Lessons From The Ebola Outbreak: Action Items For Emerging Infectious Disease Preparedness and Response

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EcoHealth 13, 200–212, 2016

DOI: 10.1007/s10393-016-1100-5

Ó 2016 International Association for Ecology and Health

Review

Lessons from the Ebola Outbreak: Action Items for Emerging


Infectious Disease Preparedness and Response

Kathryn H. Jacobsen ,1 A. Alonso Aguirre,2 Charles L. Bailey,3 Ancha V. Baranova,2,4


Andrew T. Crooks,5 Arie Croitoru,6 Paul L. Delamater,6 Jhumka Gupta,1
Kylene Kehn-Hall,3 Aarthi Narayanan,3 Mariaelena Pierobon,7 Katherine E. Rowan,8
J. Reid Schwebach,9 Padmanabhan Seshaiyer,10 Dann M. Sklarew,2 Anthony Stefanidis,6
and Peggy Agouris6
1
Department of Global and Community Health, College of Health and Human Services, George Mason University, 4400 University Drive 5B7, Fairfax,
VA 22030
2
Department of Environmental Science and Policy, College of Science, George Mason University, Fairfax, VA
3
National Center for Biodefense and Infectious Diseases, School of Systems Biology, College of Science, George Mason University, Manassas, VA
4
Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Manassas, VA
5
Department of Computational and Data Sciences, College of Science, George Mason University, Fairfax, VA
6
Department of Geography and Geoinformation Science, College of Science, George Mason University, Fairfax, VA
7
Center for Applied Proteomics and Molecular Medicine, School of Systems Biology, College of Science, George Mason University, Manassas, VA
8
Department of Communication, College of Humanities and Social Sciences, George Mason University, Fairfax, VA
9
Department of Biology, College of Science, George Mason University, Fairfax, VA
10
Department of Mathematical Sciences, College of Science, George Mason University, Fairfax, VA

Abstract: As the Ebola outbreak in West Africa wanes, it is time for the international scientific community to
reflect on how to improve the detection of and coordinated response to future epidemics. Our interdisciplinary
team identified key lessons learned from the Ebola outbreak that can be clustered into three areas: environ-
mental conditions related to early warning systems, host characteristics related to public health, and agent
issues that can be addressed through the laboratory sciences. In particular, we need to increase zoonotic
surveillance activities, implement more effective ecological health interventions, expand prediction modeling,
support medical and public health systems in order to improve local and international responses to epidemics,
improve risk communication, better understand the role of social media in outbreak awareness and response,
produce better diagnostic tools, create better therapeutic medications, and design better vaccines. This list
highlights research priorities and policy actions the global community can take now to be better prepared for
future emerging infectious disease outbreaks that threaten global public health and security.

Keywords: Ebola infection, emerging infectious diseases, epidemics, surveillance, one health, public health

Published online: February 25, 2016

Correspondence to: Kathryn H. Jacobsen, e-mail: kjacobse@gmu.edu


Ebola Action Items 201

INTRODUCTION can expose humans to a large pool of novel pathogens


(Morse et al. 2012). Ebola transmission, for example, may
As the Ebola outbreak in West Africa that claimed more be linked to bushmeat consumption and exposure to bat
than 11,000 lives wanes (Zinszer et al. 2015), it is time for guano (Bausch and Schwarz 2014). Rather than responding
the international scientific community to reflect on the to dangerous infections only after they have moved into the
lessons learned from this epidemic and time to begin human population, a better plan is to promote collabora-
preparing for the next multi-country outbreak of an tive efforts to prevent infectious diseases from jumping
emerging infectious disease. What has the Ebola outbreak from animal to human populations in the first place
taught us about how we can detect and contain future (Gortazar et al. 2014). Proactive support of surveillance,
events of other emerging infectious diseases more quickly? reporting, and trade regulation is better for health than a
What have we learned about the gaps in public health and reactive approach (Hyatt et al. 2015).
clinical systems that need to be resolved before the next The movement of animal pathogens across borders
epidemic? What laboratory tools can we use during future remains a significant risk to domestic animal health,
events to more rapidly develop and deploy diagnostic, wildlife conservation, and public health. Both well-known
therapeutic, and preventive technologies? (but often neglected) zoonotic diseases and novel patho-
Infectious disease epidemiologists use an ‘‘agent–host– gens that are poorly characterized may cross national
environment triad’’ to describe the factors that contribute borders with ease (Munro and Savel 2015; Welburn et al.
to infection emergence and spread. The environmental 2015). Incomplete data about diverse disease-causing
factors include the natural environment and the built agents, the geographies of these pathogens, and the impact
environment. The host factors include the range of social of temperature and precipitation on disease epidemiology
and behavioral characteristics and policies that facilitate or all leave animal and human populations vulnerable to
limit infection transmission and containment activities. emerging infections. Any comprehensive emerging infec-
The agent factors are those that relate to the particular tious disease preparedness program must include zoonotic
virus, bacterium, fungus, protozoan, or helminth causing infection surveillance, and wildlife surveillance must be-
the outbreak. Using this framework, our interdisciplinary come a higher global public health priority. The best de-
team identified key lessons learned from the Ebola outbreak fense against widespread infectious disease outbreaks in
that can be clustered into three areas: environmental con- wildlife, domestic animals, and humans is active surveil-
ditions related to early warning systems, host characteristics lance by international, transdisciplinary teams coupled with
related to public health, and agent issues that can be ad- new strategies for creating buffers that restrict contact be-
dressed through the laboratory sciences. The list below tween pathogens and possible hosts.
highlights actions the global community can take now to be One example of this type of early warning system is the
better prepared for future emerging infectious disease United States Agency for International Development
events that threaten global public health and security. (USAID) Emerging Pandemic Threats program, which has
supported the testing of thousands of wild animals living in
geographic ‘‘hotspots’’ where novel pathogens that could
ENVIRONMENTAL CONDITIONS RELATED TO
become a threat to human health are likely to be identified
EARLY WARNING SYSTEMS
(Dixon et al. 2014). These and other coalitions of govern-
ment agencies, universities, non-governmental organiza-
We Need to Increase Proactive Zoonotic
tions, and other partners and stakeholders are seeking to
and Animal Surveillance Activities
generate new structures for global wildlife health manage-
More than 60% of the emerging infectious disease events ment. But, despite multinational efforts at ‘‘virus hunting,’’
that affected humans over the past several decades have these research networks were unable to forecast the emer-
been zoonotic in origin (Jones et al. 2008). The introduc- gence of middle east respiratory syndrome (MERS) in 2012
tion and establishment of these zoonoses (that is, diseases or the 2014–2015 Ebola outbreak in West Africa. Although
usually affecting animals and not humans) in human no previous human pandemic originating as a zoonosis has
populations is the result of a combination of changing been predicted prior to making the jump to humans, new
human demography, health behaviors, agricultural prac- mathematical modeling programs, molecular diagnostic
tices, and other environmental interactions, all of which tools, advanced meta-genomic and communications tech-
202 K. H. Jacobsen et al.

nologies, and developments in proactive public health created a forest–agricultural mosaic that increased contact
surveillance are available for deployment in improved early between bats and humans (Despommier et al. 2006). This
warning systems (Morse et al. 2012). increased environmental exposure facilitated the Ebola
Necessary components of an improved system for early virus making the leap from wildlife to humans (Alexander
detection and response to emerging zoonoses include col- et al. 2015), likely as a result of exposure to insectivorous
laborative transdisciplinary efforts to assess local risks, de- free-tailed bats, Mops condylurus (Saéz et al. 2015). There-
velop and implement new technologies for screening new after, residents of Ebola-affected areas received often con-
and existing pathogens, manage large amounts of shared fusing or contradictory messages about bushmeat
information, create improved infectious disease models, consumption, burial practices, travel bans, traditional
and communicate quickly and effectively. Engagement with herbal medicines, and other issues related to ecological
local human populations is also critical. Global zoonotic health (Alexander et al. 2015). Decades of political insta-
surveillance activities will only be successful when they are bility and conflict had eroded the regional infrastructure
created and sustained with the support of local commu- for water, sanitation, transportation, health services, and
nities and stakeholders. Active involvement of local com- communication needed to enact recommendations for
munities builds trust, improves participation in zoonotic Ebola control. The economic implications of work shut-
monitoring activities, and fosters creative solutions to downs and disruptions in tourism and trade were disin-
improving shortcomings in existing surveillance efforts. centives to restrict movement of people, animals, and
Much more must be done to monitor diseases in animal products. A lack of pre-positioned personal pro-
wildlife globally, particularly in biodiversity hotspots. At tective equipment (PPE), essential medications, and other
present, there is no one international governmental agency biomedical supplies across much of the region put care-
that conducts comprehensive ecological surveillance and givers at unnecessarily high risk of contracting Ebola.
monitoring of diseases in animals, or that regulates trade in Meanwhile, healthcare facilities and communities struggled
wild animals and their products (Hyatt et al. 2015). The with how best to decontaminate buildings and objects that
Ebola outbreak has highlighted the critical need for a had been touched by Ebola patients, disinfect medical
coordinated response to global surveillance for zoonotic equipment, and safely discard medical waste (Decker et al.
diseases. Transdisciplinary approaches involving many 2014).
parties, including human and animal health professionals, Although its epidemiology is not yet fully understood,
ecologists, economists, social scientists, modelers, and Ebola virus in wild primates has contributed to a marked
others, would help provide comprehensive, coordinated, reduction in the populations of chimpanzees (Pan troglo-
and cohesive strategies for addressing this immense threat dytes) and gorillas (Gorilla gorilla) in Central Africa (Ryan
(Goodwin et al. 2012). Global zoonotic surveillance has and Walsh 2011). These outbreaks are likely the result of
become a necessity, not an optional policy goal. contact between these animals and an as-yet unidentified
reservoir host, most likely a bat. Several human outbreaks
of Ebola in the Central African region were traced back to
We Need to Implement More Effective Ecological
the handling and consumption of primate bushmeat. And
Health Interventions
Ebola is far from the only infectious disease instigated or
The Ebola ‘‘outbreak narrative’’ propagated by many news exacerbated by the condition of the natural and built
media outlets presented the West African outbreak as a environment.
spontaneous event in which bushmeat consumption by More broadly, nearly one-quarter of the global burden
low-income rural residents caused a zoonotic spillover and of disease has been attributed to environmental risk factors,
created an alarming threat to human health worldwide and that rate is even greater for infectious diseases (Prüss-
(Huff and Winnebah 2015). The reality is that human– Üstün and Corvalán 2007). Poor air quality contributes to
ecological interactions are not merely about local behaviors tuberculosis and other respiratory infections, poor drinking
but also about regional patterns of deforestation and land water and sanitation cause nearly all cases of infectious
use, politics and economic development, and climate diarrhea, and poor environmental management (including
change (Huff and Winnebah 2015). Human movement inappropriate pest control strategies and deforestation)
into West African forests and the reduction of ecotones increases the risk of malaria and other vectorborne infec-
(that is, buffers between settlements and protected forests) tions. Low-income communities often lack the information
Ebola Action Items 203

and means to implement environmental changes that re- interface between humans, domestic animals, and wildlife
duce the risk of outbreaks. A variety of occupational (Hyatt et al. 2015).
exposures put healthcare workers and others at risk of
acquiring infections while on the job (Prüss-Üstün and
We Need to Expand Prediction Modeling
Corvalán 2007). And many countries do not screen im-
ported wildlife for the pathogens that they might harbor. The 2014 outbreak of Ebola was the first to occur in West
Neglecting these ecological aspects of infection prevention Africa, but post-outbreak zoonotic niche models revealed
and control puts individuals and communities at risk. that the risk of Ebola transmission in West Africa was
Environmental public health interventions—improved similar to that found in central Africa, where all previous
access to clean water for drinking and hygiene, animal and Ebola outbreaks had happened (Pigott et al. 2014). This
vector control, occupational health and safety measures, information suggests that the region’s susceptibility to
and promotion of larger buffers between human settle- Ebola may have been predictable before the first cases were
ments and protected forests, among others—are an essen- diagnosed.
tial component of outbreak prevention (Patz et al. 2004; Outbreaks usually occur as the result of a complex and
Wilcox and Ellis 2006). Environmental hygiene at health- integrated set of biological, social, and environmental fac-
care facilities, schools, farms, transportation hubs, markets, tors. Predictive modeling strategies vary considerably
and other places where people gather all need to be con- regarding which of these components are included in the
sidered as well as larger-scale environmental control mea- models and which methodological approaches are used.
sures. The various outbreaks in 2014—Ebola, chikungunya, Spatial statistical techniques can identify relationships be-
polio, dengue fever, cholera, and others, including the tween disease incidence, environmental and social condi-
spread of highly pathogenic avian influenza (HPAI) types tions, and geographic location, then use those
H5 and H7 in birds—demonstrate the results of inadequate characteristics to predict disease risk in new locations with
environmental management for animal and public health similar features and to simulate the risk of a large outbreak
in diverse world regions. International collaborations can based on demographic, climatic, and other factors. Simu-
identify and disseminate best practices for each of these lation modeling approaches, such as agent-based models,
situations. Governments and their partners must then can emulate potential disease transmission within a region
implement health policies and programs with a One Health based on models of actions and interactions between ani-
approach to prevent and respond promptly to emerging mals and humans or between infected and uninfected
epidemics without compromising other ecosystem services individuals. Mathematical modeling of infection transmis-
and economic functions upon which global well-being sion can also provide frameworks for quantifying how
depends. quickly epidemics and epizootics will grow and for evalu-
Few official national or multinational programs are ating the possible impact of prevention and control inter-
documenting wildlife diseases, and the partnerships seeking ventions.
to undertake this important work are under-resourced. Because infectious disease outbreaks are usually
Wildlife surveillance in the places most likely to spark explicitly spatiotemporal phenomena, modeling efforts
animal-to-human transmission of dangerous pathogens largely focus on where and when an outbreak is likely to
must be funded and implemented by international teams occur. Geographic information systems (GIS) offer a
with the necessary expertise. Human health and domestic framework that is well suited for this task, providing the
animal health surveillance systems must be linked with ability to incorporate, integrate, and analyze disparate
systems that monitor wildlife health. Investments in these geographic and non-geographic information about dis-
types of programs will allow national governments and eases. GIS methods can be quite accurate in their risk
other organizations to develop and deploy countermea- predictions. For example, a model of the risk of Rift Valley
sures to minimize the risks wildlife-related epidemics pose fever (RVF), a disease of livestock that can also affect hu-
to trade and economics as well as to biodiversity and public mans, in eastern Africa successfully identified an elevated
health (Karesh et al. 2012). Established groups such as the likelihood of new cases several weeks before the first ones
World Organization for Animal Health (OIE) will need to were diagnosed (Anyamba et al. 2009). A diversity of online
provide leadership on One Health initiatives addressing the databases such as the EMPRES-i Global Animal Disease
204 K. H. Jacobsen et al.

Information System, and the World Animal Health Infor- trol and Prevention (CDC), and others contributed to
mation Database (WAHID) contain up-to-date animal case epidemiological and clinical efforts, but there was no strong
information, and human case information is available from central leadership (Burkle 2015). In the United States,
HealthMap and other programs (Stevens and Pfeiffer 2015). frequent updates to CDC guidelines and reactionary state-
The ever-increasing amount and quality of available implemented plans for quarantining travelers seemed to
human, animal, and ecological data has improved the fuel fear rather than provide assurance that science was
ability to explore relationships between human behaviors, guiding policy development (Gonsalves and Staley 2014).
environmental exposures, and infectious diseases. Emerg- The policy and implementation challenges encoun-
ing data sources such as volunteered and ambient geo- tered during the Ebola outbreak will require evaluation by
graphic information (VGI and AGI) and novel monitoring international experts in public health, international rela-
platforms (such as unmanned aerial vehicles) will soon tions, law, human rights, and political science who can
provide enhanced sensing capabilities. propose better options for coordinating responses to out-
The ability to predict when and where a disease out- breaks and for clarifying the roles and responsibilities of the
break is likely to occur and the probable severity of such an groups likely to participate in future containment efforts.
event creates valuable opportunities for the improvement One already-identified concern is that less than 20% of the
of both pre- and post-outbreak intervention strategies and member states of the United Nations have achieved the
initiatives (Brookes et al. 2015). Communities and regions standards spelled out by the International Health Regula-
with limited emergency management resources that are tions (IHR) treaty, which mandates that member states
predicted to have high risk of an outbreak can be offered develop the surveillance systems, laboratory capabilities,
tailored and timely assistance in building capacity for risk and health system capacity to contain epidemics (Burkle
mitigation, preparedness, response, and recovery. The RVF 2015). Little funding has been made available to promote
example above demonstrates that predictive modeling of rapid IHR improvements. Increasing financial support for
disease outbreaks is currently achievable, while the 2014 the implementation of IHR globally is necessary for pro-
Ebola outbreak demonstrates the necessity of expanding tecting the most vulnerable world citizens (Rothstein 2015)
and improving risk modeling efforts. and safeguarding global health and security (Gostin 2014;
Kimball and Heymann 2014).
In addition to supporting public health development,
it is also necessary to strengthen clinical preparedness and
PUBLIC HEALTH
response. Healthcare workers (HCWs) in Ebola-affected
West African countries were one hundred times more likely
We Need to Better Support Medical and Public
to contract Ebola than their neighbors who were not HCWs
Health Systems and Improve Local and Interna-
(Kilmarx et al. 2014). In the United States, two nurses
tional Responses to Epidemics
caring for an Ebola patient contracted the virus (Chevalier
Local and international responses to the Ebola outbreak et al. 2014). In all affected countries, hospitals and public
revealed profound limitations in preparedness for emerging health authorities struggled with how to implement
infectious disease events. In West Africa, misinformation appropriate mechanisms for diagnosing, transporting, and
about Ebola transmission, prevention, and treatment caring for Ebola patients and identifying, monitoring, and
caused confusion in the early months of the outbreak communicating with at-risk travelers and possible contacts
(Wilkinson and Leach 2015). The international response of Ebola patients. Many facilities also struggled with iden-
was poorly coordinated, and the World Health Organiza- tifying and implementing appropriate procedures for dis-
tion (WHO) did not release an Ebola response plan until posing of contaminated medical waste and household items
5 months after the outbreak had crossed its first interna- (Lowe et al. 2015). The Ebola outbreak highlighted the
tional border (Gostin 2014). The national governments of urgent need for all HCWs, including those involved in trash
affected countries, foreign medical teams (such as those of removal, patient transportation, and burials, to have access
Médecins Sans Frontières and other non-governmental to the necessary PPE and to have comprehensive training
organizations), WHO offices, the Global Outbreak Alert about and constant supervision of safe practices for don-
and Response Network (GOARN, an independent body ning and doffing PPE (Nielsen et al. 2015). In low-income
coordinated by WHO), the U.S. Centers for Disease Con- countries, few hospitals have adequate stocks of PPE and
Ebola Action Items 205

other medical supplies for routine use, and it can be dif- as the hype about Ebola began dissipating (Clemmons et al.
ficult or impossible to garner the necessary supplies during 2015).
an outbreak. PPE donations, volunteer medical workers, One of the core principles of risk communication is
and other forms of international humanitarian assistance that the hazards that kill are not necessarily those that upset
during crises like the Ebola outbreak are essential not only or frighten, and the hazards that cause fear or anxiety may
for containing epidemics before they become widespread have that effect because of social and policy concerns rather
but also for addressing issues of global and social justice than morbidity and mortality rates. Skilled communicators
(Rid and Emanuel 2014). Coordination of these efforts is have the opportunity to clarify misperceptions and to
essential for ensuring that timely assistance gets to the promote healthier attitudes and behaviors. While influen-
places with greatest need. tial public figures can cause mass alarm when they dis-
But improved responses to acute emergencies will not seminate upsetting messages—for example, by proclaiming
stave off the next outbreak. The ability to prevent rather that measles vaccines are dangerous even though scientists
than merely respond to infectious disease outbreaks re- have declared them safe—these voices do not have to be-
quires long-term investment in the sustainable develop- come the dominant ones (Kahan 2013). Messages
ment of the healthcare infrastructure in currently under- explaining that vaccination rates remain high—that is, that
resourced areas. Both clinical and public health capacities, vaccination remains the normative health behavior for the
such as routine surveillance and outbreak investigation, population—help promote adherence to expert recom-
need to be expanded. The world needs to have an improved mendations by emphasizing that vaccination is the popular
international detection, reporting, and response system in choice (Kahan 2013).
place before the next outbreak of an emergent infection like Best practices for risk communication during infec-
SARS, Ebola, or highly pathogenic strains of influenza. tious disease outbreaks are being developed (Schiavo et al.
Additionally, improved mechanisms for local and national 2014). During a recent Ebola outbreak in Uganda, village
dissemination of critical information about emerging health teams selected by community members conducted
infectious disease threats must be put in place in every home searches and contact tracing while also providing
country so that public health officials, veterinary officials, preventive health education (Mbonye et al. 2014). Because
and clinical staff can quickly prepare to safely diagnose, team members were elected from the communities they
isolate, and care for possible cases while protecting HCWs serve, they were accepted and trusted, and this resulted in
from occupational risks. greater adherence to recommended practices such as safe
burials and limited interpersonal interactions (Mbonye
We Need to Improve Risk Communication et al. 2014). In Liberia, a task force led by local chiefs helped
design and implement a village-to-village social mobiliza-
The need for improved communication about the risk from tion program to address Ebola-related concerns, collect
Ebola and appropriate responses to the outbreak was daily health surveillance data, and provide timely health
apparent in every country where Ebola patients were education (Hagan et al. 2015).
diagnosed and treated. During the 2014 outbreak in West At the global level, disaster simulations provide public
Africa, many were concerned about infection prevention information officers and health communication experts
behaviors not being adopted quickly enough as families with the tools they need to perform excellently in stressful
continued to choose home care for sick relatives and situations (Vanderford 2015), and drills with international
funerals continued to attract crowds, turning some tradi- teams may also enhance capacity for interagency coopera-
tional burial ceremonies into super-spreader events (Pan- tion during health emergencies (Gostin 2014). Additional
dey et al. 2014). In the United States, by contrast, some research will elucidate evidence-based best practices for
feared that they were likely to contract and die from Ebola earning trust, creating awareness, deepening understand-
even before the first Ebola patient had set foot on American ing, gaining agreement, and motivating enactment of best
soil. Similar observations about mismatches between actual practices for managing uncertain physical hazards.
threats to health and perceptions about risks have been Understanding cultural values and traditions is an essential
made about a range of health issues, including measles component of infectious disease risk communication.
vaccination, an issue that became a hot topic in early 2015 Anthropologists, sociologists, psychologists, and other so-
in the United States when a multi-state outbreak occurred cial scientists may play an important role in identifying
206 K. H. Jacobsen et al.

cultural considerations to incorporate into communication information disseminated through social media is not cu-
strategies. Improving risk communication throughout the rated and may therefore be incorrect (Oyeyemi et al. 2014),
span of an outbreak, from the initial cases through the it may contribute to public confusion. However, early
after-event reporting, is essential for promoting good studies have highlighted the potential usefulness of Twitter-
health behaviors and preventing harmful ones. mining and other analyses for improving public health
education (Odlum and Yoon 2015). In sum, big data sets
raise both new challenges and new opportunities for health
We Need to Better Understand the Role of Social
informatics. New applications that mine and analyze social
Media in Outbreak Awareness and Response
media (Fig. 1) are needed to reveal novel ways to trace the
The formal press played a key role in communicating spatiotemporal and social footprints of outbreaks and
information and, sometimes, fear about the Ebola outbreak provide a more timely response to social and healthcare
(Spencer 2015), but social media—Twitter, WhatsApp, and needs (Croitoru et al. 2013). For example, social media
other programs—may have been even more influential in analysis can help identify which locations require assistance
guiding how individuals reacted to the emerging situation. with basic human needs such as food and water and to alert
This was true in West Africa, where more than half of the residents about healthcare facilities that have suspended
population has a mobile phone subscription (O’Donovan admissions.
and Bersin 2015), as well as in Europe and North America. However, a current lack of understanding of the
In Nigeria, where an imported case of Ebola led to more mechanisms that drive social media participation and
than a dozen infected HCWs, tweeting and retweeting of engagement hinders the ability to fully harness the power of
misinformation was common, but the government also cyberspace during health crises and other emergencies.
used Twitter to correct falsehoods (Oyeyemi et al. 2014). Traditional models of the social amplification of risk fail to
Ebola went more dramatically ‘‘viral’’ when the pathogen capture the complex mechanisms through which the dis-
arrived in the United States and a fearful public looked to ease-related narrative is shaped in cyberspace (Kasperson
Internet and social media sites to find and disseminate et al. 1988). Studying the geosocial nature of participation
disease-related information. Google searches for the key- patterns to gain a better understanding of how a narrative
word Ebola first spiked on August 8, 2014, when WHO is formed and propagated may also allow for evaluation of
declared Ebola to be a public health emergency, and then the effectiveness of top-down communication from gov-
soared in mid-October after the first patient was diagnosed ernmental health agencies to the general public as well as
in Texas (Househ 2015). The Google Trends score re- the influence of bottom-up processes on public perception
mained elevated as a patient in New York City was diag- (Winerman 2009). Future public health campaigns have to
nosed, treated, and discharged from the hospital, and then make better use of these modern communication tools for
returned to a low level of interest by early 2015. Similarly, improving preparedness and response.
#ebola became a globally trending hashtag on Twitter. Our
Geosocial Gauge prototype (Croitoru et al. 2013) logged
more than 200,000 tweets daily during the first half of
LABORATORY SCIENCES
October, with that number spiking to more than 500,000
We Need to Produce Better Diagnostic Tools
tweets—nearly 350 tweets per minute—on October 9, the
day after an Ebola patient in Texas died from the infection. Laboratory tests that rapidly and reliably diagnose infec-
By January 2015, the number of Ebola tweets logged tions, ideally even in the early asymptomatic stages, often
through this system was down to about 8000 daily. play a key role in outbreak containment strategies (Stamm
These illustrations, from two countries that differ 2015). For maximum effectiveness, medical and veterinary
substantially in their levels of technological infrastructure diagnostic tests must be sensitive and specific, they must
but share the will of the general public to participate in provide rapid results, they must be affordable, and they
information dissemination, demonstrate how social media must use technology that is user-friendly and accessible in
and mHealth (mobile health) applications can be an diverse settings (Stothard and Adams 2014). Early diagnosis
important part of tracking outbreaks, providing health allows infected individuals to be isolated before they infect
education, and receiving and disseminating other critical community members, provides HCWs with critical infor-
information (O’Donovan and Bersin 2015). When the mation about how to protect themselves and care for pa-
Ebola Action Items 207

Fig. 1. A snapshot of streaming Twitter content discussing Ebola on October 20, 2014. The map on the top left shows the hotspots of
discussion. The window of the top right shows streaming tweets, classified into ones with a positive outlook (green), negative (red), or neutral
(no color). The word cloud (bottom left) captures the key discussion points, while the gauge (bottom right) captures the overall mood of the
crowd [A grayscale version of this image can be provided for the print version of the paper] (Color figure online).

tients, and may improve clinical outcomes by enabling Current Ebola diagnostics are based either on the detection
treatment to begin early in the course of infection. Bio- of the virus (through RT-PCR or antigen testing) in body
marker-based analyses that can be carried out at the point- fluids or on the measurement of antibody response (Martin
of-care or in a central laboratory may also be useful for the et al. 2015). None of the currently approved methods
early detection of infection in contacts of infected people accurately detect the virus during the incubation period or
and for the screening of community volunteers to establish at the beginning of the symptomatic phase (Martin et al.
geographic areas where an infection with an environmental 2015). New techniques for the rapid creation of easy-to-
reservoir might be present (Reed et al. 2014). use, safe, and accurate diagnostic tools are necessary for
208 K. H. Jacobsen et al.

improving the early containment of emerging threats to like ZMapp, TKM-Ebola, and Favipiravir were moved
global public health. Given the limited laboratory capabil- quickly into early-stage trials, but by early 2015 there was
ities in many world regions, and the related lack of reliable still no strong evidence that any of these drugs were highly
access to electricity, clean water, and reagents, the ideal tests effective against human Ebola virus disease (Choi et al.
will also be affordable and able to be used at the point of 2015).
care. When outbreaks occur, the first step of a rapid thera-
Traditional laboratory testing has been used mostly for peutic response strategy should be to identify existing, al-
the identification of pathogens. In recent years, new ap- ready-approved therapeutic agents that might increase
proaches such as transcriptional profiling have extended survival. The standard doses and durations of drug
diagnostic capabilities (Ginsburg and Woods 2012). Lab- administration for diseases in which the drug has proven to
oratory studies exploring the interactions between the im- be effective may be quite different from the regimen that is
mune system and pathogens can now lead to the most effective for other infectious agents. The urgent de-
identification of genomic and proteomic markers predic- mand for new and repurposed therapeutics during an
tive of individual susceptibility to and likely prognoses for outbreak situation does not remove the need to protect
specific infectious diseases (Burgner et al. 2006). The patients from the risk of additional harm due to inappro-
development of novel platforms capable of identifying priate use of medications (Enserink 2014).
specific signatures at both the genomic and proteomic le- It is also important to speed up the process of devel-
vels may help researchers understand the immune patho- oping new medications. Traditional therapeutics target
genesis of emerging infections and may lead to the bacteria, viruses, and parasites, but a better option for fu-
identification of humans with higher risk for developing a ture outbreaks may be the development of host-based
disease. therapeutics that target human cells or components in a
Due to the high priority on a quick roll-out of new manner that affords broad-spectrum protection to the host
tests, pre-symptomatic assays should not concentrate on (Princhard and Kern 2012; Prussia et al. 2011; Zhou et al.
achieving absolute viral specificity, but rather on the 2015). The lack of market value for specific antivirals for
recognition of a general viral intrusion, which may be infections that do not affect a large proportion of the world
achieved by comparison of the activation level of host de- population means that incentives to pharmaceutical com-
fenses to the patient-specific baseline. Several pressing re- panies may be required in order to encourage corporations
search areas have been identified. We need to develop to divert existing resources into an accelerated production
multiplex biomarker platforms that can be used in triage as program when an outbreak with high likelihood for
tools for differential diagnosis as well as for identifying expansion has been detected. Host-based therapeutics that
individuals with co-infections (Yen et al. 2015). We need have demonstrated broad-spectrum in vivo efficacy in
new molecular assays for rapid subtyping of filoviruses like animal models should be candidates for prioritization.
Ebola as well as coronaviruses, retroviruses, and other pa- Decisions about when to allow use of a candidate drug
thogens. We need to create tools for identifying biomarkers based on compassionate use prior to extensive field testing
associated with clinical outcomes and patient responses to will require a critical evaluation of drug-associated risk
therapy, which might allow for personalized medical care. versus the risk of mortality from the disease.
We need tools that will help to identify individuals who Setting up high-quality clinical trials with suitable co-
might be especially susceptible to infection, and who might horts of participants is expensive and demanding even in
benefit most from preventive interventions. Once these new optimal circumstances. Trials are even more challenging to
types of diagnostics are developed, additional work can be conduct during ongoing outbreaks. During emergencies,
done to improve the sensitivity, specificity, and cost effec- there may be a temptation to bypass the usual ethical and
tiveness of the tests. But the first priority is ramping up the regulatory requirements for drug testing, or to make
ability to quickly develop tools during public health crises. decisions about the effectiveness of a medication before
having a sample size large enough for robust statistical
We Need to Create Better Therapeutic Medications conclusions. A focused research question may help mini-
mize both the required number of participants and the
As soon as the 2014 Ebola outbreak hit the airwaves, calls duration of time needed to make a valid assessment of the
went out for novel therapeutics to treat the infection. Drugs benefits and risks of a candidate drug. Other limitations
Ebola Action Items 209

can be overcome when governmental and intergovern- available (Henao-Restrepo et al. 2015). The ‘‘ring’’ strategy
mental agencies provide leadership on leveraging existing employed in this trial is a creative new approach to the ethical
research capacities in the communities from which par- and efficient conduct of efficacy and product safety research
ticipants can be drawn, making advanced laboratory during an ongoing outbreak, but there is a need for further
capabilities available to collaborating researchers, facilitat- clarification of the ethics and legality of various approaches to
ing data sharing across study sites, and providing guidance the testing of candidate vaccines during emergency situations
on how to maintain compliance with ethical guidelines for (Cohen and Kupferschmidt 2014).
human subjects research. These compulsory ethical prac- Prior knowledge of host responses in multiple cell
tices include an emphasis on informed consent of all par- types that may respond to vaccine candidates (such as
ticipants, the protection of vulnerable populations, the dendritic cell, B-cell, and T-cell responses) and to additives
implementation of safety monitoring procedures, the such as adjuvants can greatly support emergency efforts to
management and reporting of adverse events, and the maximize efficacy of vaccine formulations in producing
protection of patient privacy and confidentiality. The ethics such strong primary responses in vaccines. Similar strate-
of using a control group must be carefully considered based gies may also apply to the use of vaccination to prevent
on the characteristics of the pathogen causing the outbreak infection in animal populations, as has been observed for
and the preliminary results about outcomes for both the foot-and-mouth (hoof-and-mouth) disease and contain-
intervention and control populations. ment efforts for other highly contagious animal pathogens
(Paton et al. 2005).
We Need to Design Better Vaccines If combinatorial vaccines that protect against two or
more infectious diseases or combinatorial interventions
To be effective during an outbreak, a vaccine must either be that provide both a preventive and therapeutic intervention
efficacious as post-exposure prophylaxis or must be able to in one are used (Kamal et al. 2011), or if multiple doses of
stimulate the production of protective or neutralizing vaccine are expected to be necessary, then additional safety
antibodies within a very short time window, usually no studies will be required to determine tolerance to additives
more than a few days. When this type of vaccine is not (such as preservatives) and to repeated doses of the antigen.
available, a more useful prophylactic strategy is the use of Definitive assays that can predict unfavorable outcomes in
passive immunization approaches (such as the adminis- individuals may be an important part of a safety strategy.
tration of therapeutic monoclonal antibodies) that are Vigilant monitoring for adverse events associated with
specific to the pathogen causing the outbreak and have few primary and booster doses will be required for any new
negative side effects (Clementi et al. 2012; Sautto et al. vaccine. Similar considerations apply to the development
2013). Immunomolecule-based interventions should only and testing of animal vaccines (Delwart 2012).
be implemented after the consideration of the possible
risks, including antigen-dependent enhancement of the
infectious disease and immunological interference with CONCLUSION
innate immunity (Wang et al. 2014). In contrast, vaccines
can be very effective for protecting healthcare personnel These lessons learned from the Ebola outbreak point to
being deployed to affected areas and for safeguarding as-yet critical research needs: enhanced wildlife and biosurveil-
unaffected communities within a region hit by an outbreak lance methods, expanded environmental and ecological
of a virulent infectious disease. assessments and intervention studies, improved modeling
Several Ebola vaccines were in development prior to the capabilities, more evaluations of health systems and public
emergence of Ebola in West Africa, and they are being health needs and policies, better risk communication and
quickly pushed into field trials (Choi et al. 2015). To be social media strategies, and the application of cutting-edge
deemed successful, these vaccines will need to produce a laboratory science to the rapid development, ethical testing,
strong primary response to the antigen, even if a sustained manufacturing, and distribution of new diagnostic, thera-
response may not be maintained. The preliminary results of a peutic, and preventive tools. They also point to urgent
ring vaccination trial that immunized individuals known to needs that can be addressed through policy prioritization:
be primary or secondary contacts of Ebola patients suggest support for early warning systems, health systems devel-
that it is likely that an effective Ebola vaccine will soon be opment, and translational medicine. We cannot wait until
210 K. H. Jacobsen et al.

the next crisis to implement these changes. We must act Choi WY, Hong KJ, Hong JE, Lee WJ (2015) Progress of vaccine and
drug development for Ebola preparedness. Clinical and Experi-
now to ensure that we are better prepared for the next
mental Vaccine Research 4:11–16. doi:10.7774/cevr.2015.4.1.11
international health emergency. Clementi N, Criscuolo E, Casterlli M, Clementi M (2012) Broad-
A multi-pronged, transdisciplinary strategy that inte- range neutralizing anti-influenza A human monoclonal anti-
grates the biomedical sciences (including cellular and bodies: new perspectives in therapy and prophylaxis. New
Microbiologica 35:399–406
molecular biology), public health, and the ecological sci-
Clemmons NS, Gastanaduy PA, Fiebelkorn AP, Redd SB, Wallace
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from the individual and local to the global levels (Ezenwa MMWR Morbidity and Mortality Weekly Report 64:373–376
et al. 2015). The recent Ebola outbreak challenges the no- Cohen J, Kupferschmidt K (2014) Ebola vaccine trials raise ethical
issues. Science 346:289–290. doi:10.1126/science.346.6207.289
tion that human health is an isolated concern removed
Croitoru A, Crooks A, Radzikowski J, Stefanidis A (2013)
from the bounds of ecology and species interactions. Hu- Geospatial gauge: a system prototype for knowledge discovery
man health, animal health, and ecosystem health are from social media. International Journal of Geographical Infor-
mation Science 27:2483–2508. doi:10.1080/13658816.2013.825724
moving closer together, and at some point it will be
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