Introduction

Today, accounts of emerging infectious diseases spill from newspaper headlines and garner lead story status on the evening news. Just as globalization has brought humanity closer together in trade and culture, infections are transmitted rapidly across the globe. The public seems as interested in ‘bird flu’ in Asia or Ebola in central Africa as in an account of neisserial meningitis at the local high school. It now seems surprising that recognition of emerging infections is less than a few decades old.

It is understandable that a sense of complacency about infectious disease took hold of medicine and public health in the late twentieth century. Improvements in sanitation, nutrition, housing, and occupational health dramatically decreased infectious disease rates in the United States. Immunizations were effective against viral infections: smallpox was eradicated world-wide; rubella was eliminated from North America; and rates of other childhood viral diseases markedly reduced.^1,2 With the development of safe and effective vaccines and drugs to treat bacterial infections, bacteria appeared defeated. All these factors caused an inappropriate confidence that infectious diseases would be completely eradicated as a public health problem. In fact, in 1967, US Surgeon General William H. Stewart announced that it was ‘time to close the book on infectious diseases, declare the war against pestilence won, and shift national resources to such chronic problems as cancer and heart disease.’³ Despite this hubris, others began to sound the alarm. The term ‘emerging diseases’ was first used by David J. Sencer in 1971.⁴ In 1976, the Centers for Disease Control (CDC) investigated an outbreak of disease affecting attendees at the National American Legion Convention in Philadelphia, and the following year CDC isolated the causative agent, Legionella pneumophila, for what is now called Legionnaire’s disease. In 1981, Richard M. Krause, director of the National Institutes of Allergy and Infectious Diseases, published an early clarion call with his book The Restless Tide: The Persistent Challenge of the Microbial World.⁵ Shortly thereafter, the epidemic of AIDS was recognized and over the next 10 years a growing sense of unease arose as new infectious disease outbreaks were identified.

Recognition and Surveillance for Emerging Infectious Disease

The Institute of Medicine triggered a landslide of interest in emerging infections when it addressed the issue in the early 1990s. In the seminal work on the topic, a 1992 Institute of Medicine report defined emerging infectious diseases as ‘infections that have newly appeared in a population or have existed but are rapidly increasing in incidence or geographic range.’⁶ Aside from numerous academic and lay-public publications, several landmark developments are notable in the history of emerging infections. The Centers for Disease Control and Prevention (CDC) started publication of the journal Emerging Infectious Diseases in January 1995. The journal continues to provide a venue for discussion of emerging diseases in human and animal populations.

ProMED-mail, the Program for Monitoring Emerging Diseases, (http://www.promedmail.org) is an internet-based reporting system established in 1994 with the support of the Federation of American Scientists and SatelLife. Since 1999, ProMED-mail has operated as a program of the International Society of Infectious Diseases. The electronic mail system provides subscribers with daily updates about emerging diseases from around the world. The importance and effectiveness of the system has been repeatedly documented. A notable example was an email sent by a travel medicine physician, Stephen O. Cunnion, on February 10, 2003.⁷ He quoted an email that he had received, stating, ‘Have you heard of an epidemic in Guangzhou? An acquaintance of mine from a teacher’s chat room lives there and reports that the hospitals there have been closed and people are dying.’ This email was an early warning of an outbreak of the previously unidentified human coronavirus causing severe acute respiratory syndrome (SARS).

The International Society of Travel Medicine (ISTM) provided seed money to establish GeoSentinel in July 1995. Initially, GeoSentinel was founded as a working group of nine US-based ISTM member travel clinics which agreed to collaborate as a sentinel emerging infections network by monitoring illness among returning international travelers. The following year the network was awarded funding from the CDC. GeoSentinel now incorporates a global network of providers at over 30 sites on all continents. A successful early recognition of disease emergence by GeoSentinel was the identification of leptospirosis among participants in the Borneo Eco-Challenge 2000 Adventure Race while many participants were still in the incubation period.⁸

Historical Observations: Plagues, Pestilences, People, Immigration

As a focused field of study, interest in emerging infections grew out of observations of a number of new diseases that emerged in the last three decades of the twentieth century. These diseases included the worldwide pandemic of a newly recognized pathogen (HIV); reemergence of the old disease of tuberculosis; newly recognized infectious syndromes associated with known pathogens, such as toxic shock syndrome caused by group A Streptococcus; and introductions of known agents into naïve populations, such as West Nile virus.

The history of epidemic diseases involves the increasing interconnectedness of people. Early societies brought together humans in large enough concentrations that epidemic disease could take hold and spread within villages and city-states. Epidemic disease took advantage of contacts between early city states and then nations engaged in wars or trade. Multiple epidemics of plague spread out of China via the Silk Road.

The opening of the New World to European settlement led to an interchange of species, including pathogens, termed the Columbian exchange.⁹ Measles and smallpox brought to the New World by immigrant Europeans devastated Native Americans. Meanwhile, syphilis, which is theorized to have arisen in the Americas, spread in epidemic fashion in Europe after 1492. The slave trade was responsible for the movement of HTLV (human T-cell lymphotropic virus)-I, HTLV-II, yellow fever virus and, importantly, its mosquito vector, Aedes aegypti, to the Americas. In the 1970s, Aedes albopictus, a mosquito vector competent for transmission of dengue was inadvertently imported into North America from Asia as a result of the international trade in used tires. Global air travel has connected distant corners of the planet like never before, offering pathogens unprecedented potential for rapid transmission to far-flung immunologically naïve populations.

Epidemiology and Modeling of Emerging Infectious Diseases

Why do some diseases emerge and spread globally, while others sputter out locally? Disease occurs when a pathogen meets a host that is vulnerable to the agent in an environment that allows the agent and host to interact. Agent, host, and environment alone are not sufficient to cause an epidemic, however. For a pathogen to be successful in causing an epidemic, an unbroken chain of transmission must be present. Given a suitable mode of spread and a chain of transmission from one susceptible host to another, an outbreak can develop. The chain of transmission may be thought of categorically as a source for the agent, the presence of the agent (pathogen), a portal of exit from the source, a mode of transmission, a portal of entry into the host, and a susceptible host.

The first link in the chain, the source for the agent, is the place where the agent originates. This may be another infected human, or the animal reservoir in the case of zoonotic infections, or the environmental reservoir in the case of pathogens acquired from environmental sources, such as soil. Influenza, for example, circulates as a zoonotic infection with the principle reservoir being waterfowl.

The second link is the presence of the agent or pathogen. Even though a host may be in contact with the source, the agent must be present in order for transmission to occur. Certain characteristics of the pathogen are important to consider. Infectivity is the capacity to cause infection in a susceptible host. Not all infections result in symptomatic disease, however. The pathogenicity of the agent is the capacity to cause disease in a host. And finally, the virulence of the pathogen determines the severity of disease that the agent causes in the host. Pursuing influenza as an example, although humans who interact with poultry are likely frequently exposed, many avian influenza viruses are either not spread to humans (low infectivity) or, of those which are, they may infect a human but are unable to cause disease (low pathogenicity). However, with reassortment of the influenza genome, there is potential for influenza viruses to cause severe illness and death in humans (i.e. H5N1).

The third link, a portal of exit, is a pathway by which the agent can leave the source. This pathway is usually related to the place where the agent is localized. Influenza is spread from human to human primarily via respiratory secretions. Another example, the dimorphic fungus Coccidioides immitis, has an environmental reservoir. The organism is found in desert sands in the American southwest and its arthrospores are blown from the earth by winds.

Once the agent leaves the source, a mode of transmission, or means of carrying it to the host, is needed. Although in the case of influenza fomite spread plays a role, with humans carrying the virus from poultry farm to farm, the main route of transmissions from person to person tends to be droplet spread of infected respiratory material. Other modes of transmission are shown in Box 18.1.

Direct transmission occurs with direct transfer of the infectious agent from person to person. This category includes transmission spread by direct contact, including touching, kissing, and sexual interactions. Rabies is spread by direct transmission via the bite of a rabid animal, for example. Droplet spread in which there is direct projection of infectious droplets onto the mucus membranes of the host also is included in this category. Droplet transmission, such as with influenza, occurs via large particles (measuring 5 microns) expelled when a person coughs, sneezes, or talks. These particles are generally propelled no more than 3 feet from the infected person in any direction. Indirect transmission may be vehicle-borne, in other words, spread via fomites, blood products (blood-borne transmission), or fecal contamination of water and food (fecal–oral transmission). Vector-borne diseases are transmitted indirectly by a live carrier, usually an arthropod, such as mosquitoes, fleas, or ticks. The transmission may be mechanical, in which the vector acts to transport the pathogen, but is not biologically necessary for replication, such as fecal coliform bacteria transported by a housefly, or biological transmission in which the vector is a site of replication of the pathogen, such as malarial parasites in mosquito species.

Airborne transmission is via droplet nuclei or dusts (measuring < 5 microns) that can remain suspended in air for long periods of time and may be carried by air currents for long distances. The classic example of a disease transmitted by the airborne route is measles. In some cases, the pathogen is not able to be transmitted effectively from one human host to another. In this case, the human is a ‘dead-end host’ and the chain of transmission is cut. Examples of dead-end infections in humans include those due to the dimorphic fungi, Histoplasma, Blastomyces, and Coccidioides.

There must be a pathway into the host, a portal of entry, which gives the agent access to tissue where it can multiply or act. Often, the agent enters the host in the same way that it left the source. This is the case with influenza or Mycobacterium tuberculosis, which leave the source through the respiratory tract and usually enter a new host through the respiratory tract.

And finally, there must be a susceptible host. The immune status of the host is generally classifiable as susceptible, immune, or infected. The susceptible host’s response to exposure can vary widely, from manifesting subclinical infection, atypical symptoms, straightforward illness, severe illness, or death. Host susceptibility is extremely complex, with intensive infectious disease research currently directed at gaining an understanding of why certain hosts are susceptible, why infected hosts display variation in clinical manifestations, and why different hosts vary in their ability to transmit disease. This understanding is being greatly advanced through evolving applications of molecular genetic techniques.

Yet even when all of the above factors are present, some diseases do not become epidemics. Mathematical modeling of infectious disease outbreaks has led to the characterization of the basic reproduction number, R₀, which describes the average number of secondary cases of disease generated by each typical case in a susceptible population. For epidemic spread of a disease, the R₀ for the pathogen must be greater than one (R₀ > 1). In its most simplistic form, the SIR model divides the population into proportions corresponding to susceptible (S), infected (I), and removed (either recovered and immune, or dead) (R).¹⁰ By definition:

The uniform mixing assumption posits that epidemics depend only on the total number of infectives (I) and susceptibles (S). Even diseases with similar R₀ values can have different patterns of epidemic spread, with one turning into a pandemic and the other extinguishing locally. This highlights problems with the SIR model. Notably, it assumes a well-mixed, homogeneous population. Populations are frequently heterogeneous, however, with people interacting through networks of relationships. Disease transmission is facilitated between members of such networks more efficiently than outside these networks. Studies of sexually transmitted infections (STIs) highlight the important role of networks in disease transmission, but networks are equally important in diseases transmitted by other routes besides sexual transmission. Tuberculosis, for example, is much easier spread to family members because it requires prolonged, close contact. Additionally, the model does not take into account stochastic events which may have profound effects on the course of an epidemic. One infectious patient traveling on an intercontinental flight to an immunologically naïve population may have a profound impact on spread of a respiratory disease. Finally, the model fails to recognize the importance of host factors that lend to epidemic potential. For example, in some diseases, there are outliers of transmission potential in which an infected individual, a superspreader, may be more efficient at transmitting the disease than the observed average R₀ of the disease.

Although modeling is far from perfect, these basic concepts help guide the selection of public health strategies to interrupt infectious disease spread. Depending on which approach might be most effective, efforts may be directed to the specific agent (e.g. screwworm), host (e.g. immunization to prevent measles), or environment (e.g. sanitation improvements to prevent salmonella). We can also target a specific point in the chain of transmission, such as limiting fomite transmission.