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2
What is epidemiology?
3
Historical developments in the
understanding of disease etiology
“for now, I will stretch out mine hand, that I may smite thee
and thy people with pestilence”
4
Historical developments in the
understanding of disease etiology
Rational thinking about disease causation started in 400
BCE with Hippocrates in the Epidemics
Related symptoms of different illnesses to seasons and
geography
Focused on illnesses and sick persons as unique
events
5
Historical developments in the
understanding of disease etiology
1546: Fracastoro in “On contagion, contagious diseases
and their treatment”
Seminaria act on the humors of the body to create
disease
Three modes of transmission: person to person,
fomites, airborne
6
Historical developments in the
understanding of disease etiology
1600s
Thomas Sydenham, “the English Hippocrates”
“All diseases then ought to be reduced to certain and determinate
kinds, with the same exactness as we see it done by botanic
writers in their treatises of plants”
Viewed diseases as distinct entities and began to hypothesize
about causes
William Petty and John Graunt
First to use numerical data to describe patterns of mortality
Proposed the establishment of a central government agency to
collect data on vital information (Petty)
Published Observations on the bills of mortality (Graunt)
Analyzed records on causes of death from each parish
7
Historical developments in the
understanding of disease etiology
1700s
Giovanni Morgagni (“clinicopathologic correlation”)
Associated certain signs and symptoms with specific
pathologic changes in tissues and organs
Spurred search for specific as opposed to general
causes of diseases
8
Historical developments in the
understanding of disease etiology
1800s
1831
Civil registration of vital status established in England
1838
England’s General Register Office established and headed by William
Farr recorded all births and deaths; Farr developed disease
classification system
Zymotic (epidemic, endemic, contagious)
Constitutional (gout, dropsy, cancer)
Local (diseases of 8 organ systems)
Developmental (diseases of childhood, old age, women, nutrition)
Violent (accidents, battle deaths, homicides, suicides, executions, etc)
9
Historical developments in the
understanding of disease etiology
“Diseases which are communicated from person to person
are caused by some material which passes from the sick to
the healthy.”
John Snow (1813-1858)
10
Historical developments in the
understanding of disease etiology
1876: Koch reproducibly transmits anthrax to mice using
the blood of infected cows
Same rod-like material recovered from cows and mice
Infection transmittable from mouse to mouse
Koch’s postulates
Proof that a particular microorganism is the
cause of a particular infectious disease
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Henle-Koch postulates
12
Nelson, Williams, Graham. Infectious Disease Epidemiology Theory and Practice. Aspen Publishers, 2001 13
Three questions in causal inference
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1. The methodological question
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Association vs. Causation
Association is an identifiable relation between an exposure and a
disease
EXAMPLES
16
Association vs causation
Therefore if association is present we have to determine if exposure is
truly a cause of disease
EXAMPLES
17
So how do we determine if something
is causal?
18
When is an association causal?
Theory
Hypothesis
Interpretation of
results 19
When is an association causal?
Hypothesis
Interpretation of
results 20
When is an association causal?
Interpretation of
results 21
When is an association causal?
Interpretation of
results 22
When is an association causal?
Interpretation of
results 23
When is an association causal?
Induction
Deduction
25
Confirmation vs. falsification
Confirmation
If A, then B, C, D
B, C, D, therefore A
Falsification
If A, then B, C, D
NOT B, C, D, therefore NOT A
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Observation
27
Experiment
28
Advantages of observational vs.
experimental studies
OBSERVATION EXPERIMENT
29
Advantages of observational vs.
experimental studies
OBSERVATION
Cheaper
MAYBE
Faster to organize and conduct
30
Advantages of observational vs.
experimental studies
EXPERIMENT
31
A few well known causes of disease
Smoking
High cholesterol
M. tuberculosis
S. viridans
Head injury
Poverty [?]
32
A few well known causes of disease
Smoking Lung Cancer
High cholesterol Cardiovascular Disease
M. tuberculosis Tuberculosis
S. viridans Endocarditis
Head injury Subarachnoid hemorrhage
? Poverty All-cause mortality
33
2. The ontological question
34
Criteria for Causal Inference
(Bradford Hill 1965)
Temporality
Strength of association
Biological plausibility
Dose-response
Replication of findings
Consideration of alternate explanations
Cessation of exposure
Coherence with established facts
Specificity of association
35
Temporality
36
Strength of association
37
Strength of association
CAVEAT
Environmental associations with very low relative risks
38
Biologic plausibility
39
Biologic plausibility
CAVEAT
High oxygen concentration causing neonatal retrolental
fibroplasia
40
Dose-response relationship
41
Smith et al. 1994
(per 10,000
Age-adjusted
Mortality Rate
person-years)
0
10
20
30
40
50
60
70
80
90
<7
7, ,5
50 00
0-
10 9,
,0 99
00 9
-1
12 2,
,5 49
00 9
-1
15 4,
,0 99
00 9
-1
17 7,
,5 49
00 9
-1
20 9,
,0 99
00 9
-2
22 2,
,5 49
00 9
-2
25 4,
$US 1980
,0 99
00 9
-2
27 7,
,5 49
00 9
-2
30 9,
,0 99
00 9
-3
2,
49
9
>3
2,
49
9
Relation between income and mortality
42
Dose-response relationship
CAVEAT
Thresholds, i.e., no disease past a certain level of
exposure
43
Replication of findings
44
Replication of findings
CAVEAT
Heterogeneity of effect in different countries
45
Consideration of alternate explanations
46
Consideration of alternate explanations
CAVEAT
Alternate explanations limited by understanding of biology
and sophistication of analysis
47
Cessation of exposure
48
Cessation of exposure
CAVEAT
Pathogenic process already started; removal of cause
does not reduce disease risk
49
Coherence with established “facts”
50
Coherence with established “facts”
CAVEAT
Data may not be available yet to directly support proposed mechanism
Science must be prepared to reinterpret existing understanding of
disease process in the face of new evidence
51
Specificity of the association
52
Specificity of the association
CAVEAT
Many exposures are linked to multiple diseases
53
Overall caveats to “criteria”
54
Therefore, causal inference…
55
What is a cause? (Rothman)
56
Sufficient and component causes
U T
A B X B
Component causes
U T
A B X B
Component causes
U T
A B X B
U T
A B X B
60
For example: Tuberculosis
M. tuberculosis
Poor Immuno- M. tuberculosis
nutrition suppression
Potato chips
Y
W
No exercise
62
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise
A
63
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise
A
NO EFFECT
64
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise
A
C
Genes
65
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise High
A
cholesterol
C
T
Genes
66
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise High
A
cholesterol
C
T
Genes
NO
EFFECT
67
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise High
A
cholesterol
C
T
Genes
X B
Smoking
Stress 68
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise High
A
cholesterol
C
T
Genes
X B
Smoking
Stress
69
Limitations of sufficient cause model
70
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise High
A
cholesterol
C
T
Genes
X B
Smoking
Stress71
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise High
A
cholesterol
C
T
Genes
X B
Smoking
Stress 72
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise High
A
cholesterol
C
T
Genes
X B
Smoking
Stress 73
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise High
A
cholesterol
C
T
Genes
X B
Smoking
Stress 74
“Causing” a myocardial infarction
Potato chips
Y
W Obesity
No exercise High
A
cholesterol
C
T
Genes
X B
Smoking
Stress 75
Tuberculosis infection
76
http://www.who.int/mediacentre/factsheets/fs104/en/index.html
Tuberculosis infection
http://www.who.int/mediacentre/factsheets/fs104/en/index.html
77
Vitamin D deficiency and TB
Nnoaham and Clarke. Int J Epidemiol. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. 2008; 37: 113-119
78
Vitamin D deficiency and TB
Vitamin Risk of
D developing
tuberculosis
79
Nnoaham and Clarke. Int J Epidemiol. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. 2008; 37: 113-119
Vitamin D deficiency and TB
80
Nnoaham and Clarke. Int J Epidemiol. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. 2008; 37: 113-119
Vitamin D deficiency and TB
81
Counterfactual thinking
Observed
Sick
Healthy
82
Counterfactual thinking
Observed
Sick
Sick
83
The counterfactual universe
84
The counterfactual universe
D No D
85
The counterfactual universe
D No D
86
The counterfactual universe
D No D D No D
87
The real universe
88
The real universe
D No D
89
The real universe
E No E
D No D
90
The real universe
D No D
91
3. Ethics and the public health balance
92
Coda
93