The causes of a disease are often considered in terms of a triad of factors: the host, the agent, and the environment. For many diseases, it is also useful to add a fourth factor, the vector (Fig. 1-1). In measles, the host is a human who is susceptible to measles infection, the agent is a highly infectious virus that can produce serious disease in humans, and the environment is a population of unvaccinated individuals, which enables unvaccinated susceptible individuals to be exposed to others who are infectious. The vector in this case is relatively unimportant. In malaria, however, the host, agent, and environment are all significant, but the vector, the Anopheles mosquito, assumes paramount importance in the spread of disease.

Figure 1-1 Factors involved in natural history of disease.

Host factors are responsible for the degree to which the individual is able to adapt to the stressors produced by the agent. Host resistance is influenced by a person’s genotype (e.g., dark skin reduces sunburn), nutritional status and body mass index (e.g., obesity increases susceptibility to many diseases), immune system (e.g., compromised immunity reduces resistance to cancer as well as microbial disease), and social behavior (e.g., physical exercise enhances resistance to many diseases, including depression). Several factors can work synergistically, such as nutrition and immune status. Measles is seldom fatal in well-nourished children, even in the absence of measles immunization and modern medical care. By contrast, 25% of children with marasmus (starvation) or kwashiorkor (protein-calorie malnutrition related to weaning) may die from complications of measles.

Agents of disease or illness can be divided into several categories. Biologic agents include allergens, infectious organisms (e.g., bacteria, viruses), biologic toxins (e.g., botulinum toxin), and foods (e.g., high-fat diet). Chemical agents include chemical toxins (e.g., lead) and dusts, which can cause acute or chronic illness. Physical agents include kinetic energy (e.g., involving bullet wounds, blunt trauma, and crash injuries), radiation, heat, cold, and noise. Epidemiologists now are studying the extent to which social and psychological stressors can be considered agents in the development of health problems.

The environment influences the probability and circumstances of contact between the host and the agent. Poor restaurant sanitation increases the probability that patrons will be exposed to Salmonella infections. Poor roads and adverse weather conditions increase the number of automobile collisions and airplane crashes. The environment also includes social, political, and economic factors. Crowded homes and schools make exposure to infectious diseases more likely, and the political structure and economic health of a society influence the nutritional and vaccine status of its members.

Vectors of disease include insects (e.g., mosquitoes associated with spread of malaria), arachnids (e.g., ticks associated with Lyme disease), and mammals (e.g., raccoons associated with rabies in eastern U.S.). The concept of the vector can be applied more widely, however, to include human groups (e.g., vendors of heroin, cocaine, and methamphetamine) and even inanimate objects that serve as vehicles to transmit disease (e.g., contaminated needles associated with hepatitis and AIDS). A vector may be considered part of the environment, or it may be treated separately (see Fig. 1-1). To be an effective transmitter of disease, the vector must have a specific relationship to the agent, the environment, and the host.

In the case of human malaria, the vector is a mosquito of the genus Anopheles, the agent is a parasitic organism of the genus Plasmodium, the host is a human, and the environment includes standing water that enables the mosquito to breed and to come into contact with the host. Specifically, the plasmodium must complete part of its life cycle within the mosquito; the climate must be relatively warm and provide a wet environment in which the mosquito can breed; the mosquito must have the opportunity to bite humans (usually at night, in houses where sleeping people lack screens and mosquito nets) and thereby spread the disease; the host must be bitten by an infected mosquito; and the host must be susceptible to the disease.

D Risk Factors and Preventable Causes

Risk factors for disease and preventable causes of disease, particularly life-threatening diseases such as cancer, have been the subject of much epidemiologic research. In 1964 a World Health Organization (WHO) expert committee estimated that the majority of cancer cases were potentially preventable and were caused by “extrinsic factors.” Also that year, the U.S. Surgeon General released a report indicating that the risk of death from lung cancer in smokers was almost 11 times that in nonsmokers.²

Advances in knowledge have consolidated the WHO findings to the point where few, if any, researchers now question its main conclusion.³ Indeed, some have gone further, substituting figures of 80% or even 90% as the proportion of potentially preventable cancers, in place of WHO’s more cautious estimate of the “majority.” Unfortunately, the phrase “extrinsic factors” (or its near-synonym, “environmental factors”) has often been misinterpreted to mean only man-made chemicals, which was certainly not the intent of the WHO committee. In addition to man-made or naturally occurring carcinogens, the 1964 report included viral infections, nutritional deficiencies or excesses, reproductive activities, and a variety of other factors determined “wholly or partly by personal behavior.”

The WHO conclusions are based on research using a variety of epidemiologic methods. Given the many different types of cancer cells, and the large number of causal factors to be considered, how do epidemiologists estimate the percentage of deaths caused by preventable risk factors in a country such as the United States?

One method looks at each type of cancer and determines (from epidemiologic studies) the percentage of individuals in the country who have identifiable, preventable causes of that cancer. These percentages are added up in a weighted manner to determine the total percentage of all cancers having identifiable causes.

A second method examines annual age-specific and gender-specific cancer incidence rates in countries that have the lowest rates of a given type of cancer and maintain an effective infrastructure for disease detection. For a particular cancer type, the low rate in such a country presumably results from a low prevalence of the risk factors for that cancer. Researchers calculate the number of cases of each type of cancer that would be expected to occur annually in each age and gender group in the United States, if the lowest observed rates had been true for the U.S. population. Next, they add up the expected numbers for the various cancer types in the U.S. They then compare the total number of expected cases with the total number of cases actually diagnosed in the U.S. population. Using these methods, epidemiologists have estimated that the U.S. has about five times as many total cancer cases as would be expected, based on the lowest rates in the world. Presumably, the excess cancer cases in the U.S. are caused by the prevalence of risk factors for cancer, such as smoking.