Tuberculosis (TB)

A 32-year-old man presents with a 2-month history of persistent cough, low-grade fever, night sweats, loss of appetite, and weight loss. He reports occasional blood-streaked sputum and fatigue. On examination, he appears thin and mildly febrile, with crackles over the upper lung fields. Chest X-ray shows upper-lobe infiltrates with cavitary lesions. Sputum NAAT is positive for Mycobacterium tuberculosis. Diagnosis?

Diagnosis is Pulmonary Tuberculosis (TB).

1. Definition

1. Tuberculosis is a chronic infectious disease caused mainly by Mycobacterium tuberculosis.
2. It most commonly affects the lungs, but may involve almost any organ.
3. TB may occur as:
1. Latent TB infection → infection without active disease
2. Active TB disease → clinically and/or microbiologically evident disease
4. Pulmonary and laryngeal TB are transmitted through airborne infectious aerosols.

2. Etiology / Risk Factors

1. Causative organism: Mycobacterium tuberculosis
2. Important risk factors:
1. Close contact with infectious TB
2. HIV infection
3. Malnutrition
4. Diabetes mellitus
5. Immunosuppression, especially TNF-α inhibitors
6. Chronic kidney disease
7. Silicosis
8. Smoking
9. Crowded living conditions
10. Previous inadequately treated TB

3. Pathophysiology

1. Inhaled bacilli reach the alveoli
2. Bacilli are engulfed by macrophages but can survive intracellularly
3. Cell-mediated immunity develops
4. Activated macrophages and lymphocytes form granulomas
5. Classic pathology:
1. Caseating granulomas
2. Epithelioid histiocytes
3. Langhans-type giant cells
6. These findings are characteristic but not pathognomonic
7. Infection may:
1. Become contained → latent TB
2. Progress → active primary TB
3. Reactivate later → reactivation TB
8. Reactivation TB classically affects the upper lobes and may cause cavitation

4. Clinical Features

4.1 Respiratory Features

1. Persistent cough
2. Sputum production
3. Hemoptysis
4. Chest pain
5. Dyspnea in extensive disease

4.2 Constitutional Features

1. Fever
2. Night sweats
3. Weight loss
4. Loss of appetite
5. Fatigue

4.3 Extrapulmonary TB

1. Lymph node TB → painless lymphadenopathy
2. Pleural TB → pleural effusion
3. TB meningitis → headache, fever, altered consciousness
4. Spinal TB (Pott disease) → back pain, vertebral destruction
5. Genitourinary TB → sterile pyuria
6. Abdominal TB → abdominal pain, ascites
7. Miliary TB → hematogenous dissemination

5. Diagnosis

5.1 Diagnostic Approach

1. Suspect TB from:
1. Compatible symptoms
2. Risk factors
3. Chest imaging
2. Obtain microbiological confirmation whenever possible
3. Rapid molecular testing / NAAT is preferred for initial microbiological diagnosis
4. Assess for drug resistance, particularly rifampicin resistance

5.2 Microbiological Tests

1. NAAT / rapid molecular test
1. Rapidly detects M. tuberculosis
2. Some assays simultaneously detect drug resistance
2. AFB smear
1. Rapid
2. Smear positivity generally indicates higher bacillary burden
3. AFB smear cannot distinguish M. tuberculosis from other acid-fast mycobacteria
3. Culture
1. Important reference microbiological method
2. Allows phenotypic drug-susceptibility testing
3. Takes longer than molecular testing

5.3 Imaging

1. Chest X-ray may show:
1. Upper-lobe infiltrates
2. Cavitary lesions
3. Fibrosis
4. Lymphadenopathy
5. Pleural effusion
2. Miliary TB → diffuse “millet seed” nodules

5.4 TST / IGRA

1. Tuberculin skin test (TST)
2. Interferon-gamma release assay (IGRA)
3. Indicate TB infection
4. Cannot alone distinguish latent from active TB

6. Differential Diagnosis

1. Bacterial pneumonia
2. Lung abscess
3. Lung carcinoma
4. Fungal infection
5. Nontuberculous mycobacterial infection
6. Sarcoidosis
7. Bronchiectasis

7. Management

7.1 Core Principle

1. Confirm diagnosis → assess drug susceptibility → combination therapy → monitor response/toxicity → prevent transmission

7.2 Drug-Susceptible Pulmonary TB

1. Conventional 6-month regimen:
1. Intensive phase, 2 months:
1. Isoniazid (H)
2. Rifampicin (R)
3. Pyrazinamide (Z)
4. Ethambutol (E)
2. Continuation phase, 4 months:
1. Isoniazid
2. Rifampicin
3. Shorthand: 2HRZE / 4HR
2. Eligible patients may receive a 4-month rifapentine-moxifloxacin regimen:
1. 2HPZM / 2HPM
3. Regimen selection depends on drug susceptibility, patient factors, disease site, and current national/WHO guidance.

7.3 Important Drug Adverse Effects

1. Isoniazid
1. Hepatotoxicity
2. Peripheral neuropathy
2. Rifampicin
1. Hepatotoxicity
2. Orange-red body fluids
3. Drug interactions
3. Pyrazinamide
1. Hepatotoxicity
2. Hyperuricemia
4. Ethambutol
1. Optic neuropathy
2. Red-green color impairment

7.4 Pyridoxine

1. Pyridoxine (vitamin B6) helps prevent isoniazid-induced neuropathy in high-risk patients
2. Important in:
1. Pregnancy
2. Malnutrition
3. Diabetes
4. HIV
5. Alcohol use disorder
6. Chronic kidney disease

7.5 Drug-Resistant TB

1. Perform appropriate drug-susceptibility testing
2. MDR/RR-TB requires specialized multidrug treatment
3. Modern regimens are increasingly shorter and all-oral
4. Drugs may include:
1. Bedaquiline
2. Pretomanid
3. Linezolid
4. Fluoroquinolones
5. Treatment should follow current WHO/national guidelines

8. TB and HIV

1. HIV greatly increases the risk of active TB
2. Advanced HIV may cause:
1. Atypical pulmonary findings
2. Less upper-lobe cavitation
3. Extrapulmonary TB
4. Disseminated/miliary TB
3. Patients with TB should undergo HIV testing
4. TB/HIV management requires:
1. Anti-TB treatment
2. Antiretroviral therapy (ART)
3. Attention to rifamycin-ART drug interactions

9. Infection Control

1. Use appropriate airborne precautions for suspected infectious pulmonary/laryngeal TB
2. Important measures:
1. Early diagnosis and effective treatment
2. Appropriate isolation
3. Adequate ventilation
4. Respiratory protection for healthcare workers
3. Perform contact investigation

10. Monitoring

1. Clinical improvement and weight
2. Treatment adherence
3. Microbiological response when indicated
4. Drug toxicity
5. Liver function when indicated
6. Vision/color discrimination with ethambutol
7. Drug interactions, especially with rifamycins

11. Complications

1. Massive hemoptysis
2. Bronchiectasis
3. Pulmonary fibrosis
4. Respiratory failure
5. Pleural effusion
6. Miliary TB
7. TB meningitis
8. Pericardial TB
9. Spinal destruction
10. Drug-resistant TB
11. Death

12. Prevention

1. Early diagnosis and effective treatment
2. Contact investigation
3. Treatment of latent TB infection when indicated
4. Infection-control measures
5. BCG vaccination
1. Protects children particularly against TB meningitis and disseminated/miliary TB
2. Protection against pulmonary TB is variable

13. Key Clinical Insight

1. Chronic cough + fever + night sweats + weight loss ± hemoptysis + upper-lobe cavitation = suspect pulmonary TB

14. Key Exam Points

1. Organism = Mycobacterium tuberculosis
2. Transmission = airborne
3. Pathology = caseating granulomas
4. Reactivation TB classically affects the upper lobes
5. NAAT = preferred rapid initial microbiological test
6. AFB smear cannot distinguish M. tuberculosis from other acid-fast mycobacteria
7. Culture allows phenotypic drug-susceptibility testing
8. TST/IGRA cannot distinguish active from latent TB
9. Conventional regimen = 2HRZE / 4HR
10. Eligible patients may receive 2HPZM / 2HPM
11. Isoniazid → neuropathy + hepatotoxicity
12. Rifampicin → orange-red body fluids + drug interactions
13. Pyrazinamide → hyperuricemia + hepatotoxicity
14. Ethambutol → optic neuropathy
15. Miliary TB = hematogenous dissemination
16. Always assess drug resistance and HIV coinfection