BASICS

Definition

Epidemiology is the study of the occurrence of disease in populations ¹ and the application of this knowledge to control or prevent disease. The underlying tenet of epidemiology is that disease does not occur randomly in a population. This means that there are always reasons why some horses become sick and others stay healthy, even if we do not always understand those reasons. This has tremendous implications for veterinarians: they can identify causes and risk factors for disease and take actions to prevent or decrease the impact of a disease. In this sense, it is critical to consider more than just disease agents and hosts; it is also critical to consider the environment and management factors that impact interactions among agents and hosts. Because of this broader implication, epidemiology is also sometimes defined as “medical ecology,” as discussed below.

The mare reproductive loss syndrome outbreak in Kentucky in 2001 was an excellent example of epidemiology in action.² Even before veterinarians and producers understood the etiology of this disease, veterinarians were able to use epidemiology to identify risk factors for disease (exposure to eastern tent caterpillars² or pasture³), which allowed farm managers to implement control measures and prevent some abortions that would have otherwise occurred.

Epidemiologic Approach

A key epidemiologic approach to understanding and controlling disease involves looking for patterns of disease in the population of interest. Which horses are sick, and what do they have in common? Which horses are healthy, and what do they have in common? Which groups have been most affected? Great insight can be gained into causal mechanisms and control points that can be exploited in disease prevention efforts by (1) describing a population and identifying patterns, (2) making comparisons among different groups within a population, (3) comparing different populations, and (4) comparing the same population at different time points.

It is useful to consider the “five Ws” when trying to understand disease occurrence in a population: who, what, where, when, and why. Who is affected (and unaffected)? Include age, breed, gender, housing, water source, and vaccination status, as well as any other variables that may be relevant. What are the circumstances related to disease occurrence, and has anything changed? Where are the affected and unaffected animals located? Use a map of the barn or farm with food, water, and ventilation sources marked, and spatially locate the ill animals. When did each ill animal develop disease? Use this information to identify groups most affected (e.g., age groups, barns, breeds) using the tools described later in this chapter. All this should be interpreted with a focus on ultimately identifying “why.” Why did these animals develop disease, and why were others not affected? Understanding why disease occurs allows identification of ways that disease can be prevented.

Disease Ecology

When trying to understand reasons why particular animals become diseased, it is clearly important to consider more than just an individual host and a particular agent as causes for a specific occurrence. The population to which an individual belongs must also be considered, in addition to the patterns of interactions and the environment that influences these interactions and impacts the likelihood of contagious transmission. Because of the importance of these broader considerations, epidemiology is sometimes referred to as medical ecology, or the interactions of all organisms and their environment as these pertain to health.

Mare reproductive loss syndrome (MRLS), which was initially reported among broodmares in central Kentucky in 2001, is one example of disease arising from a combination of host, agent, and environmental factors. An epidemic of equine abortion, endophthalmitis, and pericarditis began in late April 2001 and lasted until June 2001;⁴^–⁶ fetal losses occurred both early and late in pregnancy^3,⁷ and affected more than 60% of mares on some farms.⁷ Multiple bacterial species were identified⁸ in tissue of aborted fetuses. The syndrome was subsequently found to be associated with ingestion of the eastern tent caterpillar,⁴ and it has been proposed that bacterially contaminated barbed caterpillar hairs migrated out of the alimentary tract, spread hematogenously, and were directly responsible for the observable signs of MRLS.⁹ Eastern tent caterpillars are ubiquitous in the eastern United States but were particularly abundant in Kentucky that spring because a rapid temperature increase in early spring was superimposed on an unusually dry winter and spring.¹⁰ These climatic conditions caused an explosion of biologic activity, including growth of black cherry trees on which eastern tent caterpillar eggs are laid and larvae develop.¹¹ During that spring with its unusual climactic conditions, grazing on pasture⁴ with black cherry trees¹² exposed horses to disease; fetuses were particularly vulnerable. The sensitivity of the fetus to disease, the environmental conditions that led to the overgrowth of caterpillars, the bacteria themselves, and the management of the broodmares all contributed to the occurrence of MRLS.

Disease Agent

Characteristics of the disease agent, including infectivity, contagiousness, pathogenicity and virulence, immunogenicity, host range, life cycle, and antimicrobial susceptibility, influence the speed and scope of disease spread. Infectiousness (infectivity) refers to the ease with which an agent infects susceptible hosts, which is sometimes quantified in relation to the amount of agent required to reliably infect an individual. Contagiousness relates to the likelihood that an agent will move between infected and susceptible hosts; it is sometimes quantified by the number of new infections that will likely result from exposure to an infected animal or as the speed with which a disease agent is transmitted through a susceptible population. Equine influenza virus and equine herpesvirus are both highly infectious, but influenza virus is more contagious. Although equine protozoal myeloencephalitis (EPM) is an infectious disease, it is not a contagious disease because the etiologic agent is not transmitted directly between horses. Pathogenicity describes the likelihood that an infected horse will develop clinical disease, and virulence describes the likelihood that disease will be severe. West Nile virus (WNV) is highly virulent in horses; more than 30% of horses with clinical disease die.¹³ In contrast, EPM is not highly pathogenic; most equids exposed to the disease agent do not develop clinical disease.¹⁴^–¹⁶

Characteristics of the disease agent that enable it to survive and spread without detection are particularly important to consider when instituting preventive or control measures. Agents that can persist in the environment, such as Clostridium difficile¹⁷ or Streptococcus equi subsp. equi, require different control measures than does equine influenza, which does not persist well outside the host. Some diseases spread undetected through infected horses without clinical signs of illness. Subclinically, persistently, and latently infected animals are often important reservoirs and sources of exposure for susceptible animals in a population because they go unnoticed or undiagnosed. Animals often are infected with a potentially pathogenic organism without showing clinical signs, and this can even be the predominant presentation depending on the pathogenicity of the agent. The term subclinical is also used to describe animals during the induction or incubation period for infectious diseases. Animals that remain infected for extended periods are sometimes described as being “persistently infected,” especially if infections continue after clinical signs of disease resolve. Persistent infection and long-term shedding of S. equi subsp. equi are common¹⁸^–²⁰ and important to the spread of disease among populations.^20,²¹ In contrast, latency describes a state of dormant viral infection in which shedding stops and the virus cannot be detected until later, when the infection reactivates or recrudesces. This is a common feature among alpha herpesviruses, such as equine herpesvirus (EHV) types 1 and 4.²²^–²⁹

Host

Many host characteristics are intrinsic to the horse and relatively unchangeable, such as age, gender, and breed. Other host characteristics are highly variable among individuals and can change over time, perhaps most notably, inherent susceptibility to infectious agents or immunity. Characteristics of the host can affect both its exposure to disease and its likelihood of becoming infected if exposed. For example, geldings or spayed mares are less likely to be exposed to Taylorella equigenitalis, the agent that causes contagious equine metritis, and foals can be more vulnerable to disease than adults, as with Rhodococcus equi pneumonia.

Environment

A horse’s environment includes its location, climate, and the local surroundings and interactions created by its management.³⁰ Characteristics of a horse’s environment affect which diseases and vectors a horse is exposed to, the magnitude of that exposure, and the likelihood of developing disease if exposed. Horses that have been vaccinated with efficacious vaccines or immunized by natural exposure are more resistant to a particular disease than naive horses. Horses that are stressed for any reason, including poor diet, concurrent disease, weaning, transport, or mixing, are more likely to develop a disease than their unstressed counterparts. The risk of disease is not equal for similar horses when managed differently or housed in different environments.

Individual.

Environmental characteristics that affect risk of disease in individual horses include climate, landscape, flora and fauna, cleanliness, air quality, housing, diet, and events that affect stress levels. Some of these factors (e.g., cleanliness, ventilation, housing, diet, stress level) are directly related to management practices and may be changeable, thus affecting risk of disease. Some management strategies (e.g., housing in open pastures, using outdoor drinking-water sources) increase potential exposure to insect vectors and also increase the risk of other diseases, such as Potomac horse fever (Neorickettsia risticii infection) and vesicular stomatitis. On the other hand, indoor housing, especially if it is high density or poorly ventilated, can increase exposure to diseases transmitted by aerosol or oral-fecal routes, such as influenza virus and Salmonella. Some environments and climates support larger vector populations than others, thus increasing potential risks for diseases, such as equine infectious anemia (EIA) or the equine encephalitides, including western equine encephalitis (WEE), eastern equine encephalitis (EEE), and WNV encephalitis. Although the climate itself cannot be changed, management practices, such as using animal-safe insect repellents, treating open-water sources with larvicides, and housing horses indoors at dusk and dawn, can be used to reduce disease risk.

Population.

In addition to characteristics of individuals that affect their disease risk, the aggregate characteristics of the population to which the individual belongs affects the disease risk for that individual. This aggregate of the population’s susceptibility to disease is often called herd immunity, described as immunity of an individual that is conferred by the population to which it belongs, or the ability of a population of animals to withstand exposure without succumbing to disease because the immunity of a population is more than the sum of its parts.³¹ Herd immunity is created when the likelihood is small that an infected horse shedding a disease agent will encounter a susceptible horse (Fig. 65-1). If most horses are immune or if contact among horses is heavily restricted, it is unlikely that the few susceptible horses will have contact with the infected horse sufficient to allow transmission. For example, consider a barn in which 90% of horses are immune to influenza virus, and each horse in the barn contacts four other horses per day. If a newly introduced horse happens to be infected with influenza virus, and conditions are adequate for transmission of virus to in-contact horses, the probability that any other horse in the barn will become infected is about 35%, and the probability that more than one horse will become infected is about 12% (Fig. 65-1). For herd immunity to be effective, the disease agent (e.g., influenza) must only reside in horses, must not have an environmental reservoir, must be transmitted directly from horse to horse, and must have a short infectious period.³²

Fig. 65-1 Probability of new cases of disease with 1-day infectious period as a function of percentage vaccinated in a herd of horses where each horse contacts four other horses per day.

Disease Causation

Many veterinarians are accustomed to thinking that infectious diseases have a single cause: the disease agent. Epidemiologists think of cause in a more general sense. Any “exposure” that leads to new cases of disease can be considered a “cause” of that disease. By removing that exposure, therefore, some cases of disease can be prevented. Causation has multiple levels. Again, consider MRLS. What “exposures” are associated with MRLS? The bacteria on the caterpillar hairs,⁸ the caterpillars themselves,³³ exposure to cherry trees,² pasture grazing,^3,⁷ and the convergence of climatic factors resulting in caterpillar overgrowth have all been implicated in the epidemic occurrence of MRLS. Epidemiologically, all these factors are causes. Cases of disease can be reduced by removing bacteria from the caterpillars (an obviously impractical approach), minimizing exposure to caterpillars, reducing exposure to environments shared with the caterpillars (cherry trees or pasture), or returning to a more typical climate, as happened in subsequent years.

Likewise, consider encephalitis associated with WNV infection. This agent is propagated in a mosquito-bird-mosquito life cycle.³⁴ West Nile virus can replicate in multiple mosquito species,³⁵ although its primary vectors are Culex mosquitoes³⁶ The primary hosts are birds,³⁷ which develop transient viremia followed by long-term (lifelong) immunity. Ticks may also play a role in maintenance of WNV.^35,^38,³⁹ New cases of equine disease can therefore be reduced by minimizing exposure to mosquitoes and ticks (e.g., controlling vector populations, using animal-safe repellents, housing horses inside at dusk and dawn) or by increasing immunity to the virus, either in birds or in horses. In birds the natural immunity that develops after initial exposure reduces the total amount of virus circulating in the mosquito population, which in turn reduces equine exposures. The increase in WNV immunity among birds is one likely reason that the number of reported equine cases of WNV-associated disease in Colorado was 378 and 426 in 2002 and 2003, respectively, and then decreased to 33 in 2004.⁴⁰

One useful model used to understand complex causal relationships is to classify causes as component causes, necessary causes, or sufficient causes.³¹ In this model, a component cause is anything that contributes to new cases of disease. Component causes can be characteristics of the host (e.g., age, vaccination status), the agent (e.g., subtype), or the environment (e.g., presence or absence of caterpillars). A sufficient cause is any set of components that, when present together, is capable of causing disease; once a sufficient cause is present or complete, disease will occur. A necessary cause is a component cause that must be present for disease to occur; without the necessary cause, disease cannot occur. For infectious diseases, exposure or infection with the infectious agent is never sufficient by itself, but it is necessary for disease to occur.

Using this model, we can see that there may be multiple sufficient causes, and that disease can “flow” through any of these paths. Thus, removing exposure to one component cause will only mitigate disease through the sufficient causal paths that include that particular component cause. When a particular component cause is part of a high proportion of sufficient pathways, then exposure to this particular component cause will be strongly associated with disease occurrence. The extreme of this example is when a component cause is included in all sufficient causes, in which case the component cause can also be called a “necessary cause.” Necessary causes are rare among all component causes, and there are always multiple sufficient causal sets. Thus, by removing exposure to some of the component causes, we only expect to prevent some disease occurrence and not all occurrences. The objective is to maximize efficiency of disease prevention efforts by targeting component causes that are strongly associated with disease occurrence.