Exam 2-Public Health & Study Disease &Epidemics

Ways of Case Finding

Informed by
• Characteristics of the outbreak (known vs. unknown disease)
• Characteristics of disease

Line Listing

is a table that contains key information about each case in
an outbreak, with each row representing a case and each column
representing a variable such as demographic, clinical and
epidemiologic information (e.g., risk factors and exposures).

information describes an outbreak in terms of person, place
and time

Contact tracing

the systematic process of
identifying, assessing, managing, and supporting
contact persons of infectious individuals. (WHO)

Contact tracing steps

• Identify people who may have been exposed to
an infectious disease (ie contacts)
• Notifying (while preserving anonymity for cases)
• Monitoring contacts for development of disease
• Supporting with the aim of breaking the chain of
transmission
• May include:
• Counseling (risk, symptoms to watch for, if & how
long to isolate)
• Testing
• Preventive treatments such as medications or
vaccination

Contact

an exposure to an infectious disease that involves interaction
with an infected individual or contaminated environment during a
given period and in a manner that makes transmission likely,
considering the nature of the disease and the context of the contact

Contact person

someone who has been exposed to an infectious
disease pathogen through contact with an infectious person.
Depending on the disease mode of transmission, this can be direct or
possibly indirect.

Who is Contact?

Depends on the disease!
• When determining who is a contact person, the
following elements contribute to defining the contact:
• The mode of transmission (airborne, direct contact,
bloodborne, etc)
• The diseases’ clinical presentation and epidemiological
characteristics (e.g. incubation period, infectious period,
presence of symptoms)
• The duration of potential exposure
• The physical distance the individual was from a case
• The susceptibility of the individual (for example, immune
status) and protective factors (vaccination, personal protective
equipment)
• The type of interaction the individual had with the case
• The environment in which that interaction took place
Contact =/= Case

Descriptive Epidemiology

The process by which the outbreak is characterized by time, place,
and person

Defining Person

Characterization of the outbreak by person provides a description of who
is a case-patient and who is at risk.

• Person characteristics that are usually described include both host
characteristics (age, race, sex, and medical status) and possible exposures
(occupation, leisure activities, and use of medications, tobacco, and drugs).
• Early in an investigation, investigators may restrict the descriptive
epidemiology to numbers of cases. However, in many circumstances the
investigators also calculate rates (number of cases divided by the
population or number of people at risk). Rates are essential for identifying
groups with elevated risk of disease.

Defining Place

• Assessment of an outbreak by place provides information on the
• Geographic extent of a problem
• May also demonstrate clusters or patterns that provide important clues about
the cause
• Ex. For a spot map that indicate each patient’s residence, if the map
shows a cluster or other pattern (such as cases along a road), the
investigator must consider possible explanations — perhaps water
supplies, wind currents, or proximity to a restaurant or grocery.

Epidemic Curve

A type of histogram, used to depict
the time course of an outbreak 

-provides a simple
visual display of the outbreak’s
magnitude and time trend

Disease Dynamics

For any given pathogen, the
incubation & latency period(s) are
typically known & stay the same
• Asbestos (mesothelioma): 20 years
• E coli (food poisoning): 3-4 days

Point source outbreaks

•involve a
common source, such as
contaminated food or an infected
food handler, and all the exposures
tend to occur in a relatively brief
period.
•tend to
have epidemic curves with a rapid
increase in cases followed by a
somewhat slower decline, and all
of the cases tend to fall within one
incubation period.

Continuous common source outbreaks

occur due
to an ongoing exposure to a common source.
• The curve may also rise to a peak and then fall, but
the cases do not all occur within the span of a
single incubation period. The down slope of the
curve may be very sharp if the common source is
removed or gradual if the outbreak is allowed to
exhaust itself.

Propagated outbreaks

-transmission is
person-to-person, rather than from a
common source

- have a
series of successively larger peaks, which are
one incubation period apart. The successive
waves tend to involve more and more people,
until the pool of susceptible people is
exhausted or control measures are
implemented.

Why we need latent treatment…

CDC estimates up to 13 million people in the United States live with
latent TB.
• Without treatment, 1 in 10 people with latent TB will get sick with
active TB disease at some point in their lifetime
• Do not have to isolate during treatment

Isolate?

Cured: Sputum-smear positive patient who become sputum-smear
negative in the last month of treatment and on at least one previous
occasion
• Don’t have to stay isolated until cured

May be done at home or in hospital, depending on the patient’s
condition as well as who lives in home (immunosuppressed, young
children, etc)
• Guidance varies somewhat by jurisdiction
CDPH 2024

Treatment is DOT (Abbreviation)

Directly Observed Therapy

Category I DOT Medication Regimen (WHO)

Standard, antibiotic-sensitive, new cases of TB

Long time (4-6 months!)
• A lot of pills
• Side effects

Standard, antibiotic-sensitive, new cases of TB
• 6 months total treatment
• Isoniazid, Rifampin, Pyrazinamide, and Ethambutol daily x 2 months
• Isoniazid and Rifampin either daily or 2x per week x 4 months

Why DOT?

Studies show that 86-90% of patients receiving DOT complete
therapy, compared to 61% for those on self-administered therapy.

• Patients who fail/interrupt Category I move on to Category II, which is
8 months & includes an injectable medication for the first two
months (so…even less palatable!)
• Incomplete or incorrect treatment contributes to drug-resistance

Effectiveness of TB Treatment

Cure rates around 90-95% under
ideal conditions
• The global average treatment
success rate for people receiving
first-line TB treatment was 88% in
2022 (WHO).

Antimicrobial resistance (AMR)

accounts for resistance from
bacteria, as well as fungi, viruses,
parasites, and other microbes

DOTS

• Directly Observed Therapy
• Sometimes called DOTS
(Directly-Observed Therapy,
Short Course)
• Direct observation of taking
meds by a relative, community
member or public health worker
for entirety of treatment

How does MDR/XDR-TB Develop?

Characteristics of TB:
• Slow replication
• Granulomas
• Asymmetric replication→Increased chances for
mutation
Long Treatment Time→Increased Selective
Pressure

Societal/Structural:
• Inadequate and/or interrupted
supply of appropriate drugs
• Poor quality drugs (counterfeit
drugs)
• Poor patient education on
importance of taking entire
course of treatment
• Lack of access to care (even in
US, DOT is not covered by all
health insurers!)

Drug-Resistant TB

Multi-Drug Resistant TB (MDR-TB)
• TB that is resistant to at least isoniazid and rifampin (main drugs of Cat I DOT)
• Curable, but requires 2nd or 3rd line medications and treatments of 2 years or
more
• Extensively Drug-Resistant TB (XDR-TB)
• TB that is resistant to either (or both) isoniazid and rifampin AND which are
also resistant to any fluoroquinolone and at least one additional Group A drug
(Group A drugs are the most potent group of drugs in the ranking of second-
line medicines).
• May be able to be cured, but much less likely than regular or MDR-TB. Cure
depends on the extent of the drug resistance, the severity of the disease, and
whether the patient’s immune system is compromised.

Asymmetrical Replication

Characteristics of growth and
division in B. subtilis and
mycobacteria. B. subtilis and E. coli
grow by adding new cell wall
(gray) along the lateral cell body.

When microbes divide, you usually get more of
the same: One cell splits up and creates two
identical copies of itself.
• Mycobacteria divide asymmetrically, generating a
population of cells that grow at different rates,
have different sizes, and differ in how susceptible
they are to antibiotics, increasing the chances
that at least some will survive.
• “Older," fast-growing cells are more susceptible
isoniazid. “Younger,” slower-growing cells are
more susceptible to rifampin.
• The asymmetry is a way for mycobacteria to keep
their population diverse

Antimicrobial resistance (AMR)

accounts for resistance from
bacteria, as well as fungi, viruses,
parasites, and other microbes

Contributors to Resistance

Inappropriate antibiotic prescriptions (”just in
case,” antibiotics for viral illnesses)
• OTC antibiotics (in some countries)
• Length of antibiotic treatment
• Old thought: Not finishing the dose may allow
only the most susceptible strains to be killed,
leaving room for the hardier ones to multiply
• New thought: long antibiotic courses increase
selective pressure for resistant strains
• Likely: completing shortest, most effective dose
for the pathogen is best….scientist are working
on it!
• Overuse of antibiotics in healthcare
environments
• Antibiotic over-use and inappropriate use in
livestock

How Do You Get MDR/XDR TB?

A patient who is receiving treatment for active regular TB has
incomplete/inappropriate treatment, giving TB bacterium the chance
to develop resistance
OR
• Catch MDR-TB or XDR-TB directly from someone who has it
• Instead of the version of TB you catch being sensitive to antibiotics, it is drug-
resistant from the start
• Evidence suggests drug-resistant TB is not more easily spread/more
contagious than regular TB

Preventing MDR/XDR-TB

Rapid TB diagnosis with drug susceptibility testing
• Ensure timely access to appropriate treatment
• Enhanced infection control measures (particularly in healthcare
settings)
[This all requires a lot of infrastructure!]

Testing-For the contacts-Tuberculosis

A skin test result of 5 mm
or more is considered a
positive result for a TB
contact.
• The interpretation of IGRA
blood test results is the
same for all patients; no
cut-points are defined
differently for contacts.

Medications?-For the contacts-Tuberculosis

• Typically not for contacts who test negative
• There are some exceptions, such as some HIV-positive contacts
• If a contact tests positive, they become a case and then we treat
(refer to last lecture!)

Preventing Spread—Vaccination?-Tuberculosis

• Bacille Calmette-Guérin (BCG)
Vaccine
• BCG is an attenuated strain of
Mycobacterium bovis
• Currently the only licensed vaccine
against TB
• First developed almost a century
ago Most commonly from “raw” (unpasteurized) milk

Nope (In the US, at least)-Vaccination

• In countries where TB is common,
it is given to infants & small
children to protect from getting
severe forms of active TB disease,
such as TB meningitis and miliary
TB disease.
• In the United States, BCG is only
considered for people who meet
specific criteria, for example
children who are continually
exposed, and cannot be separated
from adults with untreated or
inadequately treated TB disease.

NOT vaccinating?!?-Tuberculosis

The vaccine is not generally used in the United States because of:
• The (relative) low risk of infection with TB bacteria in the United States
• The vaccine’s potential to cause a false-positive TB skin test reaction.
• Although BCG is protective against disseminated disease in young children, it
has variable efficacy against pulmonary TB, particularly in adults
To understand the second two…

Immune System

• The immune system distinguishes self from non-self and eliminates
potentially harmful non-self molecules and cells from the body.
• The immune system also has the capacity to recognize and destroy
abnormal cells that derive from host tissues

Antigen

Any substance that stimulates
an immune response in the body (can
be from inside or outside the body)

Pathogen

Any organism capable of
causing disease, such as a bacteria,
virus, fungus, etc.

Barrier Defenses

• Skin
• Mucous membranes
• Tears--lysozyme
• Earwax
• Mucus and cilia
• Stomach acid

The Barriers Have Been Breached….

The immune system uses white blood cells and antibodies to identify
and eliminate organisms that get through the body’s natural barriers.

Innate (natural) immunity-Immune System

• Does not require prior exposure to an invader (antigen)
• Responds immediately to an invader.
• Generic response to any invader

Acquired (adaptive) immunity

• Requires prior exposure to an invader (antigen)
• Takes time to develop after the initial encounter with a new invader.
Thereafter, response is quick.
• Specific to that antigen (and sometime closely-related ones)

Innate Immune System

The body also defends against
infection by increasing the number
of certain types of white blood cells
(neutrophils and monocytes), which
surround and destroy invading
microorganisms.
• The increase can occur within
several hours because white blood
cells are released from the bone
marrow, where they are made.
• The blood carries white blood cells
to sites of infection.

Acquired Immune System

When an infection develops, the immune system also responds by
producing several substances and agents that are designed to attack
the specific invading microorganisms

Lymphocytes can be further divided into B and T cells
• B cells and T cells work together to destroy invaders

Acquired Immune System-B cells

Fight bacteria and viruses by making Y-shaped
proteins called antibodies, which are specific to
each pathogen and are able to lock onto the
surface of an invading cell and mark it for
destruction by other immune cells.

Acquired Immune System-T-Cells

Helper T-cells stimulate B-cells to make
antibodies and help killer cells develop.
• Killer T-cells directly kill cells that have already
been infected by a foreign invader.

Antigen

Any molecule capable of being
recognized by the immune system is
considered an

Antibodies

are blood proteins
produced in response to and
counteracting a specific antigen.
-combine chemically with
substances which the body recognizes
as alien, such as bacteria, viruses, and
foreign substances in the blood.

Antibodies don't all do the same thing once they've
bound to a target.
• Some will directly neutralize a threat, preventing a
pathogen from entering a cell.
• Others may disable the invader by wrapping viruses or
bacteria in a gooey coating.
• Others tag invaders, so that killer T-cells can remove
them
• Other antibodies might signal macrophages to come
gobble up the invader.

Antibodies on B-Cells Provide Lasting
Immunity

There are about a trillion B-cells in the body, and
each one has a unique (IgM) antibody that sits on
the B-cell surface and each binds, to one antigen
• These B-cells then patrol the body
• Most of the time, they don't bind anything. But if a
B-cell does bind some foreign substance, that
triggers the B-cell to grows in size and replicate
itself

T-Cells

Helper T-cells stimulate B-cells to make antibodies
and help killer cells develop.
• Killer T-cells directly kill cells that have already been
infected by a foreign invader
• Both (but primarily Helper T-cells) secrete interferon-
gamma, which is a chemical messenger that amps up
the immune system (in addition to other things like
anti-cancer activity!)

Vaccines

Vaccines contain some part of the same germs that cause disease, but
they have been either killed or weakened to the point that they don’t
make you sick, but they DO activate your immune system
• A vaccine stimulates your immune system to produce antibodies,
exactly like it would if you were exposed to the disease.
• You develop immunity to that disease, without having to get the
disease first

Live-Attenuated (MMR, Varicella,
BCG):

Contain live pathogens from either a
bacteria or a virus that have been
"attenuated," or weakened
• The immune system typically reacts
strongly to them and it will typically
remember the pathogen for a very
long time, so booster shots, are not
always needed.
• Downside: Have to be cautious with
certain populations—e.g. caregivers
for immunocompromised people

Inactivated (Polio, Flu):

Take a live pathogen and
inactivate or kill it
• Can be mass-produced and are
relatively inexpensive to make

Subunit (Shingles, Hepatitis B)

Made from a piece of a pathogen, not
the whole organism

• Subunit vaccines only contain pieces of a
pathogen, not the whole organism, so
they cannot make you sick or cause
infection. This makes them suitable for
people who should not receive “live”
vaccines, such as young children, older
people, and immunocompromised
people

Toxoid (Tetanus)

Use inactivated toxins to target the
toxic activity created by the
bacteria, rather than targeting the
bacteria itself.
• The goal of toxoid vaccines is to
give people a way to neutralize
those toxins with antibodies
through vaccination
• Toxoid vaccines are especially good
at preventing certain toxin-
mediated diseases such as tetanus,
diphtheria, and pertussis.

Viral Vector (Ebola, J&J COVID)

Use a harmless virus to deliver to the
hosts cells the genetic code of the antigen
you want the immune system to fight
• Usually trigger a strong immune response.
Typically, only one dose of the shot is
needed to develop immunity

mRNA (COVID)

Contains RNA material that “teaches”
our body how to make a specific type
of protein that is unique to the virus,
but does not make the person sick.
• The protein triggers an immune
response, which includes the
generation of antibodies that
recognize the protein.
• Can create a lot of a vaccine much
faster than traditional technology.
• Very adaptable

Variable Efficacy of BCG

Differences in strains?
• The the strain of BCG used for vaccination was sent to different laboratories
worldwide for vaccine production.
• Over time, hundreds of passages and differences in BCG growth protocols
between laboratories have contributed to genetic variability among the
strains
• However, testing of the different strains is inconclusive as to whether this
matters to vaccine effectiveness

Variable Efficacy of BCG-“Masking Hypothesis”

• Exposure to non-tuberculous mycobacteria interferes with BCG
efficacy, either by masking or by blocking.
• The masking hypothesis is demonstrated by studies where
adolescents in London and Malawi who had not been previously
vaccinated were vaccinated with BCG.
• The children in London had low baseline mycobacterial immunity
which was significantly increased after BCG vaccination.
• The children in Malawi had high background immunity to
mycobacteria due to environmental exposure and little incremental
increase after vaccination
• This suggests that prior immunity induced by non-tuberculous
mycobacteria masks the effects of BCG.
• The background immunity induced by non-tuberculous
mycobacteria might inhibit the replication of the M. bovis strain in
BCG, which is necessary for its efficacy

Mycobacterium tuberculosis-Variable Efficacy of BCG

The human host–pathogen interaction
has evolved for thousands of years
• expresses a wide range of antigens to counteract its
recognition, phagocytosis, and destruction by immune cells.

Characteristics of TB Itself

• For a vaccination to work, your immune
system needs to “see” some part of the
outside of the bacteria to recognize and
attack it.
• The waxy cell wall of M. tuberculosis
does not give your immune system much
to “recognize.”
• It also hinders the access of immune cell
enzymes produced by CD8⁺ cytotoxic T
lymphocytes

Possible New Vaccines

• Possibly “training” macrophages to increase efficiency of eliminating
M. tuberclosis
• Using aerosol vaccines could be the key for a better immunization,
this will reproduce the natural route of infection of M. tuberculosis

IGRA

Quantitates the amount of interferon-gamma produced in response
to specific antigens from M. tuberculosis, which are distinguishable
from those present in BCG and most other non-tuberculous
mycobacteria.

Why?-IGRA

It all comes down to the antigens used in each test:

• The PPD antigens used in the skin test cross-react with the M. bovis used in
the vaccine. This means the immune system “sees” the PPD antigens and
reacts with the long-term immunity antibodies it developed when the person
received BCG

• IGRA does not cross-react with non-M. tuberculosis mycobacteria

False Positives on TST, not on IGRA

There is no reliable way (based on test result alone) to distinguish a
positive TB skin test reaction caused by BCG vaccination from a
reaction caused by true TB infection
• Before IGRAs, +TSTs had to get X-rays to rule out disease causing the positive
test
• Now often confirmed by IGRA (or, if the person tells us they’ve had BCG, they
get an IGRA from the start)

False positive TSTs

With the advent of the TB blood tests (IGRAs) this is less of a problem,
but they were introduced in 2005 and were initially significantly more
expensive than TSTs
• The entirety of the US TB prevention relied on TSTs until (relatively)
recently, so not complicating screening by regular BCG use was key!

Which of the following are reasons we do not routinely give the BCG vaccine in the US?

It has limited efficiency against pulmonary TB, especially in adults 

People in the US have relatively low risk of infection with TB 

It can create false positives on the TST skin test for TB  

The innate immune system does not require prior exposure to an antigen to be activated

True

Which part of the immune system is responsible for lasting immunity after vaccination or infection? 

Antibodies

Why does the immune system have more difficulty “recognizing” M. tuberculosis than many other pathogens?

Because the waxy surface of the bacteria’s cell wall does not provide many recognizable antigens

Audience Segment

groups within an audience defined by shared
qualities.

Credibility

Two influencers are the speed of release and the
accuracy of information

Speed of Release

Even if you do not have all of the details, do not wait to share the information that you
do know that can save lives or prevent injury.
• “If you do not communicate about your response, as far as the public knows, you are not
responding.”

Accuracy of Information:

People will depend on your organization for
accurate information about the emergency and what they can do to stay safe
or help respond.