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02
Disease Causation
Dr. Nicanor Biso

o Confounding
WHAT IS A CAUSE?  Can result to the outcome
 Merriam-Webster Dictionary  refers to the mixing of the effects of the exposure on
o Something that brings about a result especially a person or the disease with that of a third factor, which may lead
thing that is the agent of bringing something about. to an overestimate or underestimate of the true
 KJ Rothman association between exposure and disease, and can
o An event, condition, or characteristic without which the even change the direction of the observed effect
disease would not have occurred.  the confounder must be associated with both the
 M. Susser exposure and the disease, and in itself a risk factor of
o Something that makes a difference the disease

 Why is knowledge on cause important?

o Formulation of intervention measures
o Formulation of preventive and control measures

PROBLEM: HOW DO WE KNOW WHEN SOMETHING MAKES

A DIFFERENCE? * people who exercise heavily tend to be younger, as a group, than those
who do not exercise
* independent of exercise, younger people have a lower risk of MI than
 Association is not equal to causation.
older people
 Consider the following statement
o If the rooster crows at the break of dawn, then the rooster b. causal association – can be indirectly and directly
caused the sun to rise. CAUSAL ASSOCIATION
 Association: identifiable relationship between exposure and
disease (co-existence) FD
 an association between categories of events or characteristics in
o Outcome depends on the exposure
which an alteration in frequency or quality of one category is
 Causation: presence of mechanism that leads from exposure to followed by change in the other
disease (cause-effect) FD
 p must be<0.05
OVERVIEW
1. DIRECT CAUSAL
 a factor causes a disease with no other factor intervening
 Types of association:  causal factoroutcome
o Causal
 ex. Tubercle bacillustuberculosis
 Direct
2. INDIRECT CAUSAL
 Indirect
o Non-causal  A third variable, intervening variable, occupies an intermediate
stage between the cause and the effect
 Types of causal factors
o Sufficient  ADB
o Necessary  A is causally related to D (A, being the cause and D, being the
 Factors in causation effect).
o Predisposing factors  D is related to B (D, the cause, B, the effect).
o Precipitating factors  There will be a causal relationship between A and B although,
o Enabling factors the association is said to be indirect. D is considered as the
o Reinforcing factors intermediate variable
 Ecologic Models in Disease Causation  Ex. relationship of cigarette smoke to chronic bronchitis.
 A.) Breathing polluted air by cigarette and ther smoke
D.) Damage to respiratory epithelium and increases susceptibility
DEFINITIONS to infection
B.) Results to chronic bronchitis
CAUSE OF DISEASE
NON-CAUSAL OR SECONDARY STATISTICAL
ASSOCIATION
 Is an event, condition, characteristic or a combination of these
factors which plays an important role in producing the health
outcome  usually result from association of both categories of events with
a third category
ASSOCIATION & CAUSATION

 Two categories of events, e.g. factors and disease may be:

1. NOT STATISTICALLY ASSOCIATED (independent)
2. STATISTICALLY ASSOCIATED
a. no causal association
- observed association could be due to bias, confounders,
and chance
o Chance
 Affected by subject variability
 if RR = 1 or OR = 1, there is no relationship between
exposure and disease
 p-value is a guide to the likelihood that chance is an
explanation of the findings
 if p-value > 0.05, chance cannot be excluded as a
likely explanation for the findings (p < 0.05 makes the relationship
statistically significant)
o Bias
 Selection bias- refers to any error that arises on the
process of identifying and choosing the study
population
 Information bias- from systematic differences in the
way data exposure or outcome are obtained from the
various study groups (ex. recall bias, interview bias)
Ex. A. Obesity; B. Hypertenstion; C. Diabetes
STATISTICAL ASSOCIATION
 statistical dependence between 2 variables
 ex. the degree to which the disease rate in the exposed group is
either higher or lower than the rate in the unexposed group.
NECESSARY CAUSE
 a cause which in its absence, a disease cannot develop
 a cause that must be present for the disease to occur
o Ex: PTB – without Mycobacterium tubercle, there will be no
PTB, in short – NATATANGI/NAG - IISA
SUFFICIENT CAUSE
 a cause which inevitably produces or initiates a disease
 the disease always develops in the presence of the factor but is
not the sole factor or cause
 set of cause
Disease Causation
o Ex: PTB has many components for the disease to occur like
increased crowding index, malnutrition, poverty, in short –
MARAMING COMPONENTS
*from the above illustration, we can say that Factor A is a NECESSARY
cause, because it is present in all cases, thus it is needed for the
disease to develop. All other factors are SUFFICIENT causes,
because these help in the process of disease development
ITO TALAGANG PWEDE NIYO ISKIP. Pero maganda kasi ang
discussion sa part na ito ang difference between Necessary
and Sufficient Cause 
NECESSARY AND SUFFICIENT CAUSE
 this situation rarely, if ever, occurs since other factors are usually
involved.
 A one-to-one relationship of exposure to disease which is a
consequence of a necessary and sufficient relationship
NECESSARY BUT NOT SUFFICIENT CAUSE
 each factor as being necessary but not in itself sufficient to cause
disease
 multiple factors are required, often in a specific temporal
sequence
o e.g. initiation and promotion in carcinogenesis
o presence of tubercle bacilli (a necessary factor) but may not
be sufficient to produce the disease in every infected
individual
SUFFICIENT BUT NOT NECESSARY CAUSE
 the factor can produce the disease but so can other factors that
are acting alone
 the criteria of sufficient is rarely met by a single factor
o e.g. benzene or radiation leads to leukemia
o but not everyone who has experienced radiation or benzene
exposure has developed cancer; although both factors are
not needed, other co-factors are probably necessary
NEITHER SUFFICIENT NOR NECESSARY CAUSE
 more complex model which probably most accurately
represents the causal relationships that operate in most
chronic diseases
FACTORS IN CAUSATION
1. Predisposing Factors
o age, sex, previous illness
o may create a state of susceptibility to a disease agent
o e.g. extremes of age prone to infection, breast cancer in
women, respiratory tract infection that may lead to acute otitis
media
2. Enabling Factors
o May either be good or bad
o low income, poor nutrition, bad housing, inadequate medical
care
 factors that may favour the development of disease
o conversely, circumstances that assist in recovery of illness or
in the maintenance of good health could also be called
enabling factor.
o eg. Economic status: low income, less priority on health,
Health facilities: in rural areas, increased maternal mortality
rate, Poor nutrition: increased lung infection, Crowded –
increased disease transmission
3. Precipitating Factors
o Exposure to specific disease agent, noxious agent may be
associated with the onset of a disease or state.
4. Reinforcing Factors
o Repeated exposure and unduly hard work that may
aggravate an established disease state
o Eg. Prostitute – AIDS, Radiologist – cancer
Note:
 Risk Factor
o commonly used to describe factor that are positively
associated with risk of development of a disease but are not
sufficient to cause the disease. (e.g. Cancer – cigarette
cessation, DM – decrease sugar in diet, Pedia –
immunization)
ECOLOGIC MODELS IN DISEASE CAUSATION
1. EPIDEMIOLOGICAL TRIANGLE
o changes in one of the elements of the triangle can influence
the occurrence of disease by increasing or decreasing a
person’s risk for disease.
o Change in equilibrium: disease will occur
2. THE LEVER
o disease results from an imbalance between disease, agent,
and host
o When the environment favors the host results in
immunocompetency.
o When the environment favors the agent, disease will occur.
o Important: BALANCE between the host and the agent.
3. WEB OF CAUSATION
o there is no single cause
o causes of disease are interacting
o illustrates the interconnectedness of possible causes
o you can insert an intervention in any point to cure the illness
or disease
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Disease Causation

 not always possible and feasible.

2. NON-EXPERIMENTAL CHARACTERISTICS TO CONSIDER:
Temporal relation  Does the cause precede
the effect?
Plausibility  Is the association
consistent with other
knowledge? (mechanism
of action, evidence from
experimental animals)
 Lack of plausibility may
simply reflect lack of
medical knowledge
Consistency  Have similar results been
 Review other studies by shown in other studies?
4. THE WHEEL doing a meta-analysis  Different studies that offers
o sizes taken up by the different environments may change  RCT  Cohort Case- the same result
depending on their influence Control  Cross-sectional  Lack of consistence does
o centers more on host, with its genetic core  Ecologic study (a type of not mean that there is no
o Environmental factors such as biological, social, physical, all descriptive study design causal association
contribute for a disease to be produced which focuses on groups or  e.g. transfusions can cause
 Biological: infectious agents, reservoir of infection, vector aggregates of people) HIV infection but they do
that transmit the disease, plants and animals. not always do so; the virus
 Social: economic and political environment. must also be present
 Physical: heat, light, air and water  Methodological differences
in studies of exactly the
same phenomena can
provide different results
Strength  What is the strength of
 Strong associations are association between the
more likely to be causal cause and the effect?
than weak associations and
are less likely to be caused
by chance or bias
 Measured by relative risk
(RR) for cohort or odds
ratio (OR) for case-
control
GUIDELINES/CRITERIA FOR ASSESSING CAUSAL  Strong association has a
ASSOCIATION relative risk which is either
very high or very low (if
A.PROTOTYPE CRITERIA/GUIDELINES equal to 1, no causal
 HENLE- KOCH’S POSTULATES association)
1. The microorganism must be observed in every case of the  RR or OR > 2 indicates a
disease very strong association
2. It must be isolated and grown in pure culture (rare)
3. The pure culture must, when inoculated into a susceptible Dose-response relationship  Is increased exposure to
animal, reproduce the disease  A change in level of the the possible cause
4. The microorganism must be observed in, and recovered cause is associated with associated with increased
from, the experimentally diseased animal changes in frequency of effect?
Ex: Anthrax disease
B.STATISTICAL CONSIDERATIONS IN ASSESSING  The strength of association
CAUSATION should be stronger at
higher doses or levels of
ESTABLISHING THE CAUSE OF DISEASE exposure
 CAUSAL INFERENCE  e.g. More cigs/day 
o determining which observed association is causal or not higher lung ca mortality
o used for the process of determining whether observed ratio
associations are likely to be causal, the use of guidelines and Reversibility  Does the removal of a
making of judgments are involved.  Eg. 1 year no smoking  possible cause lead to a
o assessing the Relationship Between a Possible Cause and no more disease reduction of disease risk?
an Outcome Study Design  Is the evidence based on a
o Ex. Observed Association  The different study designs strong study design?
are graded accordingly,
Could it be due to selection or measurement bias? Experimental, Cohort,
 no Case-Control –problem with
Could it be due to confounding? recall bias, Cross-Sectional
 no – temporal association,
Could it be a result of chance? Descriptive
 probably not StudyEcologic Study –
Could it be causal? groups of people.
 Judging the Evidence  How many lines of evidence
Apply guidelines & make judgment lead to the conclusion?
 Meta – Analysis is a quantitative statistical analysis of several
EVIDENCE OF CAUSALITY separate but similar experiments or studies in order to test the
pooled data for statistical significance.
1. EXPERIMENTAL EVIDENCE

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