1. Jennifer Ku & Jennette Kidnie

2. Previous Theories/Beliefs
Vampires
“consumption”
Draining of blood making victim pale and weak
Masturbation
Leaving patient drained of energy
Sin
Creativity
Patients got burst of energy- made women more beautiful and men more creative

3. History of TB Origin of Word - Tuberculosis – TB: Tubercle bacillus
Has often been referred to as ‘white plague’ and ‘consumption’
18,000 year old bison found with Mycobacterium tuberculosis
Skeletal remains of prehistoric human from 7000BC
1882 Robert Koch identifies M. tuberculosis as bacteria causing disease
1980’s multi drug resistant TB strains appear

4. First evidence/case TB
Eastern Mediterranean – 9250 to 8160 years ago
TB lesions from a woman and infant buried together
PCR to examine bone samples

6. What causes TB? Mycobacterium tuberculosis Less common causes:
Slow growing
Acid fast bacillus
Has waxy layer which prevents
drying
Less common causes:
Mycobacterium bovis
Mycobacterium africanum
Mycobacterium canetti
Mycobacterium microti

7. What happens when the bacteria enter the body?
In healthy individuals or when only small amounts of bacteria are ingested, active macrophages will kill bacteria
The immune system will form a wall around the bacteria called a granuloma or tubercule, which can stay dormant for many years before reappearing (latent TB)
In some individuals a full blown infection will occur which often leads to death (miliary TB)

8. Pathogenesis
Taken from figure 19-1 in Salyers and Whitt, 2002

9. Pathogenesis cont’d
Miliary TB- TB infection in the lung that results in the bacteria getting into the pulmonary vein and going systemic
If untreated it is 100% fatal
In 25% of the cases, it will cross blood-brain barrier and cause tuberculous meningitis

10. How does it escape the macrophages?
M. tuberculosis is able to survive and grow within unactivated macrophages
Prevent fusion with lysosome (oxidative burst) due to waxy coated capsule
Inhibits IL-12 production which will prevent TH1 response

11. Host Protection Important defenses:
the T helper cells (CD4+) producing IFN-γ which will stimulate macrophage activation
the cytotoxic (CD8+) T cells killing infected phagosomes that have been unable to destroy the bacteria

12. Transmission
Respiratory droplets from coughing, sneezing, talking, or spitting
Aerosol droplets 0.5 to 5µm in diameter
A single sneeze can release up to 40, 000 droplets

13. Transmission Infectious dose of tuberculosis is very low
Inhalation of just a single bacterium can cause a new infection.
Dormant, which can later cause disease if weakened
Mechanism of transmission:
People who inject drugs using unsanitary needles
Residents and employees of high-risk congregate settings
Medically under-served and low-income populations
Children exposed to adults in high-risk categories
Patients immunocompromised (i.e. HIV/AIDS)
Immunosuppressant drugs
Health care workers serving high-risk patients

14. Transmission
Transmission can only occur from people with active — not latent — TB
Factors influencing effective transmission:
Number of infectious droplets expelled by a carrier
The effectiveness of ventilation
The duration of exposure
The virulence of the M. tuberculosis strain

15. Common Symptoms Chronic cough Blood in sputum Fever Night sweats
Weight loss
If it travels to other organs than the lungs, then a wider range of symptoms may occur

16. Diagnosis Tuberculin Skin Test Chest Radiograph
Bacteriological Smears & Cultures
Clinical Observations

17. Diagnosis- TB Test Tuberculin injected intradermally
Sensitivity of this extract that the bacteria produces will appear as red circle
Those immunized or have previously had the infection will show the same result as those that now have the disease
Patient Status
Positive Result
HIV +
>5mm
Healthy individuals with exposure history or risk factors
>10mm
Healthy individuals with no exposure history
>15mm

18. X-ray of Far-advanced Tuberculosis
The white arrows show bilateral pulmonary infiltrate, black arrows show caving formation

19. Bacteriological Smears & Cultures
Sputum smear is tested for the presence of Acid-Fast-Bacilli
Negative result will rule out TB infection.
Most definitive diagnosis will come from culture of lung secretions
Positive Acid-Fast stain of TB
M. Tuberculosis culture

20. Clinical Observations
Clinical signs of active infection:
Fatigue, fever, unexplained weight loss, night sweats.
Symptoms of pulmonary TB include:
Productive cough >3 weeks, coughing up blood, and chest pain.
Extra-pulmonary TB will have a range of signs and symptoms depending on the site of primary infection.

21. Treatment in a time before antibiotics
Sanatoriums for both the rich and poor citizens
First sanatorium in Canada was at Muskoka lake in 1897
Patients received rest, fresh air, good nutrition to support healing and isolation to prevent spread
Closed down mid 1900s after antibiotics were found to be better at treating patients

22. What treatment is used today?
First-line drugs taken for 6-8 months
Isoniazid- inhibit mycolic acid synthesis
Rifampin- inhibits bacterial RNA polymerase
Ethambutol- inhibit mycolic acid synthesis
Pyrazidamide- nicotinamide analog
Second-line drugs
Streptomycin, capreomycin, clofazamine, amikacin, ethionamide, ofloxacin, ribabutin, kanamycin, fluoroquinolones

23. First-Line Treatment
Taken from

24. DOT Directly Observed Treatment (DOT)
Used to deal with the high number of noncompliant patients who do not take the drugs every day for the full length of time
Important since not taking the drugs as prescribed is a main cause of drug resistance
Proof of its effectiveness:
1986- prior to DOT 26% of patients acquired drug resistance
After thanks to DOT, drug resistance is 7%

25. Drug Resistant TB MDR-TB -> multi-drug resistant (1980s)
-resistance to 2 of the first line drugs (often isoniazid and rifampicin)
XDR-TB -> extremely drug resistant
-first reported outbreak was in 2006
-resistance to 2 of the first line drugs, atleast 1 quinolone and atleast 1 of the second line anti-TB injection drugs
-can take 6-16 weeks to diagnose
CDR-TB -> completely drug resistant
-resistance to all known drugs

26. Prevention Screening Programs Vaccine:
Testing those in high risk groups
Vaccine:
BCG (Bacillus Calmette-Guerin)
Developed in the 1920’s
Live, attenuated M. Bovis strains
Only lasts ~15 years
Given to children to prevent TB meningitis or miliary TB
Effectiveness ranging from 0%-80%
Use was previously widespread in Canada

27. Recent Use of BCG Vaccine
Who qualifies for a BCG vaccine?
Children of families with a strong history of TB
Groups of people that display an uncommonly high rate of infection.
Health care workers who are working with the bacteria or patients
Newborn infants whose mother has infectious TB at the time of delivery
Individuals travelling to TB-laden areas for an extended period of time (i.e. six months or more).

28. The Problem with BCG Variable efficiency. Reasons may include:
Interference with non-tuberculous mycobacteria
Genetic variation in BCG strains
Genetic variation in the population
Severe local inflammation and scarring occurring in patients
Tuberculin skin test must be performed first and if positive then they can’t vaccinate
Immunocompromised individuals often will get a miliary TB infection

29. Epidemiology

30. Epidemiology Annually, 8 million people become ill with tuberculosis
2 million people will die from the disease, worldwide
Growing problem
In 2004: 14.6 million people active TB disease
9 million new cases
In Canada, still an endemic
Northwest Territories

31. Annual Incidence by Country
# (per 100, 000)
Africa
356
North & South America 41
Switzerland (2005)
1262
London 40
Portugal
31.3
China
113
Brazil 64
United States
4.9

32. Global Impact

33. Reasons for re-emergence
↑ HIV infections
Neglect of TB control programs
Drug-resistant strains
↑ migration, international travel, and tourism
↑ incidence of AIDS

38. What will make you more susceptible to TB?
Co-infection with HIV
Smoking (>20 cigarettes/day)
↑ risk by 2x-4x
Diabetes mellitus
Hodgkin lymphoma,
End-stage renal disease
Chronic lung disease
Malnutrition
Alcoholism

39. QUESTIONS?