11.1 The infectious disease process
Studying infectious disease epidemiology is important for two different reasons. First, infectious disease epidemiology provided the original model for the study of disease on a population basis. Many general epidemiologic principles emerged when studying infectious agents and have since been adopted by other fields of epidemiology. For example, the interaction of agent, host, and environmental factors in determining levels of disease in the population was first recognized in an infectious disease context, as was the importance of ordering multiple causal components into causal pathways. The insufficiency of agent-only theories of disease was initially an infectious disease concept.
There are many conceptual similarities between infectious disease epidemiology and chronic disease epidemiology. In fact, many prominent epidemiologists believe division of epidemiology into subspecialites of infectious disease epidemiology and chronic disease epidemiology is arbitrary and detrimental to the discipline (Barrett-Connor, 1979; Stallones, 1980; Susser, 1985).
Second, infectious and parasitic diseases remain a leading cause of morbidity and mortality worldwide (World Health Organization, 1992; National Institute of Allergy and Infectious Disease, 1992). Many infectious diseases have recently emerged (e.g., HIV, hantavirus) or reemerged in virulent forms (e.g., tuberculosis, yellow fever) to imperil the public’s health, and the risk of bioterrorism has increased. Therefore, studying infectious disease epidemiology in its own right has taken on added relevance.
As an introduction to infectious disease epidemiology, we consider the following components of the infectious disease process:
- agents
- reservoirs
- portals of entry and exit
- transmission
- host immunity.
Agents
Infections are caused by entry and multiplication of microorganisms and parasites in the body of humans and animals. However, “infection” is not synonymous with infectious disease, since many infections remain inapparent throughout their course. In addition, the presence of living infectious agents on the exterior of the body or on an article of clothing is not infection, but contamination of a surface.
Infectious agents may be classified according to their size, structure, and physiology. The major categories of infectious disease agents (from structurally largest to smallest) are:
- helminths (parasitic worms);
- fungi and yeast (parasitic lower plants that lack chlorophyll);
- protozoans (minute unicellular organisms often having complex life cycles);
- bacteria (microscopic unicellular organisms capable of independent reproduction);
- rickettsia (microscopic intracellular organisms transmitted by Ixodes ticks);
- viruses (submicroscopic infectious agents containing their own genetic material but incapable of multiplication external to a host);
- prions (poorly understood infectious proteins, without discernible nucleic acids, that cause central nervous system infections).
Examples of important infectious diseases from each of these categories are listed in Table 11.1
Reservoirs
The reservoir of an agent is the normal habitate in which it lives, multiplies, and grows. Without a reservoir, the agent cannot perpetuate itself in nature.
There are many types of reservoirs. These are:
- symptomatic cases
- carriers
inapparent carriers
incubatory carriers
convalescent carriers
- animals (zoonoses)
direct zoonoses
cyclozoonoses
metazoonoses
saprozoonoses
- inanimate objects
water
food
soil
air
fomites.
Symptomatic cases
Symptomatic cases are people with apparent signs of infection. Examples of human diseases in which the primary reservoirs are acute cases include influenza, measles, and smallpox. However, we should not automatically assume that the acutely ill individual always fulfills the role of a reservoir in nature; in many diseases, acute cases might represent biological dead ends in which an essential phase of the agent does not develop or, for some other reason, transmission is disabled. Even when acutely ill individuals are capable of transmitting the agent, they are not necessarily efficient in doing so; acutely ill individuals might be less likely to circulate in the general population of susceptibles and engage in activities necessary for transmission. In fact, it is often the silent carrier that provides the most efficient means of transmission.
Carriers
Carriers are people who harbor the infectious agent, manifest no discernible signs of infection, yet are potential sources of infection. There are three types of carriers:
- inapparent carriers
- incubatory carriers
- convalescent carriers.
Inapparent carriers remain free of the disease throughout the course of infection, yet are still capable of shedding the agent. An example of a disease in which transmission occurs primarily through inapparent carriers is poliomyelitis. For every 100 poliomyelitis infections, only 1 becomes paralyzed, 4 develop nonparalytic disease, and 95 remain disease-free. Nevertheless, all infected individuals may transmit the agent. An additional example of a disease in which inapparent carriers play a crucial role in perpetuating infection is hepatitis A; only 10% of hepatitis-A-infected children demonstrate jaundice, yet fully half are contagious.
Incubatory carriers transmit the agent prior to the onset of disease. Examples of infectious diseases with large incubatory carrier pools include AIDS and hepatitis B. During the long incubatory phase of AIDS, HIV carriers are contagious. Hepatitis B carriers are infectious for an average of 3 months before signs appear.
In the case of convalescent carriers, infected persons have recovered from the disease in question but still harbor the agent. A well known case of a convalescent carrier was Mary Mallon—the infamous “Typhoid Mary.” Typhoid Mary was free of typhoid symptoms yet continued to harbor and shed the typhoid bacilli throughout her life. She is, perhaps, the world’s best known chronic convalescent carrier, having infected at least 53 persons, resulting in three known deaths (Gordon, 1986). However, Typhoid Mary was hardly unique. In general, 1 typhoid patient in 20 continues to shed the infectious agent for at least a year after recovery. Some, like Mary, excrete the typhoid bacilli for life. Convalescent carriers who continue to harbor infection for more than a year are called chronic carriers. For some bacterial diseases, incomplete treatment with antibiotics increases the likelihood of the convalescent carrier state. This is why it is important to complete the full course of antibiotic therapy, even after symptoms have abated.
Animals
Zoonoses are infections naturally transmitted between lower vertebrate animals and humans. A less anthropocentric view of zoonoses suggests that they are infections in which the agent is shared between species. Zoonoses constitute a large and diverse group of diseases (over 150 such diseases exist under natural conditions), many of which still cause substantial morbidity and mortality worldwide.
Many zoonotic disease agents have complex life cycles with mandatory intermediate hosts and insect vectors. Accordingly, the following classification scheme for zoonoses has been established:
Inanimate objects
Some infectious agents are free-living in the environment, growing in inanimate objects such as water, food, soil, air, and other inert substances. Examples of infectious agents with inanimate reservoirs are legionellosis (in which the gram-negative bacillus grows and multiplies in pools of water such as those produced by cooling towers and evaporative condensers), histoplasmosis (a fungal disease with a soil reservoir), and staphylococcal food poisoning (in which the agent multiplies in food, producing toxins capable of causing gastroenteritis).
Portals of entry and exit
For an infectious agent to propagate itself in nature, it must leave one host and enter another. Exit and entry sites for pathogens are called portals. There are six portals in the body:
- respiratory tract (upper and lower);
- conjunctiva (mucous membranes surrounding the eye);
- urogenital tract (urinary tract, sexual genitalia; and organs);
- gastrointestinal tract (upper and lower);
- skin (both intact and broken skin);
- placenta (vertical transmission to offspring).
Blocking an agent’s portal can effectively prevent its transmission. Thus, condoms are recommended for the prevention of sexually transmitted diseases and rubber gloves are recommended for the prevention of nosocomial (hospital-borne) infections. Inadvertent transdermal transmission of HIV and hepatitis B can be prevented by exercising sufficient care in the disposal of needles and other sharp clinical and surgical instruments.
In general, agents exhibit preferred portals of entry and exit. For example, tuberculosis bacilli and influenza viruses enter and exit through the respiratory tract, schistosomiasis enters through the skin of humans and exits through the urine or feces (depending on species), and gonorrhea is generally transmitted though the urogenital tract. However, there are some agents that use multiple routes of entry and exit. For example, HIV may enter and exit through the urogenital tract (vagina or penis), gastrointestinal tract (rectal mucosa), skin, and placenta (mother to child).
Transmission
Mode of transmission
Transmission refers to any mechanism by which an infectious agent is spread to another host. In order for an agent to pass from one host to another, the gap between portals must be bridged. Transmission of infection can be accomplished by means of direct and indirect contact, by vectors (animate objects), and by vehicles (inanimate objects). A classification scheme for the modes of transmission is as follows:
- Contact
direct (requiring physical contact between hosts);
indirect (contact with relatively fresh bodily fluids or tissue);
droplets (large infectious particles sprayed from a respiratory portal of an infected host to a susceptible host propelled over a short distance by sneezing or coughing);
droplet nuclei (small aerosolized particles suspended in air and capable of traveling considerable distances).
- Vectors (animate intermediaries)
mechanical transmission (no multiplication of the agent in the vector);
developmental transmission (the infectious organism undergoes a necessary period of development or maturation in the vector);
propagative transmission (the organism undergoes multiplication in the vector);
cyclopropagative transmission (the organism multiplies and undergoes development in the vector).
- Vehicles (inanimate intermediates)
mechanical transmission
developmental transmission
propagative transmission
cyclopropagative transmission.
Examples of diseases transmitted by contact are sexually transmitted diseases, mononucleosis, surgical wound infections, and most respiratory diseases. Examples of vector-borne transmission are malaria (mosquito-borne), Lyme disease (tick-borne), and plague (flea-borne). Examples of diseases transmitted by vehicles are foodborne diseases (e.g., salmonellosis) and waterborne diseases (e.g., cryptosporidiosis).
Dynamics of transmission
Diseases can be transmitted by means of a common vehicle or by serial transfer. Common vehicle spread refers to transmission of an agent through a common source. Examples of common vehicles that may serve this purpose are air, water, food, and drugs. Examples of common vehicle transmission are foodborne disease outbreaks spread by the ingestion of a single contaminated food source or beverage, respiratory disease outbreaks spread by common vehicle transmission through inhalation of air from a contaminated environment (e.g., legionellosis disease), and needle sharing serving as a common vehicle for bloodborne pathogens.
Serial transfer refers to transmission from human to human, human to animal to human, and human to environment to human in sequence. Examples of serially transmitted diseases are measles (spread by the respiratory route from infected to susceptible individuals), sexually transmitted diseases, and any of the diseases requiring person-to-person contact (e.g., AIDS).
Infectious cycles in nature
Many infectious agents have complex biological cycles, requiring specific transfers between hosts of different species and within the body of a given host. For example, schistosomiasis (the human blood worm) is acquired from water contaminated with larval forms. The eggs of the worm leave the mammalian host either with the urine or feces (depending on species). Eggs hatch in water, liberating a larval form (miracidium) that enters a suitable freshwater snail host. A different larval phase (cercariae) emerges from the snail and penetrates the human skin while the human host is immersed in a contaminated water source. The cercariae enter the blood stream, are carried to the lungs, and migrate to the liver, where they develop to maturity. The mature worm migrates to the mesenteric and pelvic veins where eggs are deposited and eventually escape to the lumen of the bladder (Schistosoma haematobium) or bowel (other Schistosoma species). The complex life cycle of Schistosoma species is illustrated in Figure 11.1.