1. Tuberculosis

2. Tuberculosis is a chronic respiratory tract disease established by Mycobacterium tuberculosis complex infection and represented clinically as primary, secondary disease, or latency.
Mycobacterium tuberculosis complex: M. tuberculosis, M. bovis, and M. africanum.

3. Mycobacterium tuberculosis
was identified and described on 24 March 1882 by a German physician Robert Koch.
Morphology: slightly curved to straight bacillus.
Obligate aerobic, acid fast, non motile, non spore forming bacilli.
Contains mycolic acid in their cell wall.
Slow grower: duplication time ~24 hours

4. WHO (2012)
≈ 9 million people developed TB.
1.3 million died from the disease (including 320 000 deaths (25%) among HIV-positive people).
25% to 33% of the world’s population with silent latent infection with M. tuberculosis.
Prevalence in Saudi Arabia in 2012 ≈ 4900 case and 1100 deaths.

5. WHO report for incidence of T.B in 2011:

6. Transmission of Mycobacterium species:
Mycobacterium tuberculosis:
Reservoir: Human.
T.B spread from person to person through the air by droplet nuclei (0.5-5µm in diameter) which can be produced by coughing , sneezing, or to a lesser extent speaking or singing.
Droplet nuclei may remain suspended in the air for long time;(isolation rooms in hospitals).

7. M. bovis
Reservoir: Cattle & related animals.
Transmission:
Eating or drinking contaminated, unpasteurized dairy products.
Direct contact and inhaling of aerosol droplets from infected animals.
Infected cattle must be culled.
Symptoms of TB disease caused by M. bovis are similar to those of M. tuberculosis.

8. Risk factors for rapid spreading of Mycobacterium tuberculosis:
Crowded living conditions.
HIV infection.
Excess alcohol.
Traveling to area with high prevalence rate.

9. Pathogenesis:
Do not produce exotoxins or endotoxin.
Tubercle bacilli are able to survive inside the macrophages (chronic granulomatous inflammation).
Tissue damage is induced by the host immune response.
Clinical presentations are divided to:
Primary infection.
Latent infection.
Secondary infection

10. Primary infection:
In the middle lung zones; where airflow is greatest.
Inhaled bacilli are engulfed by alveolar macrophage where they continue to multiply leading to rupture of macrophage, reals of bacilli and infection of other macrophage (active primary T.B).

11. Infected macrophages are carried by lymphatics to regional tracheobronchial lymph nodes:
Activation of lymphocytes (TH1: cell mediated immune response).
Enlargement of lymph nodes.
Ghon’s Complex: inflammation of infected lung area associated with enlarged lymph nodes.

12. Outcome of Primary Infection:
In 90% of cases, (children ˃ 5 years old, teens and adults): strong immunity: delayed type hypersensitivity: latent dormant tuberculosis with granuloma formation.
In 10 % of cases (infants and children younger than 5 years old, elderly persons and HIV patients): weak immunity: little or no hypersensitivity immune reaction:
progressive primary tuberculosis.
lympho-hematogenous dissemination (meninges, bone, apices of lungs, kidneys……

14. A Person with Latent TB Inf.
A Person with active TB
Has no symptoms
Has symptoms that may include:
Chronic cough that lasts ˃ 3 weeks
weight loss
pain in the chest
coughing up blood or sputum
weakness & fatigue
bad appetite
Fever & chills
sweating at night
Cannot spread infection to others
May spread infection to others
Usually positive skin test or blood test
Usually positive skin test or blood test.
Has a normal chest x-ray and a negative sputum smear
May have an abnormal chest x-ray and positive sputum smear or culture
Needs treatment for latent TB infection to prevent TB disease
Needs treatment to treat TB disease n

15. Secondary Tuberculosis (Endogenous Reactivation)
It occurs within 2 years after the initial infection but can occur any time there after due to impairment of cellular immunity.
Major causes of depression of cellular immunity: immunosuppressive drugs: corticosteroids, malignancy, HIV (the most important cause).
Most common site of reactivation is the lung apex;
granulomatous lesions become necrotic (caseous necrosis), enlarge, liquefy, rupture and discharge their content into bronchi creating well aerated cavity:
Microbial proliferation.
Distribution within the lung (tuberculous pneumonia).
Coughing up bloody sputum

16. End result of primary tuberculosis:
90% Latent dormant tuberculosis
10% Progressive active infection
AIDS, old, children
Living bacteria &granuloma
Living- bacteria, granuloma
95 % No disease
-Caseous material
discharged; necrosis
-Cavity creation.
75%
3% Breaks down granuloma
25% arrested granuloma
Lympho-Hemo
Tuberculous pneumonia
Fibrosis or calcification.
Enlarged tracheobronchial lymph nodes .
Apical lung cavities
Meningitis
Osteomyelitis

17. 90%
10%

18. Other Body Parts which Can be Affected by Tuberculosis
In cervical LN: scrofula
Pott’s disease

19. HIV and Tuberculosis: HIV infection inhibit cellular immunity.
Patients with HIV infection can be infected by MTC (Mycobacterium tuberculosis complex), or MOTT (Mycobacterium other than tuberculosis). MOTT: M. avium, M. intracellulare, and M. kansasii.
Tuberculosis is an AIDS defining condition It is the leading cause of death among adults living with HIV/AIDS.
The WHO recommends TB screening at HIV infection is diagnosed and during follow up.

21. Diagnosis Chest X-ray. Mantoux skin test (Tuberculin).
Microscopy: acid-fast bacilli by Ziehl –Neelsen (ZN) stain, or by fluorescent microscope.
Culture: Isolation of mycobacterium species.
Löwenstein–Jensen medium (L.J medium)
PCR: Highly sensitive Detection of mycobacterial genetic material and to determine antibiotic susceptibility.

22. Chest X-ray
Cavitation in the right lung and fibrosis in the left.

23. Tuberculin skin tests (Mantoux test):
Delayed type hypersensitivity (DTH)
Purified protein derivative (PPD) injected intradermally.
Results: Induration is measured after hours (DTH).
Negative < 5 mm
Intermediate reaction 5-9 mm.
Positive reaction ˃ 9mm.

24. Category 3: persons with no known risk factors for TB.
Category 1:HIV-positive person, recent contacts with a TB patient, persons with chest X-ray findings consistent with old healed TB and immunosuppressed patients.
Category 2: Residents and employees of high-risk settings (e.g., prisons, homeless shelters, etc.), mycobacteriology lab personnel, chronically ill (e.g., diabetes,, leukemia, end-stage renal disease, etc.), children less than four years of age.
Category 3: persons with no known risk factors for TB.

25. M. Tuberculosis appear as thin pink rods in ZN stain
Microscopy:
Clinical specimens: Sputum, transtracheal aspiration, bronchoalveolar lavage.
ZN stain: Mycobacteria are acid fast bacilli: resist decolorization with acid (2% H2SO4 or 3% HCl ) and alcohol due to the waxy capsule. N
M. Tuberculosis appear as thin pink rods in ZN stain

26. Culture and colony morphology
Cultured for primary isolation & antibiotic susceptibility.
Strict aerobic grows slowly (2-4 weeks).
Optimum temperature growth is 37 Cᴼ.
Egg enriched medium: LJ medium, giving dry creamy colored colonies.
The growth is enhanced by adding pyruvate and glycerol to the media.
M. tuberculosis are niacin producers.

27. TB Culture
Cultivation and culture characteristics of tubercle bacilli on LJ medium (dry cream colored colonies)

28. M. tuberculosis is a non chromogenic bacteria.
Difference between M. tuberculosis and MOTT :(M. avium, M. intracellulare, and M. kansasii).
M. tuberculosis is a non chromogenic bacteria.
Does not grow on media contain p-nitrobenzoic acid. N

29. Antibiotics sensitivity test:
-Other selective media as Middle-brook are used for primary isolation and for antibiotic susceptibility test. N

30. Extensive time periods (6-9 months).
Treatment of T.B:
Extensive time periods (6-9 months).
Direct observation treatment (DOT).
Combined multidrug treatment to reduce anti tuberculous resistance.
First line Anti-T.B drugs: Isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol.
Phases of Treatment:
-Initial phase: The four drugs for 2 months.
-Continuation phase: INH and RIF for four or seven months. n

31. Bacillus Calmette – Guérin (BCG) vaccine:
Vaccination:
Bacillus Calmette – Guérin (BCG) vaccine:
Live attenuated low virulent M. bovis strain.
Effective in protection of children from serious forms of disease such as meningitis.
Not so effective to protect adults. N

32. Direct Observation Treatment