Tuberculosis (TB) Basics

Treatment Action Group

TB/HIV Advocacy Toolkit
January 2021

With thanks to Adam Almeida, Andolyn Medina, and Dr. Jennifer Furin
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 •Fundamentals of TB
•Transmission of TB
•Immune Response to TB
Overview •TB Infection vs. TB Disease
•Drug Sensitive vs. Resistant TB
•Global Statistics
•TB and COVID-19
•Key Takeaways

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 FUNDAMENTALS OF TB

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FUNDAMENTALS

What is
Tuberculosis?

• Tuberculosis, commonly known as TB, is a disease that most commonly affects the lungs
• TB infection is caused by bacteria, called Mycobacterium tuberculosis (MTB)
• Under a microscope, MTB is identified by its long, rod-like shape and its waxy
appearance

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FUNDAMENTALS

• Bacteria are single-celled organisms, able to survive

either independently or dependent on another
MTB, organism to carry out life functions
the TB-causing • Like viruses, bacteria can be beneficial, harmful, or
bacterium neutral to the human body
 Humans require several bacteria and viruses to
carry out bodily functions, like digestion or
reproduction
• MTB is often harmful to the human body
• MTB are commonly referred to as TB bacilli
• The thick, waxy cell wall allows the TB germ to
spread through the air and survive for days
outside of the body

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 TRANSMISSION OF TB

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TRANSMISSION

How is TB Transmitted?
• TB is passed (transmitted) through the air
when someone who is infected coughs,
sneezes, shouts, or sings
• Droplets of saliva contain thousands of
TB bacilli
• Once inhaled, the droplets push their way
into the lungs, settling in tiny air sacs
(alveoli)
• TB is NOT spread through touch, blood,
sperm, vaginal fluids, food or liquids,
sharing utensils, dust, dirt, or vehicle
fumes

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TRANSMISSION
Factors related to the person with TB (index case):
• Bacillary count/load (amount of MTB in the body)
• Presence of TB in lungs (pulmonary TB) and a cough
• Being on effective TB medication
 After 2-3 weeks on an effective treatment regimen,
people are usually not infectious anymore, though
What Affects must continue treatment through cure
• Wearing a mask
Transmission?
Factors related to the person being exposed to TB
(contact):
• Closeness and frequency of contact with index case
• Age of contact (children and older persons are more likely to
develop TB)
• Wearing an N-95 respirator (special kind of mask)

Environmental factors:
• ventilation
• size of room or space
• duration of exposure
• sunlight or ultraviolet (UV) light (sunlight/UV light kills TB
bacteria)

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 1.TB is a virus.
a) True
b) False

2.TB is passed (transmitted) when someone who is

infected:
a) Coughs
b) Sneezes
c) Shares utensils
d) All of the above

3.Which of the following affects TB transmission?

a) Bacillary load
b) Closeness + frequency of contact
c) Drug-resistance
d) All of the above

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 THE IMMUNE RESPONSE TO TB

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 IMMUNE RESPONSE

The Immune
Response To TB

• The immune system detects foreign particles

in the body and triggers an immune response
in order to remove them
• In a healthy individual, the immune system
coordinates different cells to act together in
order to identify and remove a potentially
harmful agent
• When an individual is exposed to TB, the
immune system is activated

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IMMUNE RESPONSE

• ANTIGEN-PRESENTING CELLS - (macrophages

and dendritic cells) patrol the body looking for
germs
The • CD4 T-CELLS - act as coordinator of the immune
Immune response instructing other cells to attack specific
invading germs
System • CYTOTOXIC T-CELLS - are involved in cell-to-cell
killing, when ordered by CD4 T-cells they seek out
and destroy cells that have been infected by a
specific germ

• B CELLS - are immune cells that, when instructed

by the CD4 T-cells, make antibodies

• ANTIBODIES – are proteins that attach to their

specific germs, marking them for destruction by
the immune system or stopping their ability to
reproduce

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 IMMUNE RESPONSE

The Immune Response to

TB

1 The antigen presenting cells

(dendritic cells and macrophages)
transport TB to the lymph nodes,
acting as the communication and
meeting center for the immune
system

2 In the lymph nodes, the cells chop

up the TB bacilli and present it to
the (helper) CD4 T-cell to
coordinate the immune response

3 Cytotoxic T-cells are activated to

kill cells infected with TB bacilli
and B cells release antibodies,
which also target infected cells to kill

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 TB INFECTION VS. TB DISEASE

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 INFECTION VS DISEASE

• There is a difference between TB INFECTION and

TB DISEASE
 It is possible to be infected with TB and
not develop TB disease
 About 10% of people living with TB infection
TB develop TB disease

Infection  People can progress directly to developing active

disease without having a long “latent” period
vs. Disease • [Latent] TB infection (LTBI) refers to the period when the
immune system is successful in containing the TB and
preventing progression to disease
 The TB bacilli remains encased in a hard shell,
called a tubercle
• Active TB disease refers to the time when TB is no
longer contained by the immune system and causes
disease
• These were previously thought to be two different disease
states; now they are thought to be part of a disease
spectrum, in which “latent” TB could be early-stage
(“sub-clinical”) active TB with a smaller number of bacteria

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 INFECTION VS DISEASE

(Latent)TB
Infection
vs.
(Active) TB
Disease
Latent TB TB Disease
TB lives but doesn’t grow in the body TB is active and grown in the body

Doesn’t make a person feel sick or Makes a person feel sick and have
have symptoms symptoms

Can’t spread from person to person Can spread from person to person

Can advance to TB disease Can cause death if not treated

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 INFECTION VS DISEASE

• TB infection can progress to active disease

when the body becomes weak, for example from
malnutrition, immune suppression, or
advanced age
• Among people living with HIV and without
Progression reliable access to effective HIV treatment, the
to TB immune system becomes compromised and
more vulnerable to the progression of TB
Disease infection into active TB
 TB is a common co-infection among, and the
leading killer of, people living with HIV
 People living with HIV are up to 21X more
likely to develop TB disease than people
without HIV
• Young children are up to 10X more likely to
develop TB and tend to develop more severe
forms of TB

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 INFECTION VS DISEASE

• Active TB disease affects the lungs

(pulmonary TB) or other parts of the body
(extrapulmonary TB)

• Pulmonary TB is the most common form of

(Active) TB disease

Pulmonary vs. • Extrapulmonary TB (EPTB) can occur in all

Extrapulmonary populations affected by TB, but is most
common among young children and in people
TB Disease living with HIV (~40% of TB cases among
people living with HIV involve extrapulmonary
TB)

 EPTB usually takes place in multiple

organs
in people with HIV
• Individuals can have pulmonary TB, EPTB,
or both

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 INFECTION VS DISEASE

When exposed to Children who

TB, young children are immuno-
(< five years) compromised
cannot usually mount due to HIV,
a robust immune malnutrition, or
response. For this other sicknesses
reason, they are more are also at risk
Immune likely to develop
severe forms of TB,
for developing
more severe
Response in including TB outside of forms of TB.
the lungs (extra-
Children pulmonary TB).

A functional immune
system takes many years to As children age Adolescents (ages
develop in a child. and their 10 to 18 years)
immune systems are more likely
develop, they to develop TB.
can better This may be due
control TB when to the impact of
exposed. If they get hormones/ puberty on
sick, they tend to have the immune response
a disease that is more to TB and increased
like adults. social activity.

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 INFECTION VS DISEASE

TB meningitis (TB in
the brain/nervous
system)
70-80% of children with
TB in Miliary or
disseminated TB (TB
TB have TB in the chest
and lungs (pulmonary
Children throughout the body) TB)

Pott’s disease (TB in the Children can become

TB can cause bones and spine) sick from a smaller
disease in any part of number of TB germs
the body, but the (paucibacillary TB)
most worrisome kinds
are: Children are more likely
than adults to develop TB
outside of the lungs—
or what is called extra-
pulmonary TB

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 1. It is possible to be infected with TB but to not have
symptoms or disease.
a) True
b) False
2. Which of the following can affect an individual’s risk
of TB infection progressing to active disease?
a) HIV
b) Malnutrition
c) Age
d) All of the above
3. Miliary TB is in what part(s) of the body?
a) Brain and nervous system
b) Bones and spine
c) Disseminated throughout the body
d) Lungs

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 DRUG-SENSITIVE VS. DRUG-RESISTANT TB

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 DRUG-SENSITIVE
VS. RESISTANT TB

• Drug-resistant TB (DR-TB) means a strain of MTB has

mutated (changed) in a way that helps it evade or resist
being killed by a specific drug(s)
• Resistance to TB drugs can be naturally occurring (“wild
type”) or develop over time as a result of inadequate or
irregular TB drug exposures, e.g., from:
 Incorrect prescription by healthcare provider
Drug  Poor quality drugs resulting in inadequate drug levels /
Resistance exposures
 Drug shortages resulting in treatment interruption /
discontinuation
 Lack of adherence to the treatment
• Most DR-TB is transmitted (primary resistance) rather than
developed (secondary resistance)
• Treatment for DR-TB is longer, more expensive, and
harder to tolerate than treatment for drug-sensitive TB
• DR-TB is generally separated into four groups, defined by
the medicine(s) to which TB bacteria are resistant

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 DRUG-SENSITIVE
VS. RESISTANT TB

Defining Drug-Resistant TB (DR-TB)

DS-TB MDR-TB Pre-XDR-TB XDR-TB

rifampicin rifampicin rifampicin rifampicin

isoniazid isoniazid isoniazid isoniazid
fluoroquinolone fluoroquinolone fluoroquinolone fluoroquinolone
aminoglycoside aminoglycoside aminoglycoside aminoglycoside
2020
2021
DS-TB MDR-TB Pre-XDR-TB XDR-TB

rifampicin rifampicin rifampicin rifampicin

isoniazid isoniazid isoniazid isoniazid
fluoroquinolone fluoroquinolone fluoroquinolone fluoroquinolone

Group A drugs Group A drugs Group A drugs Group A drugs

(bedaquiline, (bedaquiline, (bedaquiline, (bedaquiline,
linezolid) linezolid) linezolid) linezolid)

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 DRUG-SENSITIVE
VS. RESISTANT TB

TB Treatment Regimens
DRUG-SENSITIVE TB DRUG-RESISTANT TB
(DS-TB) (DR-TB)
4–6 months 6–20 months
4 drugs 3–8 drugs
first-line medicines second-line, new /
repurposed medicines

H = isoniazid Bdq, J = bedaquiline

R = rifampicin Lz, Lzd = linezolid
Z = pyrazinamide L, Lx, Lfx = levofloxacin
E = ethambutol M, Mx, Mfx =
P = rifapentine moxifloxacin
M = moxifloxacin C, Cs = cycloserine
… see module on
Dlm, D = delamanid TB Treatment for
Pa = pretomanid more information /
Am = amikacin detailed
Eto = ethionamide explanation.
Pto = prothionamide

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 1. Drug-resistant TB is less likely to be transmitted
between people.
a) True
b) False
2. How does drug resistance develop?
a) Inadequate drug exposures
b) Prescription for inappropriate/weak regimen
c) Inconsistent adherence to treatment
d) Naturally occurring mutations
3. XDR-TB is resistant to which of the following
medicines?
a) rifampicin
b) isoniazid
c) moxifloxacin
d) bedaquiline
e) All of the above

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 GLOBAL STATISTICS

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STATISTICS

Global Estimates of TB
It is There were An estimated There were an Geographically,
estimated an estimated 1.2 million estimated most people who
that one- 10.0 million children 1.2 million deaths from developed TB in
fourth of new cases of became sick TB in 2019 (nearly 5,000 2019 were in
the world TB in 2019 with TB in deaths per day) South-East Asia
is infected (active TB 2019 TB is the number one (44%), Africa
with TB disease), (children killer of people living (25%), and the
(latent TB among which account for with HIV, accounting for Western Pacific
infection) 500,000 had 12% of the an additional 208,000 regions (18%)
drug- global deaths in 2019
resistant TB disease
Until recently overtaken
burden)
by COVID-19, TB was
the leading infectious
cause of death
worldwide

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STATISTICS

29 2020 WHO Global TB Report

STATISTICS

30 2020 WHO Global TB Report

STATISTICS

8 countries contain 67% of new cases

• India. • China
• Indonesia • The Philippines
• Pakistan. • Nigeria
• Bangladesh • South Africa
31 2020 WHO Global TB Report
STATISTICS

32 2020 WHO Global TB Report

STATISTICS

33 2020 WHO Global TB Report

STATISTICS

34 2020 WHO Global TB Report

STATISTICS

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STATISTICS

See Full Report and Country Profiles:

Where https://www.who.int/teams/global-tuberculosis-programme
/tb-reports/global-tuberculosis-report-2020
to Find
Country-level
Statistics/
Information

See Interactive Maps and Country TB Dashboards:

http://www.stoptb.org/resources/cd/

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 TB AND COVID-19

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TB AND COVID-19

• COVID-19 caused by SARS-CoV-2 is a respiratory

pathogen that emerged in late 2019 and has caused
sickness in millions of persons worldwide;
• Symptoms of COVID-19 and TB may overlap (e.g.,
fever, cough), and persons being tested for COVID-19
should be tested for TB (many platforms used for TB
TB and testing can also be used for COVID-19 testing, e.g.,
GeneXpert);
COVID-19 • Persons with current TB or a history of TB may be at
increased risk of poor outcomes if they become sick
with COVID-19 so should take extra care to practice
mask-wearing, social distancing, and other protective
behaviors;
• The global COVID-19 pandemic has put at risk many of
the strides made in addressing TB on a global level
• WHO model estimates that a 25% drop in the number
of people diagnosed and treated for TB over a three-
month period will result in 200,000 excess TB deaths
(rolling global progress against TB back to where we
were in 2015)
• STBP model predicts that COVID-19 could cause an
additional 6.3 million TB cases globally between
2020 and 2025

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 TB AND COVID-19

39 2020 WHO Global TB Report

TB AND COVID-19

40 2020 WHO Global TB Report

TB AND COVID-19

2020 WHO Global TB Report, Chapter 3:

https://www.who.int/teams/global-tuberculosis-program
me/tb-reports/global-tuberculosis-report-2020

More WHO TB and COVID-19 Resource Page:

Information https://www.who.int/teams/global-tuberculosis-pr
and ogramme/covid-19

Resources
2020 UNSG Report on TB:
https://www.who.int/news/item/21-10-2020-un-secretar
y-general-outlines-priority-recommendations-to-acceler
ate-the-tb-response-and-reach-targets

A Deadly Divide: TB Commitments vs.

TB Realities:
http://www.stoptb.org/communities/divide.asp

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 KEY TAKEAWAYS

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KEY TAKEAWAYS

The Main Points

1 3 4 5
Tuberculosis (TB) Drug TB is a common
There is a resistance,
is a disease
spectrum of
caused a result of co-infection
TB disease,
by the bacteria, inadequate among, and the
including:
Mycobacterium or irregular number one
tuberculosis (Active) TB TB drug killer of, people
Disease: when exposures, living with HIV
the presence is on the rise
2 of MTB causes and evolving 6
TB is spread Coordinated
disease with
through saliva efforts are
(Latent) TB increased use
droplets in the air needed to
Infection: when of new and
when a person sick address TB
MTB is present repurposed
with pulmonary TB in the era of
without disease TB medicines
coughs, sneezes, COVID-19
shouts, or sings

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