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 Emerging and Reemerging Infectious Diseases
BD Anderson and GC Gray, Division of Infectious Diseases, Duke University, Durham, NC, USA
© 2014 Elsevier Inc. All rights reserved.

Glossary
Emerging infectious disease(s) Infections that are newly recognized in a population or have existed previously but are rapidly
increasing in incidence or geographic range.
One health An interdisciplinary approach that brings together human, animal, and environmental health professionals to
address complex global health problems.
Urban sprawl The uncontrolled movement of urban development away from a city central.
Vector Any organism, though usually an arthropod, that can transmit an infectious agent to a host.
Zoonoses Diseases that can be transmitted from an animal to human or a human to animal.

Introduction

Throughout history, infectious diseases have vastly impacted human civilization. This impact has been demonstrated by the
relentless appearance of various infectious disease outbreaks, including plague that scourged Europe during the Middle Ages,
yellow fever that decimated Napoleon’s forces in Haiti during the early nineteenth century, and influenza that claimed the lives of as
many as 50 million people in 1918 (Zietz and Dunkelberg, 2004; Patterson, 1992; Johnson and Mueller, 2002). In the twentieth
century, public health knowledge and interventions increased, particularly in more developed countries, reducing the burden of
infectious diseases (Armstrong et al., 1999). Industrialization and urbanization influenced improvements in sanitation, structural
development (e.g., window screening), and vector control that collectively lowered transmission rates by reducing the population’s
contact with infectious agents (Armstrong et al., 1999). In addition, the discovery of penicillin in 1928 and the continual
development of vaccines ushered in an age of treatment and prevention strategies that many believed could eradicate infectious
diseases from the globe (Clardy et al., 2009; 1999).
This idea was personified by organizations that made pronouncements to ‘take up arms’ against the most burdensome diseases.
A well-known example comes from the Rockefeller Foundation, an organization that allocated substantial resources in the early
twentieth century to combat yellow fever in the United States and other highly impacted territories, efforts that established
precedence for future work (Fosdick, 1989). After World War II, new health organizations were established, including the US
Centers for Disease Control and the World Health Organization (WHO) that led multiple campaigns to completely eradicate
specific infectious diseases. One of the most notable efforts was the vaccination campaign against smallpox, a highly infectious viral
disease that was completely eradicated by 1980 (Henderson, 2009). These campaigns established a great confidence and optimism
in the ability to combat and control infectious diseases worldwide.
Despite these achievements, infectious diseases still pose a considerable threat today (Jones et al., 2008). Currently, it is
estimated that at least 25% of total global mortality is attributable to infectious diseases, translating into over 15 million deaths
per year (Mathers et al., 2008). The majority of deaths occur among children less than 5 years of age, living in countries with low to
middle incomes (Mathers et al., 2008). Certain diseases have greater mortality, such as acute respiratory infections, tuberculosis,
diarrheal diseases, malaria, measles, and HIV/AIDS, which account for 9 out of every 10 infectious disease deaths (2001).
Data from the past 30 years reflect various degrees of resurgence or reemergence of different infectious diseases worldwide. Two
important examples of this phenomenon include the increased incidence of wild-type poliomyelitis across geographic pockets of
Northern Africa, as well as an increase in the number of individuals being infected by the mosquito-borne disease caused by dengue
viruses. Additionally, novel infectious diseases continue to emerge in virtually every region of the world. Examples include Hendra
virus, discovered in 1994 in Australia (Murray et al., 1995); Nipah virus, identified in 1999 as the causative agent of outbreaks
among pig farmers in Malaysia (Chua et al., 2000); severe acute respiratory syndrome (SARS) responsible for an outbreak of
respiratory disease in multiple countries in 2003 (Marra et al., 2003; Peiris et al., 2003); and the 2009 emergence of a new influenza
strain, originating in North America, responsible for the first pandemic of the twenty-first century (2009b). In public health, these
types of events are referred to as emerging or reemerging infectious diseases, or collectively known as emerging infectious diseases
(EIDs). EIDs have been defined as infections that are newly recognized in a population or have existed previously but are rapidly
increasing in incidence or geographic range (Morse, 2004; Morens et al., 2004; Fauci, 2005, 2001; Institute of Medicine (US).
Committee on Emerging Microbial Threats to Health et al., 1992). EIDs can be considered emerging, recently reemerging/resurging,
or deliberately emerging, depending upon the pathway of emergence (Morse, 2004; Fauci, 2005; Morens et al., 2008).
EIDs are influenced by a wide variety of often complex factors, including ecology, human behavior, globalization, microbial
adaptation, and public health infrastructure (Morse, 1995, 2004; Lashley, 2003; Morens et al., 2004, 2008; Fauci, 2005; Jones et al.,

This article is a reprint of B.D. Anderson, G.C. Gray,Emerging and Reemerging Infectious Diseases, Reference Module in Biomedical Sciences, Elsevier, 2014.

112 Encyclopedia of Microbiology, 4th Edition [Link]

 Pathogenesis and Immunology | Emerging and Reemerging Infectious Diseases 113

2008). More recently, the threat of bioterrorism, or the deliberate release of viruses, bacteria, or other agents used to cause illness or
death in people, animals, or plants (Inglesby et al., 2002; Jernigan et al., 2002; Traeger et al., 2002), has added its own complexities
to how EIDs affect global health. A number of recent bioterrorism events have had a dramatic impact on public health policies and
resource allocations. New research and technology have provided better detection and response capabilities, as well as basic general
knowledge of the various factors and determinants affecting the emergence and spread of EIDs; however, much is still unknown.
This article offers a review of the most relevant literature associated with EIDs, as well as perspectives on how to address the most
critical future public health questions.

Global Distribution

EIDs exist in most regions of the world, often with distinct and identifiable transmission patterns that are driven by various
predictors or risk factors. These include the globalization of travel and trade, country and individual social–economic status, as well
as population dynamics. Risk factors are used to identify trends in the movement of EIDs throughout various populations. When
coupled with Geographic Information Systems mapping software, transmission patterns can be modeled, offering a pictorial view of
EID distribution. These models are very useful, allowing for predictions to be made as to where future EID events are likely to occur
and estimating the impact of public health interventions.

Globalization
Modern globalization has created ubiquity in world travel and trade. For example, a piece of fruit that is grown in Chile today can be
purchased in a market on the other side of the world in 1–2 days. EIDs travel via these rapid global transport systems as made
evident by the frequent international foodborne epidemics and zoonotic disease outbreaks that have occurred over the past few
decades. SARS in 2003 demonstrated how quickly a highly transmissible respiratory pathogen can be spread, originating in China,
and making its way to more than 15 countries in just a few months (Shen et al., 2004). Another example is the cholera outbreak that
began in Haiti following a devastating earthquake in 2010, with genomic evidence suggesting that the epidemic Vibrio strain that
ignited the outbreak was likely carried into the country by foreign security forces (Keim et al., 2011; Chin et al., 2011; Pun, 2011;
Piarroux et al., 2011; Ali et al., 2011). These types of events make control extremely difficult, reflecting how quickly EIDs can be
transmitted and established in new populations before public health officials can intervene.

EIDs and Economic Status

Geographically, EIDs are often more highly prevalent among underdeveloped and economically disadvantaged populations. Along
with a high incidence of EIDs these populations also experience a greater severity from infections, often translated into higher rates
of mortality (Farmer, 1996). This trend is attributed to various social determinants of health that elevate the susceptibility of an
individual or population to infection (Marmot, 2005). Poverty both promotes and results from social determinants including access
to health care, clean water, food, and other important environmental factors that influence disease transmission (Marmot, 2005).
The cyclic nature of this relationship makes public health interventions complicated, since most, if not all, determinants must be
addressed in order to have a lasting positive impact.
The socioeconomic status of a country can be an important determinant for the transmission of EIDs, influenced by both the
availability of an appropriate public health infrastructure and the necessary resources to carry out prevention and control strategies.
This could include instituting effective surveillance systems, as well as providing adequate health-care services to individuals affected
by EIDs. Without this necessary capacity, a disease can quickly become well established or endemic in a population before a public
health response can be initiated, if one is initiated at all.
Historically, tuberculosis, chiefly caused by Mycobacterium tuberculosis, is an EID associated with economics, often being coined a
‘disease of poverty’ due to the increased impact it has on economically poor individuals. Today, data indicate 95% of all tuberculosis
cases and deaths occur in the developing world (2012b). In the past 30 years, tuberculosis has begun to reemerge across the globe,
partly due to the emergence and spread of HIV, which is now a primary risk factor for tuberculosis transmission. Nearly half of all
individuals in the developing world who have HIV also are coinfected with M. tuberculosis (2012b). This emphasizes the importance
economics play as a driver for disease emergence and reemergence, as well as the treatment strategies available for those infected.
Despite a disproportional distribution of EIDs in low- and middle-income countries, high-income countries experience their
own burden of EIDs. In the United States, West Nile virus continues to cause disease in man. Lyme disease is also well established
with an annual incidence that has increased in over the past 10 years, reaching over 30 000 and 60 000 reported annual cases in the
United States and Europe, respectively (Radolf et al., 2012). In 2003, the global pet trade contributed to an outbreak of monkeypox
virus in the United States that originally infected individuals who had close contact with prairie dogs purchased as pets through a
common supplier. Epidemiological studies traced the origin of this outbreak back to an exotic African rodent species that
transmitted the virus to the prairie dogs during transport to the United States (Reed et al., 2004).
Higher socioeconomic countries also experience a substantial burden of foodborne related EIDs, the more common pathogens
being bacteria, including Salmonella spp., L. monocytogenes, Brucella spp., Campylobacter spp., and pathogenic strains of E. coli
(Newell et al., 2010). Even with strict regulations on food production, outbreaks frequently occur due to the centralization and
mass production by the food industry, which is capable of distributing large quantities of food over vast geographic areas. In this
114 Pathogenesis and Immunology | Emerging and Reemerging Infectious Diseases

type of system, if food becomes contaminated, then rapid dissemination of the pathogen before detection is much more likely.
This is especially dangerous when the pathogen being disseminated is very pathogenic and the population is more susceptible.
This was the case when a rare subtype of enterohemorrhagic E. coli (O104:H21) was responsible for a foodborne outbreak
throughout Europe in 2011 that caused over 3800 cases and 54 deaths (Frank et al., 2011). Upon investigation, the source of the
outbreak was found to be sprouts that were grown with contaminated seed attained from a supplier in another country (Buchholz
et al., 2011).

Population Density and Expansion

Since 1960, the global population has more than doubled, from 3 billion to nearly 7 billion people (2012a). As the population has
grown, population density has also increased, creating in some countries what are called megacities (e.g., Tokyo, Mexico City,
New York City, etc.). These cities may have upward of 20 million people or more, sometimes residing in extremely confined
geographic areas. These conditions promote the proliferation of new diseases, especially when the pathogen is highly transmissible,
forming emerging disease ‘hot spots’ (Jones et al., 2008; Heymann and Rodier, 2001). In addition, some of these countries operate
wet markets where livestock, including poultry and swine, are slaughtered in poor hygienic conditions and sold directly to the
public (Webster, 2004). These practices further promote favorable environments for disease emergence, with SARS and highly
pathogenic avian influenza (HPAI) virus being recent examples.
In response to rising population densities, many cities have seen an increase in urbanization, particularly away from a city
central. This practice is often referred to developmentally as urban sprawl. While the practice has helped to reduce the rate of
growing population density inside cities, it has concurrently moved more groups of people into previously undeveloped areas. This
rapid expansion in land use and development has combined what was once fairly separated animal and human habitats, allowing
for more frequent exposure of humans to potential disease reservoirs, increasing the risk of EID proliferation.

Pathways of Emergence

It has been proposed that EID events occur in two steps (Morse, 2004). A pathogen must first be introduced into a new population
and then disseminated within that population. With this construct in mind, understanding the origin of novel microbes becomes
critical. Microbes often exist in the environment in a nonpathogenic state, with limited contact with a viable host. However, when
appropriate conditions are met, opportunistic microbes can exploit new niches, including human hosts, resulting in a successful
introduction. Once successful, this type of event is sometimes referred to as a microbial ‘jump’ or ‘crossover’. This crossing of the
species barrier is often necessary before widespread dissemination can occur.
Dissemination is then dependent upon the transmissibility of the pathogen in the new population. Dissemination can occur
directly from one host to another, or can establish an intermediate host in its transmission cycle, such as a vector. If a pathogen is
unable to be transmitted beyond an immediate or intermediate host, then further dissemination is not possible. These interactions
can often be complex, involving pathogen, environment, and host, making it challenging to understand and identify what
contributes to the most optimal conditions promoting disease emergence.

Zoonoses
The transmission of a pathogen between animals and humans is known as zoonotic transmission or zoonosis. Zoonosis is perhaps
one of the most important pathways of emergence, with an estimated 75% of all known EIDs originating from some type of animal
reservoir (Taylor et al., 2001). Disease examples include HIV/AIDS, Lyme disease, plague, SARS, several hemorrhagic fevers, and
zoonotic influenza. Each of these possesses a unique etiology, and though it is not an exhaustive list, it highlights the diversity of
disease emergence related to zoonosis. Additionally, effectively controlling zoonotic diseases is particularly difficult, since recog-
nizing an emerging zoonotic disease often does not occur until a major outbreak is already underway. If the responsible zoonotic
pathogen is highly transmissible, then future epidemic spread occurs even after recognition.
As previously discussed, population growth has had a drastic impact on society. Greater zoonotic disease potential can result
from this growth primarily due to an increased interaction between humans and animal habitats, Figure 1. Population growth has
also resulted in a higher demand for food commodities. To meet this growing demand, industrialization of food production is
increasing, especially in developing countries. This is true of all types of food, including meat production that has moved away from
small farms toward large-scale cattle, poultry, and swine operations, Figure 2. These sites have been able to streamline meat
production; however, it comes at the cost of creating favorable environmental conditions for the zoonotic transmission of
opportunistic microbes (Drew, 2011).
Other food acquisition practices pose a greater risk of acquiring an EID. This includes the long-standing practice in Africa, Asia,
and the Americas of hunting and consuming wild animals, also called bushmeat. Eating bushmeat has been associated with a
number of new diseases, including two highly fatal hemorrhagic diseases caused by Ebola and Marburg viruses (Peters, 2005; Wolfe
et al., 2005). Additionally, the practice of consuming raw or unpasteurized milk products (e.g., milk, cheese) can increase the
transmission risk of certain zoonotic bacteria, such as L. monocytogenes, Brucella spp., and Camylobacter spp. This is particularly
common in areas where pasteurization is not an accepted practice.
 Pathogenesis and Immunology | Emerging and Reemerging Infectious Diseases 115

Figure 1 The risk of zoonotic transmission of a pathogen is increased with man’s close and frequent contact with other species.

Figure 2 Large dense populations of animals, particularly in herds, can promote zoonotic pathogen transmission to man.

Vectors
Some EIDs are vector-borne, caused by the transmission of a pathogen through the feeding activity of a vector, usually an arthropod.
Some of the most common and effective vectors are insects including flies and flees, as well as arachnids such as ticks and mites.
These vectors are often attracted to humans and animals because they are obligate blood feeders, using biting or piercing
mouthparts to obtain a blood meal from their host. Pathogens have coevolved with vectors to exploit this behavior, often relying
on transmission to allow for the propagation of new progeny. An example of a model vector that does this is the mosquito, which is
the most widely distributed and abundant vector in the world. Mosquitoes are of particular concern due to their sometimes
aggressive feeding behavior and ability to effectively transmit a broad range of pathogens, causing diseases such as malaria, dengue
fever, and many others.
In terms of importance to emergence, it has been suggested that vector-borne EIDs constitute nearly a quarter of all EID events
occurring in the last decade (Jones et al., 2008). Also, there has been an increase in the total number of vector-borne EIDs during this
same time period, while other types of EIDs have slightly decreased (Jones et al., 2008). Increased human population density and
changing demographics seem to be associated with this rising trend of vector-borne EIDs, as well as climate change that some have
suggested is promoting an expansion in vector distribution and range (Jones et al., 2008; Epstein, 2001).
Animals are also important in the life cycles of vector-borne diseases, since many can be competent hosts and serve as reservoirs
for different pathogens. In fact, some EIDs only occur when humans become an incidental or dead-end host in an already
established transmission cycle between an animal and vector. This is true for Japanese Encephalitis (JE), a flavivirus transmitted
by certain mosquitoes, causing viral encephalitis cases primarily in Asia. For JE, humans are dead-end hosts, capable of infection if
bitten by an infected mosquito, but unable to amplify and transmit the virus further, whereas, swine and other wild birds are able to
propagate the virus and maintain a complete transmission cycle. Hence, if humans are removed from the environment, the virus
would still be sustained as long as the vector, pathogen, and reservoir were to remain.
116 Pathogenesis and Immunology | Emerging and Reemerging Infectious Diseases

Factors Associated with EIDs

Since the early 1990s, discussion has been centered on the factors that are most associated or attributable to EIDs. A report
published by the Institute of Medicine in 1992 originally identified six contributing factors (Institute of Medicine (U.S.). Committee
on Emerging Microbial Threats to Health et al., 1992). Since the list was published, new emerging threats have resulted in additional
factors being added, all thought to be important contributors by the global health community, Table 1.
This list provides guidance as to where research efforts and interventions should be targeted. It is important to note that many of
these factors are often interrelated with each other. For instance, a lack of political measures will often result in the breakdown of
public health measures. Economic development and land use can be associated with technology and industry, as well as changing
ecosystems, and shaping conditions of poverty. Hence, effective interventions must be multidimensional for sustained change.

Ecological Changes
Perhaps one of the most apparent and pervasive factors affecting the incidence of EIDs is environmental alterations that result in a
drastic change in ecology. One common ecological model works from a premise that disease occurs at the intersection of
environment, pathogen, and host, Figure 3. A change to any one of these entities could impact the disease outcome. It has been
suggested that classical ecological tools are limited in their ability to effectively assess the multifaceted complexities of EIDs. This is
clearly indicated by the limited number of published studies that have effectively evaluated EIDs from an ecological perspective
(Meentemeyer et al., 2012). An ecological relationship could be as simple as the symbiosis of certain types of fungus and plants
where no other factors play a role in the survival of everyone. Others can be much more complicated, such as the multistage life cycle
of the guinea worm (cause of the disease dracunculiasis), a parasitic nematode that uses two different species, a copepod and
humans, to complete its life cycle. These parasites are impacted by human movement, water availability, copepod abundance, as
well as climate, all of which can impact the nematode life cycle.
However, the research that does exists suggests that the most important ecological changes encouraging EIDs are those that put
humans in closer or more frequent contact with current or potential pathogen reservoirs. For instance, the incidence of Lyme disease
in the United States and Europe seems to be associated with the number of available hosts in a given area. Deer and small mammals
play an important role in the life cycle of ticks that vector the spirochete causing Lyme disease. Studies have shown that host
populations directly correspond to tick abundance, often influenced by ecological factors that promote population growth (Levi
et al., 2012). When this is coupled with urbanization and reforestation, transmission can drastically increase, since both the host
and environment serve as the drivers for disease emergence.

Climate Change
Evidence shows that the earth’s average surface temperatures have increased at least 0.6 C over the past century (Houghton and
Intergovernmental Panel on Climate Change. Working Group I., 2001). While many agree with the empirical evidence of rising
temperatures, there is still controversy as to why the earth is warming. Some argue that the earth is experiencing a natural
temperature fluctuation similar to what has occurred throughout history, citing previous ice ages and warming periods. Others
have suggested that the rising temperatures are attributed to increased atmospheric concentrations of carbon dioxide related to the

Table 1 Factors of emerging and reemerging infectious diseases

• Microbial adaptation and change

• Human susceptibility to infection
• Climate and weather
• Changing ecosystems
• Human demographics and behavior
• Economic development and land use
• International travel and commerce
• Technology and industry
• Breakdown of public health measures
• Poverty and social inequality
• War and famine
• Lack of political will
• Intent to harm

Reproduced from Smolinski, M.S., Hamburg, M.A., Lederberg, J., Institute of Medicine (U.S.)
Committee on Emerging Microbial Threats to Health in the 21st Century, 2003. Microbial Threats
to Health: Emergence, Detection, and Response. National Academies Press, Washington, DC;
Morse, S.S., 1995. Factors in the emergence of infectious diseases. Emerg. Infect. Dis. 1, 7–15;
Lashley, F.R., 2003. Factors contributing to the occurrence of emerging infectious diseases. Biol.
Res. Nurs. 4, 258–267; and Morse, S.S., 2004. Factors and determinants of disease emergence.
Rev. Sci. Tech. 23, 443–451.
 Pathogenesis and Immunology | Emerging and Reemerging Infectious Diseases 117

Figure 3 A basic ecological model illustrating the interaction of host, pathogen, and environment in disease.

burning of fossil fuels and deforestation. Despite the discourse, the reality of climate change in the context of EIDs remains an
important topic, with research showing associations between disease indicators and climate factors (Patz et al., 1996;
Epstein, 2001).
Climate change primarily impacts the range of infectious diseases, particularly those that are transmitted by vectors. Warmer
temperatures allow vectors to more readily survive conditions at higher altitudes and latitudes, as well as having shorter periods of
overwintering. Weather patterns are also influenced, as the hydrolytic cycle can be disrupted by warmer ocean temperatures, causing
severe weather at greater frequency. Particularly concerning are weather events that release high volumes of rain, as they may result
in temporary explosions in vector populations, especially mosquitoes.

Microbial Adaptation and Change

From a pathogen perspective, microbial adaptation and change significantly contribute to the likelihood that a microbe will become
pathogenic in a population. As mentioned, when certain environmental conditions are met, a microbe can experience alterations in
genetic makeup that can affect its pathogenicity or virulence. This type of adaptation can either occur gradually or rapidly by means
of random mutations, reassortments, or adaptive pressures brought on by stressors such as antimicrobial agents.
A good example of microbial adaptation is demonstrated by the influenza A virus, an RNA virus that has been shown to undergo
both gradual and rapid genetic changes. Just in the last 20 years, new variants of influenza have caused major human outbreaks,
including HPAI subtype H5N1, first detected in 1997 (1997) and the pandemic influenza subtype H1N1, first detected in 2009
(2009a). Influenza A contains two surface proteins (glycoproteins), called hemaglutinin (HA) and neuraminidase (NA): HA
proteins are associated with viral attachment and cell entry using a fusion pathway, while NA proteins regulate the release of
progeny virus from an infected cell. Antigenic drift and shift are two mechanisms that create variations in the antigenic properties of
these two proteins that allow influenza A to bypass the acquired immunity of a population, Figure 4. Antigenic drift occurs when
small point mutations accumulate gradually, altering the antigenic properties of the two surface proteins. This can cause population
immunity to partially decrease, resulting in seasonal epidemics. Antigenic shift involves major changes in proteins, sometimes
through the swapping of entire gene segments. The genetic reassortment occurs when two or more unique viruses infect the same
cell and generate mixed progeny viruses (Chen and Deng, 2009; Kaye and Pringle, 2005). In particular, genetic reassortments of the
HA antigens may result in large worldwide epidemics or pandemics. Waterfowl are thought to be the largest source of diverse viruses
from which gene reassortment may occur, as they are known to carry viruses with 16 different HA proteins. When a population has
no or little immunity to a new subtype and the new subtype is highly transmissible, pandemics may result.
Like influenza A virus, other pathogens undergo similar mechanistic adaptive changes and sometimes variation results from
external pressures that promote microbial evolution. Antibiotic resistance is an example of this kind of adaptation. Since their
discovery, the use and variety of antibiotics have greatly increased over time and many pathogens have adapted to their presence.
These antimicrobial resistant pathogens are having an increased impact upon clinical care and medical costs.
Bacteria, such as methicillin-resistant Staphylococcus aureus and multidrug resistant M. tuberculosis, are good examples of the severe
impact that this type of microbial adaptation can have on individual health outcomes. Individuals infected with these bacteria are
often prescribed newer and more expensive, ‘last defense’ antibiotics. These diseases may be life-threatening and require specialized
care. Hospitalized patients with these resistant pathogens may seed the hospital staff and environment and cause nosocomial
transmission among immunocompromised patients.

Important EID Examples

EIDs result from a large variety of causative agents, each one possessing a unique etiology and ecology. Agents may be organized
according to transmission pathways, genetic markers, or the pathology a pathogen might exhibit in a population. Most often,
118 Pathogenesis and Immunology | Emerging and Reemerging Infectious Diseases

Figure 4 Graphical representation of antigenic drift and shift among influenza A viruses. Top panel: Antigenic drift – minor genetic changes (e.g., through
mutation) lead to slight changes in surface glycoproteins or season variation in strains. Bottom panel: Antigenic shift – exchanges of entire segments of genome lead
to major changes in the surface glycoproteins, which may lead to pandemics.

however, EIDs are categorized into bacteria, virus, fungus, parasites, and more recently prions. Table 2 presents key examples of each
of these disease categories.

Conclusions

As the world’s population rises and public health problems increase in complexity, it will be critical to establish innovative and
dynamic strategies to counter EID threats. These strategies should include the reinforcement of public health systems, better
diagnostics for EIDs, stronger surveillance systems, and better interdisciplinary and international collaborations. A novel interdis-
ciplinary strategy, called One Health, is gaining popularity as an approach that attempts to focus efforts on complex public health
issues such as EIDs.

Public Health Infrastructure

Public health infrastructure is critical to the current mitigation and future prevention of EID events. An effective infrastructure
should include the following: a legal framework that allows for enforcement of public health measures and a system to monitor
outcomes; dissemination and utilization of health knowledge, including the training of health workers; and physical environ-
ments or services conducive to targeting important health threats, like sanitation infrastructure (e.g., sewers). Infrastructure can
subsist on a local level, but most often relies upon the coordination and leadership of nationallevel governments, providing
guidance for task prioritization and implementation. However, national and international organizations can also provide
assistance by supporting government-led efforts with technical and financial resources, or filling in the necessary gaps of a
fragmented infrastructure.

EID Diagnostics
Diagnostics are an important tool for identifying and characterizing infectious disease agents from both clinical and environmental
samples. Common techniques include molecular assays, such as multiplexing, microarrays, deep sequencing, and traditional and
real-time polymerase chain reaction, as well as immunoassays, including variations of the enzymelinked immunosorbent assay and
other techniques exploiting antigen and antibody binding activity. The variety and availability of these techniques have greatly
improved over the last two decades, with significant increases in sensitivity and specificity, as well as marked decreases in costs. For
instance, the cost of full genome sequencing of a moderately large virus has seen substantial reductions in the past decade, dropping
from tens of thousands of dollars per run to a couple thousand dollars, with much more accurate analysis. Much of this
improvement can be attributed to new technological developments, such as third and fourth generation sequencing that is greatly
improving novel pathogen detection capabilities.
Table 2 Examples of recent human emerging infectious disease threats

Emerging infectious disease threat Pathogen Emerging/reemerging Primary transmission Key geographic area(s)

Bacteria
Bartonella infections Bartonella spp. Emerging Zoonotic Australia, Europe, United States
Vancomycin-resistant Staphylococcus aureus infections Staphylococcus aureus Reemerging Person-to-person Worldwide
Pathogenic Escherichia coli infections Escherichia coli Emerging Foodborne Europe, United States
Cholera Vibrio cholerae Reemerging Waterborne Africa, Asia, South America, Haiti
Plague Yersinia pestis Reemerging Vector-borne Africa, Asia, South America, United States
Typhoid fever Salmonella typhi Reemerging Foodborne, waterborne Africa, Asia, Latin America, Carribean
Diphtheria Corynebacterium diphtheriae Reemerging Respiratory (person-to-person) Eastern Europe, India
Multidrug-resistant tuberculosis infections Mycobacterium tuberculosis Reemerging Respiratory (person-to-person) Worldwide
Lyme disease Borrelia spp. Emerging Vector-borne Eastern Asia, Europe, United States
Fungal
Cryptococcus gattii infections Cryptococcus gattii Emerging Environmental exposure Australia, Canada
Parasite
Cyclosporiasis infections Cyclospora cayetanensis Emerging Foodborne, waterborne Worldwide
Drug-resistant malaria Plasmodium spp. Reemerging Vector-borne Africa, Asia, South America
Protein
Variant Creutzfeldt–Jakob disease Prion Emerging Zoonotic, foodborne Europe
Virus
West Nile fever West Nile virus Reemerging Vector-borne Africa, Asia, Europe, North America
Hantavirus pulmonary syndrome Hantavirus Emerging Zoonotic Canada, East Asia, Europe, South America, United States
Dengue fever Dengue virus Reemerging Vector-borne Central Africa, Central America, Latin America, Southern Asia
Yellow fever Yellow fever virus Reemerging Vector-borne Central Africa, South America
Lassa fever Lassa fever virus Emerging Zoonotic Central and Western Africa
Marburg hemorrhagic fever Marburg virus Reemerging Zoonotic Central Africa
Ebola hemorrhagic fever Ebola virus Reemerging Zoonotic Central Africa
Rift Valley fever Rift Valley fever virus Reemerging Vector-borne Africa
Hendra virus infection Hendra virus Emerging Zoonotic North-eastern Australia
Nipah virus infection Nipah virus Emerging Zoonotic Asia
Highly pathogenic avian influenza H5N1 influenza virus Emerging Zoonotic Asia
Severe acute respiratory syndrome SARS coronavirus Emerging Respiratory (person-to-person) Asiaa
2009 pandemic influenza 2009 H1N1 influenza virus Emerging Respiratory (person-to-person) Worldwide
Japanese encephalitis Japanese encephalitis virus Reemerging Vector-borne Asia
a
Originated in Asia, but had rapid global transmission.
Reproduced from Armstrong, G.L., Hollingsworth, J., Morris, J.G., Jr., 1996. Emerging foodborne pathogens: Escherichia coli O157:H7 as a model of entry of a new pathogen into the food supply of the developed world. Epidemiol. Rev. 18, 29–51; Rey, M., 1996. Resurgence of
diphtheria in Europe. Clin. Microbiol. Infect. 2, 71–72; Collinge, J., 1999. Variant Creutzfeldt-Jakob disease. Lancet 354, 317–323; Wongsrichanalai, C., Pickard, A.L., Wernsdorfer, W.H., Meshnick, S.R., 2002. Epidemiology of drug-resistant malaria. Lancet Infect. Dis. 2, 209–218;
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zoonotic importance to animals and human beings. J. Vet. Emerg. Crit. Care (San Antonio) 20, 8–30; Field, H., Schaaf, K., Kung, N., Simon, C., Waltisbuhl, D., Hobert, H., Moore, F., Middleton, D., Crook, A., Smith, G., Daniels, P., Glanville, R., Lovell, D., 2010. Hendra virus outbreak
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120 Pathogenesis and Immunology | Emerging and Reemerging Infectious Diseases

A major need is the better recognition of EIDs, especially in low-resource areas where EIDs are common. This can be
accomplished by prioritizing laboratory infrastructure development, continuing to direct efforts in targeting disease ‘hot spots’
where EID outbreaks are most likely to occur. Emphasis should be placed on making new diagnostic assays timely, affordable, and
feasible for laboratories with limited resources. In addition, employing assays that are able to detect multiple agents in a single
specimen is important in EID management. This kind of technique allows for more rapid identification of causative agents, an
important component in how public health responses are planned and delivered.

Global Surveillance and Communication

Disease surveillance is defined as the ongoing systematic collection, consolidation, and analysis of outcome specific data for the
purpose of planning, implementation, and evaluation of various health-related events (Thacker, 1988). Many information and
surveillance networks that are currently in place can be characterized as fragmented or unrepresentative of actual disease circulation
in a population, making it difficult to estimate actual incidences. There have been some successes in improving surveillance
capabilities, particularly passive surveillance that uses techniques such as monitoring healthcare clinics and emergency rooms for
various health outcomes indicative of an EID.
For instance, global influenza surveillance, following the 2009 H1N1 pandemic, received substantially more prioritization and
resource allocations from countries that were lacking such capabilities beforehand. This has resulted in a rather comprehensive
collection and dissemination of data to stakeholders worldwide, through a network called FluNet. This network is overseen and
coordinated by WHO, and helps provide a more comprehensive resource regarding the incidence and circulation of different strains
of influenza. Information is used not only to enhance outbreak response, but is also the source of prototype strains that are used in
annual seasonal vaccination manufacturing. This is an example of how successful surveillance can greatly improve the public health
response capabilities.
For EIDs this may be more difficult, only since it takes a large amount of coordination and resources to create global surveillance
for any specific pathogen. Furthermore, loweconomic countries often do not have the necessary resources to carry out such
endeavors. The Internet may be useful in supporting countries that lack traditional surveillance capabilities, as has been demon-
strated by the international e-service called ProMED-mail. This service is a consortium of public health professionals that
disseminate disease outbreak updates, often in real time, through a global e-mail distribution list. Since telecommunications are
becoming well established, even in low-economic countries, this has proven to be a very practical approach, providing the
international community with reliable information and even sometimes serving as a first report of an index case. Further developing
these types of approaches will be useful in communicating EIDs, pre- and postevent.

International Collaboration
Today, EIDs impact our entire world. It will be important that governments and agencies concur with the need for strong
international communication and collaboration regarding EID events. This will include the sharing of resources and knowledge,
particularly regarding EIDs that are considered a global threat. It is also ideal that low-economic countries receive priority in the
enhancement of their public health systems, since a large proportion of EID risk exists in these areas. Collaborations offer unique
diversity in expertise, improve cultural competencies, and enhance response efforts in the event of an EID outbreak.

‘One Health’
It is clear that EID ecology is often complex, requiring a sophisticated, interdisciplinary response to mitigate disease impact. One
attempt to address these complexities has been coined ‘One Health’. One Health is a moniker for the interdisciplinary approach,
bringing together human, animal, and environmental health professionals, to address complex global health problems. While the
terminology may be relatively new, the foundations of the approach are not. Throughout history, individuals from different
disciplines have often worked together to create solutions for some of the most important health threats. One Health attempts to
convert those cooperative successes into a practical methodology to be used in future public health problems.
One of the strongest arguments for One Health is the role zoonoses play in the emergence of new infectious diseases, and the
recognized long-standing gap of cooperation that has existed between the fields of animal and human health. As previously
described, the global impact of HIV, H5N1 avian influenza, SARS, and 2009 H1N1 pandemic influenza, all diseases with origins
from animal reservoirs, have led to a consortium of doctors, veterinarians, and public health officials beginning to work together to
identify effective solutions that bridge the gap between each discipline. In addition, experts from fields of geography have begun to
pursue new models to help predict the movement of different EIDs. Engineers are developing new technologies, based upon the
recommendations of field workers that may mitigate contamination of food and water supplies. Economists are calculating the cost
effectiveness of vaccination campaigns to help guide policy makers in better using resources.
Overall, One Health is an approach that can improve effectiveness of public health response and interventions, as it allows for a
more targeted application of multiple areas of expertise, not relying on a single discipline approach that may not address all of the
minute facets that accompany most public health problems of today. To be successful, it will require an intentional effort of current
public health professionals reaching out to one another, to strengthen collaborations, communication, and the ability to be open to
novel ideas. Since this approach promotes flexibility, it should be able to adapt to the rapid changes demonstrated by emerging
 Pathogenesis and Immunology | Emerging and Reemerging Infectious Diseases 121

diseases in the last two decades. It is this characteristic that makes One Health not just a temporary solution, but a philosophy that
can have serious long-term impact on EID morbidity and mortality.

Acknowledgments

We thank Whitney S. Krueger, PhD, for her much appreciated editorial review of this work.

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