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5
Infectious Disease Emergence:
Past, Present, and Future
OVERVIEW
Emerging infections, as defined by Stephen Morse of Columbia University
in his contribution to this chapter, are infections that are rapidly increasing in
incidence or geographic range, including such previously unrecognized diseases
as HIV/AIDS, severe acute respiratory syndrome (SARS), Ebola hemorrhagic
fever, and Nipah virus encephalitis. Among his many contributions to efforts to
recognize and address the threat of emerging infections, Lederberg co-chaired
the committees that produced two landmark Institute of Medicine (IOM) reports,
Emerging Infections: Microbial Threats to Health in the United States (IOM,
1992) and Microbial Threats to Health (IOM, 2003), which provided a cru-
cial framework for understanding the drivers of infectious disease emergence
(Box WO-3 and Figure WO-13). As the papers in this chapter demonstrate,
this framework continues to guide research to elucidate the origins of emerging
infectious threats, to inform the analysis of recent patterns of disease emergence,
and to identify risks for future disease emergence events so as to enable early
detection and response in the event of an outbreak, and perhaps even predict its
occurrence.
In the chapter’s first paper, Morse describes two distinct stages in the emer-
gence of infectious diseases: the introduction of a new infection to a host popu-
lation, and the establishment within and dissemination from this population.
He considers the vast and largely uncharacterized “zoonotic pool” of possible
human pathogens and the increasing opportunities for infection presented by
ecological upheaval and globalization. Using hantavirus pulmonary syndrome
and H5N1 influenza as examples, Morse demonstrates how zoonotic pathogens
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MICROBIAL EVOLUTION AND CO-ADAPTATION
gain access to human populations. While many zoonotic pathogens periodically
infect humans, few become adept at transmitting or propagating themselves,
Morse observes. Human activity, however, is making this transition increasingly
easy by creating efficient pathways for pathogen transmission around the globe.
“We know what is responsible for emerging infections, and should be able to
prevent them,” he concludes, through global surveillance, diagnostics, research,
and above all, the political will to make them happen.
The authors of the chapter’s second paper, workshop presenter Mark
Woolhouse and Eleanor Gaunt of the University of Edinburgh, draw several gen-
eral conclusions about the ecological origins of novel human pathogens based on
their analysis of human pathogen species discovered since 1980. Using a rigor-
ous, formal methodology, Woolhouse and Gaunt produced and refined a catalog
of the nearly 1,400 recognized human pathogen species. A subset of 87 species
have been recognized since 1980—and are currently thought to be “novel” patho-
gens. The authors note four attributes of these novel pathogens that they expect
will describe most future emergent microbes: a preponderance of RNA viruses;
pathogens with nonhuman animal reservoirs; pathogens with a broad host range;
and pathogens with some (perhaps initially limited) potential for human-human
transmission.
Like Morse, Woolhouse and Gaunt consider the challenges faced by novel
pathogens to become established in a new host population and achieve efficient
transmission, conceptualizing Morse’s observation that “many are called but few
are chosen” in graphic form, as a pyramid. It depicts the approximately 1,400
pathogens capable of infecting humans, of which 500 are capable of human-to-
human transmission, and among which fewer than 150 have the potential to cause
epidemic or endemic disease; evolution—over a range of time scales—drives
pathogens up the pyramid. The paper concludes with a discussion of the public
health implications of the pyramid model, which suggests that ongoing global
ecological change will continue to produce novel infectious diseases at or near
the current rate of three per year.
In contrast to other contributors to this chapter, who focus on what, why,
and where infectious diseases emerge, Jonathan Eisen, of the University of
California, Davis, considers how new functions and processes evolve to generate
novel pathogens. Eisen investigates the origin of microbial novelty by integrating
evolutionary analyses with studies of genome sequences, a field he terms “phy-
logenomics.” In his essay, he illustrates the results of such analyses in a series
of “phylogenomic tales” that describe the use of phylogenomics to predict the
function of uncharacterized genes in a variety of organisms, and in elucidating the
genetic basis of a complex symbiotic relationship involving three species.
Knowledge of microbial genomes, and the functions they encode, is severely
limited, Eisen observes. Among 40 phyla of bacteria, for example, most of the
available genomic sequences were from only three phyla; sequencing of Archaea
and Eukaryote genomes has proceeded in a similarly sporadic manner. To fill
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INFECTIOUS DISEASE EMERGENCE
these gaps in our knowledge of the “tree of life,” his group has begun an initiative
called the Genomic Encyclopedia of Bacteria and Archaea. Eisen describes this
effort and advocates the further integration of information on microbial phylog-
eny, genetic sequence, and gene function with biogeographical data, in order to
produce a “field guide to microbes.”
The chapter’s final paper, by Peter Daszak of the Consortium for Conser-
vation Medicine, Wildlife Trust, makes the leap from knowing how infectious
diseases emerge to predicting where, and under what circumstances, an emergent
disease event is likely to occur. Daszak presents several examples of his group’s
efforts to build predictive approaches to infectious disease emergence based on
a thorough understanding of the underlying ecology. These include construct-
ing a model to predict relative risks for Nipah virus reemergence in Malaysia,
where a 1999 outbreak devastated a thriving pig farming industry; identifying
likely sources by which West Nile virus could spread to Hawaii, the Galapagos,
and Barbados; and determining likely reservoirs of H5N1 influenza for specific
geographic locations worldwide.
Daszak’s group constructed a database of emerging infectious disease
“events” first reported in human populations between 1940 and 2004, which they
have used to examine correspondences between events and ecological variables,
such as human population density and wildlife diversity, in a geographical con-
text. These analyses have revealed “hotspots” for infectious disease emergence.
Daszak discusses the implications of hotspot location for global infectious disease
surveillance, and describes how he and coworkers have used their knowledge of
hotspots to target surveillance for Nipah virus in India, and also to discover a
virus with zoonotic potential in Bangladesh.
EMERGING INFECTIONS: CONDEMNED TO REPEAT?
Stephen S. Morse, Ph.D.1
Columbia University
We have all learned about the importance of infectious diseases throughout
history, including the Plague of Justinian (541-542), the first known pandemic on
record (McNeill, 1976), and the Black Death in the fourteenth century. Stanley
Falkow, who is included in this volume, has extensively studied Yersinia pestis,
the responsible organism, and given us important insights into its pathogenesis.
Another devastating disease that was once much feared is smallpox, which is said
to have killed more people than all the wars in history. The eradication of small-
pox was therefore a triumph of public health. Ironically, smallpox has the unique
property of being the only species to date that human beings have intentionally
1 Professor
of epidemiology and founding director of the Center for Public Health Preparedness at
the Mailman School of Public Health.
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MICROBIAL EVOLUTION AND CO-ADAPTATION
driven to extinction. While we have unintentionally driven so many species to
extinction, it is nice to know we can actually intentionally do some good. Chol-
era was, of course, a very big concern in the nineteenth century and remains a
concern today, especially in places like Bangladesh, as Gerald Keusch of Boston
University and a member of the Forum can affirm.
The 1918 influenza pandemic is one of our paradigms of a nightmare emerg-
ing infectious disease event. It may very well have been the greatest natural
disaster in the early days of the twentieth century. The “official” mortality esti-
mates keep rising as investigators keep finding data from further away, in devel-
oping countries and more remote places. But that pandemic is thought to have
accounted for about 50 million or more deaths, depending on how you want to
count it, and is obviously a matter of great concern.
Despite that, we have had years of complacency about infectious diseases,
partly for reasons already discussed—the antibiotic era, immunizations, improved
public health measures—all of which have led to the fact that we now live longer
and tend to die later of chronic diseases. Unfortunately, this has not been true
everywhere. It has not been true in many developing countries. Infectious dis-
eases remain the major causes of morbidity and mortality in much of the world.
But in this paper, I would like to concentrate on emerging infections, the
ones that are not previously recognized and that seem to appear suddenly and
almost mysteriously—if you will, The Andromeda Strain (Crichton, 1969). Figure
WO-7 graphically shows a number of examples. Of course, there are also forgot-
ten infections that reappear. We sometimes call those “reemerging infections.” I
tend to think of most of the “reemerging” infections as reminding us that many
infectious diseases in our highly mechanized modern societies, with the standard
of living we enjoy, have been pushed to the margins, but have never been entirely
eliminated. So when public health measures are relaxed or are abandoned because
of lack of money or complacency—complacency being a very big problem—you
then see forgotten infections reappearing. An example is diphtheria in the former
Soviet Union and Eastern Europe in the early 1990s when those countries no
longer had the money to maintain their immunization programs. It reminds us
that many of these diseases may be forgotten, but they are not gone.
HIV/AIDS is, of course, the infection that got our attention initially and
made it possible at least to think about shaking ourselves out of the growing
complacency about infectious diseases. HIV infection and AIDS, starting from
obscurity, rose to become a leading cause of death in the United States by 1993
(Figure 5-1). There are recent reports dating HIV to the early twentieth cen-
tury, but it didn’t appear to take off until mid-century. You can find a molecular
example of HIV in Zaire in 1969, but that is almost a one-off, and then there were
reports of a few cases in the 1970s in Africa, if anyone had been paying attention.
Then suddenly, in the early 1980s, it appeared in the United States and took off
like the proverbial rocket to overtake all other causes of death in healthy young
people. Of course, this is the same age group killed in the 1918 flu, but also the
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INFECTIOUS DISEASE EMERGENCE
FIGURE 5-1 Leading causes of death in young adults, United States, 1987-2005. Red
line: Rise of HIV infection to become leading cause of death.
SOURCE: CDC (2008). Figure 5-1 COLOR
Original file colors
very people we generally expect to have the best survival rate. They have survived
childhood and we expect that they ought to be fine. As shown in Figure 5-1, all
the other causes of death were unchanged during that period.
HIV was therefore quite a surprise. When you think about it, this does seem
rather like The Andromeda Strain. We had thousands of years of experience with
infections, some of them historically recorded in some detail. Some of these are
still unidentified, and we still argue about what they were. But a disease that actu-
ally kills by undermining the immune system directly was a novel mechanism of
pathogenesis. How often does one find a new mechanism of pathogenesis in an
infectious disease, considering the thousands of years of experience that we have
had? I think it was quite remarkable.
Since its peak (around 1995), the HIV/AIDS death rate in the young adult
population in the United States has dropped (Figure 5-1), thanks largely to the
fact that a few effective drugs were finally developed, including in particular the
protease inhibitors. As a result, the trend reached a plateau and has recently been
going down. HIV/AIDS is now a treatable disease, with many lives saved among
those who can afford the medication. But it also worries me that this fortunate
situation may not last very long. Inevitably, antiviral resistance has already been
identified in some patients. Another concern is that some of the younger people
have now become quite complacent about this disease, not knowing the devasta-
tion that many of us witnessed in the 1980s, before it could be effectively treated.
We are seeing young people now regarding this with less seriousness than they
should.
So there we are, facing complacency again. If there is a bottom line to the
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MICROBIAL EVOLUTION AND CO-ADAPTATION
theme of the Forum on Microbial Threats, it is that we cannot afford to be com-
placent anymore.
What are emerging infections? I always like informally to define emerging
infections as those that would knock a really important story off the front page of
the newspaper, whether the runaway bride or the Texas polygamy case, at least for
a day or two. However, I do have a more formal definition: those infections that
are rapidly increasing in incidence or geographic range. In some cases, these are
novel, previously unrecognized diseases. But, as I am going to show you, many
of them are not The Andromeda Strain. They do not come from space. Actually,
in many cases, they have already existed in nature. Very often, anthropogenic
causes—often as unintended consequences of things we do—are important in the
emergence of these infections.
There are many examples. You can pick your favorite: Ebola in 1976; han-
tavirus pulmonary syndrome, which I will discuss briefly in a moment; Nipah,
which Peter Daszak addressed at the workshop (and his group has done some
excellent work on this); SARS; and, of course, influenza, which still continues
to surprise us.
You could think of the many events shown in Figure 5-2 as “a thousand
points of light” (or at least those of you who are old enough to remember the first
President Bush). But these are really a lot of little fires all over the world, most of
which we did not spot in time before they became big brush fires or even wild-
fires. That includes many examples, such as West Nile virus entering the United
States in 1999, the enteropathogenic Escherichia coli (made famous by the “Jack
in the Box” case2), and a number of others, including SARS, of course.
I have divided the process of disease emergence into two steps, for analysis:
(1) what I call introduction, where these “Andromeda-like” infections are coming
from; and (2) establishment and dissemination, which (fortunately for us) is much
harder for most of these agents to achieve. The basic lesson there is that many
may be called, but few are chosen.
In this two-step process, as you all know, the opportunities are increasing
thanks to ecological changes and globalization, which gives the microbes great
opportunities to travel along with us, and to travel very quickly. Even medical
technologies have played an inadvertent role in helping to disseminate emerging
infections.
I will spend most of my time talking about what seems to be the most myste-
rious step—and I hope we can demystify it a bit here—and that is the introduction
of a “new” infection. What we now know is that many of these infections, exotic
as they may seem, are often zoonotic. Some of them do not do very much, and
2 In 1993, four children died and hundreds became ill after eating undercooked hamburger pat-
ties contaminated by E. coli bacteria at Jack in the Box restaurants (see http://www.about-ecoli.
com/ecoli_outbreaks/view/jack-in-the-box-e-coli-outbreak).
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FIGURE 5-2 Global examples of emerging and reemerging infectious diseases, some of which are discussed in the main text. Red represents
Figure 5-2 COLOR.eps
newly emerging diseases; blue, reemerging or resurging diseases; black, a “deliberately emerging” disease.
bitmap image
SOURCE: Reprinted from Morens et al. (2004) with permission from Macmillan Publishers Ltd. Copyright 2004.
landscape
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00 MICROBIAL EVOLUTION AND CO-ADAPTATION
may cause no infection at all; while others may cause a truly dramatic infection,
like Ebola.
So that zoonotic pool, if I may use that term, is not fully chlorinated, and it
is a rich source of potential emerging pathogens. There is so much biodiversity
out there, including a tremendous biodiversity of microbes. Some of that biodi-
versity—we do not know how much, even now—is still untapped.
Changes in the environment may increase the frequency of contact with a
natural host carrying an infection, and therefore increase our chances of encoun-
tering microorganisms previously unknown to humans. Of course, the role of
food animals, as well as wildlife (one of the subjects of Peter Daszak’s contribu-
tion to this volume), has come very much to fore in recent years.
There are a number of examples associated with activities like agriculture,
food-handling practices, and, for the vector biologists, of course, changes in water
ecosystems. Table 5-1 lists just some of these cases. The basic point is that there
are a number of ecological changes, many of them anthropogenic, which provide
new opportunities for pathogens to emerge and gain access to human populations.
Think of these as a sort of microbial explorers, discovering new niches—us—and
exploring new territory.
It is important not to overlook the very important role of evolution as well.
One role is obviously what evolution has already been doing for a long time, lead-
ing to the biodiversity of pathogens that we see existing in nature. It is remark-
able, when you think about how great that biodiversity is. We don’t even know
how many viruses human beings are subject to, even how many inhabit us at this
very moment. But when I think about just the herpesviruses, which are pretty well
studied, that number could be very large indeed. There are eight known human
herpesviruses, and at least six of them—you might argue, even seven of them,
except for Human herpesvirus 8, the one that causes Kaposi’s sarcoma—are ubiq-
TABLE 5-1 New Opportunities for Pathogens: Ecological Changes
Agriculture Hantaan, Argentine hemorrhagic fever,
Nipah, West Nile (Israel), possibly pandemic
influenza
Food-handling practices SARS, H5N1 influenza, HIV?,
enteropathogenic E. coli
Dams, changes in water ecosystems Rift Valley fever, other vectorborne diseases,
Schistosomiasis
Deforestation, reforestation Kyasanur Forest, Lyme disease
Climate changes Hantavirus pulmonary syndrome (HPS),
vectorborne diseases
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INFECTIOUS DISEASE EMERGENCE
uitous in the human population. They can be found all over the world. Several of
them are present at very high prevalence in the human population.
That just gives you an idea of some of that great biodiversity. As it happens,
these herpesviruses are all specialized for humans. There are, of course, herpes-
viruses of other species. So a lot of coevolution between host and pathogen goes
on as well.
Of course, there is adaptation to new hosts and environments through natu-
ral selection. We see this with influenza most notably, but with many other
examples—the coronaviruses, like SARS—as well. Of course, antimicrobial resis-
tance has been mentioned so many times. If anyone needs to be convinced about
the role of evolution in the world, I think this is a pretty good demonstration—one
of the rare examples in which you can do in vitro exactly the same thing as what
happens in the real world, just on a different scale.
There are many case studies. I’ll briefly discuss a few, just to illustrate some
key points.
Hantavirus pulmonary syndrome was ironically one of the first things to
happen suddenly in the United States after the original Institute of Medicine
Emerging Infections report came out in October 1992. Hantavirus pulmonary
syndrome suddenly appeared in the southwestern United States in the following
spring and summer.
My friend Richard Preston wrote a book called The Hot Zone. He has a very
philosophical chapter at the end where he talks about the “revenge of the rainfor-
est.” I think it is a good thought, in that we should be kinder to our environment,
for many good reasons. The rainforests are great sources of biodiversity and, to
a great extent, that biodiversity was largely unexplored.
But an emerging infection can occur anywhere. Even the southwestern United
States, which looks so dry, arid, and inhospitable to life, has its share, different
from the rainforest, but just as significant.
Jim Hughes, who is a Forum member and was the director of the National
Center for Infectious Diseases (NCID) at the Centers for Disease Control and
Prevention (CDC) at the time of the outbreak, knows this story firsthand. Start-
ing in the late spring and then going through the summer of 1993, people started
appearing at emergency departments and clinics with respiratory distress. Many
of them were hospitalized. I believe the case fatality rate at that time was about
60 percent, even with treatment. It is a little lower now, but it is still hovering
near 40 to 50 percent.
The health departments did the usual investigations: There is a pocket of
plague in that area, so the local health departments tested for that. Another possi-
bility could be influenza out of season. These, and other likely possibilities, were
ruled out. The state health departments then called in CDC, which did a number
of tests and identified, perhaps surprisingly, a hantavirus as the most likely cul-
prit. This was tested both by serology and, later, shedding of virus was tested by
polymerase chain reaction (PCR). Of course, when you think of hantavirus, you
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0 MICROBIAL EVOLUTION AND CO-ADAPTATION
usually think of rodents, with a few minor exceptions. So a number of rodent
species trapped near patients’ homes were tested. The most frequent rodent was
apparently also the most frequently infected: Peromyscus maniculatus, the deer
mouse. This is a very successful and prolific rodent that is essentially the major
wild rodent in this entire area. Ruth Berkelman likes to refer to this as your typi-
cal hardworking single mom, as shown in the illustration (Figure 5-3).
Of course, once a test was developed and people started looking for the virus,
they were able to find it in a great number of other places, including serum and
tissue samples that had been saved earlier because the etiology was unknown, but
FIGURE 5-3 A deer mouse (Peromyscus maniculatus), natural host for the Sin Nombre
(hantavirus pulmonary syndrome) Figure 5-3.eps
virus, with her young.
SOURCE: Image courtesy of Bet Zimmerman, www.sialis.org.
bitmap image
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INFECTIOUS DISEASE EMERGENCE
FIGURE 5-4 Hantaviruses of the Americas. Viruses associated with human disease are
Figure 5-4 COLOR.eps
shown in bold.
bitmap image
SOURCE: Adapted from Peters (1998) with permission from ASM Press and Jim Mills.
inverted colors
odd—cases of acute respiratory distress. There were even some cases outside the
geographic range of Peromyscus maniculatus, which turned out to be hantaviruses
that were natural infections of other rodent species.
This point is illustrated in Figure 5-4 (I thank C. J. Peters, then at CDC, for
the illustration). Before 1993, the United States had one known hantavirus, not
associated with human disease (Prospect Hill virus) and another hantavirus of
rats, Seoul virus, and related variants that could be found in port cities; neither
was associated with serious acute disease in the United States. After 1993, we
had to add another: the virus that causes hantavirus pulmonary syndrome. Then,
when people started looking for hantaviruses, there was no shortage of previously
unrecognized cases. In Figure 5-4, the virus names in bold have been associated
with human disease, while many others have not. So throughout North and South
America, suddenly there was a whole rash of hantaviruses that nobody knew
existed.
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Figure 5-21 COLOR.eps
FIGURE 5-21 Global richness map of the geographic origins of EID events from 1940 to 2004. The map is derived for EID events caused
by all pathogen types. Circles represent one degree grid cells, and the area of the circle is proportional to the number of events in the cell.
bitmap image
SOURCE: Jones et al. (2008).
landscape
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INFECTIOUS DISEASE EMERGENCE
the greatest numbers of EID events. We corrected for that by geographically
plotting the coordinates of every author—about 17,000 of them—of every paper
published in the Journal of Infectious Diseases (JID) for the last 20 years, and
used this information in our analyses.
We were able to use this database to address some key questions in emerg-
ing disease biology. First, whether EIDs are really on the rise (Jones et al.,
2008). Decade by decade, from the 1940s to the 1990s, the number of EID
events has increased significantly, even after accounting for the increasing num-
bers of scientists over this period. This has another implication: It is reasonable
to expect that this trend will continue in the future. We also found that a major-
ity of EID events were associated with drug-resistant microbes. Second, we
were able to examine whether zoonoses such a HIV/AIDS, which are the most
high-profile EIDs, are truly the most significant threat. We found that zoonoses
emerging from wildlife (i.e., HIV, SARS, Ebola and Nipah viruses) are indeed
significantly rising over time and during the 1990s, represented the dominant
type of emerging disease.
Testing Hypotheses
We used our database approach to examine two simple questions: (1) Is dis-
ease emergence an “anthropogenic” process (i.e., are human changes to demog-
raphy, the environment, and other factors the key drivers of EIDs)? (2) Can we
obtain a more accurate map of the emerging disease “hotspots”—the regions most
likely to cause the next new emerging disease?
To test these theories, we first found a way around the dilemma of not know-
ing where the diversity of pathogens resides by assuming that each mammalian
species harbors a similar number of host-specific pathogens. If this is true, then
the global distribution of wildlife diversity approximates the potential zoonotic
pathogen diversity. In our analysis, we used a global dataset on mammalian host
richness.
We then used a simple multiple logistic regression to assess the correlation
between the risk of an EID historically and some key factors thought respon-
sible for disease emergence, correcting for reporter bias with the dataset on JID
authors. We addressed the first hypothesis by testing global human population
density against EID risk and showed that this is a significant predictor of risk for
each group of pathogen. This specifically shows that the risk of a disease emerg-
ing (not spreading) is dependent on human population density (i.e., those regions
with dense human populations and presumably lots of human-driven changes are
most likely to lead to a new EID).
By plotting out our risk measures globally, we were able to produce the first
ever global distribution maps of emerging disease risk, corrected for reporter
bias, and based on correlated trends in EIDs. These predictive maps of EID
“hotspots” show different global distribution patterns when we sorted EID events
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MICROBIAL EVOLUTION AND CO-ADAPTATION
according to their origins (e.g., zoonotic diseases from wildlife; vector-borne
pathogens; drug-resistant pathogens; Jones et al., 2008). For EIDs of wildlife
origin (the high-profile zoonoses), these hotspots are primarily tropical areas
where wildlife diversity is highest, and particularly where human density is also
high, as occurs in southern Brazil, northern India and Bangladesh, and Southeast
Asia (Figure 5-22). However, Europe and the United States also have significant
potential for zoonotic disease emergence, due to continued, high-level environ-
mental changes.
However, perhaps one of the key findings of our analysis is that if we plot
out the geographic distribution of all 17,000 JID authors, we find that the global
effort for infectious disease research has largely focused on regions from where
the next EID is least likely to emerge. Indeed, few EID hotspots—located pri-
marily in developing countries—are under thorough surveillance for infectious
pathogens (Jones et al., 2008). We therefore concluded that global efforts to
detect emerging infections should be slightly refocused to the Tropics if we are
to rapidly intervene with this process of emergence.
Using Predictive Approaches: “Smart Surveillance”
Can we use this hotspot approach to increase our capacity for preventing the
next EID? If we return to Nipah virus, we see that this emerging pathogen fits into
the high-profile group of zoonoses that are lethal to humans and have emerged
from wildlife in tropical regions. During the last decade, antibodies to this patho-
gen have been reported in bats across Southeast Asia, South Asia, Madagascar,
China, and even continental Africa. But this knowledge has been gleaned through
different groups working independently and often serendipitously. There has been
no focused, global surveillance for viruses related to NiV in bats.
If we examine the wildlife zoonotic disease hotspot map (Figure 5-22) in
one of the highest risk regions, Bangladesh, the human population has been
subject to a series of repeated outbreaks of NiV with higher case-fatality rates
than in Malaysia (average around 70 percent), evidence of foodborne infection,
and evidence of up to five chains of human-to-human transmission. Bangladesh
has the densest population of any country on Earth that is not an urban city-state:
2,595 people per square mile, as compared with a global average of 128 persons
per square mile (the United States has 80 people per square mile; http://www.
worldatlas.com, 2006). The country also has surprisingly high wildlife diversity,
given its population. Thus, it appears that in Bangladesh, Nipah virus is closer to
stage three, or pandemic emergence. This raises important questions: Why were
there no programs to identify NiV in Bangladesh once the virus was discovered
in Malaysia? What other regions globally might harbor spillover of NiV or related
viruses? What other zoonotic pathogens might be lurking in the South Asia hot-
spot within bats or other wildlife hosts?
I propose that a more efficient strategy to address future emerging diseases
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FIGURE 5-22 Global distribution of the relative risk of an EID event. Maps are derived for EID events caused by (a) zoonotic pathogens
Figure 5-22 COLOR.eps
from wildlife; (b) zoonotic pathogens from nonwildlife; (c) drug-resistant pathogens; and (d) vector-borne pathogens. Green corresponds to
bitmap image
lower values; red to higher values.
landscape
SOURCE: Jones et al. (2008).
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MICROBIAL EVOLUTION AND CO-ADAPTATION
is to combine rigorous analyses of the fine-scale ecological and demographic
changes within hotspot regions (the risk factors) with state-of-the-art molecular
approaches to viral discovery. This will give us a more accurate predictive model
for future disease emergence, and better definition of the size and diversity of
the zoonotic pool. Techniques such as pyrosequencing and mass tag polymerase
chain reaction (PCR) will rapidly decrease the expense and logistical challenges
involved in identifying new viral groups, and if applied to key groups of wildlife
species (those most often responsible for disease emergence in the past) within
hotspot regions, will provide the most cost-effective way to proactively address
the EID challenge. This model for virus-hunting in the future is, of course, still
somewhat crude. It is impossible, for example, to determine the future ability of
a novel virus to jump hosts successfully to humans, and its likely pathogenicity.
However, by focusing first on viral groups known to be pathogenic, and by target-
ing viral discovery within these clades, significant progress can be made toward
dealing with the EID threat.
Acknowledgments
The work described in this chapter was carried out by a large number of
collaborators, including members of the Henipavirus Ecology Research Group
(HERG),14 especially Jon Epstein (Consortium for Conservation Medicine) and
Juliet Pulliam (Fogarty International Center). The work on West Nile virus and
avian influenza was led by A. Marm Kilpatrick (Consortium for Conservation
Medicine, University of California Santa Cruz) and the hotspots analyses were
conducted in collaboration with Kate Jones (Institute of Zoology) and Marc A.
Levy (Center for International Earth Science Information Network, Columbia).
This work was supported in part by a National Institutes of Health/National
Science Foundation “Ecology of Infectious Diseases” award from the John E.
Fogarty International Center R01-TW00824, by core funding to the Consortium
for Conservation Medicine from the V. Kann Rasmussen Foundation and is
published in collaboration with the Australian Biosecurity Cooperative Research
Center for Emerging Infectious Diseases (AB-CRC).
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