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Definitions, History and
Infections
September 30 2004
Epidemiology 511
Autumn 2004
W.A. Kukull
Forecasting the future
• “On the basis of what has happened in the last
30 years…the most likely forecast about the
future of infectious disease is that it will be very
dull…outbreaks of infections from exotic
animals…will doubtless occur in the future but
they will presumably be safely contained”.
Nobel Laureate, Sir McFarland Burnet, 1972
Definitions of Epidemiology
• The study of the distribution and determinants
of health and diseases, morbidity, injuries,
disability, and mortality in populations.
• The study of the distribution and determinants of
health-related states or events in specified
populations and the application of this study to
control of health problems [Gordis]
Assumptions
• “Disease” does not occur at random
• “Disease” has causal and preventive
factors that can be identified through
systematic study of populations (persons,
places, times)
– Factors may be genetic or environmental
Prevention of disease
• Primary Prevention: prevent the disease
from occurring in a well person
• Secondary Prevention: early detection of
disease to change the natural history
• Tertiary Prevention: reducing disease
disability after clinical treatment
Determinants?
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Infectious agents
Carcinogens, chemicals
Behaviors/Habits/Lifestyle
Occupational exposures
Aging
Genetic constitution
Socio-political factors
Distribution
• Who is affected?
– what are their characteristics?
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Where are the affected persons?
When are persons affected ?
How many persons are affected?
Is the distribution changing; how?
Population ?
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Geographic
Organization Membership
Employment
School
High risk subgroups vs entire Population
Can we enumerate (count) all members?
West Nile Virus numbers
Science,297:1988,(2002) and CDC
6000
5005
5000
4000
Cases
Deaths
3000
2000
1460
1000
62 7
21 2
66 9
66
1999
2000
2001
2002
95
0
2003(Sep)
U.S. counties reporting human WNV disease cases,
1999 (N = 6 counties)
U.S. counties reporting human WNV disease cases,
2000 (N = 10 counties)
Incidence of WNME in Humans, by County, United States, 2002*
*Reported as of 01/21/2003
U.S. Counties Reporting Human WNV Disease Cases, 2002*
3,862 cases
708 counties
39 states & D.C.
WNV Human Disease Cases, Demographics &
Mortality, United States, 1999-2002*
1999-2001
(All)
1999-2001
(Fatal)
2002
(All)*
2002
(Fatal)*
149
18
3,862
248
WN ME
95%
100%
70%
98%
WN Fever
5%
22%
2%
n
Clinical category
Unknown
8%
Age (yr)
median
66
75
55
78
5 – 90
44 – 90
0 – 99
24 – 99
Males
59%
44%
53%
64%
Mortality
12%
range
* Reported as of 01/21/2003
6%**
** 9% of WN ME cases
Human WNV Disease Incidence, by Age Group
and Clinical Category, United States, 2002*
WNME
WNF
Incidence per 100,000**
5
4
3
2
1
0
0-9
-19
0
1
-29
0
2
-39
0
3
-49
0
4
-59
0
5
-69
0
6
-79
0
7
-89
0
8
-99
0
9
Age group (yr)
* Reported as of 01/21/2003
* *Entire US population
John Snow and Cholera (1)
• Snow: vital statistics for 1832 epidemic
– higher cholera death rates in areas served by
Southwark (11 per 1000 vs. 2 per 1000)
• Epidemic of 1848-49: observed similar
death rates in areas served by
Southwark, and Lambeth water
companies
– all draw water from same place on Thames
Cholera (2)
• William Farr, 1848-49 epidemic: low
altitude associated with higher death rate:
Miasma or cloud transmitted disease
• Snow, 1853: Lambeth water source now
moved upstream => Cleaner water
– lower death rates in Lambeth service areas:
ECOLOGIC design
Materies Morbi: Snow’s hypothesis
• Living transmissible agents
– small amounts can enter host and multiply
– transmitted by contact with patient or fomites
– agent can remain dormant, like a seed
– can be transmitted great distances while
dormant, e.g. by water supply
– body portal of entry and exit
Cholera (3)
• Snow, 1854 Epidemic, Field epidemiology
• 3 water companies served households in
the area in a “random” distribution
– Determined # of deaths in households served
by each water company.
– S&V= 71 per 10,000; Lambeth 5 per 10,000
– RETROSPECTIVE COHORT Design
Cholera (4)
• 1854 The Broad Street Pump
– remove the handle: public policy change
• Did cholera cases use Pump?
• Did Non-Cases use pump?
– Brewery workers
– Workhouse inmates
– Other pumps
• CASE-CONTROL design
Important generalizations: Snow
and Cholera
• Careful observation of vital statistics
– numerators: numbers of events (deaths)
– denominators: total persons at risk
– calculation of rates
• Etiology: causal hypothesis
• Exposure ascertainment: field
epidemiology
• Public policy change
Koch’s postulates
• The agent must be recovered from all
individuals with disease
• Recovered agent must grow in culture
• Cultured organism must cause disease in
susceptible animal
• Agent must be recovered from diseased
experimental animal
Revised causal criteria
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Temporal relationship
Strength of Association (RR)
Biologic plausibility
Risk factor changes occurrence or
severity of disease
• Consistency : association is replicated by
other investigators
• Dose-response
Endemic or Epidemic
Cases per 1000
population/time
Expected Level
Time
The Epidemiologic Triad of a
Disease
Host
Vector
Agent
Environment
Influenza A epidemic excess
mortality in U.S.
• A/Japan/57 (H2N2)
1957-58
69,800
• A/Japan/62 (H2N2)
1963
43,200
• A/HK/68 (H3N2)
1968-69 33,800
• A/Eng/72 (H3N2)
1972-73 24,800
Influenza
• Surface Antigens: Hemagglutinin;
Neuraminidase
• Antigenic Shift: MAJOR changes in H, N
– May cause pandemics
• Antigenic Drift: MINOR changes in H, N
– RNA mutation
– Change in antigenicity but not serotype
Antigenic Shift serotypes
Pandemic
Serotype
1889
H2N?
1899
H3N8
1918
H1N1
1957
H2N2
1968
H3N2
1977
H1N1
Antigenic Drift
• A/Sidney/5/97
H3N2
– Many variants of H3N2 since 1968
• A/New Caledonia/20/99
H1N1
– Over 66% of H1N1 strains isolated in 19992000 were antigenically different from
previous
– Included in 2000-01 vaccine
Natural Hx of infection
Observable
illness
Exposure
Treatment
Infection
Incubation
period
Pre Clinical
period
Clinical Period
Outcome
Outbreak Investigation (1)
Define the epidemic
• Define the numerator (cases)
– Clinical features
– Culture, serology
– other causes
• Define denominator
– population at risk; susceptibles
• Calculate Attack Rates
Outbreak investigation (2)
Distribution of cases
• Time-Place interactions
• Characteristics of persons; risk subgroups
• Combinations of relevant variables
– cross-tabulation of attack rates
• Develop hypotheses
– existing knowledge of disease (if any)
– analogy to known diseases
Outbreak investigation (3)
• Test Hypotheses
– Calculate ratios of Attack rates
– Further analyze existing data
– Collect additional data
• Recommend Control Measures
– Control present outbreak
– Prevent future outbreaks
Critical Questions
• When did exposure take place?
• When did disease begin?
• What was disease incubation period?
• If we know any two answers, we can
calculate the answer to the other.
Herd Immunity
• Number of susceptibles
• Does infection induce persistent
immunity?
• Is agent restricted to single host--humans?
• Is transmission relatively direct?
• High proportion immune protects others
– Vaccine programs
– lack of susceptibles limits spread
Attack Rates
Attack Rate = Number of people at risk who develop illness
Total number of people at risk
Secondary Attack Rate = Number of contacts developing disease
within one incubation period
Measure of
the disease’s tendency to spread
in a population
Total number of susceptible
contacts
Distribution of SARS cases by days since exposure
Average days estimates incubation period
Estimated Incubation Period
Age-specific case fatality rate
Time before hospital
admission after symptoms
had occurred
Secondary Attack Cases
(SSE= super spreading event)
Attack Rates
(% who became ill)
ATE
Did Not Eat
67.8%
44.0%
Iced Double- 77.9%
tall vanilla
Latte
37.0%
Croissants
Which one is the cause of illness?
Attack Rates (2)
Drank
DTV Latte
Did not drink
DTV Latte
Ate
Croissants
75.6%
26.4%
Did NOT
Eat
Croissants
80.0%
25.0%
Emerging Infections:
newly appeared or has existed but is rapidly increasing in
incidence or geographical range
• Promoters of pre-existing pathogens
– Ecologic changes; shifts in human
populations
– International travel/commerce
– changing industry and technology
– microbial adaptation; lapses in public health
system
Bio-weapons
(MMWR; 2000; 49:1-14)
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Easy person-to person transmission
High mortality or case fatality
Public panic; social disruption
Require special public health action or
preparedness
Summary
Important concepts
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Epidemic vs endemic
Host response and incubation period
Prevention and herd immunity
Epidemic curves/ Outbreaks
Attack and Secondary Attack rate
Case Fatality rate