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EPID: Focus on Surveillance
The Transition from Pandemic Response to Pandemic Prevention**

 
Dr. Nathan Wolfe, M.A., D.Sc.
Director of the Global Viral Forecasting Initiative (GVFI)
The Lorry I. Lokey Visiting Professor, Stanford University
 
 

Summary

 
We live in an era of unprecedented threats from microbes.  Various factors have conspired to make the global human population more susceptible than ever to pandemics with the potential to devastate health and economies.  The speed and frequency of contemporary pandemics make the relatively slow and resource-intensive traditional public heath responses — such as the development of diagnostics, vaccines, and treatments — insufficient.  Fortunately, a new wave of scientific research has revealed that far from random occurrences, pandemics share a number of features which make them amenable to prediction and prevention.  A percentage of the global disease control portfolio must now be re-focused on the creation of a global pandemic immune system, aimed at seeking out novel infections in humans and animals before they spread regionally, identifying quickly and effectively the agents causing them, and sounding alarms which permit rapid response and containment weeks, months, and years earlier than current systems allow.  Such systems will provide much-needed protection from both natural as well as artificial microbial threats, helping move global disease control toward a truly preventative science.
 
 

Current realities

 
The global population is increasingly vulnerable to pandemics that have the potential to devastate economies as well as health.   Human incursion into regions of wildlife diversity and the increasing trade in global wildlife both cause an escalation of microbes jumping from animals to humans.   Increased density of human populations provides critical “fuel,” permitting such cross-species jumps to persist in human populations long enough to adapt and spread. For example, a 2004 serological survey of rural villagers exposed to primates found that 1 percent of the villagers had antibodies to simian foamy virus.  Elsewhere, Africans who had reported contact with nonhuman primate blood were identified as serologically active for a wide array of primate T lymphotrophic viruses.  High concentrations of domesticated animals also provide opportunities for the mixing of human and animal pathogens.  This situation lends itself to the emergence of an incredible range of diversity in microbes — some with the potential to spread and cause disease (Pike et al., 2010).  These issues are exacerbated by the recent explosion of air travel, which geographically connects disparate human populations who were once isolated into a massive population; thus, the probability that a localized outbreak (stemming from natural or man-made sources) will become a global pandemic is further amplified.
 
Fortunately, scientific techniques are now available to begin tackling the difficult task of predicting and preventing pandemics.  Viral detection through RNA sequencing and polymerase chain reaction (PCR) has become increasingly accurate and sensitive.  Less sample volume is required to yield robust results and increasingly smaller amounts of virus can be definitively identified.  Advancements in molecular phylogeny allow for novel viruses to be recognized and for patterns of emergence to be determined.  Importantly, information technology makes it possible to survey remote communities at the human-animal interface and share that data in a “real time” manner with coordinating centers around the world.
 
 

Scientific challenges and opportunities

 
Breakthroughs in the science of pandemic prevention over the past decade have shown that, far
from isolated random occurrences, a set of processes underlies the birth of pandemics (Pike et al., 2010).  Pandemics almost always emerge as the result of the movement of an animal microbe into the human population.  While domestic animals can play vital intermediary roles in this process, the greater diversity of wild animal hosts and viruses provides the ultimate source of most human pandemics.  Pandemics also arise disproportionately in certain geographic regions, with those areas of high biological diversity (including diverse wild animal hosts and their viruses) playing a central role.  Additionally, pandemics are not evenly distributed among known groups of microbes.  Certain pathogen classes, particularly those such as RNA viruses (which have high capacity to generate novel genetic diversity) represent more substantive threats.
 
While future scientific results will certainly increase our ability to predict pandemics, the existing body of information already provides concrete steps that can be taken to decrease pandemics.
Monitoring the interface between humans and wild animals, along with the mediating influence of domestic animals, and working to decrease levels of exposure to animals, will increase the rate at which we identify and stop new pandemics.  Current serological survey techniques allow monitoring schemes to be implemented in a variety of field settings.  Such efforts need not be deployed indiscriminately, but can be focused on individuals with particular exposures to animals and in specific regions of the world.  For example, this could involve systematic (perhaps every six months) sampling of blood from known bushmeat hunters in a hotspot such as Cameroon.
 
While information and laboratory tools have radically increased our ability to catch pandemics before they spread, access to these tools is not uniform across the globe.  Breakthroughs in viral discovery techniques, including pathogen microarrays and direct sequencing, have dramatically increased our ability to identify novel pathogens.  Yet such techniques remain limited by insufficient bioinformatics resources and have not yet been widely distributed to sites near viral hotspots.  Increased communications infrastructure means that outbreaks may be more quickly identified, yet information technology must be improved and deployed to remote regions to take full advantage of the emerging viral detection technology.  Upgrading technology infrastructure alone is not enough.  An investment must be made in equipping laboratories and field stations in viral hotspots, and in training and maintaining a dedicated staff.
 
 

Policy issues

 
The science of pandemic prevention has advanced to the point where specific, internationally directed policies have the potential to move global disease control from the current responsive
posture to a future where pandemics are predicted and prevented.
 
  • Regular and systematic disease surveillance, involving specimen collection and general health survey at the interface of human and animal populations, should be radically and systematically expanded to cover populations of hunters, market workers, and farmers in viral hotspots throughout the world.  With the majority of emerging viruses being RNA viruses, monitoring could initially focus on this subset of viruses and then expand to monitor other viruses, bacteria and parasites.

  • Viral discovery capacity should be improved through increased resources aimed at improving bioinformatics and expanding laboratory capacity to viral hotspots throughout the world.  These resources should include the equipment and materials to test and analyze specimens and share the data worldwide, trained personnel to carry out the surveys and report the data, and general maintenance of sites positioned in viral hotspots. 

  • Infrastructure for communicating human outbreaks and animal die-offs rapidly from remote regions should be improved, coordinated and deployed in viral hotspots.  This includes upgrading or introducing new Internet and phone capabilities, ensuring that the integrity of the system allows for reliable and consistent exchanges of information, and implementing appropriate low-tech alternatives where possible.

  • Long-term disease baselines should be established in human and animal populations in viral hotspots and among other selected populations.  This would require a complete serological survey of individuals in regular contact with wildlife in the regions of viral hotspots.  After the baseline samples are taken, a biannual serologic survey of statistically significant portions of the populations would allow for the identification of novel viruses.

  • Along with surveillance of humans at the human-animal interface, surveillance of wildlife such as non-human primates would help facilitate the prediction of which viruses will jump the species barrier.  Obtaining samples from behavioral studies of wild populations or from wildlife relocation programs in preserves would allow for pathogen sampling of these populations. 

  • In addition to surveillance, behavioral modification campaigns should be implemented in areas with high human-animal contact.  This strategy has been implemented in Sierra Leone to combat Lassa Fever and involves mapping, contacting relatives of infected individuals, prevention posters, songs by local musicians, and other outreach activities.  Educational programs should also include “health hunter” sessions to teach proper handling of bushmeat.
 
 

References

 
Pike B.L., Saylors K.E., Fair J.N., LeBreton M., Tamoufe U., Djoko C.F., Rimoin A.W., and Wolfe N.D. (2010). The origin and prevention of pandemics. Emerging Infections. 50:1636-40.
 
 
** A policy position paper prepared for presentation at the conference on Emerging and Persistent Infectious Diseases (EPID): Focus on Surveillance convened by the Institute on Science for Global Policy (ISGP) Oct. 17-20, 2010, at Airlie Conference Center, Warrenton, Va.
 
 

Debate summary

 
The following summary is based on notes recorded by the ISGP staff during the not-for-attribution debate of the policy position paper prepared by Dr. Nathan Wolfe (see above) and presented by Dr. Travis Taylor.  Dr. Taylor initiated the debate with a 5-minute statement of his views and then actively engaged the conference participants, including other authors, throughout the remainder of the 90-minute period.  This Debate Summary represents the ISGP’s best effort to accurately capture the comments offered and questions posed by all participants, as well as those responses made by Dr. Taylor.  Given the not-for-attribution format of the debate, the views comprising this summary do not necessarily represent the views of either Dr. Taylor or Dr. Wolfe, as evidenced by Dr. Wolfe’s policy position paper.  Rather, it is, and should be read as, an overview of the areas of agreement and disagreement that emerged from all those participating in the critical debate.
 
 

Debate conclusions

  • Efforts made in pursuing basic scientific research on infectious diseases and efforts to protect the public’s health are distinct activities having different priorities, but mutually supportive goals.  While their short-term priorities may differ, their overall contributions need to be integrated to achieve optimum benefits for protecting human health.

  • While the value of active surveillance for increasing the lead time in identifying infectious disease outbreaks was acknowledged, its utility for improving the response of public health officials to such outbreaks was considered debatable.  The appropriate utilization of surveillance information by policy makers was seen as a major barrier. 

  • Differing priorities of the many communities involved in the surveillance of infectious diseases routinely hinder the analysis of surveillance data and consequently, often result in a confusing characterization of the risk to the public.
     
  • A standardized method or system of risk communication should be developed to aid in decision-making processes.  Candid, ongoing evaluations of the strengths and limitations of these methods and systems need to be used to adapt to changing public needs and responses.

  • The capabilities of each model for the analysis of surveillance data, including its strengths and limitations, need to be properly presented to policy makers.  A systematic method for communicating the degree of public risk emerging from these models also needs to be developed to aid in the decision-making process. 

  • The expanding volume of data for the characterization of infectious diseases makes the analysis of that data the key factor in determining if it can be effectively used to inform public policy.  Collecting and generating the scientific data is easier than appropriately utilizing it in the formulation and implementation of public policy.

  • To ensure the optimal use of pathogen discovery as a public health tool, molecular biology data must be combined with epidemiological and behavioral data.

  • The discovery of pathogens does not necessarily equate to identifying a disease of significant human impact for which a vaccine or other medical countermeasures will be needed. 
 
 

Current realities

 
There is great need for the development of new methods to detect novel pathogens and, thereby, to protect the public from new disease outbreaks.  In an age of increasing globalization and travel, pathogens can spread rapidly.  Currently, there are more than 30 diseases spreading among communities worldwide that were not even known to exist just a few decades ago (e.g., HIV and SARS).  Novel pathogens emerge, on average, every 16 months.  Given that a large portion of novel diseases are zoonotic in nature, monitoring the animal/human interface is an essential component of any effective surveillance system designed to predict the onset of epidemics or pandemics from novel pathogens.
 
Wider use of currently available scientific techniques can strengthen current pandemic prevention efforts.  Viral detection has become increasingly accurate and sensitive.  Smaller sample volumes are required to yield robust results and increasingly smaller amounts of a virus can be definitively identified.  Advancements in molecular phylogeny allow for many novel viruses to be recognized.  However, while these technologies facilitate the detection of novel viral pathogens, they do not yet indicate which pathogens will cause disease in humans, which pathogens will jump from animals to humans (i.e., zoonotic diseases) and start circulating in humans, and which will cause a pandemic.
 
The ability of current surveillance systems to predict a pandemic is unclear.  It is also unclear whether the novel approach to viral surveillance using ribonucleic acid (RNA) sequencing and polymerase chain reaction (PCR) would be able to improve the impact of disease surveillance for pandemic prevention.  While an increasing amount of data is being generated, uncertainty remains as to whether present analysis methods are useful in pandemic prediction.  The nature of viral behavior may not conform to a well recognized model and more research is needed to develop a robust method for determining which new virus(es) will cause a pandemic. 
 
There was considerable debate regarding the difference between basic research results and the decisions and practices used to protect the public’s health.  A consensus was reached that basic research on infectious diseases and public health activities are not equivalent, but should be coordinated to produce the best results.  These two activities may inform one another, and basic research can provide important epidemiological and biosurveillance information. 
 
 

Scientific opportunities and challenges

 
While the value of active surveillance for increasing the lead time in identifying infectious disease outbreaks was acknowledged, its utility for improving the response of public health officials to such outbreaks was considered debatable.
 
While molecular techniques and scientific technologies have made significant advances in the area of viral detection, those advances have not translated into an increased capacity to predict which novel virus will be pathogenic, or which novel virus will jump the species barrier from animals into humans.  There was consensus that the volume of data generated will continue to increase through efforts such as novel virus detection.  For these data to be useful for decision-making, the analysis methods must also continue to evolve in the direction of producing clear and concise conclusions. 
 
Even though the scientific methodologies designed to detect novel pathogens are increasingly accurate, and therefore more useful in the predictive models used for infectious diseases, the epidemiological data are often either not available or as well developed. 
 
Consensus was reached surrounding the need for a complete baseline picture of a disease.  An accurate baseline of what pathogens are in a community, when and how they appear, and the extent of their intrusion would allow for the detection of unusual events that could signal the emergence of a novel pathogen.
 
Advancement of scientific technologies has progressed rapidly in wealthy regions of the world, but that advancement has not been effectively transferred to less-wealthy areas, where even basic technology can be routinely unavailable.  Consensus was expressed that capacity building in less-wealthy countries is a significant challenge that needs to be addressed, especially given that novel pathogens are most commonly found in these countries.  Within the realm of capacity building, it was widely agreed that increased laboratory capacity is also essential to the success of surveillance and, accordingly, to the effectiveness of pandemic prediction.  The strengthening and, in many cases, the creation of regional networks also were widely seen as critical to the building of in-country capacity needed to improve surveillance for novel pathogens.
 
A tangential discussion took place regarding the appropriate actions to be taken once a potential pandemic is identified.  Current knowledge allows a vaccine to be created quickly for select diseases, such as influenza, once the genetic signature of a pathogen is known.  There are several challenges to the development and implementation of intervention methods, such as identifying the safety of such a vaccine.  Dissenting opinions were expressed concerning the requirements to prove vaccine safety and how those requirements should be viewed in light of a potential pandemic.  The challenge of vaccine safety was considered to be intertwined with the challenge of the efficacy of a vaccine that could be used as a potential agent to combat a pandemic.  It was pointed out that even if safety concerns were removed, data from novel pathogen surveillance in animals might not be directly applicable to humans.  This is because the strain of the pathogen circulating in animals could be different from the strain of pathogen that would cause a pandemic in humans.  More in-depth research is needed to resolve these issues associated with zoonoses.
 
Overall, a consensus was reached that while infectious disease data collection will continue to grow, primarily due to expanding scientific capabilities, methods for analysis and accurate risk communication are needed for optimal utilization of that data within decision-making processes. The expansion of data collection should be developed in ways that include laboratory capacity building for those areas that lack appropriate technological resources.  The capabilities of each model for the analysis of surveillance data, including its strengths and limitations, need to be properly presented to policy makers.  A systematic method or system for communicating the degree of public risk emerging from these models also needs to be developed to aid in the decision-making process.  Candid, ongoing evaluations of the strengths and limitations of these methods and systems must also be put in place to adapt to changing public needs and responses.
 
 

Policy issues

 
The absence of effective risk communication to policy makers and the public was the major policy theme identified.  As a whole, emphasis was placed on the importance of conveying the degree of uncertainty in the analysis of surveillance data as an inherent factor in any scheme of infectious disease pandemic prediction.  Public health officials and scientists should determine effective ways to communicate that uncertainty to decision makers.  The development of methodologies to assess risk and to communicate risk accurately would aid in this effort.
 
There was agreement regarding the need to determine which actions would be implemented upon discovery of a novel pathogen.  The policy implications of using preventive vaccinations are complex and need to be addressed comprehensively in a proactive, anticipatory way by multiple governmental agencies.  The question was raised as to which organization (e.g., the WHO) should take on the primary leadership role in deciding which strain of influenza virus should be used in the development of a vaccine for pandemic influenza and how to practically proceed with the vaccine development in an economically rational way.  It was noted that the rapid development of vaccines can occur only for known and well-characterized pathogens.  It is unlikely that effective vaccines can be obtained in time to control a pandemic associated with a novel pathogen.  Analogously, the question of which organizations should decide which vaccines should be made for diseases other than influenza was also voiced.  The conflicting views expressed clearly identified this question as an important issue to be resolved through negotiation among the various national and international organizations.
 
Although there was consensus on the need to develop population-based infectious disease baselines, the personal rights of the individuals required for those surveys were seen as a policy issue to be resolved.  To what extent an individual’s civil rights and freedoms have to be balanced with the public health needs of the global community has yet to be determined.
 
The need for measurable indicators of success was often stated.  Preventing an infectious disease outbreak is a success, but one that is difficult to gauge and rarely recognized by the public at large.  Metrics to evaluate programs and demonstrate achievement are essential to aid both the public health community and policy makers.
 

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