Jessica Ochs; Sherry L. Roper; Susan M. Schwartz

Learning Outcomes

By the end of this section, you should be able to:

12.3.1 Discuss the interaction and interdependence of agent, host, and environment (epidemiologic triad) in communicable disease transmission.
12.3.2 Explain the components of the natural history of disease.
12.3.3 Describe the chain of infection and implications for understanding causative factors.
12.3.4 Discuss the web of causation.

The epidemiological triad posits that disease is caused by the interaction between a susceptible host, an external agent, and an environment that brings the host and agent together (CDC, 2012). It reflects the idea that health is not the result of one factor but rather results from the interaction of these elements (Celentano & Szklo, 2019).

The host can be an individual, a family, a group of high-risk individuals, or a community. Host factors include immunologic characteristics such as prior history of infection or immunization; modifiable factors such as exercise level, nutrition, and lifestyle; and non-modifiable factors such as age, race, and genes.

The agent is something that can cause a health issue, and the environment is the context within which the agent and host interact. Agents are classified into five categories: physical (trauma, radiation, heat), chemical (pollutants, medications, drugs, alcohol, smoke), nutritional (lack of or excess of), psychosocial (stress, social isolation), and biologic (bacteria, viruses, arthropods, toxins). The pathogenicity of the agent, or its ability to cause disease, influences disease onset. An agent must be present for a disease to occur, but the presence of an agent does not always cause disease; a variety of factors influence whether exposure to an agent will result in disease (CDC, 2012).

Environmental factors include the biologic environment of plants, animals, and toxins, including vectors (life forms such as mosquitoes or ticks that carry infectious agents) and the reservoirs where vectors and infectious agents are normally found. Other environmental factors are physical and social in nature, such as neighborhoods, housing, temperature, altitude, presence of crowding, air pollution, radiation, water quality, and noise.

The epidemiological triad (Figure 12.3) shows how host, agent, and environment can interact to cause disease. (Note that this model is incomplete for diseases that have other kinds of contributing causes, such as cardiovascular disease.) A good example of the epidemiological triangle is cholera, the diarrheal illness that John Snow linked to contaminated water. In the John Snow example, the host was the susceptible individual who consumed the contaminated water. The agent was Vibrio cholerae bacteria. The environment was the contaminated water system.

A diagram shows three circles, one at each of the points of a triangle. The circles are labeled agent, environment, and host. A double-sided arrow connects each circle, indicating their affect on one another.

Figure 12.3 The epidemiological triad demonstrates the three factors that interact to cause illness. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Natural History of Disease

In the absence of treatment, diseases in individuals follow a natural progression, referred to as the natural history of disease (CDC, 2012). The natural history of disease encompasses events that occur before, during, and after the conclusion of a disease. The process involves multiple interactions between host, agent, and environment.

The natural progression of a disease has four stages: susceptibility, subclinical (preclinical) disease, clinical disease, and resolution (recovery, disability, or death) (CDC, 2012) (Figure 12.4). The initial interactions between agent, host, and environment occur during the susceptibility stage, or the pre-pathogenesis period, during which primary prevention measures could be implemented to prevent onset of the disease. Pathogenesis (onset and progression of a disease) begins when the host has clinical disease, and secondary prevention measures focus on early diagnosis and treatment to limit resulting disabilities (CDC, 2012).

The four stages of disease progression are shown in order from left to right along an arrow. The stages are susceptibility, subclinical disease, clinical disease, and recovery, disability, and death. Perpendicular lines cross the arrow to marking the event that signals the shift from one stage to the next. Exposure marks the shift from susceptibility to subclinical disease. Pathologic changes mark the shift from subclinical disease to clinical disease. Onset of symptoms and usual time of diagnosis mark the shift from clinical disease to recovery, disability, or death.

Figure 12.4 There are four stages of disease progression: susceptibility, subclinical (preclinical) disease, clinical disease, and resolution (recovery, disability, or death). (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

The process begins with the susceptibility stage, or exposure of a susceptible host. In communicable diseases, the exposure is to a microorganism. In noncommunicable diseases like cancer, the exposure could be a factor that instigates the process, such as tobacco smoke (lung cancer). Once the disease process begins, pathologic changes occur without the host being aware of them. In this subclinical disease stage, individuals have no overt symptoms. In infectious diseases, this stage includes an incubation period during which the pathogen multiplies to produce clinical symptoms. In noninfectious disease, it includes a latency period (the time from exposure to onset of symptoms). The latency period may be as brief as seconds for acute hypersensitivity (allergic) reactions or as long as decades for certain chronic diseases. In the clinical disease stage, signs of the disease develop, and diagnosis may occur. In the resolution stage, the disease may end with a return to health, a chronic form of the disease with limitations, or death (CDC, 2012).

In the subclinical stage, although disease is not yet apparent, there may be pathologic changes that can be detected with laboratory evaluation of blood work, radiographic evidence, or other screening methods. Many screening programs aim to identify the disease process early, as intervention in the early stage is often more effective than after the disease has progressed to symptoms (CDC, 2012).

The onset of symptoms marks the clinical disease stage in which most diagnoses occur. Some individuals may never progress to clinical disease, while others may have mild to severe illness. The severity of a disease is impacted by the infectivity, pathogenicity, and virulence of infectious agents. With any infectious disease, there are often many undiagnosed cases, as there will always be individuals who never progress to the clinical stage.

Individuals who have only subclinical disease but are infectious are termed carriers. Carriers are individuals with incubating disease or preclinical infection. For example, an individual infected with measles becomes infectious days before symptoms appear. Carriers are usually unaware they are infectious and are more likely to spread infection than those with obvious illness (CDC, 2012). Chronic carriers carry pathogens after recovering from the initial illness and may carry these pathogens for months or years. Examples include chronic carriers of hepatitis B virus and Salmonella Typhi, the causative agent of typhoid fever. Typhoid Mary, Mary Mallon, was an asymptomatic chronic carrier of Salmonella Typhi who, as a cook in the early 1900s, unknowingly infected many individuals in New York before her condition was identified and she was quarantined (CDC, 2012).

Chain of Infection

The chain of infection is an epidemiological model that allows for a more complex and nuanced interplay between the host, agent, and environment of the epidemiological triad (Figure 12.5). The agent is the virus or bacteria itself. The other elements of the chain of infection are discussed below.

Figure 12.5 The components of the chain of infection are interlinked, similar to the epidemiological triad but with the added inclusion of transmission modes. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Reservoir

The reservoir is where the causal agent normally lives and reproduces. Reservoirs include the environment, humans, and animals. Communicable diseases that are transmitted from person to person—for example, sexually transmitted infections (STIs), measles, mumps, and many respiratory pathogens—are considered to have human reservoirs (CDC, 2012). As discussed, human reservoirs may be symptomatic, asymptomatic, or chronic disease carriers. With animal reservoirs (when the disease is transmissible from animals to humans, referred to as zoonosis), humans become accidental hosts. Examples include plague (from rodents) and rabies (from bats, dogs, and other mammals). Many newly recognized infectious diseases in humans, including West Nile encephalitis, acquired immunodeficiency syndrome (AIDS), Ebola infection, and severe acute respiratory syndrome (SARS), are thought to have emerged from animal hosts (CDC, 2012). Soil, water, and plants are considered environmental reservoirs. Many fungal agents live in the soil, and Legionella bacteria, the cause of Legionnaires’ disease, often live in water within evaporative condensers (CDC, 2012).

Portal of Exit

The portal of exit from the reservoir is how the agent leaves its home, which enables it to act as the mode of transmission. Respiratory viruses such as influenza or tuberculosis exit the respiratory tract where the pathogen resides within its host. In pregnant individuals, some bloodborne agents such as syphilis can cross the placenta and infect the baby. Another portal of exit for bloodborne agents can be via cuts or needle punctures in the skin as can occur with hepatitis B or C, or even via a blood-drinking mosquito, as occurs with malaria (CDC, 2012).

Mode of Transmission

Diseases can be transmitted directly or indirectly (CDC, 2012). See Table 12.1 for more information.

Transmission Method	Description	Example
Airborne transmission	Transmission occurs via infectious agents capable of remaining suspended in the air over long distances and long periods of time, in stark contrast to droplets that fall to the ground within a few feet. Airborne transmission is considered a form of indirect transmission since the agent can be suspended in air particles for long periods of time.	The measles virus remains suspended in the air for long periods of time and is capable of infecting susceptible hosts even after the person with measles has left the room.
Direct transmission	Transmission occurs when an infectious agent is transmitted by direct contact or droplet spread. This person-to-person direct contact can occur via skin contact, kissing, and sexual intercourse. Transmission may also occur from direct contact with soil that harbors infectious pathogens. Droplet spread is considered direct transmission as infected material is transmitted by direct spray of relatively large, short-range aerosols of the pathogen over a few feet prior to the droplets falling to the ground.	Examples include infectious mononucleosis, which is transmitted through kissing and sharing saliva; chlamydia, which spreads from person to person via direct contact; and hookworm, which is transmitted by direct contact with contaminated soil. Many illnesses such as influenza, pertussis, and meningococcal disease are spread when an infected host talks, sneezes, or coughs near a susceptible host who then breathes in these infected droplets.
Indirect transmission	Transmission occurs when an infectious agent is transmitted via an inanimate object, also known as a vehicle or vector intermediary. Vehicle-borne vectors that may indirectly transmit infectious agents include food, water, and inanimate objects such as bedding, countertops, or surgical equipment. A vehicle such as food or water can passively carry pathogens. Diseases can also be transmitted indirectly from touching a contaminated surface such as a countertop and then touching the eyes, nose, or mouth. Indirect transmission can also occur via vectors such as mosquitos or ticks. These vectors carry the infectious agent to a susceptible host.	Hepatitis A is a vehicle-borne vector disease; it can be passively carried in food or water, and once ingested, it transmits disease. Lyme disease and malaria are examples of vector-borne diseases. Lyme disease is transmitted by ticks, and malaria is transmitted by mosquitoes. Influenza, norovirus, COVID-19, and conjunctivitis are all examples of diseases that can also be transmitted indirectly from touching a contaminated surface.

Table 12.1 Methods of Transmission

Portal of Entry

The portal of entry is how the agent infects a susceptible host. The portal of entry must provide contact with tissues that will allow it to reproduce or allow the toxin of the agent to act (CDC, 2012). Many infectious agents use the same portal to enter a host that they used to exit the source; for example, pertussis (whooping cough) exits the respiratory tract of the original host and enters the respiratory tract of the new host. The portal of exit and portal of entry can be the same, as in the case of malaria via a mosquito bite. Some infectious pathogens exit the source host in feces and are carried via unwashed hands to a vehicle-borne vector, such as food, to enter the new host through the mouth. This is known as the fecal-oral route (CDC, 2012). The skin, mucous membranes, and blood are other portals of entry (CDC, 2012).

Host

A susceptible host is a key component and final link in the chain of infection. Host susceptibility depends on a multitude of genetic, nonspecific, and lifestyle factors. Genetic factors of age, gender, physical health, and immune status; nonspecific factors such as skin integrity, gastric acidity, and respiratory tract anatomy; and lifestyle factors such as malnutrition, chronic disease, and alcoholism (CDC, 2012) all contribute to a host’s susceptibility. An example of a genetic makeup that decreases a host’s susceptibility is the sickle cell trait. Individuals with this genetic alteration are partially protected against certain types of malaria. Immunity refers to either prior immunization or prior exposure to a pathogen affording protective antibodies. By interrupting and stopping the chain of causation at any of the links, disease can be prevented.

Web of Causation

By the mid-20th century, antibiotics and vaccines to prevent or treat infections shifted public health attention away from infectious diseases to noninfectious diseases like cancer and diabetes. In the 1960s, the web of causation became an epidemiological model to demonstrate the concept of multiple causation in the health and illness spectrum (Ventriglio et al., 2016). This model helps describe the multiple factors that underlie many chronic illnesses, giving each causative factor equal prominence in identifying determinants of disease. The emergence of the web of causation represented a shift in thinking about disease and suggested that the combination of multiple factors was the determining influence in the development of poor outcomes (Ventriglio et al., 2016). Epidemiologists today continue to make associations among lifestyle choices, behaviors, the environment, and even the social determinants of health and their relationship to health outcomes.

12.3 Epidemiological Approaches