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Concept of causeAlick Mwambungu

Mwambungup@yahoo.com

Session 11

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Cause

• An understanding of the cause of disease is important in the health field not only for prevention but also in diagnosis and the application of correct treatment.

• A cause of a disease is an event,condition,characteristic or a combination of these factors which plays an important role in producing the disease.

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Causality

• We are interested in finding the causes of diseases because we want to be able to intervene to prevent disease from occurring.

• The ideas about why, where and how are influenced by concepts of diseases and the wider frame of reference in which we operate.

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Causality

• Logically a cause must precede a disease.

• A cause is termed sufficient when it inevitably produces or initiates a disease

• termed necessary if a disease can not develop in its absence.

• A sufficient cause is not usually a single factor, but often comprises several components.

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Types of Causes

• Necessary cause–a factor found in all cases

• Sufficient cause–a combination of factors that makes disease inevitable

Causes that act together are classified as necessary and sufficient.

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• Example: Cigarette smoking is one component of the sufficient cause of lung cancer.

• Smoking is not sufficient in itself to produce the disease.

• Some people smoke for 50 yrs without developing lung cancer; other factors mostly unknown are required.

• However, the cessation of smoking reduces the number of cases of lung cancer in a population even if the other component are not altered.

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• Each sufficient cause has a necessary cause as a component eg.In a study of an outbreak of food borne infection, it may be found that chicken salad and creamy dessert were both sufficient causes of salmonella diarrhoea.

• The occurrence of salmonella is the necessary cause of this disease.

• Similarly, there are different components in the causation of tuberculosis, but the tubercle bacillus is a necessary cause.

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• A single component cause is rarely a sufficient cause by itself.

• For example, even exposure to a highly infectious agent such as measles virus does not invariably result in measles disease-the host must be susceptible; other host factors may also play a role.

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• An agent which rarely causes disease in healthy persons may be pathogenic when other conditions are right.

• Pneumocystits carinii is one such organism, harmlessly colonizing some healthy persons but causing potentially lethal pneumonia in persons whose immune systems have been weakened by HIV.

• Presence of Pneumocystitis carinii organisms is therefore a necessary but not sufficient cause of pneumocystis pneumonia.

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Factors in causation

• Three types of factor play a part in causation of disease. All may be necessary but they are rarely sufficient to cause a particular disease or state.

• Predisposing factor :sex,age,previous illness • Enabling factors: Low income, poor nutrition,

bad housing, inadequate medical care.• Precipitating factors: Exposure to a specific

agent or noxious agent.

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Establishing the cause of diseases

• Causal inference:

This is the term used for the process of determining whether observed associations are likely to be causal.

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Interaction

• The effect of two or more causes acting together is often greater than would be expected on the basis of summing the individual effects:

Lung cancer=Smoking + Asbestos exposure.

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Sanitary movement

• Cause: a combination of unfavourable living conditions thought to lead to the general burden of disease.

• Where: factors operating at community level were the causes of disease.

• How: Documented mortality rates in different communities and found many associations between mortality rates and these population based variables.

• They took these associations to be proof of causation.

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Germ theory

• Cause: A single specific agent that inevitably produced specific disease outcome-physical entity, that could be isolated in lab

• Where: Efforts at disease prevention were concentrated at the individual level.

• How:- the agent must be found in every case

-the agent must not be found in other disease.

-should be able to reproduce disease in experimental animals.

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• Pasteur's work on microorganisms led to the formulation of the following rules by Koch for determining whether a specific living organism causes a particular disease.

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Koch’s Postulates

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Multi-causality

• Cause: any factor that plays an essential role in producing an occurrence of diseases i.e. a number of factors act together.

• Where: there are no upper or lower limits to the level at which we could search for causes.

• How: find association between exposure and outcome.

• Decide whether the association is valid considering alternative explanations.

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Multi-causality

• We do not make judgement about causality on the basis of one association

• We need to take into account other evidence from a number of different sources and the coherence of the association with existing theory and knowledge.

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Hills Criteria of Causation

• Outlines the minimal conditions needed to establish a causal relationship between two items. 

• These criteria were originally presented by Austin Bradford Hill (1897-1991).

• A British medical statistician• As a way of determining the causal link

between a specific factor (e.g. cigarette smoking) and a disease (such as emphysema or lung cancer). 

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• Hill's Criteria form the basis of modern epidemiological research, which attempts to establish scientifically valid causal connections between potential disease agents and the many diseases that afflict humankind. 

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Sir Austin Bradford Hill(1897-1991)

-Temporality

-Strength

-Consistency

-Dose-response relationship– Specificity– Biological plausibility– Coherence– Reversibility (Experimental)– Analogy

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1.Temporality or Time Sequence

• For judgement of causality to be reasonable, the exposure of interest should precede the outcome by a period of time consistent with biologic mechanism

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Bradford Hill Criteria

• Temporality Exposure must precede outcome

Exposure Outcome Time

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2.Strength

• The strength of an association is measured by risk ratio, or odds ratio.

• The stronger the association the more likely it is to be causal.

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3.Consistency

• Cause-effect relationship can be supported if the outcome is consistency.

• The outcome has been supported by a number of studies conducted by different investigators at various times using various epidemiological study designs (cross-section, case-control or cohort studies) among different populations and cultural setting.

• Have similar results been shown in other studies?

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4.Biological gradient

• Risk of an outcome increases with an increase in the dose of exposure (dose- response relationship). e.g. the more cigarettes smoked per day, the higher the risk of developing lung cancer.

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5.Specificity

• This is established when a single putative cause produces a specific effect. 

• This is considered by some to be the weakest of all the criteria. 

• The diseases attributed to cigarette smoking, for example, do not meet this criteria. 

• When specificity of an association is found, it provides additional support for a causal relationship. 

• However, absence of specificity in no way negates a causal relationship.   

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6.Biological Plausibility

• Postulated biologic mechanism by which the exposure might reasonably alter the risk of developing the disease.

• For example the belief that the daily consumption of small to moderate amounts of alcohol reduces the risk of developing CHD.

• This is enhanced by the fact that there is a plausible biologic mechanism that alcohol raises high-density lipoprotein (HDL) Cholesterol.

• Increased levels of which decrease risk of CHD.

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7.Coherence

• A causal relationship is more likely if it does not conflict with current knowledge about natural history and biology of disease.

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8.Experimental(Reversibility)

• Causality is supported if removal of the exposure leads to a reduction in the risk of the outcome.

• Provides very strong evidence in favour of causal relationship.

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9.Analogy

• If we already know that a particular exposure causes a specific outcome, then we are more likely to accept that a similar exposure is the cause for a similar outcome.

• when one class of causal agents is known to have produced an effect, it can easily be accepted that another agent of that class produces a similar effect.

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• Human papilloma virus causes Cervical cancer.

• Other DNA tumour viruses can induce cancers in humans, and species-specific papillomaviruses can induce cancers in animals.