Skip directly to search Skip directly to A to Z list Skip directly to navigation Skip directly to site content Skip directly to page options
CDC Home

Slide Set— Self Study Modules

Module 1: Transmission and Pathogenesis of TB

Text Only Version

Return to Main Menu

Slide 1

(Title Slide).  Self-Study Modules on Tuberculosis, 1-5. 
Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, 2010.

Slide 2

CDC Self-Study Modules on Tuberculosis, 1-5

  • Module 1: Transmission and Pathogenesis of TB
  • Module 2: Epidemiology of TB
  • Module 3: Targeted Testing and the Diagnosis of Latent TB Infection and TB Disease
  • Module 4: Treatment of Latent TB Infection and TB Disease
  • Module 5: Infectiousness and Infection Control

[Image: Front cover of the print-based Self-Study Modules on Tuberculosis, 1-5.]

Slide 3

(Title Slide).  Self-Study Modules on Tuberculosis.  Transmission and Pathogenesis of Tuberculosis.

Slide 4

Module 1: Objectives
At the completion of this module, learners will be able to:

  • Briefly describe the history of tuberculosis (TB)
  • Explain how TB is spread (transmission)
  • Define drug-resistant TB
  • Explain the difference between latent TB infection (LTBI) and TB disease
  • Explain how LTBI and TB disease develop (pathogenesis)
  • Describe the classification system for TB

Slide 5

Module 1: Overview

  • History of TB
  • TB Transmission
  • Drug-Resistant TB
  • TB Pathogenesis
  • Progression from LTBI to TB Disease
  • Sites of TB Disease
  • TB Classification System
  • Case Studies

Slide 6

(Title Slide).  History of TB

Slide 7

History of TB (1)

  • TB has affected humans for millennia
  • Historically known by a variety of names, including:
    • Consumption
    • Wasting disease
    • White plague
  • TB was a death sentence for many

[IMAGE: Red Cross Christmas Seal Campaign vintage image circa 1919.  Image says “The Next to Go.  Fight Tuberculosis.” Image credit: National Library of Medicine.]

Slide 8

History of TB (2): Scientific Discoveries in 1800s

  • Until mid-1800s, many believed TB was hereditary
  • 1865 Jean Antoine-Villemin proved TB was contagious
  • 1882 Robert Koch discovered M. tuberculosis, the bacterium that causes TB

[IMAGE:  Mycobacterium tuberculosis. Image credit: Janice Haney Carr.]

Slide 9

History of TB (3): Sanatoriums

  • Before TB antibiotics, many patients were sent to sanatoriums
  • Patients followed a regimen of bed rest, open air, and sunshine
  • TB patients who could not afford sanatoriums died at home

[IMAGE:  Sanatorium patients resting outside]

Slide 10

Breakthrough in the Fight Against TB (1)

Drugs that could kill TB bacteria were discovered in 1940s and 1950s

  • Streptomycin (SM) discovered in 1943
  • Isoniazid (INH) and p-aminosalicylic acid (PAS) discovered between 1943 and 1952

[IMAGE:  TB drugs pill bottle]

Slide 11

Breakthrough in the Fight Against TB (2)

  • TB death rates in U.S. began to drop dramatically
  • Each year, fewer and fewer people got TB
  • Most TB sanatoriums in U.S. had closed by mid 1970s

Slide 12

TB Resurgence

  • Increase in TB in mid 1980s
  • Contributing factors:
    • Inadequate funding for TB control programs
    • HIV epidemic
    • Increased immigration from countries where TB is common
    • Spread in homeless shelters and correctional facilities
    • Increase and spread of multidrug-resistant TB

[IMAGE:  March 16, 1992 Newsweek Magazine cover titled, “TB: Why It’s back.  How We Can Protect Ourselves”]

Slide 13

TB Prevention and Control Efforts

  • Increased governmental funding for TB control programs beginning in 1992
  • Number of TB cases has steadily declined since 1993

[IMAGE:  Graph showing the number of TB cases per year from 1982-2008. The resurgence of TB in the mid-1980s was marked by several years of increasing case counts until its peak in 1992. Case counts began decreasing again in 1993, and 2008 marked the sixteenth year of decline in the total number of TB cases reported in the United States since the peak of the resurgence. From 1992 until 2002, the total number of TB cases decreased 5%–7% annually. From 2002 to 2003, however, the total number of TB cases decreased by only 1.4%. In 2008, a total of 12,904 cases were reported from the 50 states and the District of Columbia. This represents a decline of 2.9% from 2007 and of approximately 50% from 1992.]

Slide 14

TB History Timeline

[IMAGE: 1865: Jean-Antoine Villemin proved TB is contagious. 1882:  Robert Koch discovers M. tuberculosis. 1884: First TB sanatorium established in U.S. 1943: Streptomycin (SM) a drug used to treat TB is discovered. 1943-1952: Two more drugs are discovered to treat TB: INH and PAS. Mid-1970s: Most TB sanatoriums in U.S. closed. Mid-1980s: Unexpected rise in TB cases. 1993: TB cases decline due to increased funding and enhanced TB control efforts. Please reference Figure 1.1. Timeline of major events in the history of TB, in Module 1, pg. 6 (pdf)]

Slide 15

History of TB: Study Question 1.1

In what year was each of the following discoveries made? (pg. 7)

  • TB was proven to be contagious
    1865
  •  The bacterium that causes TB was discovered
    1882
  • The first drug that could kill TB was discovered
    1943

Slide 16

(Title Slide) TB Transmission

Slide 17

TB Transmission (1)

Transmission is defined as the spread of an organism, such as M. tuberculosis, from one person to another.

Slide 18

TB Transmission (2): Types of Mycobacteria

  • M. tuberculosis causes most TB cases in U.S.
  • Mycobacteria that cause TB:
    • M. tuberculosis
    • M. bovis
    • M. africanum
    • M. microti
    • M. canetti
  • Mycobacteria that do not cause TB

e.g., M. avium complex

[IMAGE:  M. tuberculosis]

Slide 19

TB Transmission (3)

  • TB is spread person to person through the air via droplet nuclei
  • M. tuberculosis may be expelled when an infectious person:
    • Coughs
    • Sneezes
    • Speaks
    • Sings
  • Transmission occurs when another person inhales droplet nuclei

[IMAGE:  A man sneezing]

Slide 20

TB Transmission (4)

  • Dots in air represent droplet nuclei containing
    M. tuberculosis

[IMAGE: TB is spread person to person through the air. In this image, the dots in the air represent droplet nuclei containing tubercle bacilli. Droplet nuclei containing M. tuberculosis expel into the air from one person’s lungs and are inhaled into another person’s lungs.  Please reference Figure 1.2 Transmission of TB. in Module 1, pg. 9 (pdf)]

Slide 21

TB Transmission (5)

  • Probability that TB will be transmitted depends on:
    • Infectiousness of person with TB disease
    • Environment in which exposure occurred
    • Length of exposure
    • Virulence (strength) of the tubercle bacilli
  • The best way to stop transmission is to:
    • Isolate infectious persons
    • Provide effective treatment to infectious persons as soon as possible

Slide 22

TB Transmission: Study Question 1.2

  • What organism causes TB? (pg. 11)
    M. tuberculosis
  • What are 4 other tuberculous mycobacteria? (pg. 11)
    M. bovis, M. africanum, M. microti, and M. canetti

Slide 23

TB Transmission: Study Question 1.3

  • How is TB spread? (pg. 11) 

TB is spread from person to person through the air via droplet nuclei containing M. tuberculosis.

Slide 24

TB Transmission: Study Question 1.4

  • The probability that TB will be transmitted depends on what four factors? (pg. 11)
    • Infectiousness of person with TB disease
    • Environment in which exposure occurred
    • Length of exposure
    • Virulence (strength) of tubercle bacilli

Slide 25

(Title Slide.) Drug-Resistant TB 

Slide 26

Drug-resistant TB (1)

  • Caused by M. tuberculosis organisms resistant to at least one TB treatment drug
    • Isoniazid (INH)
    • Rifampin (RIF)
    • Pyrazinamide (PZA)
    • Ethambutol (EMB)
  • Resistant means drugs can no longer kill the bacteria

[IMAGE: Isoniazid, Rifampin, Pyrazinamide, and Ethambutol pill bottles]

Slide 27

Drug-Resistant TB (2)

Primary Resistance

Caused by person-to-person transmission of drug-resistant organisms

Secondary Resistance

Develops during TB treatment:

  • Patient was not treated with appropriate treatment regimen

OR

  • Patient did not follow treatment regimen as prescribed

Slide 28

Drug-resistant TB (3)

Mono-resistant

Resistant to any one TB treatment drug

Poly-resistant

Resistant to at least any 2 TB drugs (but not both isoniazid and rifampin)

Multidrug resistant (MDR TB)

Resistant to at least isoniazid and rifampin, the 2 best first line TB treatment drugs

Extensively drug resistant
(XDR TB)

Resistant to isoniazid and rifampin, PLUS resistant to any fluoroquinolone AND at least 1 of the 3 injectable second-line drugs (e.g., amikacin, kanamycin, or capreomycin)

Slide 29

Drug-resistant TB: Study Question 1.5

  • What is drug-resistant TB? (pg.11)

           
Drug-resistant TB is caused by M. tuberculosis organisms that are resistant to at least one TB treatment drug.  Drug-resistant TB can be difficult to treat.

Slide 30

Drug-resistant TB: Study Question 1.6
           

  • What is the difference between primary and secondary drug-resistant TB? (pg. 11)
    • Primary resistance is caused by person-to-person transmission of drug-resistant organisms.
    • Secondary resistance develops during TB treatment.  Either the patient was not treated with the right TB drugs or the patient did not properly follow the prescribed treatment regimen.

Slide 31

(Title Slide).  TB Pathogenesis

Slide 32

TB Pathogenesis (1)

Pathogenesis is defined as how an infection or disease develops in the body.

Slide 33

TB Pathogenesis (2): Latent TB Infection (LTBI)

  • Occurs when tubercle bacilli are in the body, but the immune system is keeping them under control
  • Detected by the Mantoux tuberculin skin test (TST) or by blood tests such as interferon-gamma release assays (IGRAs) which include:
    • QuantiFERON®-TB Gold test (QFT-G)
    • QuantiFERON®-TB Gold In-Tube (QFT-GIT)
    • T-Spot®.TB test (T-SPOT)
  • People with LTBI are NOT infectious

Slide 34

TB Pathogenesis (3):  TB Disease

  • Develops when immune system cannot keep tubercle bacilli under control
    • May develop very soon after infection or many years after infection
  • About 10% of all people with normal immune systems who have LTBI will develop TB disease at some point in their lives
  • People with TB disease are often infectious

Slide 35

TB Pathogenesis (4)

  • Droplet nuclei containing tubercle bacilli are inhaled, enter the lungs, and travel to small air sacs (alveoli)

[IMAGE: Tubercle bacilli are inhaled and enter the lungs. Please reference image 1 of Figure 1.4. Pathogenesis of LTBI and TB disease, in Module 1, pg. 17 (pdf)]

Slide 36

TB Pathogenesis (5)

  • Tubercle bacilli multiply in alveoli, where infection begins

[IMAGE:  Section of the bronchiole, alveoli, and tubercle bacilli within the alveoli.  Please reference image 2 of Figure 1.4. Pathogenesis of LTBI and TB disease, in Module 1, pg. 17 (pdf)]  

Slide 37

TB Pathogenesis (6)

  • A small number of tubercle bacilli enter bloodstream and spread throughout body

[IMAGE: Anatomical view showing the brain, lung, kidney, and bones.  Please reference image 3 of Figure 1.4. Pathogenesis of LTBI and TB disease, in Module 1, pg. 18 (pdf)]

Slide 38

TB Pathogenesis (7)

  • Within 2 to 8 weeks the immune system produces special immune cells called macrophages that surround the tubercle bacilli
  • These cells form a barrier shell that keeps the bacilli contained and under control (LTBI)

[IMAGE:  Close view of the alveoli, where special immune cells form a barrier shell around the tubercle bacilli.  In this example, the bacilli are in the lungs.  Please reference image 4 of Figure 1.4. Pathogenesis of LTBI and TB disease, in Module 1, pg. 18 (pdf) ]

Slide 39

TB Pathogenesis (8)

  • If the immune system CANNOT keep tubercle bacilli under control, bacilli begin to multiply rapidly and causeTB disease
  • This process can occur in different places in the body

[IMAGE:  Close view of the alveoli, where the special immune cells break down and the tubercle bacilli escapes.  In this example, TB disease develops in the lungs.  Please reference image 5 of Figure 1.4. Pathogenesis of LTBI and TB disease, in Module 1, pg. 18 (pdf)]

Slide 40

LTBI vs. TB Disease

Latent TB Infection (LTBI)

TB Disease (in the lungs)

Inactive, contained tubercle bacilli in the body

Active, multiplying tubercle bacilli in the body

TST or blood test results usually positive

TST or blood test results usually positive

Chest x-ray usually normal

Chest x-ray usually abnormal

Sputum smears and cultures negative

Sputum smears and cultures may be positive

No symptoms

Symptoms such as cough, fever, weight loss

Not infectious

Often infectious before treatment

Not a case of TB

A case of TB

[IMAGE: Please reference Table 1.1. LTBI vs. TB Disease, in Module 1, pg. 14 (pdf)]

Slide 41

TB Pathogenesis: Study Question 1.7

  • When a person inhales air that contains droplet nuclei containing M. tuberculosis, where do the droplet nuclei go? (pg. 15)
    • Most of the larger droplet nuclei become lodged in the upper respiratory tract, where infection is unlikely to develop
    • However, droplet nuclei may reach the small air sacs of the lung (the alveoli), where infection begin

Slide 42

TB Pathogenesis: Study Question 1.8

  • After the tubercle bacilli reach the small air sacs of the lung (the alveoli), what happens to them? (pg. 15)
    • Tubercle bacilli multiply in alveoli and some enter the bloodstream and spread throughout the body 
    • Bacilli may reach any part of the body
    • Within 2 to 8 weeks, the immune system usually intervenes, halting multiplication and preventing further spread

Slide 43

TB Pathogenesis: Study Question 1.9

  • In people with LTBI (but not TB disease), how does the immune system keep the tubercle bacilli under control? (pg. 15)

The immune system produces special immune cells that surround the tubercle bacilli.  These cells form a shell that keeps the bacilli contained and under control.

Slide 44

TB Pathogenesis: Study Question 1.10

  • How is LTBI detected? (pg. 16)

    LTBI is detected by the Mantoux tuberculin skin test (TST) or blood tests such as interferon-gamma release assays (IGRA), which include the QuantiFERON®-TB test (QFT-G), QuantiFERON®-TB Gold In-tube (QFT-GIT), or T-SPOT.

Slide 45

TB Pathogenesis: Study Question 1.11

  • What are the major similarities and differences between LTBI and TB disease? List characteristics of each. (pg. 16)

Latent TB Infection (LTBI)

TB Disease (in the lungs)

Inactive, contained tubercle bacilli in the body

Active, multiplying tubercle bacilli in the body

TST or blood test results usually positive

TST or blood test results usually positive

Chest x-ray usually normal

Chest x-ray usually abnormal

Sputum smears and cultures negative

Sputum smears and cultures may be positive

No symptoms

Symptoms such as cough, fever, weight loss

Not infectious

Often infectious before treatment

Not a case of TB

A case of TB

Slide 46

TB Pathogenesis: Study Question 1.12

What happens if the immune system cannot keep the tubercle bacilli under control and the bacilli begin to multiply rapidly? (pg. 16)

When this happens, TB disease develops. The risk that TB disease will develop is higher for some people than for others.

Slide 47

(Title Slide).  TB Pathogenesis: Progression from LTBI to TB Disease

Slide 48

Progression to TB Disease (1)

  • Risk of developing TB disease is highest the first 2 years after infection
  • People with LTBI can be given treatment to prevent them from developing TB disease
  • Detecting TB infection early and providing treatment helps prevent new cases of TB disease

Slide 49

Progression to TB Disease (2)

  • Some conditions increase probability of LTBI progressing to TB disease
  • These conditions include:
    • Infection with HIV
    • Chest x-ray findings suggestive of pervious TB
    • Injection drug use
    • Recent TB infection (the past 2 years)
    • Prolonged therapy with corticosteroids and other immunosuppressive therapy, such as prednisone and tumor necrosis factor-alpha [TNF-α] antagonists
    • Organ transplant
    • Silicosis
    • Diabetes mellitus
    • Severe kidney disease
    • Certain types of cancer
    • Certain intestinal conditions
    • Low body weight

Slide 50

Progression to TB Disease (3)

[IMAGE:  Flowchart. People who are exposed to TB may or may not develop TB infection. People with LTBI may or may not develop TB disease. Please reference Figure 1.5 Progression of TB  in Module 1, pg. 19 (pdf)]

Slide 51

Progression of TB Disease (4):  TB and HIV

In an HIV-infected person, TB can develop in one of two ways:

  • Person with LTBI becomes infected with HIV and then develops TB disease as the immune system is weakened
  • Person with HIV infection becomes infected with M. tuberculosis and then rapidly develops TB disease

[IMAGE:  Poster that reads, “TB/ HIV. Double Trouble.  People with HIV infection face greater risk of also developing TB.  Don’t take chances. Get tested.” Image credit: Mississippi State Department of Health.]

Slide 52

Progression to TB Disease (5): TB and HIV

  • People who are infected with both M. tuberculosis and HIV are much more likely to develop TB disease

TB infection
and NO risk factors

TB infection
and HIV infection
(pre-Highly Active Antiretroviral treatment [HAART])

illustration of TB infection and NO risk factors

illustration of TB infection and HIV infection

Risk is about 5% in the first 2 years after infection and about 10% over a lifetime

Risk is about 7% to 10% PER YEAR, a very high risk over a lifetime

[IMAGE:  Persons with TB infection and no risk factors have a 5% risk of developing TB within the first 2 years after infection and about a 10% risk over a lifetime.  Persons living with HIV that are coinfected with TB have a 7%-10% risk of developing TB disease per year (pre-Highly Active Antiretroviral treatment [HAART]. Please reference Figure 1.6 Risk of developing TB disease over a lifetime, in Module 1, pg. 21 (pdf)]

Slide 53

Progression to TB Disease: Study Question 1.13

  • What percentage of people with LTBI (but not HIV infection) usually develop TB disease? (pg. 22)
    • About 10% of all people with LTBI will develop disease at some point
      • In U.S., about 5% of recently infected will develop TB disease in first year or two after infection 
      • Additional 5% will develop disease later in life
  • Remaining 90% will stay infected, but free of disease, for the rest of their lives

Slide 54

Progression to TB Disease:  Study Question 1.14

What conditions appear to increase the risk that LTBI will progress to TB disease? (pg. 22)

  • Infection with HIV
  • Chest x-ray findings suggestive of previous TB
  • Substance abuse
  • Recent TB infection
  • Prolonged therapy with    corticosteroids and other immunosuppressive therapy, such as prednisone and tumor necrosis factor-alpha [TNF-α] antagonists
  • Organ transplant
  • Silicosis
  • Diabetes mellitus
  • Severe kidney disease
  • Certain types of cancer
  • Certain intestinal conditions
  • Low body weight

Slide 55

Progression to TB Disease: Study Question 1.15

  • How does being infected with both M. tuberculosis and HIV affect the risk for TB disease? (pg. 22)
    • Much more likely to develop TB disease
    • Risk of developing TB disease is 7% to 10% EACH YEAR (pre-HAART)
  • In an HIV-infected person, TB disease develops when:
    • Person with LTBI becomes infected with HIV and then develops TB disease as the immune system is weakened
    • Person with HIV infection becomes infected with M. tuberculosis and then rapidly develops TB disease

Slide 56

(Title Slide.) TB Pathogenesis: Sites of TB Disease

Slide 57

Sites of TB Disease (1)

  • Bacilli may reach any part of the body, but common sites include:

[IMAGE:  Anatomical view showing the brain, larynx, lung, kidney, lymph nodes, pleura, spine, and bones.  Please reference Figure 1.7 Common sites of TB disease, in Module 1, pg. 25 (pdf)]

Slide 58

Sites of TB Disease (2)

 

Location

Frequency

Pulmonary TB

Lungs

Most TB cases are pulmonary

Extrapulmonary TB

Places other than lungs such as:

  • Larynx
  • Lymph nodes
  • Pleura
  • Brain
  • Kidneys
  • Bones and joints

Found more often in:

  • HIV-infected or other immuno-suppressed persons
  • Young children

Miliary TB

Carried to all parts of body, through bloodstream

Rare

Slide 59

Sites for TB: Study Question 1.16

  • What part of the body is the most common site for TB disease? (pg. 27)
    Lungs are the most common site
  • What are some other sites?
    • Larynx
    • Lymph nodes
    • Pleura (membrane around the lungs)
    • Brain
    • Kidneys
    • Bones and joints

Slide 60

(Title Slide).  TB Pathogenesis: TB Classification System

Slide 61

TB Classification System (1)
Based on pathogenesis of TB

Class

Type

Description

0

No TB exposure
Not infected

No history of TB exposure
Negative result to a TST or IGRA

1

TB exposure
No evidence of infection

History of TB exposure
Negative result to a TST (given at least 8-
10 weeks after exposure) or IGRA

2

TB infection
No TB disease

Positive result to a TST or IGRA
Negative smears and cultures (if done)
No clinical or x-ray evidence of active
TB disease

 [IMAGE:  Please reference Table 1.3 Classification System for TB, in Module 1, pg. 26 (pdf)]

Slide 62

TB Classification System (2)
Based on pathogenesis of TB

Class

Type

Description

3

TB, clinically active

Positive culture (if done) for M. tuberculosis Positive result to a TST or IGRA, and clinical, bacteriological, or x-ray evidence of TB disease

4

Previous TB disease
(not clinically active)

Medical history of TB disease
Abnormal but stable x-ray findings
Positive result to a TST or IGRA
Negative smears and cultures (if done),
No clinical or x-ray evidence of active TB disease

5

TB suspected

Signs and symptoms of TB disease, but evaluation not complete

[IMAGE:  Please reference Table 1.3 Classification System for TB, in Module 1, pg. 26 (pdf)]

Slide 63

Classification System: Study Question 1.17

  • What is the classification system for TB based on? What is it used for? (pg. 27)

    Current classification system is based on the pathogenesis of TB. Many health departments and private health care providers use this system when describing patients.

Slide 64

(Title Slide) Case Studies

Slide 65

Module 1: Case Study 1.1 (1)

A 30-year-old man visits the health department for a TST because he is required to have one before starting his new job as a health care worker.  He has an 18mm positive reaction to the TST.  He has no symptoms of TB, and his chest x-ray findings are normal. (pg. 16)

Slide 66

Module 1: Case Study 1.1 (2)

  • Should this be considered a case of TB?
    No.  The man described above has TB infection.  He has an 18mm positive reaction to TST, but he has no evidence of TB disease.  Therefore, this is not a case of TB.

  • Should this man be considered infectious?
    No, he should not be considered infectious.  This man has LTBI, not TB disease.  People with TB infection and no evidence of TB disease are not infectious.

Slide 67

Module 1: Case Study 1.2 (1)

A 45-year-old woman is referred to the health department by her private physician because she was found to have LTBI as part of an employee testing program.  She is obese, with high blood pressure.  Upon further questioning, she reports that she has injected illegal drugs in the past, but has never been tested for HIV infection. (pg. 23)

Slide 68

Module 1: Case Study 1.2 (2)

  • What conditions does this woman have that increase the risk that she will develop TB disease?

    Injection of illegal drugs increases the risk that LTBI will progress to TB disease. This woman is also at risk for HIV infection, which is the strongest known risk factor for developing TB disease.  This woman should be offered HIV counseling, testing, and referral.

    Obesity and high blood pressure are NOT risk factors for TB disease.

 

 
Contact Us:
  • Centers for Disease Control and Prevention
    Division of Tuberculosis Elimination (DTBE)
    1600 Clifton Rd., NE
    MS E10
    Atlanta, GA 30333
  • 800-CDC-INFO
    (800-232-4636)
    TTY: (888) 232-6348
  • Contact CDC–INFO
USA.gov: The U.S. Government's Official Web PortalDepartment of Health and Human Services
Centers for Disease Control and Prevention   1600 Clifton Rd. Atlanta, GA 30333, USA
800-CDC-INFO (800-232-4636) TTY: (888) 232-6348 - Contact CDC–INFO
A-Z Index
  1. A
  2. B
  3. C
  4. D
  5. E
  6. F
  7. G
  8. H
  9. I
  10. J
  11. K
  12. L
  13. M
  14. N
  15. O
  16. P
  17. Q
  18. R
  19. S
  20. T
  21. U
  22. V
  23. W
  24. X
  25. Y
  26. Z
  27. #