Family and Community Medicine Department King Saud University Models of Disease Causation

Learning objectives: At the end of this lecture you (will) be able to: Explain basic models of disease causation.Explain basic models of disease causation. Identify purpose of studying the disease process.Identify purpose of studying the disease process.

12/10/2009Dr. Salwa Tayel Causation&Association 4 Purpose of studying causal models  Studying how different factors can lead to ill health is important to generate knowledge to help prevent and control diseases.  Quote Hippocrates "To know the causes of a disease and to understand the use of the various methods by which the disease may be prevented amounts to the same thing as being able to cure the disease".

12/10/2009Dr. Salwa Tayel Causation&Association 5  In epidemiology, there are several models of disease causation that help understand disease process.  The most widely applied models are: The epidemiological triad (triangle), the wheel, and the web. And The sufficient cause and component causes models (Rothman’s component causes model) General Models of Causation

12/10/2009Dr. Salwa Tayel Causation&Association 6 The epidemiologic triad Model  The epidemiologic triangle or triad is the traditional model of infectious disease causation.  It has three components: an external agent, a susceptible host, and environmental factors that interrelate in a variety of complex ways to produce disease in humans.  When we search for causal relationships, we must look at all three components and analyze their interactions to find practical and effective prevention and control measures.

12/10/2009Dr. Salwa Tayel Causation&Association 7 The Epidemiologic Triad HOST AGENTENVIRONMENT

Agent factors Infectious agents: agent might be microorganism—virus, bacterium, parasite, or other microbes. e.g. polio, measles, malaria, tuberculosis Generally, these agents must be present for disease to occur.Infectious agents: agent might be microorganism—virus, bacterium, parasite, or other microbes. e.g. polio, measles, malaria, tuberculosis Generally, these agents must be present for disease to occur. Nutritive: excesses or deficiencies (Cholesterol, vitamins, proteins)Nutritive: excesses or deficiencies (Cholesterol, vitamins, proteins) Chemical agents: (carbon monoxide, drugs, medications)Chemical agents: (carbon monoxide, drugs, medications) Physical agents (Ionizing radiation,…Physical agents (Ionizing radiation,…

Host factors Host factors are intrinsic factors that influence an individual’s exposure, susceptibility, or response to a causative agent.Host factors are intrinsic factors that influence an individual’s exposure, susceptibility, or response to a causative agent. Host factors that affect a person’s risk of exposure to an agent:Host factors that affect a person’s risk of exposure to an agent: e.g. Age, race, sex, socioeconomic status, and behaviors (smoking, drug abuse, lifestyle, sexual practices and eating habits)e.g. Age, race, sex, socioeconomic status, and behaviors (smoking, drug abuse, lifestyle, sexual practices and eating habits) Host factors which affect susceptibility &response to an agent:Host factors which affect susceptibility &response to an agent: Age, genetic composition, nutritional and immunologic status, anatomic structure, presence of disease or medications, and psychological makeup.Age, genetic composition, nutritional and immunologic status, anatomic structure, presence of disease or medications, and psychological makeup.

Environmental factors Environmental factors are extrinsic factors which affect the agent and the opportunity for exposure. Environmental factors include: physical factors such as geology, climate,.. physical factors such as geology, climate,.. biologic factors such as insects that transmit an agent; and biologic factors such as insects that transmit an agent; and socioeconomic factors such as crowding, sanitation, and the availability of health services. socioeconomic factors such as crowding, sanitation, and the availability of health services.

12/10/2009Dr. Salwa Tayel Causation&Association 11 Agent Host Environment Vector Malaria

12/10/2009Dr. Salwa Tayel Causation&Association 12 Agent: Amount, infectivity, pathogenicity, virulence, chemical composition, cell reproduction Environment: Physical, biological, social Host: Intrinsic factors, genetic, physiologic factors, psychological factors, immunity Health or Illness ? The epidemiologic triad Model

12/10/2009Dr. Salwa Tayel Causation&Association 13  Web of Causation is devised to address chronic disease – can also be applied to communicable disease) due to multi- factorial nature of causation in many diseases Other Models of causation

12/10/2009Dr. Salwa Tayel Causation&Association 14 Web of Causation  There is no single cause  Causes of disease are interacting  Illustrates the interconnectedness of possible causes

Web of Causation RS Bhopal Disease behaviour Unknown factors genes phenotype workplace social organization microbes environment

Web of Causation - CHD RS Bhopal Disease smoking Unknown factors gender genetic susceptibility inflammation medications lipids physical activity blood pressure stress

12/10/2009Dr. Salwa Tayel Causation&Association 17 Example of a Web of Causation Susceptible Host InfectionTuberculosis Vaccination Genetic Overcrowding Malnutrition Tissue Invasion and Reaction Exposure to Mycobacterium

12/10/2009Dr. Salwa Tayel Causation&Association 18 The Wheel of Causation  The Wheel of Causation de-emphasizes the agent as the sole cause of disease,  It emphasizes the interplay of physical, biological and social environments. It also brings genetics into the mix.

12/10/2009Dr. Salwa Tayel Causation&Association19 The Wheel of Causation Social Environment Genetic Core Physical Environment Biological Environment Host (human)

The sufficient cause and component causes model Rothman’s component causes model

12/10/2009Dr. Salwa Tayel Causation&Association 21 Necessary and sufficient causes  A necessary cause is a causal factor whose presence is required for the occurrence of the effect. If disease does not develop without the factor being present, then we term the causative factor “necessary”. Agent in Malaria: plasmodium Falciparum parasite is necessary factor ( always present) such as A in the previous slide.  Sufficient cause is a “minimum set of conditions, factors or events needed to produce a given outcome. Usually there’s no sufficient factor “rare”.> Rabies is both necessary and sufficient.  The factors or conditions that form a sufficient cause are called component causes.

12/10/2009Dr. Salwa Tayel Causation&Association 22 Example  The tubercle bacillus is required to cause tuberculosis but, alone, does not always cause it,  so tubercle bacillus is a necessary, not a sufficient, cause.

12/10/2009Dr. Salwa Tayel Causation&Association 23  Rothman's model has emphasised that the causes of disease comprise a collection of factors.  These factors represent pieces of a pie, the whole pie ( the sufficient causes for a disease.  These factors represent pieces of a pie, the whole pie (combinations of factors) are the sufficient causes for a disease.  It shows that a disease may have more that one sufficient cause, with each sufficient cause being composed of several factors. Component Causes and Causal Pies Model Rothman’s Component Causes and Causal Pies Model

12/10/2009Dr. Salwa Tayel Causation&Association 24 component  The factors represented by the pieces of the pie in this model are called component causes. sufficient necessary  Each single component cause is rarely a sufficient cause by itself, But may be necessary cause.  Control of the disease could be achieved by removing one of the components in each "pie" and if there were a factor common to all "pies“ (necessary cause) the disease would be eliminated by removing that alone. Component Causes and Causal Pies Rothman’s Component Causes and Causal Pies

 Exercise If a particular disease is caused by any of the three sufficient causes in the diagram. which components, if any, are a necessary cause? (Circle ALL that apply.) A. A B. B C. C D. D E. E F. F G. None

Causal pies representing all sufficient causes of a particular disease

12/10/2009Dr. Salwa Tayel Causation&Association 27 Exercise  Some of the risk factors for heart disease are smoking, hypertension, obesity, diabetes, high cholesterol, inactivity, stress, and type A personality. - Are these risk factors necessary causes, sufficient causes, or component causes? none of them is necessary or sufficient, but each 1 of them is a component factor.

12/10/2009Dr. Salwa Tayel Causation&Association 28  Causation - implies that there is a true mechanism that leads from exposure to disease  Epidemiology does not determine the cause of a disease in a given individual  Instead, we determine the relationship or association between a given exposure and frequency of disease in populations. Causation and Association

12/10/2009Dr. Salwa Tayel Causation&Association 29  Association is an identifiable relationship between an exposure and disease  Association implies that exposure might cause disease  Finding an association does not make it causal  We infer (assume) causation based upon the association and several other criteria. Association vs. Causation

12/10/2009Dr. Salwa Tayel Causation&Association 30  An association rarely reflects a causal relationship but it may.  Criteria for causality provide a way of reaching judgements on the likelihood of an association being causal. Epidemiological criteria (guidelines) for causality

12/10/2009Dr. Salwa Tayel Causation&Association 31 Hill’s Criteria for Causal Relation  Strength of association  Consistency of findings  Specificity of association  Temporal sequence  Biological gradient (dose-response)  Biological plausibility  Coherence with established facts  Experimental evidence

12/10/2009Dr. Salwa Tayel Causation&Association 32 Strength of association association  Does exposure to the cause change disease incidence?  The strength of the association is measured by the relative risk.  The stronger the association, the higher the likelihood of a causal relationship.  Strong associations are less likely to be caused by chance or bias

12/10/2009Dr. Salwa Tayel Causation&Association 33 Consistency of findings  Consistency refers to the repeated observation of an association in different populations under different circumstances.  Causality is more likely when the association is repeated by other investigations conducted by different persons in different places, circumstances and time-frames, and using different research designs.

12/10/2009Dr. Salwa Tayel Causation&Association 34 Specificity of association  It means that an exposure leads to a single or characteristic effect, or affects people with a specific susceptibility easier to support causation when associations are specific, but easier to support causation when associations are specific, but this may not always be the case this may not always be the case  as many exposures cause multiple diseases  This is more feasible in infectious diseases than in non- infectious diseases, which can result from different risk agents.

12/10/2009Dr. Salwa Tayel Causation&Association 35 Temporal sequence (temporality)  Did the cause precede the effect?  Temporality refers to the necessity that the cause must precede the disease in time.  This is the only absolutely essential criterion.  This is the only absolutely essential criterion.  It is easier to establish temporality in experimental and cohort studies than in case-control and cross-sectional studies.

12/10/2009Dr. Salwa Tayel Causation&Association 36 Biological gradient  Does the disease incidence vary with the level of exposure? (dose-response relationship)  Changes in exposure are related to a trend in relative risk  A dose-response relationship (if present) can increase the likelihood of a causal association.

12/10/2009Dr. Salwa Tayel Causation&Association 37 Biological gradient

12/10/2009Dr. Salwa Tayel Causation&Association 38 Biological plausibility  Is there a logical mechanism by which the supposed cause can induce the effect?  Findings should not disagree with established understanding of biological processes.

12/10/2009Dr. Salwa Tayel Causation&Association 39 Coherence implies that a cause-and- effect interpretation for an association  Coherence implies that a cause-and- effect interpretation for an association  does not conflict with what is known of the natural history and biology of the disease

12/10/2009Dr. Salwa Tayel Causation&Association 40 Experimental evidence  It refers to evidence from laboratory experiments on animal or to evidence from human experiments  Causal understanding can be greatly advanced by laboratory and experimental observations.

12/10/2009Dr. Salwa Tayel Causation&Association 41 Judging the causal basis of the association  No single study is sufficient for causal inference  It is always necessary to consider multiple alternate explanations before making conclusions about the causal relationship between any two items under investigation.  It is always necessary to consider multiple alternate explanations before making conclusions about the causal relationship between any two items under investigation.  Causal inference is not a simple process consider weight of evidence consider weight of evidence requires judgment and interpretation requires judgment and interpretation

12/10/2009Dr. Salwa Tayel Causation&Association 42 Figure 5.12 The scales of causal judgement Weigh up weaknesses in data and alternative explanations Weigh up quality of science and results of applying causal frameworks

Pyramid of Associations RS Bhopal Causal Non-causal Confounded Spurious / artefact Chance

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