Irwin Aras, M.D., M.Epid., M.

MedEd
Community Medicine Dept.
FMUH
 Natural history of disease = progression of
disease in an individual over time.
 When considering a single cause, we look at 4
stages
 Susceptibility
 Sub-clinical
 Clinical
 Recovery, disability or death
Sometimes called “pure determinism”
1. The agent is present in every case of the
disease
2. It does not occur in any other disease as a
chance or nonpathogenic parasite (one
agent one disease)
3. It can be isolated and if exposed to healthy
subjects will cause the related disease
 “Cause” is not easily defined
 Definitions are metaphysical
 Rothman & Greenland’s (1998) definition:
 any event, act, or condition
 preceding disease
 without which disease would not have occurred
 or would have occurred at later time
A causal pathway may be direct or indirect

 In direct causation, A causes B without

intermediate effects

 In indirect causation, A causes B, but with

intermediate effects

In human biology, intermediate steps are virtually

always present in any causal process
Note: there is more than
one sufficient
mechanism for a given
ailment
 A necessary cause - a factor found in all
cases
 Contributing cause – a non-necessary
factor that is needed in some cases
 Sufficiency – combination of factors
that make disease inevitable 
completed “pie”
 The effect of a factor in a population
depends on prevalence of causal
complements;
 The effect of Mycobacterium exposure in a
fully immune population is nil (increases risk
by 0%)
 The effect of Mycobacterium exposure in a
fully susceptible population is 100%
 We cannot talk about cause in isolation.
 Necessary and sufficient – without the factor, disease never
develops
 With the factor, disease always develops (this situation rarely occurs)
 Necessary but not sufficient – the factor in and of itself is not
enough to cause disease
 Multiple factors are required, usually in a specific temporal sequence (such
as carcinogenesis)
 Sufficient but not necessary – the factor alone can cause disease,
but so can other factors in its absence
 Benzene or radiation can cause leukemia without the presence of the
other
 Neither sufficient nor necessary – the factor cannot cause
disease on its own, nor is it the only factor that can cause that
disease
 This is the probable model for chronic disease relationships
All may be necessary but rarely sufficient to cause a
particular disease or state;
 Predisposing – age, sex or previous illness may create a state of
susceptibility to a disease agent
 Enabling – low income, poor nutrition, bad housing or inadequate
medical care may favor the development of disease
▪ Conversely, circumstances that assist in recovery or in health maintenance
may be enabling
 Precipitating – exposure to a disease or noxious agent
 Reinforcing – repeated exposure or undue work or stress may
aggravate an established disease or state
 A causal complement is a factor or set of factors that
complete a sufficient causal mechanism (pie)
 e.g., Consider tuberculosis
 The agent (Mycobacteria sp.) is necessary
 “Susceptibility” is complementary

Mycobact

Susceptibi
lity
 Cause is the cumulative effects of
multiple factors acting together (“causal
interaction”).
 Causal factors almost never act alone
 Multi-causality requires a more
sophisticated view of “incubation”.
 Induction period = time between causal action and
disease initiation
 Latency period = time between disease initiation and
detection
 Empirical induction period = induction + latency
 Spectrum of illness –
most ailments have a
broad range
manifestations &
severities
 We often detect only
the tip of the iceberg
 e.g., dog bite injuries:
Upstream causes

Individual level
causes

Downstream
causes
 Person
 Place
 Time

I keep six honest serving men

(They taught me all I know);
Their names are what and why and when
And how and where and who.
(Kipling)
Example of a person variables: age and sex in relation to
recreational injuries (Fig 2.13, p. 50). Rates are per 1000 per year.
 Illustrative example: Regional Differences in Breast
Cancer Mortality (Table 2.14, p. 52)
 Fig. 2.14 (p. 52) shows large regional difference in
breast cancer rates
 Rate in U.S. = 20 per 100,000 in 1962
 Rate in Japan = 4 per 100,000 in 1962
 What is not shown: rates in Japanese-Americans women
increase with each generation
 Conclusion: environment plays large role in determine
breast cancer risk
 Table 2.5: Examples of
time variables
 Fig 2.15
1. Proceeding : Epidemiology Kept Simple, Chapter 2;
Causal Concepts.
2. Proceeding : Dona Schneider, Ph.D, MPH, FACE;
Showing Cause, Intriduction to Study Design;
Lecture 4.
3. Rothman, K. J : Epidemiology An Introduction; 2002.
4. Murti, B : Prinsip dan Metode Riset Epidemiologi;
Edisi ke-2; 2003.