Epidemiology- the definition
• Derived from the word ‘epidemic’
• Greek words meaning:
‘Epi’ upon ‘Demos’ people ‘logy’ the study of…
• The study of something that comes upon people,
usually that of disease or illness…
• Concerned with distribution and determinants of health
and disease, morbidity and mortality, injuries and
disabilities in human populations
• Determinants refer to factors or events that are capable
of bringing about a change in health
− Biological agents
− Chemical agents
− Physical agents
Classical vs. Clinical Epidemiology
• CLASSICAL: population-oriented
• Community origins of health problems
• Discovering risk factors that might be altered in
population to prevent or delay disease or death
• CLINICAL: use research designs and stats to study
patients in health care settings in order to improve
diagnosis and treatment of diseases
• Improve clinical decisions
Infectious vs. Chronic Epidemiology
• INFECTIOUS: acute, infectious, communicable
diseases
• Rely heavily on laboratory and microbiological
supports for confirmation
• CHRONIC: complex sampling and statistical methods
to looking at longevity of chronic illnesses, their cause
and prognosis
Etiology & Natural History of Disease
• If medical or public health does not intervene, disease
can cause havoc
• Public health & medical use stages, mechanisms, &
causes when and how to intervene
• Preventive (P.H.) or therapeutic (medical) is to alter
natural history of disease
Stages, Mechanisms & Causes of Diseases
Stages of Disease:
• Predisease stage- before pathology begins; any primary
prevention efforts
• Latent stage- disease process begun but asymptomatic;
secondary prevention such as screenings or drugs to
prevent more serious outcomes
• Symptomatic stage- disease manifestations; tertiary
prevention to slow or arrest progression of disease
Mechanisms & Causes of Disease
• Go back far as possible to look for societal causes of
disease
• Can be used for methods of prevention
• Biological mechanisms of the human body or of insect
adaptations
• Social and environmental causes can also exacerbate
disease, such as climate changes, etc.
Rebecca Stepan
Epidemiology
• Distribution- the frequency and patterns of disease and
health events within groups or populations. Descriptive
epidemiology is used to accomplish this
• Descriptive epidemiology: amount of disease within a
population by:
− Person- age, sex, race, occupation,
− Place- natural barriers, urban/rural
− Time- seasonal, cyclical, short/long term
• Also attempts to search for causes or factors that are
associated with increased risk or probability of diseasehere they are asking “how” and “why” is this disease
occurring- this is called Analytical Epidemiology
• Epidemiology deals with populations and NOT with
individual people
Morbidity & Mortality
• Morbidity- refers to illness or disease- sickness
• Mortality- refers to death; looks at causes of death and
ratios of death per so many thousand people
• Epidemic- occurrence of disease in clear excess of
normal expectancy
• Endemic- the usual level of a disease in a population or
region
• Pandemic- epidemics that affect several countries or
continents
Foundations of Epidemiology
• Interdisciplinary Approach
− Biostatistics
− Social & behavioral sciences
− Toxicology/pathology/virology/microbiology
− Clinical medicine
• Methods & Procedures
− Quantification of data is essential!
− Counting number of cases and their
distribution to demographic variables
Historical Background of Epidemiology
• Had its real beginnings with studies of great epidemic
diseases of all times
• Miasma Theory- belief that ‘bad odors’ caused disease!
Moral and religious sin caused disease!
• Contagion theory- ancient Roman physicians theorized
that some human diseases were caused by ‘pathogens’
that reproduced inside the human body
• Bubonic plague (Black Death)- infectious disease of
inflamed and swollen lymph nodes; came from infested
rats and fleas
• Cholera- intestinal diarrhea from contaminated water;
high fatality rate
• Smallpox- viral disease; very contagious- similar to
chickenpox but more deadly
• Smallpox- completely eradicated from the world in
Dec. 1979
• Later, chronic diseases, accidents, etc were studied via
epidemiological principals
Bubonic Plague- Black Death
• 60% fatality rate
• 20-40 million died in Europe in 5 year period!
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 1
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•
•
Bacteria not discovered until 1894!
Bubos- lymph nodes- red spots that turn black
Cholera
• Severe intestinal diarrhea from drinking contaminated
water
• ½ people die from bacterial disease
Hippocrates (400 BC)
• First to make correlations between environmental,
dietary, behavioral conditions
• Wrote “On Airs, Waters, and Places”- discussed his
theories that disease might be associated with the
physical environment and not by superstition or the
supernatural
Girolamo Fracastoro (1546)
• The first to develop a coherent germ theory- that living
organisms through direct or airborne contact were
responsible for infecting people with illness (microbial
theory of contagion)
• He recognized 3 modes of disease transmission- person
to person; air; personal objects – like common comb or
drinking cup
• Though accurate in his theory, it was not accepted for
another couple hundred years later!
Edward Jenner (1749- 1823)
• Experimented with inoculating people with cowpox
virus
• Cowpox vaccine was then used to immunize against
smallpox
• Discovered first technique of vaccination
• Demonstrated that person injected with fluid from
coxpox lesion was cross-protected against smallpox
Raw human sewage dumped into the Thames River
or cesspools, or just dumped out of windows onto
streets below- causing pollution or water supplies
Snow’s Epidemiological Investigation
• First suspected contamination of water at Broad
Street pump- 500 people in that neighborhood had
died within 10 day period
• Made a geographical map to chart deaths of
outbreak- who lived in proximity of pump and who
had taken their water from that pump
• Also tracked down people who did NOT have
cholera and where did they get their water from
• Convinced town officials to remove pump handle so
people couldn’t drink water- outbreak ended!!!
Three Epidemiological Models
1. Epidemiologic Triangle
• model for many years
• Three segments
− Host- degrees that person is able to adapt to
stressors
− Agent- bio, chem., physical
− Environment- influences probability of
contact between host and agent
• Implies that each segment must be analyzed and
understood in order to predict a disease
• if you remove anyone of them you get rid of the
problem (host on meds kills the agent, or elim the
environment such as don’t go to class if you are sick)
Dr. John Snow (1813- 1858)
• One of most famous epidemiologist of all time
• Was a British medical doctor surgeon (obstetrics
and anesthesiology)
• Huge cholera outbreak in summer of 1854 in Soho, a
London suburb
• Was convinced that disease was spread by
contaminated water- observed a mother washing
her baby’s poopy diapers at the town square pump
(baby had just died of cholera!)
Cholera
• Intestinal diarrhea disease that causes death within
hours after first symptoms of vomitting or diarrhea!
• Old theory of “Miasma” prevailed in that period of
time- breathing dirty air from the atmosphere
• In 20 year period, tens of thousands people died in
England
Agent – bugs, environ = living area (crowded, poor sanitation,
etc)
2.
Web of Causation
• Effect never depends on single isolated causes
• develop as a result of chains of causation
• each link is the result of a complex geneaolgy
London Cholera Outbreak
• People did not have running water and no septic
systems
• Communal pumps for drinking water, cooking and
washing
Rebecca Stepan
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 2
Example: pregnancy outcomes: if low income, homeless,
unplanned, drug use, poor diet  poorer outcome. As MD pt
education is key!
3.
The Wheel Model
• Consists of Hub (host/human) which has genetic
make up as its core
• Surrounding host is the environment
− Biological
− Social
− Physical
• Implies a need to identify multiple etiological factors
of disease without emphasizing the agent of disease
“E” Environmental Factors
• Air or water pollution
• Effects of poor or good sanitation
• Occupational exposures
• Repetitive strain injuries
• Outdoor exposures to vectors
“I”.mmunologic Factors
• Vaccinations
• Herd immunity- vaccine protects vaccinated person
from infection in addition to not spreading disease to
others
• Passive immunity from mother to child
• Immunodeficiency disorders
“N”.utritional Factors
• Importance of diet or lack of healthy diet
• High fat, sodium, cholesterol, etc related to CVD and
other chronic illnesses
• Problems with overweight and obesity issues
• Poverty and starvation; limited nutrients cause health
deficiencies; scurvy; ricketts, etc
“G”.enetic Factors
• Most difficult factor to change
• Genetic inheritance to protect against disease, or to
promote illness in the person or family
• Distribution of normal and abnormal genes in the
population
• Genetic mutations that lead to diseases, particularly
cancers
• Genetic drifts or shifts in viral changes in disease
outbreaks
“S”.ervices, Social, & Spiritual Factors
• Medical (or lack thereof) care services
• Social support systems of patients and providers
• Spiritual meaning and purpose of life in relation to
healing and therapy
• Religious practices to self-healing and healthier
lifestyles (Mormons & 7th Day Adventists)
Quick Quiz Assessment – from textbook!! Similar to final
exam questions!
Models: triangle, web, wheels, BEINGS!
•
•
The “B.E.I.N.G.S.” Model (textbook)
Many risk factors are responsible for why people do
or do not become sick
“B” biological & behavioral Factors
• Biological factors: (limited control over)
− age, weight, gender
• Behavioral factors: (controllable)
− sex practices, smoking, drugs/alcohol
Rebecca Stepan
1. Epidemiology is defined as study of factors that influence
health of populations. Application of epidemiologic findings in
populations to decisions in the care of individual patients is:
A. Chronic disease epidemiology
B. Infectious disease epidemiology
C. Clinical epidemiology
D. Descriptive epidemiology
2. For an infectious disease to occur, there must be interaction
between:
A. Behavioral & genetic factors
B. Agent and vector
C. Host and agent
D. Vector and environment
E. Vector and host
Answers:
1. C
2. C
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
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MEASURES OF MORBIDITY & MORTALITY- DISEASE
FREQUENCY MEASUREMENTS – CHAPTER 2
*NO CALCULATIONS ON THE EXAM.
Epidemiologic Measurements
• Clinical phenomena must be measured accurately to
develop and test hypotheses
• Measures that summarize what has happened in
populations
• Fundamental epidemiologic measure used is the
frequency with which an event in a population is
studied
Epidemiological Data Sources
• Denominator data- population at risk such as census
statistics
• Numerator data- events or conditions of concern such
as health, disease, births, death registries and surveys
• National census
• Vital Statistics Registration System- births & deaths
• Notifiable Disease Surveillance System
• National center for Health Statistics
• Disease Registries
Frequency - Frequency of disease, injury, or death can be
viewed and measured in different ways
Incidence- frequency (number) of new occurrences of
disease, injury, or death;
− i.e. well  ill
− i.e. uninjured  injured
− i.e. alive  dead
Prevalence- number of persons in a pop who have a
specified disease or condition at a specific point in time
−
−
point prevalence- specific point in time, like NOW
period prevalence- specified period of time (6 months)
Example:
• Prevalence- # of existing cases of disease in
population at some designated time (frequency of
existing disease)
• Point prevalence= # people ill
total # in group at time point
Ex: do you smoke cigarettes now?
Period prevalence= # people ill
average population during time period
Ex: have you ever been diagnosed with cancer?
•
Incidence Rate- describes the rate of development of new
disease in group over certain period of time
Example:
IR= # new cases
total population at risk over time period X multiplier
100,000
Ex: Soho Cholera outbreak 1884
IR= 500/ 1,000 in 10 day period
Rebecca Stepan
Candidate population- population of people at risk of
getting a disease
Attack Rate- a type of incidence rate expressed as a % for a
short time period- epidemic or outbreak; # new cases of
disease per number in healthy population at risk
• AR= # ill people
# ill + well people x 100
Ex: 200 people sick with food poisoning from a banquet of
500 people (buffets need to do an attack rate on each food
item, interview well people to narrow down culprit).
AR= 200/500 x 100 = 40%
Risks
• Proportion of persons who are unaffected at beginning
of study period but who undergo a risk event during
the study period
− You are unaffected from pandemic influenza
at the beginning of outbreak; what will your
risk be during or end of outbreak of
contracting pandemic flu?
− Susceptible population- might be better to
discuss risk events
• Risks Using Susceptible Populations
• Number of susceptible ÷ total population
• Number of exposed ÷ number susceptible
• Number of infected ÷ number of exposed
• Number of ill ÷ number of infected
• Number of dead ÷ number of ill
• Number of dead ÷ total population
Case fatality ratio- proportion of ill persons who die
• Higher CFR  more virulent, infectiousness, or
pathogenicity of organism
Types of Calculations
• Three types of calculations used to describe &
compare measures of disease occurrence:
− Proportions
− Rates
− Ratios
Introduction to Enumeration
COUNT- simplest and most frequently used measure
–Number of cases of a disease
–# cases of hepatitis at UMD
–Traffic fatalities in city of Duluth
–Lung cancer cases in state of Minnesota
•Numerator (x)
Denominator (y)
Proportion
• In order for a “count” to be descriptive, it must be
looked at relative to size of group-one number
divided by another; also known as a fraction
• Number of hepatitis at UMD- how many cases out of
how many students? Are we talking 5 cases out of
10,000 on campus? Or was it 500 cases?
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
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Ratio
•
•
•
•
•
10 cases of hepatitis in a residence hall- does hall
hold 100 students or 500?
if 100 in dorm- 10/100= 10%; 10/500= 2%
Looks at magnitude of the problem by looking at the
Denominator of the numbers
5/10,000 or 500/10,000 – big difference
A fraction, similar to ‘proportions’, but there is no
specific relationship between numerator and
denominator
In UMD hepatitis outbreak, 15 were men and 5 were
women
# male cases/# female cases
15/5= 3:1 male to female ratio
Ratio= a/b
Rates: Crude, Specific, & Standarized
• Aimed at measuring occurrence of events during a
certain time period
• Relative number which relates the absolute number
of times an event occurs to the total population in
which it occurs
• Rate= event x round number (constant multiplier)
Population
• event= # occurrences; population= group at risk
with the event; r.n. base for comparison, usually
100, 1,000, or 10,000
Crude Rates
• Summary rates based on actual number of events in
a given population over given period of time
• Crude death rate- proportion of population that dies
during a time period; total # deaths from all causes
per 100,000 people; usually expressed for a one
year period
• Crude birth rate- number of live births during
specified period of time (usually one calendar year)
per resident population during the time period per
1,000
Rate example- Crude Death Rate
(summary rates based on actual # events in pop.)
•CDR= # deaths/in a year
reference pop.
X 100,000
#deaths in US in 1990- 2,148,463
Population of US 1990- 248,707,873
CDR= 2,148,463
248,707,873 x 100,000
CDR= 863.8 / 100,000
Specific Rates
• Sometimes crude rates are not good to use in making
comparative statements about disease frequencies in
populations
• To correct for factors that may influence the makeup
of populations, specific rates are used to define a
particular subgroup of the population, such as race,
age, sex, or particular type of death
–Age-specific rates
Rebecca Stepan
–Sex-specific rates
Age-Specific Rates
• Subdivide a population into age groups, usually by
5-10 year intervals
• Divide frequency of disease in that age group by
total number persons in age group
• #deaths of children aged 5-14
• Total # children aged 5-14 x 100,000
Standarized Rates
• Also known as ‘adjusted rates’
• Crude rates that have been modified (adjusted) to
control for effects of age or other characteristics and
allow for valid comparisons
• Usually used for death rates
− Direct standardization- most common; used
to remove bias- uses standard population as
a basis
− Indirect standardization- if age specific data
is not available for population- uses
standard rates
Cause –Specific Rate
• Cause-specific mortality rate- uses numerator to
make homogeneous according to diagnosis
• CSR= mortality of given disease
population size x 100,000
•Example: 22,795 deaths HIV x 100,000
83,761,000
CSR= 27.2 per 100,000
Proportional Mortality Ratio (PMR)
• Number of deaths within population due to specific
disease or cause, divided by total # deaths in
population
• PMR (%)= mortality specific cause
mortality to all causes x 100
Quick Quiz Assessment
1. To report the prevalence of disease ‘X’, it would be
necessary to know:
A. Cure rate
B. Duration of illness
C. Number of cases at a given time
D. Rate at which new cases developed
2. The number of new cases over a defined study period,
divided by the mid-period population at risk would use
which formula?
A. Crude birth rate
B. Prevalence rate
C. Case fatality ratio
D. Incidence rate
Answers: (my guesses to the answers)
1. C
2. D
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 5
Investigating Disease Outbreaks – CHAPTER 3
“Chain of Infection”
• Infectious Disease Process
• Results from the interactions of the 3 components of
the epidemiological triangle:
− Agent
− Host
− Environment
• Chain of infection includes 6 chain links which all
must happen in succession- break any link in the
chain, the disease spread will cease
3.
4.
5.
urinate in the lake; eggs enter skin while wading in
water, enters bloodstream
Alimentary tract- mostly related to food- by mouth;
also vomitus, feces, saliva
Rabies- dog bite
Cholera-intestinal tract
Skin- Superficial wounds- cuts, gashes, burns,
puncture wound—or smallpox
Transplacental mode (mother to fetus)- pregnant
woman passes disease thru placenta-umbilical cord
to baby
Rubella, Syphilis, Hepatitis B, HIV+
Chain of infection-4. Mode of transmission of agent to new
host
• Direct transmission (person to person)- touching,
biting, kissing, sexual intercourse
• Indirect transmission− Vehicle borne (inanimate) blood, water,
food, surgical equipment, eating utensils,
clothing, etc
− Vector borne- feces, eggs, biting (saliva)
Chain of infection-1 Causative Agent:
• The entity capable of causing disease
• Agents are one of three types:
1. Biological- protozoa, metazoa, bacteria,
viruses, fungi, rickettsia
2. Chemical- pesticides, additives, industrial
chemicals
3. Physical- heat, light, ionizing radiation, noise,
vibrations
• note- most diseases are caused by biological agents;
chemical and physical agents cause chronic long term
illnesses
Chain of infection-2 Reservoir of Agent
• The normal habitat in which an infectious agent lives,
multiplies, and grows (not all diseases have one)
• These habitats include humans, animals, and
environment
• 2 major categories of human sources of infection:
1. Acute clinical cases. Less likely to cause
transmission due to early diagnosis and
treatment (going to doctor)
2. Carriers- person who harbors infection but
has no overt signs or symptoms
• Why is a carrier dangerous? Don’t express symptoms
but spread to others.
Chain of infection-3 - Portal of exit of agent from Host
There are 5 means of exit from the human body:
1. Respiratory tract- very common but difficult to
control. Ex. Common cold, Influenza, TB, Airborne
droplets
2. Genito-urinary tract- urine, semen
Syphilis, Gonorrhea, Schistosomiasis (blood
flukeworm inside body, eggs leave thru urineRebecca Stepan
Chain of infection-5 - Portal of entry into new Host
• Basically the same as #3- portal of exit
• Mouth, nose, Skin, Genital/anal, transplacental
Chain of infection-6. - Host susceptibility
• Depends upon:
− Genetic factors
− General resistance
− Specific acquired immunity (natural or thru
vaccinations)
+skin toughness
-malnutrition
+gastric acidity
-poor health
+cough reflex
-repressed immune
Surveillance of Disease
• Entire process of collecting, analyzing, interpreting,
and reporting data concerning incidence of disease,
injuries, or death
• USA- Centers for Disease Control (CDC) federal agency
responsible for surveillance activities of acute and
infectious diseases
• Local and state health departments also responsible
on local and state level for surveillance
Baseline Data
Endemic levels of disease- usual level of disease in a
community
Evaluation of time trends:
• Long term secular trends- over time period a disease
is looked at to determine trends
• Seasonal variation trends- based on route of spread;
i.e. respiratory route for influenza is during winter
and early spring; insect vectors in summer time for
Lyme or West Nile;
Epidemic - Disease outbreak at an unusual or unexpected
frequency; above and beyond usual endemic level
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 6
Pandemic- epidemic outbreak affecting several countries or
continents; pandemic flu will likely be pandemic over many
countries in the world when it happens
Epizootic- ‘upon animals’- unusual pattern of disease in
animal populations
Procedures- 5 steps
1.
Define the problem and establish diagnosis:
determine from outset whether this epidemic (outbreak)
is real. What needs to be looked at?
− Surveillance
− Endemic levels
Foodborne Outbreak Definition
− Two or more persons (except for botulism and
chemical poisoning it may be only one person
affected)
− Who all ate the SAME food at the same location…..
− AND ALL became ill at about the SAME time, and
with the SAME symptoms.
− Oh, yeah.. The Poo-Poo Story! Outbreak in residence
hall, dinner party, all ate subs, 45/60 sick. Sx 6-12
incubation, V/D, nausea, cramps, headache, Staph
aureas infection! Baby poop in kitchen.
2.
Appraise the existing data: evaluate known
distribution of cases with respect to person, place, and
time
Case identification- find all potential cases involved in the
outbreak; start with index case- first person to get sick and
transmit to others; how did it spread?
Clinical observations- record number, types, and patterns of
symptoms associated with disease
Tabulation & spot maps- cases of disease are plotted on a
map (Dr. John Snow- Cholera); these can be done by
date/time of disease onset of symptoms, geographical
clustering; graphing can show time of onset over period of
time
− Plot an epidemic time curve graph
− Identification- determine the responsible agent
(biological, chemical, physical)- How?
3. Formulate a hypothesis:
− What are possible sources of infection?
− What is likely agent?
− What is likely method of transmission?
(spread of disease)
− What is best approach to control the
outbreak?
4.
Test the hypothesis:
− collect data needed to confirm or refute your
initial suspicions; continue to look for more
cases; evaluate alternative sources of data;
− begin laboratory investigations
Rebecca Stepan
5. Initiate Control Measures and Draw conclusions to
formulate practical applications
− Sanitation
− Prophylaxis
− Diagnosis and treatment
− Control of disease vectors
− based on results of investigation, likelihood of
new programs, policies, or procedures will need
to be implemented
− long term surveillance and prevention efforts to
prevent recurrence of similar outbreaks
Measures of Disease Outbreaks
Attack rate- same as ‘incidence rate’; looking at number of
new cases of disease per unit of population per unit of time.
Occurrence of disease in population increases greatly over a
short period of time, often related to specific exposure.
Attack rate= # ill persons
x 100%
# ill + # well persons
Attack Rate Table- to find specific food responsible for
outbreak
A (ate the food)
ill
not ill
‘A’ total
attack rate%
ex: 10 + 3
13
77%
B (did not eat food)
ill not ill
‘B’ total
attack rate%
ex: 7 + 4
11
64%
Identifying Food that Caused Outbreak
1. List all foods consumed at event
2. Persons involved in outbreak:
A. (ate food)
B. (did not eat the food)
3. Calculate attack rates for each food item with well
and ill persons
4. After calculating AR, find difference in attack rates
A-B between those who ate and those who did not
eat
5. Repeat process for each food item suspected in
outbreak
6. Foods that have greatest difference in attack rates
may be the foods that were responsible for the
illness
Secondary Attack Rate
− S.A.R.= Number of cases of an infection that occur
among contacts within the incubation period
following exposure to a primary case in relation to
the total number of exposed contacts
− Denominator is restricted to susceptible contacts
when these can be determined
− Is a measure of contagiousness and useful in
evaluating control measures
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 7
Secondary Attack Rate Formula
SAR%= # new cases in grp - initial case(s)
# susceptible persons in grp – initial case x100
Initial case- index case + co-primaries
Index case- case that first comes to attention of public
health officials
Co-primaries- cases related to index case so closely in timesame generation of cases
Epidemic Curve
• Defined as a graph in which cases of a disease that
have occurred during an epidemic period are graphed
according to the time of onset of illness in the cases
• Provides a simple visual display of the outbreak’s
magnitude and trends
How to Draw an Epidemic Curve
• You must first know time of onset of illness
• Number of cases plotted on the y-axis (vertical axis)
• Unit of time on x-axis (hortizontal axis)
• Time is usually based on hours
• Show pre and post epidemic period on your graph
Interpreting Epidemic Curve
• Consider overall shape- this will determine pattern of
epidemic- common source or person-to-person
transmission
• Curve with steep up  slope and gradual down slope
indicates a point source epidemic where people were
exposed to same agent over brief period of time
• Person-to-person transmission spread will have series of
progressively taller peaks one incubation period apart
• Cases that stand apart are called ‘outliers’ and also
should be looked at closely
Study of Causation in Epidemiologic
Investigations - Chapter 4
Causal Relationships
• Finding specific cause or reasons for a disease,
whether for infectious or chronic disease
• Variable of ‘risk factor’ must also be looked at
• Three types of causation
3 Types Causal Relationships
1. Sufficient cause- precedes disease;
− If cause is present, disease will occur
• Ex: smoking is not cause of lung cancer
because not all people who smoke get lung
cancer
2.
Necessary cause- precedes disease
• Cause must be present for disease to occur
• Cause may be present without disease
occurring
• Ex: M. tuberculosis is absent in person,
person cannot get tuberculosis, though
person could be a ‘carrier’
Rebecca Stepan
3.
Risk factor• If characteristic is present and active, the
probability of a particular disease in a group
who have the risk factor compared to those
who do not, likely will get the disease
• Neither necessary nor sufficient cause
Associations between Cause and Non-cause
• Association- between outcome of disease and
presumed cause
• Outcome must occur either more clearly often or
clearly less often in persons who are exposed to
presumed cause than those not exposed
• Exposure to presumed cause must make a
difference; otherwise it is not a cause
• Direct causal association- the factor under
consideration exerts its effect without any
intermediary concerns
− A severe blow to the head will likely cause
brain damage and death without other
external causes being required
• Indirect causal association- a factor influences one
or more other factors that are in turn directly casual
− Poverty may not cause disease and death,
but by preventing adequate nutrition,
housing, and medical care, may lead to ill
health and premature death
• Noncausal association- a relationship between two
variables is statistically significant, but no causal
relationship exists; association is not necessary for
proving causal relationship.
− Male baldness is associated with risk of
coronary artery disease; it is noncausal
because coronary artery disease and
baldness are functions of age and gender
Determination of Cause & Effect
• In order to guide epidemiologic investigators in
their scientific thinking about disease causation, a
model must be available
• To determine causation has 3 steps:
− Investigation of statistical association
− Investigation of temporal relationship
− Elimination of all known alternative
explanations
• Police use a similar model when investigating
murder crimes
Investigation of Statistical Association
• For a hypothesis to be true in an investigation, risk
factor must be significantly present more often in
persons with the particular disease than those
without the disease in question
• A statistical association will be likely to occur if the
following are true:
− Strength of the association being made
− Consistency is always observed if risk factor
is present
− Biological plausibility
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 8
−
Presence of dose-response relationship
(stronger exposure to disease)
Investigation of temporal relationship
• Suspected causal factor must have occurred or been
present before the effect (disease) developed
• Has to do with a ‘time’ element
• Hard to determine onset of chronic diseasesexample: when did atherosclerosis begin?
• Onset of risk factors are unclear
Elimination of All Known Alternative Explanations
• Necessary to demonstrate that there are no other
likely explanations for the causal association as
much as possible
• However, all alternative explanations can never be
fully met all the time
Common Pitfalls in Causal Research
• Bias- a differential error that usually produces
findings consistently distorted or deviated in one
direction owing to nonrandom factors
− Selection bias- human subjects are self
selected and not randomly assigned to a
study group
− Allocation bias- researchers do not use
random methods of assigning patients to
control or experimental groups
Detection Bias
• Detection and measurement bias- once clinical
studies are underway, care must be taken in
detecting disease properly, patients being followed
carefully, etc.
• Collection of baseline data or follow up data is also
important so bias does not occur to skew the data
results
Confounding & Synergism
• Confounding: (Latin meaning “to pour together”)
confusion of two supposedly causal variables so that
part of the effect of one variable is actually due to
the other.
• Synergism: (Greek meaning “to work together”)
interaction of two or more causal variables so that
the combined effect is clearly greater than the sum
of the individual effects.
Quick Assessment
1. Cigarette smoking is a ________ of the relationship
between alcohol and lung cancer.
A. Biological plausibility
B. Confounder
C. Measurement bias
D. Sufficient cause
Rebecca Stepan
2.
A systematic distortion in retrospective studies is
known as _______________.
A. Confounder
B. Synergism
C. Recall bias
D. Internal validity
Answers: 1. B 2. C.
Common Research Designs in Epidemiology
Chapters 5 & 6
Functions of Research Designs
• To permit unbiased comparison of a group with and
without a risk factor or intervention
• Allows comparison data to be quantified
• Hypothesis development critical in making
predictions
• Each design has advantages and disadvantages
Study Designs: Cohort Studies
• Subset or population group that is followed over a
period of time
• Can be performed retrospectively or prospectively
• Used to obtain true measure of risk
• Time consuming and costly to conduct
Prospective Study
• Subsets of population identified to who have or have
not been exposed to a disease factor
• Subjects are followed forward in time for
development of disease under study
• Advantage- selected on basis of exposure and
identified before disease outcome occurs
• Disadvantage- not suitable for diseases that have
long latency period; expensive and takes long time
to study
Cohort Studies- also called Prospective or Longitudinal
• Birth cohort: Group members by age; i.e. all people
born in 1982 will be looked at & followed over time
• Occupational cohort: those exposed to something at
a particular job setting
• Other groupings possible, so long as they have some
shared characteristic
Sampling & Cohort Formulation Options
1. Population-based cohort study
− Includes either entire population or
representative sample of population
− Starts with N size, then baseline is set to
determine ‘exposed’ or ‘not exposed’ status
2. Exposure-based cohort study
− Used for those cases of rare exposure to
toxic or disease
− Low numbers of subjects are available- few
cases and controls
− Use incidence rates to determine effects
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 9
Prospective 2 x 2 Table
Stimulus
Variable
Present
Absent
Total
With
Diseaes
A
C
A+C
Without
Disease
B
D
B+D
Total
A+B
C+D
N
Retrospective Cohort Study
• Makes use of historical (past data) to determine
exposure level at some baseline in the past
• Begins with exposure (though it is past exposure)
and looking to subsequent occurrence of disease in
the future
• Advantages:
− Only short period of time needed to do
follow-up work
− Amount of exposure data is quite large and
can be performed cheap
Measures of Interpretation
• Data from 2 x2 table can be used to determine
“relative risk”
• Relative risk (RR) is defined as:
− Ratio of the risk of disease or death among
the exposed, to the risk of the unexposed
Relative = Incidence rate in Exposed
Risk
Incidence rate in Non-exposed
•
Using 2 x2 table, formula can now be expressed as:
R.R. = [A/(A+B) ]
[C/C+D)]
Relative Risk
• RR= 1.0 implies risk of disease among exposed is no
different than risk of disease in unexposed
• RR= 2.0 implies risk is twice as high
• RR = 0.5 indicates exposure of interest is associated
with half the risk of disease
Sample Problem= R.R.
• Cohort: chemically dependent boys; looking at
suicide ideation;
• Who more likely to contemplate suicide?
• Those who had been exposed to physical or sexual
abuse as a child, or those not exposed to such
abuse/neglect
History
Suicide
No
Abuse
attempt
attempt
Yes
A= 14
B= 9
No
C= 49
D= 149
Relative Risk= [A/(A+B) ]
[C/C+D)]
RR= (14/23) ÷ (49/198)
RR= 0.609/0.247
RR= 2.46
Rebecca Stepan
total
A+B=23
C+D=198
Conclusion= 60.9% of boys who were abused likely to
commit suicide; only 24.7% not abused likely to commit
suicide
Study Designs
• Ecological Studies
• Cross-sectional Studies
• Case Control Studies
Study Designs- Observational Studies
• Dependent on the amount of information already
known about health issue
• Uses existing data- quick and easy and economical
• Number of observations made
• Data collection methods used
• Timing of data collection- short
Observational vs Experimental
• Manipulation of study factors (M)- exposure of
problem is controlled by investigator; i.e. city water
supply chlorinated for residents; residents have no
choice about their water supply- its already
chlorinated
• Randomization of study subjects (R) key issue
• Observational- M and R are not used
• Experimental- M and R are used
Observational Studies
• Manipulation and randomization are NOT used in
study subjects
• Do use careful measurements of patterns of
exposure and disease in population to draw
inferences about etiology of disease
• Two types of observational studies:
− Descriptive studies: morbidity of time,
place, and person
− Analytic studies: ecological, case control
and cohort studies. These designs use
specific etiological hypotheses and
eventually generate preventive hypotheses
for disease control
The 2 by 2 Table
• Important tool in evaluating the association
between exposure and disease
• Columns represent disease status or outcome (yes
or no)
• Rows represent exposure status (yes or no)
• First column always refer to those w/ disease
• First row always refer to those exposed to disease
The 2 by 2 Table
Disease Status
Yes
No
Total
Exposure Yes
A
B
A+B
Status No
C
D
C+D
_________________________
A+C
B+D
N
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 10
Ecological Study
• Examines a group as a unit for analysis
• Most other study designs use individual as the unit
of analysis
• Used for generating hypotheses and for analytic
studies
• Uses diseases of an environmental nature: i.e. lung
disease from air pollution, cancers, etc.
Two types Ecological Studies
• Ecological comparison study- Involves assessment
of correlation between exposure rates and disease
rates among different groups or populations
(usually 10 or more groups) over same time period
• Ecological trend study- Involves correlation of
changes in exposure and changes in disease over
time within same community or unit
Cross-Sectional Studies
• Also known as prevalence study
• Exposure and disease measures are obtained at the
level of the individual
• Includes single period of observation
• Typically are descriptive in nature- providing
quantitative estimates of magnitude of a problem
• Does not measure cause and effect
• Easiest way is by random sampling
Case Control Studies
• Two groups are studied- people who have the
disease (cases) and a comparable group where
everyone is free from the disease (controls)
• CCS seeks to identify possible causes of disease by
finding out how two groups differ
• Used to assess vaccine effectiveness
• Sources of cases- all participants have equal
(random) chance of getting selected for the study
• Ideal control subjects should have same
characteristics as the cases
• Equal number 1:1 ratio should be used
• Objective of CCS is to identify differences in
exposure frequency that might be associated with
one group having disease and the other group not
having disease
Measure of Association
• Objective of case-control studies is to identify
differences in exposure frequency that might be
associated with one group having disease and other
group not having it
• Proportion of cases exposed is A/(A+C)
• Proportion of cases not exposed is C/(A+C)
Odds Ratio
• Ratio of the two proportions:
[A/(A+C)] ÷ [C/(A+C)]
• A/C represents odds of exposure among case group
• B/D represents odds of exposure among control
group
• Together a ratio of these two odds are created
Rebecca Stepan
•
•
•
•
OR: (A/C) ÷ (B/D)
OR measures the odds of exposure of a given disease
OR of 1.0 implies odds of exposure are equal among
cases and controls
OR of 2.0 indicates cases were twice as likely as
controls to be exposed
Quick Assessment
1. Studies may be conducted to generate or test
hypotheses. The best design for testing a hypothesis
is a :
A. Case-control study
B. Cross-sectional survey
C. Randomized controlled study
D. Retrospective cohort study
2. The members of a public health team have a continuing
interest in controlling measles infections through
vaccination. To estimate the immunity in a particular
population in a quick and efficient manner, what type of
study should they conduct?
A. Case control study of measles infection
B. Cross-sectional survey of vaccination status
C. Randomized trial of measles vaccination
D. Retrospective cohort study of measles vaccination
E. Ecologic study of measles in the population
3. In a case control study that is being planned to study
possible causes of myocardial infarction, patients with M.I.
serve as the cases. Which of the following would be a POOR
choice to serve as the controls?
A. Subjects who have no history of M.I.
B. Subjects who were admitted to the hospital for noncardiac diseases
C. Subjects whose age distribution is similar to that of
the cases
D. Subjects whose cardiac risk factors are similar to
those of the cases
E. Subjects whose sociodemographic characteristics
are similar to those of the cases
Answers: 1. C 2. B 3. D
ERRORS & DECISIONS in Clinical Medicine - Chap 7 & 8
Goals of Data Collection & Analysis
• Errors in medicine unfortunately do occur and are
many times difficult to eliminate
• Measure and explain variations in medicine
• Facilitate interpretations of data needed for medical
diagnosis, prognosis,and treatment
Promoting Accuracy & Precision
• Accuracy- ability of measurements to be correct on
average; if measure is not accurate, it is biased
•
Precision (reproducibility/reliability)- ability of
measurement to give same result with repeated
measurements of the same thing
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 11
Observer Variability
• Goal of data collection & analysis is to reduce
amount of observer variability
• Intra-observer (within observers) variability− Same physician takes successive
measurements of blood pressure of same
patient over time some differences in the
measurements or interpretation will occur
Intra & Inter Observers
• Inter-observer (between observers) variability− Two physicians measure the same blood
pressure of a patient independently of each
other will usually yield some differences
Studying Accuracy & Usefulness of Screening &
Diagnostic Tests
• False positives and false negatives
• Sensitivity and specificity
• Predictive values
• Ratios, odds ratios, & cutoff points
False Positives & False Negatives
• If something is said to be true when it is false:
− Type I error: false positive error: alpha error
• If something is said to be false when it is true:
− Type II error: false negative error: beta error
Stage of Disease - Influences test results- some diseases
more readily detected or more accurate in various stages of
the disease; i.e. middle of infection period or much later as in
case of HIV
Sensitivity & Specificity
• Important measures of test function
• Results placed in 2 x 2 table
• Sensitivity- ability of a test to detect a disease when it
is present; if test is not sensitive, it will fail to detect
disease
• Specificity- ability of test to indicate nondisease when
no disease is present
Improving Decisions in Clinical Medicine
• Evidence-based medicine- medical decisions today
are based on combination of clinical experience and
knowledge gained from the literature
− Most relevant research data
− Which studies are most trustworthy and
applicable to clinical question under
consideration
− Use best methods available to weigh
diagnostic, therapeutic, prognostic
probabilities of each medical intervention
Clinical Tools for Evidence Based Medicine
• Bayes’ Theorem
• Clinical decision analysis
• Meta-analysis
• These tools can help physicians to understand
quantitative basis for making clinical decisions in
medicine
Bayes’ Theorem
• Imposing statistical formula developed by English
clergyman is actually a formula for positive
predictive value
• Helpful in community screening programs
Decision Analysis - Improve decision making under
conditions of uncertainty
Meta- Analysis
• Increasingly becoming popular in medicine to obtain
a qualitative or quantitative synthesis of the
research literature on a particular subject.
• Fairly new method, though gaining more in
popularity
− Pooled quantitative analysis
− Methodologic qualitative analysis
MEDICAL BIOTERRORISM
Predictive Values
• If patient’s test results is positive, what is
probability he/she has the disease under
investigation?
• If results are negative, what is probability that
patient does not have disease?
• Predictive values indicate proportion of subjects
who had positive test results have disease
Medical Aspects of Bioterrorism
• Practice of medicine has changed since World Trade
Towers 9-1-1, inhalation of anthrax in Florida, and
others.
• Earlier historical or theoretical interests regarding
biological warfare & bioterrorism have vastly
changed to become commonplace in medical
practice today.
• There are dozens of agents that can cause human,
animal & plant diseases .
Likelihood Ratios, Odds Ratios, & Cutoff Points
• Ratio of sensitivity of a test to the false positive
error rate of the test
• Higher the ratio, better the test
• Ex: patient complains of chest pain; physician takes
medical history and orders various tests to screen or
“rule out” (discard false hypothesis). Tests with
high degree sensitivity have lower false-negative
error rate
Identification of Diseases
• Many are uncommon, making it difficult for most
clinicians to diagnose
• Classic symptoms are usually altered depending on
method of dispersion
• Importance of prodromal surveillance and
awareness by physicians & other health care
providers
• Look for epidemiologic clues, clusters of disease, etc.
Rebecca Stepan
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 12
Bioterrorism Agents
• Odorless, colorless, invisible
• Dispersion
− Point source- ex: letter containing anthrax sent
in the mail
− Line source- crop dusters or spraying devices
• Rapid reporting of suspected bioterrorism to local PH
officials crucial!
Categories of Human Pathogens
• US Centers for Disease Control and Prevention
reclassified in 2000
• Three categories:
− Cat A- highest priority; includes agents
which are easiest to disseminate and
transit; causes greatest public health crisis
− Cat B- 2nd highest priority; moderately easy
to disseminate; cause moderate morbidity
and mortality
− Cat C- only those emerging pathogens that
could potentially be developed into
bioweapons
CATEGORY ‘A’ AGENTS - Easily transmitted; high
mortality; cause public panic/social disruption
• ANTHRAX
• BOTULISM
• PLAGUE
• SMALLPOX
• TULAREMIA
• VIRAL HEMORRHAGIC FEVERS  Ex. Ebola,
Marburg, Lassa
ANTHRAX
• Gram-positive spore-forming rod bacteria; Bacillus
anthracis
• Both human & animal disease
• Endemic worldwide
• Cutaneous infection most common; inhalational more
rare but what is being seen in latest bioterrorismrelated; gastrointestinal form very uncommon and never
been diagnosed in US
• Transmission- not person to person
• Incubation- following inhalation spores- 6 days
depending on level of exposure
• Initial symptoms- fever, malaise, headache, dry cough,
influenza-like
• Diagnosis- early dg difficult based on clinical grounds
only; rapid deterioration w/ respiratory & shock;
• Patients w/ suspicious chest radiograph, follow up w/
CT scan & blood cultures
• Look for hyperattenuation of mediastinal hemorrhage
• Cutaneous- pruritic papule 1-7 days after inoculation,
then vesicles form with fluid. As lesion matures, nonpitting edema surrounds it; vesicles rupture undergoing
necrosis with blacken ulcer
• Treatment- Rx Ciprofloxacin; acellular vaccine available
for pre-exposure prophylaxis (3 dose regiment)
• Case fatality rate- if undiagnosed, 80- 100%
Rebecca Stepan
SMALLPOX
• Single stranded DNA virus
• No animal reservoirs exist
• World free of smallpox since 1980 (Russia & US have
stock cultures)
• Transmission- respiratory droplets from infected person
• Incubation- 7- 17 days
• Diagnosis- febrile, severe headaches fever, backache; 23 days later- oral enanthem (lesions) followed macules
over face and extremities (chickenpox)
• Treatment- no antiviral agents effective; vaccination
confers immunity in 95% of population
• Case fatality- worldwide deaths more than all wars and
epidemics of 20th century; very high fatality rate
PLAGUE
• Gram-negative coccobacillus bacteria- Yersinia pestis
• Enzootic with rodent reservoirs
• Transmission- person bitten by infected flea which came
from rat reservoir (bubonic- not common anymore)
• Person to person transmission can occur in pneumonic
form via respiratory droplets- highly contagiousbioterrorism
• Incubation- 2-4 days (pneumonic)
• Diagnosis- productive cough, chest pain, dyspnea;
sputum gram stain & culture
• Treatment- Rx Streptomycin; no vaccine available
• Case fatality- nearly 100% without treatment and up to
15% w/ antibiotics
Tularemia
• Organism- Francisella tularensis
• Endemic zoonosis to small animals (rabbits) and ticks
• Cutaneous or pneumonic (rare) form
• Transmission- bite from tick; handling of small
infected game with broken skin
• Diagnosis- fever, fatigue, chills, headache; pneumonic
ulceroglandular; culture& serologic tests
• Treatment- RX Streptomycin for 10 days;
investigational new drug vaccine available- some
immunity
• Case fatality- 30-60% untreated; <2% for those
receiving treatment
VIRAL HEMORRHAGIC FEVER
• Viruses small RNA forms weaponized by both
former USSR and US; among most feared and least
understood in entire world
• Ebola, Marburg, Lassa
• Transmission- contact with excreta of infected
rodents; infected person then transmits virus
through close contact; dispersion of virus difficult
• Incubation- 2- 21 days
• Diagnosis- high fever, headache, arthralgias,
abdominal pain; conjunctivitis and pharyngitis
develop, hemorrhages occur w/ multiorgan failure,
shock and death soon follow
• Treatment- primarliy supportive; no antiviral agents
available; no vaccine
• Case fatality- up to 90% by virus
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 13
BOTULINUM TOXIN
• Anerobic bacteria Clostridium botulinum neurotoxin
• By-product of bacteria; do not replicate within the
host & not communicable
• Inhalation botulism- delivered as aerosol
• Incubation- 48 hrs
• Diagnosis- cranial nerve palsy; flaccid muscle
weakness; respiratory distress; eventually paralyzes
breathing apparatus
• Treatment- antitoxin polyvalent equine
• Case fatality- up to 50%
CATEGORY ‘B’ AGENTS - Moderate easy to disseminate;
moderate morbidity and low mortality
• Brucellosis
• Food safety threats- salmonella, E. coli
• Psittacosis; Q fever
• Water safety threats- cholera; Cryptosporidium
CATEGORY ‘C’ AGENTS - Emerging pathogens which could
be engineered for mass dissemination in future based on
availability, ease of production and potential for high
morbidity or mortality Ex. Nipah virus; hantavirus
Other Venues of non- Bioterrorism for MDs to know
• Chemicals actually pose a more immediate threat
• Deliberate attacks or industrial accidents
• Symptoms and damage from chemicals begin
immediately and require rapid diagnosis and treatment
by the clinician
• Toxicology of basic syndromes important to know
CHEMICAL TERRORISM
• Biological terrorism- patients presenting one by one in
disparate sites with emerging rare disease or in
strange age groupings
• Chemical terrorism- groups of people in close
proximity to the release are rapidly affected; problems
arise in minutes and hours.
CHEMICAL POISONING ASSESSMENT
• Initial assessment – focus on ABCs
• Look for markers of poisoning severity: altered mental
state, loss of consciousness; respiratory or cardio
instability
• Time is critical factor- empirical diagnosis
FOUR BASIC CLINICAL CLASSES OF CHEMICAL POISONS
• Asphyxiants− Simple- nitrogen, methane, carbon dioxide;
these displace oxygen
− Toxic- deny oxygen to tissues; carbon
monoxide, cyanide, hydrogen sulfide
• Cholinesterase inhibitors− Nerve agents such as sarin, organophosphate
pesticides
− Produce cholinergic excess, profuse
secretions, visual problems
• Pulmonary irritants− Chlorine, phosgene, ammonia
Rebecca Stepan
Do not cause systemic poisoning but major
respiratory effects can be fatal
Vesicants or blister agents− Industrial caustics- acids or bases- copious
flushing with water to rid of the agent
− military- sulfur mustard- chemical warfareeyes and skin damage
−
•
EPIDEMIOLOGICAL Clues of A BIOTERRORISTIC Attack
Unusual temporal or geographic clustering of illness
1. Unusual age distribution of common disease (such
as chickenpox in adults when it is really smallpox)
2. Large epidemic with greater case loads than
expected
3. More severe disease than expected
4. Unusual route of exposure
6. A disease outside its normal transmission season
7. Multiple simultaneous epidemics of different
diseases
8. Disease outbreak with health consequences to
humans and animals
9. Unusual strains or variants of organism or
antimicrobial resistance patterns
SENTINEL CLUES FOR CAT ‘A’ BIOLOGICAL AGENTS
• DIAGNOSIS 1: Chest pain, dry cough, possible nausea and
abdominal pain; followed by sepsis, shock, widened
mediastinum, hemorrhagic pleural effusions and
respiratory failure. Consider?
•
Diagnosis 2: febrile illness w/ myalgias followed in 2-3
days by generalized macular or papular vesicular
pustular eruption, with greatest concentration of lesions
on face and distal extremities. Consider?
•
Diagnosis 3: gram negative coccobacillus associated
with pleuritis and lymphadenopathy, particularly in an
otherwise normal host. Consider?
•
Diagnosis 4: paralytic illness characterized by
symmetric descending flaccid paralysis of motor and
autonomic nerves, usually beginning with the cranial
nerves. Consider?
•
Diagnosis 5: gram negative bacillus pneumonia
associated with muco-purulent sputum, chest pain, and
hemoptysis in otherwise normal host. Consider?
•
Diagnosis 6: abrupt, influenza-like illness with fever,
dizziness, myalgias, headache, nausea, abdominal pain;
evidence of ‘leaky capillary syndrome’ with edema,
bleeding from conjunctival hemorrhage, and organ
dysfunctions. Consider?
Diagnosis Case Answers
1. Inhalation Anthrax 4. Botulism
2. Smallpox
5. Tularemia
3. Bubonic Plague
6. Hemorrhagic Fever Virus
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 14
Viruses
• Influenza viruses constantly changing (mutating) to
cause different strains every flu season
• Genetic material of virus consists of DNA or RNA, but
never both
• Material is protected by protein coating (capsid)
• Genetic material contains info to make millions of copies
of itself
• Virus is obligate parasite – it cannot reproduce by
itself- it needs living organism
• Picture of Virus Anatomy
• Virus is not a cell in which it can process genetic
information and reproduce
• Invades host cells and use host cell machinery to
replicate
• Most viruses can survive outside host for short period of
time, but without host cell, they cannot multiply or grow
Types of Influenza Viruses
• Three types of influenza
− Type A, Type B. Type C
• These have similar and different characteristics
Characteristic
Capable of infecting
humans
Capable of infecting
swine, birds &
mammals
Responsible for
seasonal outbreaks
Virulent and quickly
spreads
Capable of mutation –
“drift”
Capable of genetically
changing – “shift”
Type A
Yes
Type B
Yes
Type C
Yes
Yes
No
No
Yes
Yes
No
Yes
No
No
Yes
Yes
No
Yes
No
No
*Type A is the dangerous one to watch out forr
‘H’ and ‘N’ Antigens
• Influenza A virus named according to molecular
composition and structure
• Genetic material of type A consists of 8 segments of
single strand RNA, covered in protein coating
• The coating is covered with 100s of ‘spikes’-surface
antigens of glycoproteins
Surface Glycoproteins
• ‘H’..emagglutinin (HA)
• 16 different subtypes have been identified (H1- H16)
• Hemagglutinin allows the influenza virus to attach to a
cell and enter inside that host cell
• Virus now begins to replicate inside the body
•
‘N’..euraminidase (NA)
• 9 different subtypes of neuraminidase glycoprotein
identified and confirmed (N1- N9)
• Neuraminidase allows the mature virus to escape from
the host cell
Rebecca Stepan
Flu Strains
• Type B and Type C Influenza viruses do not have any
‘H’ and ‘N’ subtypes
• Flu vaccines are produced each season to target
different strains of influenza
• Hence reason to be aware of circulating flu strains
such as
− H5N1 China strain- 2006
− H7N2 New York strain- 2003
Antibodies & Antigens
• Numerous proteins & glycoproteins cover surface of
influenza virus- these are known as antigens- and
recognized by the antibodies, which are produced by
body’s immune system
• Antibodies are created by human immune systemthey attach to and destroy viral antigens (the bad
guys) before the virus can infect host cells
• When viral surface glycoproteins change, antigenic
variations are said to have occurred
• But when viral antigens have changed, antibodies that
immune system had produced don’t recognize these
“new guys”; hence the bad guys-viruses- can go ahead
and infect the cells and start the damage
Antigenic Drift
• Caused by small accumulating mutations within the
virus genetic material
• RNA genetic material in a virus mutate internally more
than DNA genes do
• These changes in the viral genetic material cause
glycoproteins to also change, resulting in new variant
of influenza strain
• This gradual accumulation is done to foil the human’s
immune system
• These small changes do not produce novel virus, but
rather a strain that is closely related to the existing
circulating viral strains
• Hence the reason why we need to get a new flu shot
every year
Antigenic Shift
• Another type of antigenic variation which occurs less
frequently than antigenic drift
• Occurs only in Type A influenza viruses
• Introduces a brand new or novel viral strain which
causes pandemics easily due to the fact that no prior
immunity exists against these new mutatants
• Process known as genetic re-assortment
Genetic Reassortment
• Occurs when genetic material from two different
viruses are exchanged in the same host cell
• Example: a pig may become infected by both human
and bird viral strains; during viral replication inside
the swine the genetic material from these 2 viruses
exchange and “reassort” to produced a new strain
• Causes major changes in glycoprotein HA that creates
the new novel strain; swine could then infect humans
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
Page 15
with this new strain which humans would have no
natural immunity to it
What’s the Evidence?
1. These are small changes in the virus that happen
continually over time…
2. Immune system of a person infected with a
particular flu virus strain develops antibodies
against that virus. As newer variations of this strain
appear, antibodies against the older can no longer
recognize the virus and re-infection can occur…
3. This results in a new influenza A subtype which
most people have little or no protection against…
4. Influenza type B viruses historically have changed
only by this more gradual process…
5. Genetic re-assortment creates an abrupt, major
change in the influenza A virus…
Answers – 1. Drift 2. Drift 3. Shift 4. Drift 5. Shift
Avian Bird Flu ~Potential Implications on Public Health
• Influenza (flu) caused by bird viruses
• Occur naturally in birds
• Wild birds carry virus in their intestines; very common
• Very contagious among birds, especially those in close
confines: chickens, ducks, turkeys on farms; poor
sanitation; All Kinds of Birds At Risk
Epidemiology of Bird Flu- How do birds transmit it?
• Shed virus in their saliva, nasal secretions, and feces:
coughing, sneezing, touching
• In close confines, other birds breathe these viruses or
peck/drink at contaminated food or water, thus
picking up virus
• Fecal contamination most common mode of spread
between birds
What happens to the infected birds?
• Wild birds are host to virus- can transmit virus, but
they don’t get sick
• Low pathogenic form of virus may cause only mild
symptoms in birds- ruffled feathers or drop in egg
production
• High pathogenic form of virus spreads more rapidly;
highly contagious which affects internal organs;
mortality can reach 90-100% in 48 hours!!
Where and when did all this begin?
• Regarding the current problem, first noted in
Southeast Asia in 1997: bird to human transmission in
Hong Kong
• 18 humans infected; 6 died
• 1.5 million chickens & birds destroyed
• The rest is history and takes us to the present
What is the current situation with birds?
• To date, millions of birds have died or been destroyed
to curb outbreak
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Now humans are being infected and dying in several
countries, and bird flu among birds is slowing
spreading from SE Asia to Africa and Europe.
Will North America become next?
What is the current situation with humans?
• To date, 408 (366 in 2/08) confirmed human cases
have been reported (WHO; as of February 18,2009) in
15 countries
• 254 (232 in 2008) have died
• 52% of deaths <20 yrs of age
• Or 89% of deaths <40 yrs of age
• Lowest CFR of 40% >50 yrs age
Only Saving Grace So Far…
• Avian Bird Flu has ONLY been transmitted from birds
to humans
• The H5N1 strain is a difficult virus to transmit and to
mutate, hence the low numbers of humans being
infected
• All human cases were in close contact with infected
birds to get the virus
• The BIG problem will become when the virus mutates
enough so humans can transmit the virus to other
humans, much like the common cold or flu…………
Hype or Fear?! Why all the fuss of something that might
not happen?
• Dr. Michael Osterholm, noted Epidemiologist from
Minneapolis projects:
− 180 million people worldwide will die
− 1.7 million in the USA
− 30,000 in Minnesota
− Likely to last 12- 18 months, whenever it hits
− Why does he predict this?
Let’s Look At Past History
• Pandemic influenza has rampaged around the world
10 times in past 300 years
• 3 times in past century alone!
− Endemic level of common flu in the U.S. is
about 36,000 people die each year
− Avian virus resembles more like the 1918
virus, hence the concern for being dangerous
• Because of the mutation possibility, humans do not
have a built-up immunity, being more at risk for
getting the severe viral strain
Changing Conditions “Compared with 1918, how is the
world different today, and how might that difference
contribute to more or less death and illness when a
pandemic occurs?”
Compared with 1918 to today
• Urbanized population allows spread to occur more
easily
• Global travel allows virus to spread more rapidly
• Larger elderly population and people with chronic
medical conditions are at risk for more complications
and death
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
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1918 Spanish Flu (H1N1) Pandemic
• Swept across world and killed estimated 20 million
people
• ¼ American population became ill and ½ million of
them died
• Most interesting thing about this pandemic mortality
was the age distribution of the dead= young adults
more than young or elderly died!
• New twist- Feb. 2009- Strep was culprit?
1957 Avian Flu Pandemic
• Southern Chinese province subtype of influenza
identified
• Virus reached US by summer 1957 and killed 70,000
people, w/attack rates highest in school-aged
classrooms
• A second wave hit in winter 1958 attacking the
elderly much higher
1968 Hong Kong Flu Pandemic
• First isolated in Hong Kong
• When hit USA 1968-69, attack rates highest in young
children and mortality high among elderly
• <34,000 died in US
1976 Swine Flu Scare
• Same subtype of H virus strain that caused 1918
Spanish flu
• First discovered at Ft. Dix, NJ military base
• 500 infected, 1 died
• Vaccination campaign instituted thinking worst case
scenario was about to reoccur, which did not
• Vaccine program halted due to unforeseen side effects
(neurological)
• Fortunately no one outside Ft Dix was infected and
epidemic did not occur
1977 Russian Flu Threat - Northern China & Russia; it did
not become pandemic, or spread; nothing more became of it
Present Day 1997-2009 Phenomenon
• H5N1 virus identified for first time to directly transmit
from birds to humans
• First recognized in southeast Asia
• Since 2003, avian outbreaks documented in >40
countries
• 2006- H5N1 virus found in humans in 15 countries
So, when is the next Pandemic??!!
• Influenza pandemics are unpredictable
• With the situation regarding H5N1 virus circulating,
possibility for pandemic is greatly increased
• Last pandemic was 1968; we are due for another
major threat!
• H5N1 has been slowly but steadily infecting more
birds and humans, so this strain remains a credible
threat to the human population
1918 Virus vs Avian Virus
• virus (H1N1) replicated not only in respiratory system
but in the brain and liver too; causes acute respiratory
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•
distress syndrome (ARDS); affected more young and
healthy individuals; was caused by a bird flu
Avian virus can reproduce faster than typical virus we
get; is also affecting more younger than older people
Flip Side of Pandemic Possibility
• H5N1 avian virus has been around since the 1950s
• Only in last 9 years it has infected millions of birds and
only 400+ humans
• Though we are unprepared for the worst, it may not
happen for another 10 years from now- so why worry
now?! Or should we start doing something about it
now??
When is the next Pandemic? Three conditions must exist to
make a pandemic happen
1. Existence of new novel influenza A virus which
there no human immunity exists
2. Emerging novel virus must make humans sick, as
not all influenza viruses do
3. Novel new virus must be able to spread person-toperson transmission easily
• Pandemic usually occurs every 27-30 yrs; last one
37 yrs ago! So we ARE overdue for one!
WHO Preparedness Plan World Health Organization
revised Pandemic Flu Plan in 2005
• Divides the events of a pandemic into 6 phases, with
the phases additionally categorized into periods
Phase 1- Interpandemic Period
• No new influenza virus subtype is replicating in
humans
• An influenza subtype might be circulating in animals
and risk to humans is considered to be low
Phase 2- Interpandemic Period
• Circulating animal influenza virus subtype could pose
substantial risk to humans
• Distinction between phase 1 & 2 is based on risk of
human infection resulting from the circulating strains
in animals
• Factors include pathogenicity in animals and humans,
occurrence in domesticated animals vs wildlife, is
virus geographical localized, is virus occurring at
increased rates in animal population?
Phase 3- Pandemic Alert Period
• Human infection with new or novel subtype, but no
human-to-human spread
• Occurrence of human cases increases the chance that
the virus may adapt or reassort and become
transmissible from human to human
Phase 4- Pandemic Alert Period
• Small clusters of cases with limited human to human
transmission
• Spread is localized as virus is not fully adapted to
humans yet
• Clusters can be groups of people in same geographical
area with suspected, probable, or confirmed influenzalike illnesses within 2 week period
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
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Phase 5- Pandemic Alert Period
• Larger clusters of human to human transmission of
the virus, though still localized
• Likely to be last chance to coordinate global
intervention to delay or contain the virus
Phase 6- Pandemic Period
• Increase and sustained transmission in general
population
• Marks major change in global surveillance and
response, as all countries need to work closely to
contain the disease
Post Pandemic Period
• Return to interpandemic period- expected levels of
disease with a seasonal strain
• Transition period may be different for different
countries
Influenza- the disease
• Acute, febrile, respiratory illness affecting nose, throat,
bronchial tubes, and lungs
• Symptoms include fever, muscle aches, headache, lack
of energy, dry cough, sore throat
• Fever and body aches- 3-5 days
• Cough and lack of energy- 2 weeks
Influenza- Transmission
• Incubation- 2 days; range 1-4 days
• Viral shedding- can begin 1 day before symptoms
onset
• Peak shedding first 3 days of illness; correlates with
temperature
• Subsides usually by 5th- 7th day in adults; 10+ days in
children
• Contact, droplet spread via coughing or sneezing
• Death occurs about 9-10 days after onset of symptoms
Influenza- Demographics
• Annual deaths in US- 36,000
• Over 85% of mortality in persons aged 65 and older
• Attack rates in general population is 5-20%
• Nursing home attack rates of 60%
• 1918 pandemic however…
Influenza- 1918 Demographics
• 20 million worldwide died
• ½ million in US died
• Very deadly to young healthy adults
• Age 20-40 hardest hit
• Unclear why virus so deadly to younger population
Preventive Medicine
• Preparedness- time sensitive
• Stockpile vaccines and antivirals
• Expand influenza vaccine research
• Encourage and increase flu vaccinations
• Restrict air travel to and from infected areas
• Remove infected domestic bird flocks and vaccinate
poultry handlers
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Vaccine Production
• Vaccine production is s-l-o-w!
• Very archaic method of production based on eggbased method
• Takes 6-9 months; early decision must be made in JanFeb for fall distribution of vaccines;
• Trivalent (3) vaccines are produced: targets 2
influenza A and 1 influenza B strains
Vaccine Production- H5N1
• H5N1 virus is extremely virulent
• Development of vaccine is substantially challenged
• H5N1 virus kills fertilized chicken eggs and therefore
can not grow in them
• Production of vaccine will require a new technologyreverse genetics
• This process will entail removing genes that are thought
to give virus ability to cause disease, converting RNA to
DNA and converting back again to RNA
Preventive Medicine- Antivirals
• Antivirals will be of great value in early pandemic
stages when vaccines are in low supply
• Some antivirals take 12 months to produce, so
stockpiling is recommended
• HHS wants to acquire sufficient quantity to treat 25%
population
Antivirals
• Used to contain outbreaks
• Treatment- lessens severity of symptoms and shortens
time to recovery, if administered within 2 days of
onset
• Makes one less contagious to others
• Capable of preventing symptoms if taken prior to
infection (use as prophylaxis)
• 4 prescription antivirals currently available in US
• Antivirals are not substitute for vaccines
In Summary
• Avian flu IS spreading in bird population around the
world
• Limited number of human cases thus far in the world;
mostly SE Asia and Middle East countries
• Virus is difficult to mutate in such a way to become
easy to transmit from human to human, but it could
• Vaccines are being made available, but not fast enough
and not enough quantities to date; same with
antivirals- many are made overseas and if borders
close, USA could be in trouble! (US is far behind other
countries in stockpiling antiviral meds)
• Most countries, including USA are not prepared or
ready (look at NYC 9-11 or Hurricane Katrina)
• There could (likely) be a pandemic of human bird flu
• Individually, we must stay in good health and practice
preventive hygiene measures; social distancing, hand
washing, etc.
Med Epidemiology – Lecture 1, 2, 3,4 5, 6, & 7 Summaries
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