Multifactorial Diseases

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The simplest way to consider the cause of a disease is to think of it as occurring when a person is exposed to a pathogenic agent. In the nineteenth century, most people got typhoid, cholera, smallpox, or plague when they were exposed to the agents that caused these diseases. Whether or not a particular person actually got these diseases was, of course, affected by the pathogenicity of the agent and the susceptibility of the person to that agent. This disease paradigm led to the well-known epidemiologic triad of host, agent, and environment. But the emphasis in those days clearly was on pathogenic agents of overwhelming pathogenicity and virulence. In 1965, a famous microbiologist, Rene Dubos, pointed out that this way of thinking about disease agents was not as useful in modern times as it once was. He said that the microbial diseases most common today arise from the activities of microorganisms that are ubiquitous in the environment. These microorganisms are much less virulent, they often persist in the body without causing obvious harm, and they cause disease only when the infected person becomes vulnerable to them. This concept caused a shift in emphasis from the virulence and pathogenicity of disease agents to those factors that strengthen or weaken people's resistance to them. This way of thinking about microbial diseases is just as relevant when people think about diseases caused by physiochemical and behavioral factors.

Consider cigarette smoking. There is no question that cigarette smoking enormously increases the risk of many diseases, including coronary heart disease. But is smoking the cause of these diseases? Many people who smoke cigarettes do not develop heart disease. Why are some people vulnerable to the disease agent (cigarette smoking) while other people are not? There clearly are other agents involved in the cause of this disease, and those studying this, or any other disease must consider a variety of disease agents that are involved in the causal chain. Since not one of them is the single and inevitable cause of the disease, they are referred to as "risk factors" for the disease; and diseases such as coronary heart disease are referred to as "multifactorial diseases." Most diseases of concern today are multifactorial diseases.

The problem faced with multifactorial diseases in public health is how to think about interventions to prevent them. How do those concerned with the prevention of coronary heart disease, for example, develop a strategy to prevent it? A focus on cigarette smoking only ignores other risk factors such as hypertension, high serum cholesterol, obesity, and physical inactivity. An expanded prevention program on these other risk factors, however, still does not solve the problem. If a multifactorial prevention program was developed that simultaneously focused on all the risk factors for coronary heart disease, and if everyone currently involved successfully lowered their risk, new high-risk people would continue to enter the population to take their place. This is because there is another, more fundamental layer of risk factors. For example, people in lower socioeconomic levels of society are at a higher risk for cigarette smoking, hypertension, elevated serum cholesterol, and obesity than those who are better off financially. Thus, even as one reduced the risk of people already at high risk, new people will continue to enter the at-risk population.

When dealing with the prevention of multifactorial diseases, there are many risk factors operating at many different levels. Some exist at the societal level, others at the community or neighborhood level, others at the level of individual behavior, and others at the biological level. Prevention programs for multifactorial diseases must be designed to deal with as many of these levels as possible. This requires many disciplines working together. The success that has been achieved in reducing cigarette smoking in the United States has come about because of laws restricting smoking in designated areas, increases in taxes on cigarettes, limitations on advertising, increased understanding of the biology of addiction, and the development of effective methods for helping people stop smoking. Not one of these approaches could be successful on its own. Even with this impressive achievement, however, young people continue to take up cigarette smoking at high rates. Clearly, multifactorial intervention approaches are necessary to deal with multifactorial diseases, and a continued effort is needed to expand the reach of current prevention programs. These prevention programs will become even more important as the population continues to age and as medical care delivery systems become increasingly overburdened.

S. Leonard Syme

(see also: Causality, Causes, and Causal Inference; Environmental Determinants of Health; Health Promotion and Education; Prevention; Risk Assessment, Risk Management; Social Determinants; Tobacco Control )


Cassel, J. (1976). "The Contribution of the Social Environment to Host Resistance." American Journal of Epidemiology 104:107123.

Dubos, R. (1965). Man Adapting. New Haven, CT: Yale University Press.