This document provides an overview of tuberculosis (TB), including its definition, causes, pathogenesis, clinical presentation, investigations, types, treatment regimens, and relationship to HIV/AIDS. TB is caused by mycobacteria, commonly Mycobacterium tuberculosis, which can affect any organ but typically affects the lungs. It is transmitted via airborne droplets from someone with active pulmonary TB. Primary infection may result in latent TB or active TB, depending on immune response. Symptoms vary based on location of infection. Diagnosis involves chest x-ray, sputum smear, and Mantoux test. Treatment involves a combination of bactericidal and bacteriostatic drugs. Multi-drug resistant TB can develop if treatment is not completed

1. TUBERCULOSIS

2. Objectives
• Definition
• Aetiology
• Pathogenesis and pathology
• Clinical presentation
• Investigations
• Types of TB
• Treatment regimens
• Relationship to HIV/AIDS

3. Definition
• A chronic infectious disease caused by
mycobacteria (commonly Mycobacterium
tuberculosis)
• It may affect any organ or tissue but
commonly affects the lungs

4. Aetiology
• Mycobacteria that may produce disease
indistinguishable from that caused by
Mycobacterium tuberculosis include:
M. bovis
M. Leprae
M. kansasii
M. avium
M. intracellulare

5. Mode of transmission
• Transmission occurs by airborne
(infectious droplets).
• The source of infection is a person with
pulmonary-TB who is coughing and is
sputum smear-positive.

6. Note
• Transmission generally occurs indoors.
• Two factors determine an individual’s risk
of exposure:
– The concentration of the droplet in air.
– The length of time somebody breathes
that air.

7. Pathogenesis
• TB may involve any organ but the lungs
are the usual site of primary lesion.
• TB bacilli for lungs is directly related to its
requirement for oxygen for growth
• The inhaled bacilli implants in the distal
airspaces of the lower part of the upper
lobe or the upper part of the lower lobe

8. Cont’d
• TB bacilli lodge within an alveolus:→ rapidly
phagocytized, mostly by alveolar
macrophages.
• Because TB bacilli are resistant to
destruction, they multiply within
macrophages
• Bacilli has naturally slow multiplication
rate, hence appearance of signs and
symptoms may require several weeks.

9. Cont’d
• When the number of TB bacilli becomes
significant, an inflammatory cellular exudate
appears known as the ‘Primary’ or
‘Ghon’s’ focus. Usually the primary focus
heals completely.
• The center undergoes caseous necrosis
• If not: dissemination of TB bacilli from the
focus may follow, probably within hours
• Dissemination is primarily by lymphatics

10. Primary Pulmonary TB
The gray-white parenchymal focus is under the pleura under the
lower part of the upper lobe. Hilar lymph nodes with caseation are
seen on the left

11. Cont’d
• Early extensive lymphangitis and
involvement of hilar lymphnodes
• Involvement of the Primary focus,
lymphangitis and the regional (hilar)
lymphnodes is called Primary complex.
• Cellular immunity develops three to eight
weeks after the initial infection
• Spill over of TB bacilli from lymphatics
into blood stream may occur leading to
seeding of bacilli to other organs → milliary.

12. Cont’d
• Primary complex - caseated areas - heals
in the majority, within few weeks and
undergo calcification
• In some cases: seeding of bacilli advances
→ wide spread disease → death if no
treatment is given.
• NB: at least 20% of calcified primary
lesions contain TB bacilli, initially lying
dormant but can reactivate

13. Pathogenesis
Ghon Focus – lungs,
regional lymph nodes
Mycobacterium
tuberculosis

14. Pathogenesis
Ghon Focus – lungs,
regional lymph nodes)
Immune response
Mycobacterium
tuberculosis
Successful Fails
Latent TB Active TB

15. Clinical feature
• Haemoptysis.
• Chest pain: It is only suggestive of TB if
localized or pleuritic in nature.
• Difficult in breathing.
• Cough of 2 weeks or more

16. Cont’d
Constitutional symptoms:
• Evening fever.
• Night sweats.
• Tiredness/weakness.
• Loss of appetite.
• Weight loss

17. Cont’d
• Wasting.
• Respiratory distress: Respiratory rate of
more than 30 breathes per minute is
significant in adults.
• Lymphadenopathy:
• Anterior rather than posterior cervical and
the axillae.
• Generalized lymphadenopathy is more
likely to be HIV related.

18. Cont’d
• Varies; crepitations, bronchial breath
sounds to reduced air entry.

19. Investigations
Chest x-ray:
Sputum smear:
ESR
Mantoux Test

20. CHEST XRAY TB
Right apical consolidation

21. The Mantoux Test
• Infection with M. Tuberculosis → delayed
hypersensitivity which can be detected by
the tuberculin test (Mantoux)
• A positive tuberculin test does not
differentiate infection and disease but
signifies cell-mediated hypersensitivity to
tubercular antigens
• Induces an induration ≥ 5mm

22. The Mantoux Test
• A false negative result may occur due to
malnutrition, Hodgkin’s lymphoma,
immunosuppression and overwhelming
active TB
• False positives occur in atypical
mycobacteria infections

23. Differential diagnoses of
chest x-ray findings
Chest x-ray findings Differential diagnoses
Pleural effusion. •Malignancy: Often causes
blood stained effusion.
• Pneumonia.
•Heart failure.
•Renal failure.
•Nephrotic syndrome.

24. Cont’d
Differential diagnoses Pointers to the correct
diagnosis
•Congestive cardiac failure.
•Heart failure.
Symptoms and signs of heart
failure.
Bronchial asthma. Intermittent symptoms (episodic)
and generalised expiratory
wheezes.
COPD. Presence of risk factor e.g.
smoking; chronic symptoms,
prominent dyspnoiea, generalised
wheezes.
Bronchiectasis. Large amount of purulent sputum
production.

25. Cont’d
Differential diagnoses Pointers to the correct
diagnosis
Bronchial carcinoma. Weight loss and
presence of risk factor
e.g. smoking.
Bacterial pneumonia. Responds to broad-
spectrum antibiotics.
Lung abscess. Foul-smelling breath and
abscess with fluid level
on chest x-ray.

26. Cont’d
Differential diagnoses Pointers to the correct
diagnosis
Pneumocystis Jirovecii
pneumonia
• Symptoms: Progressive
dyspnoiea, dry cough
•Signs: No crept.
•CXR: Normal or butterfly
infiltrations.
Kaposi’s sarcoma of the
lungs.
Presence of oral or skin KS
lesions.

27. Complications of PTB
• Massive haemoptysis.
• Cor pulmonale.
• Lung fibrosis
• Emphysema.
• Lung or pleural calcification.
• Obstructive airways disease.
• Bronchiectasis.
• Bronchopleural fistula.
• Pneumothorax.

28. Cont’d
• Pleurisy with effusion
• Miliary tb
• Meningitis
• Bone and joint disease

29. Tuberculous lymphadenopathy
• The course of lymph node disease is as
follows: (in descending order)
• Firm, discrete lymph nodes.
• Fluctuant nodes matted together.
• Skin breakdown to form ‘collar-stud’
abscess or chronic sinuses.
• Healing with scarring.

30. Tuberculous lymphadenopathy
• Differential diagnoses:
–Persistent generalized
lymphadenopathy (PGL).
–Lymphoma.
–Kaposi’s sarcoma.
–Carcinomatous metastases.
–Pyogenic lymphadenitis.

31. Miliary-Tuberculosis
• Miliary-TB results from widespread blood-
borne dissemination of TB bacilli.
• This is either the consequence of the
recent primary infection or the erosion of a
tuberculous lesion into a blood vessel.

32. Miliary TB of the spleen. Section
shows numerous gray-white
granulomas

33. Diagnosis
• Hx
• Chest X-ray: Diffuse, uniformly distributed,
small miliary shadows. Miliary means ’like
small millet seeds’.
• Full blood
• Blood culture.

34. Differential diagnoses
• HIV wasting syndrome.
• Typhoid fever.
• Necrotizing pneumonia.
• Septicaemia.
• Disseminated carcinoma.
• Pneumoconiosis.

35. Tuberculous Serous Effusions
Includes:
• Pleural effusion.
• Empyema.
• Pericarditis with effusion.
• Peritonitis.

36. Tuberculous Pleural Effusion
Clinical features:
• Chest pain.
• Dry cough.
• Breathlessness.
• Constitutional clinical features.
• Stone dullness.

37. Other forms of
extrapulmonary tuberculosis
Site of the disease Clinical features Diagnosis
TB-spine
(Pott’s disease)
•Backache.
•Gibbus deformity.
•Spinal cord
compression.
•Paraplegia.
X-ray of the spine
shows erosion of
anterior edges of the
superior and inferior
borders of adjacent
vertebral bodies with
narrowing of the
intervertebral disc
space.

38. Other forms of
extrapulmonary tuberculosis
Site of the disease Clinical features Diagnosis
TB of the bone Chronic Osteomyelitis. Tissue biopsy.
Gastrointestinal-TB Right iliac fossae
mass.
Chronic diarrhoea.
Subacute intestinal
obstruction.
Barium enema of the
small and large bowel.
Colonoscopy
Renal and urinary tract
TB
•Urinary frequency.
•Dysuria.
•Haematuria.
•Loin pain or swelling.
•Sterile pyuria urine
culture.
•Intravenous pyelogram.

39. Procedures and tests on
lymph nodes
Procedure Test Result Diagnosis
Needle
aspiration of
the lymph
node.
Look at the
material
aspirated.
Caseation. TB.
Smear for
AFB.
AFBs
present.
TB.
Smear for
cytology.
Malignant
cells seen
Malignancy
e.g. KS,
lymphoma,
carcinoma etc.

40. Laparotomy or laparoscopy
• They reveal multiple white tubercles over
the peritoneal and omental surfaces.
Confirms the diagnosis of TB-peritonitis.

41. First-line anti-TB drugs
Bactericidal drugs:
Isoniazid: (H)
Highly potent Anti-TB drug most effective
against the metabolically active, continuously
growing bacilli.
Mode of action: Inhibitor of mycobacterial cell
wall synthesis.
Common side effects:
Peripheral neuropathy due to pyridoxine
deficiency. Drug-induced hepatitis.

42. Bactericidal drugs:
Rifampicin: (R)
Highly potent Anti-TB drug that can kill the
semi-dormant bacilli (persisters) which
Isoniazid cannot.
Mode of action: Inhibitor of DNA transcription.
Common side effects:
Anorexia, nausea, vomiting and abdominal
pain.
Drug-induced hepatitis.
Reduced effectiveness of oral contraceptive

43. Bactericidal drugs:
Pyrazinamide: (Z)
Anti-TB drug with low potency that can kill
bacilli in an acid environment inside cells e.g.
macrophages.
Mode of action: Unknown.
Common side effects:
Joint pain.
Drug-induced hepatitis.

44. Bactericidal drugs:
Streptomycin (S):
Anti-TB drug with low potency.
Mode of action: Inhibits mycobacterial
protein synthesis.
Common side effects:
Auditory and vestibular nerve damage.
Renal damage.

45. Bacteriostatic drug:
Ethambutol: (E)
Anti-TB drug with low potency.
Mode of action: Inhibits mycobacterial
cell wall synthesis.
Common side effects:
Optic neuritis

46. Bacteriostatic drug:
Thiacetazone: (T)
Anti-TB drug with low potency.
It is contraindicated in HIV infected
patients because of high risk of severe
and potentially fatal skin reaction.

47. MECHANISM OF MDR TB

48. Introduction
• MDR mycobacterium tuberculosis is a major
and increasing problem in TB treatment and
control
• Resistance to both isoniazid (INH) and
rifampicin (RIF) (Zambia and most parts of the
world)
• INH and RIF are the two most potent
antituberculous drugs. they kill more than 99%
of TB bacilli within 2 months of initiation of
therapy
• Pyrazinamide (PZ) has a high sterilizing effect
acting on semi dormant bacilli

49. Patients at risk of developing MDR TB
• Pts who remain or turn +ve after 4 months of
ATT
• Pts previously treated for TB
• Contact with known MDR pt or one who died
while on DOTS
• Hospital and health care workers
• HIV pts
• Prisoners

50. Types of resistance
Primary:
• infection by mycobacterial strain that is
already resistant to INH and RF
Acquired:
• most prevalent in developing countries
• Development of Resistance in a bacilli that
was previously sensitive to the regular Rx

51. Mechanism of resistance
• Specialized cell wall has significantly
reduced permeability to many compounds
• Modifications by mutations in the drug
target genes leading to an altered target
• Change in the titration (dosage) of the
drugs through overproduction of the target

52. Resistance contd
• MDR TB reflects the stepwise accumulation of
individual mutations in several independent
genes
• Mutations are generally chromosomal

53. Diagnosis of MDR TB
• Drug susceptibility testing (DST)
–Solid media
• Incubation at 35-37 degrees for 8 wks
–Liquid media middle brook 7H09
• Incubation 4-14 days
• PCR