Epidemiology of disease causation

1. DISEASE CAUSATION
DR KHEM R SHARMA
SPH&CM, BPKIHS

2. Objectives
• Understand differences between association and causation
• Causal inference
• Characteristics of a cause for disease
• Factors affecting causation
• Explain basic theories of disease causation
• Postulates of disease causation
• Understand the applicability of causation criteria as applied to
epidemiological studies

3. Disease
• Dis-ease or ill health
• Disease is usually considered the opposite of health, a
deviation from the normal function.
• Disturbance in equilibrium between man and his total
environment
• An understanding of the cause of the disease is the key to
finding remedies for the cure of diseases.

4. What is a cause?
• a person or thing that gives rise to an action,
phenomenon, or a condition to bring about a result.
• Cause is that which produces an effect, result or
consequences
• WHAT CAUSES DISEASES????
• Cause can be considered as the precursor of disease and
health conditions in any population

5. What is a cause?...
• Descriptive studies help in the identification of the
disease problem in the community; and by relating
disease to host, agent and environmental factors, it
suggests an aetiological hypothesis.
• Analytical/experimental studies test the hypotheses
derived from descriptive studies and confirm/refute the
observed association between suspected causes and
disease.

6. What is a cause?...
• However the presence of association does not necessarily
imply that there is a causal relationship between the two
factors
(e.g.: There is an association between the rooster crowing at dawn
and the rising sun; This does not mean that rooster causes the sun
to rise.
• Causal Inference: term used for the process of
determining whether observed association are likely to
be causal for establishing disease.

7. Epidemiological two step process
for causal inferences
I. A valid association exists only when Bias, Confounding
and Random errors are excluded
• Bias: Systematic error in selection/data collection
(Diseased people in highly polluted areas participate
more in studies than those in non polluted areas)
• Confounding: Distortion in results due to comparison of
dissimilar groups (Air pollution & mortality/Cig smoking )
• Random error: chance

8. Epidemiological two step process
for causal inferences…
II. When these have been excluded, epidemiologists
believe the association is real and proceed to the
second step for causal inference
• Assess whether the exposure has actually caused the
outcome

9. Characteristics of a cause
• 3 Attributes: Association,Time order and Direction
1) Association: The effect occurs together with the cause
(Statistical dependence)
2) Time order : Cause must precede the effect
3) Direction: Asymmetrical relationship between cause
and effect (eg: prenatal cig smoke exposure and lbw)
• Includes host and environmental Factors

10. Factors affecting Disease causation
• Predisposing: create a state of susceptibility (eg age/sex)
• Enabling: Assist in the development/recovery of disease
(eg: ses, housing)
• Precipitating: Associated with immediate exposure to
disease agent or onset of disease (eg: close contact with
tb, drinking contaminated water)

11. Factors for Disease causation…
• Reinforcing: Aggravate an already existing disease
(malnutrition, repeated exposure)
• Risk factors: Conditions/quality or attributes , the presence
of which increases the chances of developing or being
adversely affected by a disease.
• A risk factor does not cause a disease but increases the
probability that the exposed person gets the disease easily.

12. • i.Theories of the pre-modern era
• ii. Germ theory of disease
• iii. Biomedical model
• iv. Epidemiological triad
• v.Theory of multifactorial causation
• vi. Web of Causation
Theories of disease causation:

13. i)Theories of the pre-modern era:
• These theories were in play before the existence of
microorganisms was established, till the end of the 18th
century.
a) The demonic theory: Disease is a result of being
possessed by demons, or evil spirits.
-Hence the sick person was subjected to sorcery to rid
the body of the evil occupant.

14. i)Theories of the pre-modern era…
b) The punitive theory: Disease occurs as a punishment for
any bad deed done, as an outcome of the outrage of Gods.
- Hence the diseased individual is to appease the deity to
rid himself of the disease.
c) The miasmatic theory: It is the notion of bad air.
Breathing in certain areas was proposed to cause disease,
such as air around swamps, marshes and air at night times
was thought to cause an array of diseases.
d) Contagion theory: Hippocrates believed TB
(Consumption) is contagious

15. i)Theories of the pre-modern era…
e) Theory of four humors: It proposes that the body is a
constituent of four humors; blood, phlegm, yellow bile &
black bile and any imbalance results in disease.
-Bloodletting was considered the most common method
of treating disease.
• The Ayurveda believes that the imbalance of the three
Doshas (tridosha) is the reason behind disease causation.
• Chinese medicine considers a discrepancy between the
male (yang) and female (yin) principle results in disease

16. ii. Germ theory of disease
• The demonstration of bacterial presence in the air by Louis
Pasteur and the fact that anthrax is caused by bacteria
brought about a dramatic shift in the understanding of
disease causation.
• Focus shifted from empirical causes such as bad air and
wrath of God to scientifically plausible causes like the
presence of specific microorganisms.

17. ii. Germ theory of disease…
• The germ theory implies the causal effect is one to one -
a single microorganism is the culprit behind a specific
disease. (MTB causes tuberculosis.)
• Not always true, as many diseases cannot be explained by
this one to one causal relation which in reality is an
interaction between various contributory factors.

18. iii. Biomedical Model
• It envisions the healthy human body as an efficiently
functioning machinery, and any resulting aberration as
malfunction of the component organs.
(Hypothyroidism- improper functioning of thyroid gland.)
• This theory overlooks the complex and summative role of
psychological and social attributes as the human body
seldom functions independently of its surrounding
environment.

19. iv. Epidemiological triad
• Disease is an outcome of imbalance of interactions between
three essential components, Host, Agent, and Environment.
-Disease is caused when a susceptible host is exposed to the
causative agent in a compatible environment.
• It’s a broader concept and overcomes the limitations of germ
theory.
• Intercepting any of the three links provides a means of
halting the disease process, thereby highlighting areas to
focus preventive efforts.
• Tetrad:Time element added

20. v. Multifactorial causation
• Pettenkofer proposed that disease is a result of many
factors as opposed to germ theory where the idea of a
single cause was used.
• Improvements in public health and medicine brought
about a decline in communicable diseases.
• But other non-communicable ailments were on a rise
which could not be explained based on the germ theory
of disease.

21. v. Multifactorial causation…
• Hence single cause was deemed to be oversimplified etiology
of a disease where social, cultural, genetic and economic
factors were overlooked.
• In addition, having multiple causes for a disease meant
numerous methods of preventing that disease.
• However, it was essential to prioritize the sequence of
modification of the causal factors to tackle disease causation.

22. vi. Web of causation
• Proposed by MacMahon, Pugh, and Ipsen (1960),
• Argued that multiple factors causing a disease cannot be
explained using a linear causal relation as there are
complex precursors to each causal component in the
chain that have their respective complex interactions that
overlap each other.
• They gave a metaphorical appearance of a complicated
web of interactions rather than a linear causal relation.

23. vi.Web of causation…
• This web of causation gives each component equal
prominence in recognizing determinants and helps in
planning interventions.

24. Rothman’s Component Causes and
Causal Pies Model
• Proposes that the causation of disease is by a collection
of factors, which are represented by a pie
• Model classifies the causal factors into Sufficient and
Necessary causal factors.
• Sufficient cause: is a set of minimum conditions, events,
or factors that are required to produce a given outcome.
These factors that form the sufficient cause are called
component causes. A disease can have more than one
sufficient cause.

25. Rothman’s Component Causes…
• Necessary cause: causal factor whose presence is
imperative for the emergence of the effect.
• If the disease cannot occur without the factor being
present then the cause is termed as “Necessary”.
• A component that appears in every pie or pathway is a
necessary cause.
• The disease can be controlled by removing one
component from the pies or removing the factor that is
common to all pies.

26. Conceptual scheme for causes of a
hypothetical disease

27. Rothman’s Component Causes…
• Eg: Mycobacterium Tuberculosis bacteria is necessary to
cause tuberculosis but cannot cause the disease in isolation,
i.e. is not sufficient to cause the disease.
• A host of other factors are required such as impaired nutrition
or immunity which can be deemed sufficient cause.
• a necessary cause is a condition without which the effect
cannot occur, and a sufficient cause is a condition with which
the effect must occur

28. Postulates of Disease Causation
• Postulates explaining the process of disease causation have
been given by Koch in 1877 and Hill in 1965.
• These postulates helped the germ theory of disease gain
popularity over other theories in the 1800s.
• Certain sets of criteria needs to be met before a particular
infectious disease agent can qualify as a cause of disease.
1) The microorganism must be found in abundance in the
diseased subject, but not in healthy subjects.

29. Postulates of Disease Causation…
2) The causal microorganism should be isolated from the
diseased subject and be grown in pure culture.
3) The cultured microorganism should cause disease when
introduced into a healthy organism.
4) The microorganism must then be re-isolated from the
inoculated, diseased experimental host subjects and
cultured and identified as the original causative agent.
• However, Koch’s postulates can’t be applied in all
scenarios. (asymptomatic carriers of diseases such as
typhoid/cholera, where two or more microorganisms
cause disease)

30. Hills Postulates
• Austin Bradford Hill (1965) proposed criteria for assessing
whether associations are causal.
• Each criterion contributes to the strength of the causal
relationship between a factor and disease.
1) Strength: Stronger the association between the factor
and the disease, more likely it is the causative agent.
2) Consistency: Consistent observations seen in different
scenarios and across different populations strengthens
the likelihood of the causal effect.

31. Hills criteria for assessing causation

32. Hills criteria…
3) Specificity: More specific an association between a
factor and an effect, greater the probability of the
effect.
4) Temporality: Exposure to the cause should precede the
effect.
5) Biological gradient: Greater exposure should cause a
greater incidence of disease. The strength of causality is
reinforced when lesser exposure decreases incidence.

33. Hills criteria…
6) Plausibility: A valid scientific explanation of the causal
relationship is essential, although it might be limited by
the existing knowledge.
7) Coherence: The cause and effect interpretation of
assimilated information should not seriously conflict
with generally known facts of the natural history of the
disease.

34. Hills criteria…
8) Experiment: Investigator initiated intervention that
modifies the exposure through prevention, treatment or
removal should result in less disease (Eg; smoking
cessation program result in lower lung cancer rates)
9) Analogy: Has a similar relationship been observed with
another exposure (eg With knowledge of the effects of
drug thalidomide and the disease rubella on the fetus
during pregnancy, we should be ready to accept that
another drug/virus could produce similar effects)

35. Thank you