years and was already present in Guinea when asked to help identify the first cases in March 2014. Additional patients were soon detected near the country’s porous borders with Sierra Leone and Liberia and, shortly thereafter, in the capital city of Conakry. By late June Ebola had been confirmed in 60 locations in the 3 countries. This unprecedented geographic distribution was a key reason outbreak control efforts were quickly overrun. Another was the unwillingness of national leaders and the World Health Organization (WHO) to acknowledge the seriousness of the outbreak and mobilize an aggressive response. Other factors magnified the vulnerability of these countries, including extreme poverty, weak governance, recent history of conflict (in 2 countries), and especially their extremely weak health systems and poor health outcomes.2

In June 2014 MSF declared publicly that the epidemic was out of control and that it had insufficient capacity to respond to reports of disease in new locations. The organization continued calling for assistance from the international community, the medical humanitarian community, and, at the United Nations, even for military biohazard response capacity. At the same time, MSF accelerated the pace of its mobilization, including scaled-up training for national and international staff, and—after WHO finally declared an international public health emergency on August 8—those from other organizations that gradually began preparing to respond. Scrambling to adapt the response to the constant movement of the outbreak and the ever-shifting realities on the ground represented one of the most difficult challenges MSF and others faced.

At the onset, responders were working among terrified populations who had never heard of Ebola and often saw foreign health teams in their hazmat suits not as providing assistance but as spreading the disease; at times there was hostility, even violence, directed at outreach workers. During the outbreak’s peak in Monrovia, the Ebola management center (EMC) was open for only 30 minutes daily to accept new patients in place of those who had died overnight. Overwhelming patient loads exceeded the capacity of caretakers to meet patients’ basic needs, while case-fatality rates in most MSF EMCs fluctuated around 60% at that time. For staff this situation created an enormous emotional toll, exacerbated by exhaustion from long working hours, extreme heat, limitations of working in full protective suits, and concerns about their own health and safety. National staff had the additional burdens of infection risk in their communities, stigmatization, and grief over the loss of family and friends. Infections among staff (28 in total, 25 among national staff) and 14 deaths among national staff also had a profound psychological effect, both in the field and for the organization as a whole.

By late 2014, case numbers were decreasing as some changes began to take hold. Ending an Ebola outbreak requires much more than isolation and care of affected patients. A cornerstone of the response is to earn the population’s trust and mobilize communities so that other essential activities, such as surveillance, contact tracing, health promotion, and safe burial—all of which have challenges specific to local culture and context—can succeed. Many communities had begun to heed public health messages and change their risk-associated behaviors, although the outbreak response was still inconsistent across the affected regions. The decline meant not only having ample numbers of beds; it also allowed intensification of the quality of patient care (including the provision of psychosocial support and the use of biochemistry to individualize fluid management) and creation of more family- and visitor-friendly EMCs.

However, the world’s attention declined faster than the outbreak: transmission continued steadily into 2015, and only in late July finally declined to very low numbers (3 cases/week in mid-August).1 Yet the risk remains that transmission can reignite, and a strong commitment of responders is needed to finish the job of getting to—and staying at—zero.3 However, there may be hope from a potentially promising advance involving an experimental vaccine (rVSV-ZEBOV). If preliminary clinical trial findings showing high efficacy of this vaccine4 are confirmed, it could represent a powerful new tool.

Going forward, rebuilding and strengthening the region’s decimated health infrastructure will require a massive international effort. This must address basic medical needs, from safe delivery to malaria treatment and routine vaccination, as well as capacity-building to rapidly expand the health care workforce that lost hundreds of staff to Ebola. MSF and others are helping to safely reopen hospitals so they have the triage, alert, and infection control systems needed to identify and isolate new Ebola cases. In March 2015 MSF opened a pediatric hospital in Monrovia and is currently exploring investments in other hospitals and projects to address urgent non-Ebola needs.

Care for people who have recovered from Ebola represents another important need. Many among the thousands of survivors experience medical and mental health sequelae. The most common appear to be eye problems, joint and muscle pain, headaches, and extreme fatigue, as well as psychological symptoms including trauma and grief. Multiple organizations are providing support for survivors and are conducting research. MSF has 2 projects offering mental health and medical treatment and referral for ophthalmic care, with a third project in planning and now doing initial outreach. These programs will also collect prospective data for monitoring and evaluation of post-Ebola complications. The National Institutes of Health–funded PREVAIL project in Liberia will follow up 1500 survivors and 5000 household contacts over the course of 5 years.

Notwithstanding the decrease in Ebola cases, it is essential to continue and intensify R&D involving anti-Ebola products. Ebola laid bare not just the inadequacy of the international community’s ability to respond to outbreaks but also how the current R&D system fails the poorest patients. For example, efficacy of the rVSV-ZEBOV vaccine in nonhuman primates was demonstrated 10 years ago,5 but no phase 1/2 safety and dosage studies were conducted before the current outbreak. Potential anti-Ebola therapeutics, such as ZMapp, also languished in the preclinical development pipeline.

Compelled by this urgent need, MSF joined clinical research consortia and hosted trials of favipiravir, an antiviral agent, and of convalescent blood and plasma; a trial of the antiviral brincidofovir began but was terminated prematurely as patient numbers declined and the drug manufacturer withdrew support. Interim data on favipiravir have shown encouraging signs for patients older than 7 years and with moderate or lower viremia.6 Studies with convalescent blood and plasma from Ebola survivors were recently completed, and although efficacy results are not yet available, use of convalescent plasma is continuing in Guinea based on good safety, tolerability, and feasibility findings.7 Additional efficacy data on the rVSV-ZEBOV vaccine is forthcoming, including results from an ongoing trial involving frontline workers in Guinea, by a consortium that includes MSF.

As the international community works to end this Ebola epidemic, it must take concrete steps to ensure that there is more to offer future patients. This problem is not limited to Ebola: there is a paucity of tools for many other diseases that affect primarily poor populations and therefore do not provide lucrative markets. Finding ways for the international R&D system to incentivize innovation while ensuring patient access is imperative.8

MSF is involved in a WHO-led effort to establish a biobank and data platform for R&D of new anti-Ebola products and diagnostic tools. More than 80 000 laboratory samples and specimens collected from West Africa during the outbreak are stored in laboratories around the world. A biobank and data platform would allow laboratories to share material and information, with the aim of accelerating and prioritizing research that engages scientists from affected countries and directly benefits their populations.

The sheer scale and magnitude of the Ebola outbreak, at a time of considerable needs in other global emergencies, strained and tested MSF. The challenges have been about human resources and capacity, of course, but also about the international political will needed to stop an epidemic. During this emergency MSF not only used its voice and experience to raise the alarm and mobilize an international response but also pushed its own institutional limits, from capacity-building of non-MSF staff to broad international collaboration. Thousands of staff risked their lives on the front lines. Just as MSF continues to ask itself how it could have done better, the ongoing global discussions precipitated by this emergency must lead to significant improvements in preparedness and response to future emergencies.

 read more at JAMA

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