2- Infectious Disease Epid.pptx

Disease Causation
1
10/5/2023 By Abera G(BSc, MPH in Epidemiology).

• Disease is often classified according to:
– 1) Its time course, or
– 2) Its cause – Etiology
• The time course classifies disease as acute or
chronic
• The cause of a disease may be classified as infectious
(caused by living organisms which are transmissible)
or non-infectious (NCD).
2
Disease Classification

Cause of disease: is an event, condition,
characteristic or a combination of these factors
which plays an important role in producing the
disease.
The causes of disease can be classified in to two:
A. Primary causes – these are the factors which
are necessary for a disease to occur, in whose
absence the disease will not occur.The term
”etiologic agent” can be used instead of primary
cause for Infectious causes of diseases. For e.g.
“Mycobacterium tuberculosis” is the primary cause
(etiologic agent) of pulmonary tuberculosis.
1. Cause of disease
3

B. Risk factors (contributing, predisposing, or
aggravating factors).
•These are not the necessary causes of disease
but they are important for a disease to occur.
•A factor associated with an increased
occurrence of a disease is risk factor for the
exposed group; and a factor associated with a
decreased occurrence of a disease is a risk factor
for the non exposed group.
•Risk factors could be related to the agent, the
host and the environment.
4

1.1 Causal Concepts of Disease
• Not all associations between exposure and
disease are causal.
• A cause: A factor that preceded the disease
and without which the disease would not occur.
• If disease does not develop without the factor,
then the causative factor is “necessary”.
• No specific factor is sufficient to produce
disease.
5

• An agent is considered to be a ‘necessary’ but
not sufficient cause of disease because
suitable conditions of the host and the
environment must also be present for disease
to develop.
• A “sufficient cause” : defined as a set of
conditions and events that surely produce
disease;
• That all of the conditions or events are
necessary.
• For example, tobacco smoking is a cause of lung
cancer, but by itself it is not a sufficient cause.
6

• If the disease always results from the
factor, then we term the causative factor
“sufficient”.
• Example:
–Tubercle bacilli is a necessary
factor for TB
–Rabies virus is sufficient for
developing
clinical rabies
7

A E
U
Fig 5. An example of three sufficient causes of a disease
U
A B
U
B E
• Assume that these three causes are operating in the diagram
• Without U, there is no disease. U is considered as necessary cause, but all
disease is not due to U alone.
• E causes disease through two mechanisms, II and III, all diseases arising
from II and III are due to E.
• No component cause acts alone, the factors interact with their
complementary factors to produce disease
I II III
Sufficient causes
8

Fig 6. Rothman’s Causal Pies: Conceptual
scheme for disease causation
III
Sufficient causes
I II
A
E
An example of three sufficient causes of a disease
B C
D A
H G
F
B
A
J I
F
C
9

Epidemiological Principle of Causation
Two principles of disease causation:
1.The single germ theory and
2.The ecological Models
1.The Germ theory
• Luis Pasteur isolated microorganism.
•This discovery led to Koch's postulate in 1877.
• It was a set rule for the determination of causation.
Koch's Postulate states that:
•The organism must be present in every case.
•The organism must be isolated and grown in culture.
•The organism must, when inoculated into a
susceptible animal, cause the specific disease.
•The organism must then be recovered from the
animal.
10

2.The ecological Models
•Ecology: is defined as the study of the
relationship of organism to each other as well as
to other aspect of environment.
•Ecology of disease includes all the factor that
contribute to the occurrence of disease
•In epidemiology, the occurrence and
distribution of disease are studied against the
background of various circumstances in
human's total environment.
•Those factors are related to agent, Host and
environment
11

Three ecological models:
The epidemiological triangle
The web of causation
The wheel
12

1. Epidemiologic triangle and
triad (balance beam).
Host
Agent
Agent
Host Environment
Environment
Fig 3. Epidemiologic triangle Fig 4. Balance beam
13
Traditional model of infectious disease causation

Examples of causes of disease by host,
agent and environmental factors.
Host factors
 Age
 Sex
 Previous disability
 Behaviour
 Genetic inheritance
 Height
 Weight
Agent factors
 Virulence of organisms
 Serotype of organisms
 Antibiotic resistance
 Infectiousness
 Pathogenesis
10/5/2023 By Abera G(BSc, MPH in Epidemiology). 14

Environmental Factors
 Home overcrowding
Air pollution
Workplace hygiene
Weather
Water composition
Food contamination
Animal contact

• The host, agent, and environment can coexist
harmoniously.
• Disease and injury occur only when there is
interaction or altered equilibrium between them.
• an agent, in combination with environmental
factors, can act on susceptible host to cause
disease
• disruption of any link among these three
factors can also prevent disease.
16

2.The web of causation
•The process that generates disease or leads to
injury is much more complex.
•This complexity is better portrayed in web of
causation model
•The web of causation was developed especially
to enhance understanding of chronic disease,
such as cardiovascular disease.
• It can also be applied to the study of injury
and communicable diseases.
• web of causation de‐emphasizes the role of the
agent and highlights other factors that
encourage the onset of disease. 17

• In this approach, the causes of disease are
considered to be agents, exposures, or risk
factors.
• The factors may include microbes, chemicals,
nutrients, physiologic, genetic characteristics,
as well as behaviors, mental states, race or
socioeconomic status.
18

Web of Causation for the Major Cardiovascular Diseases
Cont…
By Abera G(BSc, MPH in Epidemiology). 19
10/5/2023

3.The Wheel
•The wheel consists of a hub (the host or human), which
has genetic makeup as its core.
• Surrounding the host is the environment, schematically
divided into biological, social, and physical.
• The relative sizes of the different components of the wheel
depend upon the specific disease problem under
consideration.
• For hereditary diseases, the genetic core would be
relatively large.
• In contrast to the web of causation, the wheel model
does encourage separate delineation of host and
environmental factors.
20

Fig 7. Wheel model of infectious
diseases
Genetic
core
(Humans)
Social
environment
Physical
environment
Biologic
environment
Host
•The interaction of humans with infectious agents and their environment, a
person’s state of health represents a dynamic equilibrium – a balance of forces.
21

2. Chain of Infection
• Infection: implies that the agent has
achieved entry and begun to multiply in the
host, whether or not the process leads to
disease.
• This is sometimes called the chain of
infection, or transmission cycle.
• For infection to occur, a chain of events must
take place.
22

Fig 8. Chain model of infectious
diseases
Susceptible
host
Causative
agent
Reservoir
Portal of
entry Mode of
transmission
Portal of
exit
23

•A model to conceptualize the transmission of a
communicable disease from its source to a susceptible
host.
Chain of Infection
10/5/2023

Pathogen
• Is the disease causing agent
Cont…
10/5/2023

Pathogen
• Is the habitat in which an infectious
agent normally lives and grows.
Reservoir
• Human: symptomatic or asymptomatic
• Animal: called zoonoses
• Environmental: plants, soil, and water
Cont…
10/5/2023

Pathogen
•Is the path by which an agent
leaves the source host.
Reservoir
Portal
of exit
Cont…
10/5/2023

Pathogen
•How pathogens
are passed
Reservoir
Portal
of exit
Modes of Transmission
Direct Indirect
- Direct contact -Airborne
- Droplet spread -Vehicle-borne
- Vector-borne
Trans-
mission
Cont…
10/5/2023

Pathogen
Reservoir
Portal
of exit
Trans-
mission
•Agent enters
susceptible host
Portal
of entry
Respiratory
Oral
Skin
Intravenous
Gastrointestinal
Cont…
10/5/2023

Pathogen Reservoir
Portal
of exit
Trans-
mission
•Final link is a
susceptible host
Portal
of entry
New
Host
Cont…
10/5/2023

Horton & Parker: Informed Infection Control Practice (www)
Chain of Infection
10/5/2023

2. Reservoir:The habitat of an infectious agent
where it normally lives, grows and multiplies.
• Carrier: A person without apparent disease
who is nonetheless capable of transmitting the
agent to others.
Types of Carrier
• Asymptomatic carrier: transmitting
infection without ever showing signs of the
disease.
32

• Incubatory carrier: transmitting infection
by shedding the agent before the onset of
clinical manifestations.
• Convalescent carrier:Transmitting
infection after the time of recovery from the
disease
• Chronic carrier: Shed the agent for a long
period of time, or even indefinitely.
33

34
Fig 9. Time course of a disease in relation to its
clinical expression and communicability
Time of infection
(biologicalonset)
Agent starts
being shed
1st manifestation of
disease (clinical onset)
Recovery Agent stops
being shed
Relaps
e
TIME
Incubation period
Latent period
Prepatent
period
Communication period
Generation
Clinical
Threshold
Asymptomatic
Symptomatic
Clinical case
Asymptomatic carrier
Chronic
carrier
35

3. Modes of Transmission of
Infectious Agents
• The transfer of an infectious agent from an
infected host (reservoir) to a susceptible host.
• Direct transmission: Immediate transfer of
the agent from a reservoir to a susceptible
host.
• Indirect transmission:Transmission of an
infectious agent to a susceptible host through
the aid of a vehicle, a vector or suspended air
particles.
35

• Direct transmission
 Touching
 Kissing
 Biting
 Direct projection
 Blood
transfusion
• Indirect transmission
 Airborne
 Vehicle-borne
 Vector-borne
 Non-vector
intermediate host
 Parenteral injections
36

37
Factors Affecting Disease Transmission
and Symptomatic Clinical Disease
Host
Vector
Agent Environment
-- Susceptibility
-- Immune response
-- Resistance
--- Portal(s) of entry
-- Virulence Toxigenicity
-- Infectivity Resistance
-- Pathogenicity Antigenicity
VECTOR
-- Prevalence
-- Portal(s) of entry
-- Balance of immune to
susceptible individuals
--- Opportunity for
exposure (e.g. crowding)

4. Portal of Exit
• Portal of exit is the way the infectious
agent leaves the reservoir.
• Possible portals of exit include all body
secretions and discharges: Mucus, saliva,
tears, breast milk, vaginal and cervical
discharges, excretions (feces and urine),
blood, and tissues. For example feces is the
portal of exit for the eggs of hook worm.
38

5. Portal of entry - is the site where an infectious
agent enters a susceptible host.
Examples:
-Nasal mucosa is portal of entry for common cold
-Conjunctiva is the portal of entry for trachoma
-Injury site is portal of entry for tetanus
6. Susceptible human host: The susceptible
human host is the final link in the infectious
process.
Host susceptibility or resistance can be seen at
the individual and at the community level.
39

3. Infection and Disease Outcome
• Exposure to an infectious agent does not
necessarily lead to infection, and
• An infection does not necessarily lead to
disease
• Infection may remain asymptomatic or sub-
clinical, or may lead to overt clinical disease
40

• The progress of an infectious agent and disease
outcome can be quantified as follows:
1. From exposure to infection
 Infectiousness: the proportion of an exposed
susceptible host who become infected (measured
by infection rate), as:
No. infected/No. susceptible and exposed x 100
41

2. From infection to disease
 Pathogenicity: the proportion of
infected people who develop clinical disease,
and measured by the clinical-to subclinical
ratio, as:
(No. of clinical cases) : (No. of subclinical cases)
42

3. From disease to disease outcome
 Virulence: the proportion of persons with
clinical disease who become severely ill or
die, and measured by:
– Case-fatality-rate
– Hospitalization rate
43

Fig . Outcomes at each stage of infection
Exposure Infection Disease Disease
outcome
Infectiousness Pathogenicity Virulence
44

Variation in Severity of Illness
• Infectious disease has a wide spectrum
of clinical effects.
CFR = No. of deaths/No. of cases of that disease
Inapparent
infection
Mild
disease
Severe
Disease Death
No signs or
symptoms
Clinical illness with symptoms
Fig 11. The spectrum of disease from communicable disease
45

3. Natural History of Diseases
• Refers to the progress of a disease process, in
the absence of intervention.
• Begins with exposure with the causative
agent capable of causing disease.
• Without intervention, the process ends with
recovery, disability or death.
• Halted at any time in the progression by
intervention, host factors, other influences.
46

NATURAL HISTORY OF DISEASE
• Each disease has its own natural history
• Helps in understanding the intervention measures
that could be undertaken in order to prevent or
control the disease
• Four main stages:
• Stage of Susceptibility
• Stage of Pre-symptomatic Disease
(Sub clinical stage)
• The Clinical Stage
• Stage of Outcome
47

48
I. Stage of Susceptibility
Disease has not yet developed but there are
factors that favor occurrence (risk factors).
II. Stage of Pre-symptomatic Disease (Sub clinical
stage)
The disease process has already begun but the
disease is not manifested (no signs and symptoms
of disease are detectable).
The initiation of the disease process can be
evidenced by investigation methods, e.g., serology
test for certain diseases

49
III.The Clinical Stage
• Signs and Symptoms of the disease are manifested in this
stage. The severity of the disease is variable depending on the
interaction of certain factors:-
 Nutritional status
 Immunity of individuals
 Virulence of the disease causing agent
 The presence / absence of medication
 The presence of underlying illness (TB and HIV/AIDS)
IV. Stage of Outcome
In this stage the disease has occurred and left over damage
to the body which limits the activity of the victim (disability)
or depending on the seriousness of the condition has ended
with the death of the victim.
N.B: Recovery can take place at any stage in the course of the
disease.

The natural history of infectiousness includes:
Prepatent period: the time interval from infection to
becoming infectious (shedding of the agent).
Infectious period: the time during which an infected host
could infect another host or vector.
Incubation period: the time from infection to
symptomatic disease. Persecutor
The probability of developing symptomatic disease after
becoming infected is pathogenicity (the capability of an
infectious agent to cause disease in a susceptible host).
50

51
Fig 1. Natural history time lines for infection and disease

Disease Transmission Probability
 The transmission probability is the probability that, given there
is contact between an infective source and a susceptible host,
successful transfer of the infective agent will occur so that
susceptible host become infected
 Transmission probability, helps understanding of the dynamics
of infection and effects of intervention.
 Infectious Host Susceptible Host
Transmission depends on: -infectious host
-susceptible host
-contact definition
-infectious agent
10/5/2023

Cont…
 Spread of disease through person to person transmission of
infectious agent depends on:-
Generation time
Herd immunity
10/5/2023

Cont…
1. Generation time: the time between exposure and maximum
communicability of disease.
 In case of apparent infections generation time may be
equivalent to incubation period.
2. Herd immunity: This refers to a community resistance to
spread of an infectious agent as a result of immunity gained
by high proportion of individual members of the community.
 Though it may not be important to achieve 100% immunity
for successful breakage of the chain of infection.
10/5/2023

• The resistance to an infectious agent of an entire group
or community (and, in particular, protection of
susceptible persons) as a result of a substantial
proportion of the population being immune to the
agent.
• Herd immunity is based on having a substantial number
of immune persons, thereby reducing the likelihood
that an infected person will come in contact with a
susceptible one among human populations, also called
community immunity
Example - If 90 % of the children are vaccinated for measles, the
remaining 10 % of the children who are not vaccinated might not become
infected with measles because most of the children (90 %) are vaccinated.
That means transmission from infected person to other susceptible
children will not be easier 55
Herd immunity

56
Conditions under which herd immunity best
function.
-Single reservoir
-Direct transmission
-Total Immunity
-Number of shedding of agents by Immune host
-Uniform distribution of Immunes
-No over crowding.
• One problem is that, in highly immunized populations,
the relatively few susceptible persons are often clustered
in subgroups defined by socioeconomic or cultural
factors. If the pathogen is introduced into one of these
subgroups, an outbreak may occur.

Measure of Transmission Probability
 There are two/three common ways of estimating transmission
probability.
1. Secondary Attack Rate
2. Binomial Model
3. Attack Rate
10/5/2023

1. Secondary Attack Rate (SAR):
• Refers to number of cases arising from one case
• Given one case  observed case/s
 Hence SAR gives clue as to whether there is successful
transmission
 SAR is a proportion, not a rate.
Cont…
* SAR = number of new cases
number of susceptible contacts
10/5/2023

Age in
Years
Population Cases
Total
No. susceptible
before primary
cases occurred
Primary Secondary
2-4 300 250 100 50
5-9 450 420 204 87
10-14 152 84 25 15
Secondary Attack Rate
%
100
X
Cases
Initial
of
Number
group
the
in
es
Susceptibl
of
Number
Cases
Initial
of
Number
Cases
of
Number
Total
Rate
Attack
Secondary



%
33
%
100
X
100
250
100
150
%
100
X
Cases
Initial
of
Number
group
the
in
es
Susceptibl
of
Number
Cases
Initial
of
Number
Cases
of
Number
Total
)
Years
4
2
(
Rate
Attack
Secondary 







Cont…
10/5/2023

 Household SAR: is used for assessment of vaccine efficacy and
for directly transmissible disease e.g. measles.
 Also, it is calculated during out breaks.
Cont…
* Secondary AR= New cases among contacts of index cases
during the period
Total number of contacts with the index cases
* SAR = Number of persons exposed (have contact
with a known case) who develop disease X 10n
Total number of susceptible exposed person
10/5/2023

 The data required for estimating secondary attack rate are:
The time of onset of disease for each case in the household;
Knowledge of who is susceptible;
Estimates/assumptions about minimum and maximum
incubation periods;
The latent period; and
The maximum time that a person remains infectious;
sometimes it can assumed that the onset of symptoms
coincides with the onset of infectiousness and that there are
no in-apparent cases.
Cont…
10/5/2023

2. Binomial Models of Transmission Probabilities:
 This model is often used when susceptible individuals are
exposed to more than one potentially infectious case.
 The following notations and formulas are used for this model:
Cont…
10/5/2023

Cont…
P The probability of transmission during a contact between a susceptible and
infectious person
Q=1-p The probability of the susceptible person’s escaping infection during the
contact
N Number of contacts with an infective or with different infective individuals
qn=(1-p)n The probability of escaping infection from all n potentially infective contacts
1-qn=1-(1-p)n The probability of being infected after n contacts (the probability of not
escaping infection from all n contacts
P^ The maximum likelihood estimate if the transmission probability under the
binomial model is: Number of susceptible who become infected
Total number of contacts with infective
Note:-The numerator is the same as for secondary attack rate (SAR).
-The denominator in here is total number of potentially infectious
contacts that susceptible individuals make, while in SAR each
susceptible person had just one potentially infectious contact with
infective case.
The two formulas would the same if everyone in the binomial model made
just one potentially infectious contact.
10/5/2023

3. Attack Rate(AR)
 An attack rate is a variant of an incidence rate, applied to a
narrowly defined population observed for a limited time, such
as during an epidemic.
 It is usually expressed as a percent.
Cont…
* AR= New cases among the population during the specified period
Population at risk at the beginning of the period
10/5/2023

Communicable Diseases ......
Levels of Disease Occurrence
• Diseases occur in a community at different levels at a
particular point in time.
• Some diseases are usually present in a community at
a certain predictable level, this is called the expected
level,
• At times disease may occur in excess of what is
expected
65

1. Expected levels
a) Endemic: a persistent level of low to
moderate occurrence
b) Hyper-endemic: a persistently high level of
occurrence
c) Sporadic: occasional cases occurring at
irregular intervals
66

2. Excess of what is expected
a) Epidemic/Outbreak: occurrence of disease in
excess of what is expected in a limited period.
b) Pandemic: an epidemic spread over several
countries or continents, affecting a large number
of people.
67

68
Time
Number of
cases
Endemic
Hyper-endemic
Epidemic/Outbreak
Levels of disease occurrence

• Disease Clustering: is defined as an aggregation of
relatively rare events or diseases in time and/or
place.
• A disease cluster is a mini-epidemic of a rare event
in which occurrence of the disease is clearly in excess
of than expected.
• Clusters may provide useful clues to public health
action, but often they are difficult to handle because
of small numbers.
69

4. Levels of Disease Prevention
• The aim is to implement interventions that
prevent infections or ameliorate infections.
• Involves the interruption or slowing of disease
progression through appropriate intervention.
• Epidemiology plays a central role in disease
prevention by identifying modifiable causes of
disease and their risk factors
70

1. Primordial
 Underlying condition for disease
causation exists
 Prevention of factors contributing to
increased risk of disease
Eg. smoking, environmental pollution
• Target
-Total population
- Selected groups
71
Four levels of disease prevention

2) Primary prevention:-
• Specific causal factors exist
• The causative agent exists but the aim is to
prevent the development of disease by
eliminating causes of disease or increasing
resistance to disease.
Target
• Total population
• Selected groups
• healthy individual
 Primary prevention has 3 components.
• These are health promotion, prevention of
exposure, and prevention of disease.
72

A. Health promotion
•It consists of general non-specific
interventions that enhance health and the
body's ability to resist disease.
•Improvement of socioeconomic status,
provision of adequate food, housing,
clothing, and education are examples of
health promotion.
73

B. Prevention of disease:-
is the prevention of disease development after the
individual has become exposed to the disease
causing factors. Immunization is an example of
prevention of disease.
• Immunization acts after exposure has taken
place.
• Immunization does not prevent an infectious
organism from invading the immunized host, but
does prevent it from establishing an infection.
If we take measles vaccine, it will not prevent the
virus from entering to the body but it prevents
the development of infection/disease. 74

C. Prevention of exposure:- is the
avoidance of factors which may cause disease if
an individual is exposed to them.
Examples can be provision of safe and adequate
water, proper excreta disposal, and vector control
3) Secondary prevention:-
• After the biological onset, but before the
advancement of disease
•The objective of secondary prevention is to stop
or slow the progression of disease so as to
prevent or limit permanent damage.
75

• Secondary prevention can be achieved through
detecting people who already have the disease
as early as possible and treat them. It is carried
out before the person is permanently
damaged.
• Target : Patients
Examples:
• Prevention of blindness fromTrachoma
• Early detection and treatment of breast cancer
to prevent its progression to the invasive stage,
which is the severe form of the disease.
76

4) Tertiary prevention:– is targeted towards
people with permanent damage or disability. Tertiary
prevention is needed in some diseases because
primary and secondary preventions have failed, and in
others because primary and secondary prevention are
not effective.
It has two objectives:
• Treatment to prevent further disability or death and
• To limit the physical, psychological, social, and
financial impact of disability, thereby improving
the quality of life. This can be done through
rehabilitation, which is the retraining of the
remaining functions for maximal effectiveness.
Target : Patients
77

78
Example:
1. When a person becomes blind due to vitamin A
deficiency, tertiary prevention (rehabilitation) can help
the blind or partly blind person learn to do gainful work
and be economically self supporting.
2. Diabetes mellitus a disease that can not really be
prevented or cured so primary and secondary
prevention are not effective .Hence .the goal of Tertiary
prevention in diabetics is to control the level of their
blood sugar using drugs and/or diet and to treat
complication properly in order to improve the quality of
life. Prevent permanent damage such as blindness .and
prevents early death.

Table 1. Levels of prevention in relation to the
stage of the disease.
Levels of
prevention
Natural history of diseases Stages of disease Target
Primary Healthy person
exposure
recovery
Specific causal
factors exist
Total
population,
selected
groups, healthy
individuals
Secondary Biological/sub-clinical pre-symptomatic
stage
recovery
Clinical onset
Early stage of
disease
Clinical stage
A/symptomatic
patients
Tertiary
Permanent damage, disability, Death
Late stage of
disease
Patients

5. Managing Communicable diseases
1. Measures Directed Against the Reservoir
2. Measures that Interrupt the Transmission of Organisms
3. Measures that Reduce Host Susceptibility
10/5/2023 80
Measures Directed Against the Reservoir
Domestic animals as
reservoir
•Immunization
•Testing of herds
•Destruction of infected animals
Wild animals as reservoir •Post-exposure prophylaxis
Humans as reservoir •Removal of the focus of infection
•Isolation of infected persons.
•Treatment to make them non-infectious.
•Disinfection of contaminated objects.
By Abera G(BSc, MPH in Epidemiology).

Cont…
10/5/2023 81
Measures that Interrupt the Transmission of Organisms
For diseases
transmitted by
ingestion
•Purification of water
•Pasteurization of milk
•Inspection procedures designed to ensure safe food supply.
•Improve housing conditions.
For disease
transmitted by
respiratory routes
•Chemical disinfection of air and use of ultraviolet light.
•Work on ventilation patterns, like unidirectional
("laminar") air flow to reduce the transmission of
organisms in hospitals
For diseases whose
cycles involve an
intermediate host
•Clearing irrigation farms from snails to control
schistosomiasis.

Cont…
10/5/2023 82
Measures that Reduce Host Susceptibility
Active immunization • Mass vaccination
• Selective vaccination
Passive immunization •Transfer of maternal antibodies to the
fetus through the placenta.
•Prophylaxis administration of immune
serum globulin (ISG).
Chemoprophylaxis •Use of antibiotics for known contacts of
cases
•Use of prophylaxis to persons travelling
to endemic areas.

2- Infectious Disease Epid.pptx

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2- Infectious Disease Epid.pptx