Tuberculosis (TB): Definition Treatments

Tuberculosis

Tuberculosis (TB) is a chronic infectious disease caused by the Mycobacterium tuberculosis complex, primarily affecting the lungs but capable of involving almost any organ system in the body. TB has been one of humanity’s deadliest diseases for centuries and continues to remain a leading cause of morbidity and mortality worldwide, especially in low- and middle-income countries.

Despite the availability of effective chemotherapy for over half a century, TB still poses a global health challenge due to drug resistance, HIV co-infection, poverty, and social determinants of health. The disease not only impacts individuals biologically but also carries a heavy economic and social burden.

2. Definition

Tuberculosis is defined as a contagious, granulomatous infectious disease caused primarily by Mycobacterium tuberculosis. It is transmitted via airborne droplets and typically affects the pulmonary system, although extrapulmonary involvement is common, especially in immunocompromised individuals.

TB is characterized by a delayed-type hypersensitivity reaction, leading to the formation of tubercles—organized collections of immune cells—and in advanced cases, caseous necrosis and tissue destruction.

3. Epidemiology of Tuberculosis

3.1 Global Burden

According to the World Health Organization (WHO) Global Tuberculosis Report 2023:

• An estimated 10.6 million people fell ill with TB in 2022.
• About 1.3 million deaths occurred among HIV-negative individuals, with an additional 214,000 deaths among HIV-positive individuals.
• TB is the second leading infectious killer worldwide, after COVID-19.

3.2 High-Burden Countries

• India accounts for the highest number of TB cases globally.
• Other high-burden countries include Indonesia, China, the Philippines, Pakistan, Nigeria, and South Africa.

3.3 Demographics

• TB affects all age groups, but the productive age group (15–49 years) is most affected.
• Men are disproportionately more affected than women.
• Children are highly vulnerable to severe forms of TB, such as TB meningitis and miliary TB.

4. Etiology and Causative Organism

4.1 Mycobacterium tuberculosis Complex

The major causative agents of TB are:

• Mycobacterium tuberculosis (most common in humans)
• M. bovis (zoonotic; from cattle)
• M. africanum (mainly in Africa)
• M. microti, M. canetti, and M. caprae (less common)

These bacteria are acid-fast bacilli (AFB)—rod-shaped, non-motile, obligate aerobes with a waxy cell wall rich in mycolic acid, which makes them resistant to desiccation and many disinfectants.

5. Mode of Transmission

• TB spreads primarily via inhalation of aerosolized droplets released when an infected person coughs, sneezes, talks, or spits.
• Close, prolonged exposure in poorly ventilated areas increases the risk.
• TB is not spread by touch, sharing food, or kissing.

6. Pathogenesis of Tuberculosis

6.1 Primary TB Infection

Upon inhalation, M. tuberculosis reaches the alveoli, where it is phagocytosed by alveolar macrophages. Some bacilli survive intracellularly, multiply, and spread to regional lymph nodes, forming a Ghon complex.

6.2 Latent TB Infection (LTBI)

In most immunocompetent individuals, the infection is contained by the immune system, leading to latent TB, where the bacilli remain dormant for years without causing symptoms. 5–10% of such cases may reactivate.

6.3 Reactivation TB

Occurs when immune defenses are compromised, as in:

• HIV/AIDS
• Malnutrition
• Diabetes mellitus
• Aging
• Immunosuppressive therapy (e.g., corticosteroids)

6.4 Granuloma Formation

The hallmark of TB pathology is granuloma formation, where macrophages, T-cells, and fibroblasts surround the bacilli, forming a caseating center that may liquefy and spread infection.

Pathophysiology of Tuberculosis

Step 1: Entry of Bacteria

Tuberculosis is caused by Mycobacterium tuberculosis. The bacteria usually enter the body through the airways when a person breathes in droplets released from an infected patient’s cough or sneeze.

Step 2: Reaching the Lungs

After inhalation, the bacteria settle in the alveoli (tiny air sacs of the lungs). Here, they are first attacked by immune cells called macrophages, but the bacteria can survive inside these cells instead of being destroyed.

Step 3: Early Spread and Primary Infection

The bacteria multiply inside macrophages and spread to nearby lymph nodes, forming a primary complex (Ghon focus + lymph node involvement). At this stage, many people have no symptoms, or they may just feel mild fever and cough.

Step 4: Immune Response and Granuloma Formation

The body’s immune system (especially T-cells) becomes active. It sends more macrophages to surround the bacteria. This creates a wall-like structure called a granuloma (tubercle), which tries to trap the infection. The center of the granuloma may die, forming caseous necrosis (cheese-like material).

Step 5: Latent Infection

In many people, the granulomas succeed in containing the bacteria. The bacteria become “dormant” but remain alive in the body. This stage is called latent TB. People with latent TB usually have no symptoms and are not infectious.

Step 6: Reactivation (Secondary TB)

If the immune system becomes weak (due to HIV, malnutrition, stress, or age), the dormant bacteria can become active again. This is called secondary TB. It usually affects the upper lobes of the lungs, causing cough with sputum, blood (hemoptysis), fever, night sweats, and weight loss.

Step 7: Dissemination (Severe Cases)

In some cases, the bacteria spread through the blood to other organs, leading to miliary TB (tiny spots in many organs). TB can also affect the bones, kidneys, meninges, or other tissues.

7. Types of Tuberculosis

7.1 Pulmonary TB

• Most common form.
• Involves lungs, especially upper lobes.
• Symptoms: persistent cough (>2 weeks), hemoptysis, chest pain, weight loss, night sweats, and fever.
• Highly infectious.

7.2 Extrapulmonary TB

Occurs when the infection spreads outside the lungs:

• Lymph node TB (common in children and HIV patients)
• Pleural TB
• Skeletal TB (Pott’s disease of the spine)
• Genitourinary TB
• Meningeal TB (TB meningitis)
• Pericardial TB
• Abdominal TB

7.3 Miliary TB

• Severe, disseminated form with numerous tiny tubercles in multiple organs.
• Common in immunocompromised patients.
• Life-threatening if untreated.

7.4 Latent TB Infection (LTBI)

• No symptoms.
• Not contagious.
• Positive tuberculin skin test or interferon-gamma release assay (IGRA).
• Requires preventive therapy in high-risk individuals.

7.5 Drug-Resistant TB

• Multidrug-resistant TB (MDR-TB): Resistant to at least isoniazid and rifampicin.
• Extensively drug-resistant TB (XDR-TB): Also resistant to fluoroquinolones and second-line injectables.
• Totally drug-resistant TB (TDR-TB): Rare but virtually untreatable with current regimens.

8. Clinical Manifestations

General Symptoms

• Low-grade fever
• Fatigue
• Anorexia
• Night sweats
• Weight loss

Pulmonary Symptoms

• Persistent cough
• Sputum production
• Hemoptysis
• Pleuritic chest pain

Extrapulmonary TB Symptoms

• Site-specific: lymphadenopathy, joint pain, neurological deficits, abdominal pain, urinary issues, etc.

9. Diagnosis of Tuberculosis

9.1 Clinical Evaluation

• History of symptoms
• Contact with known TB cases
• Travel or residence in endemic areas

9.2 Microbiological Tests

• Sputum smear microscopy (Ziehl-Neelsen staining)
• Culture (Lowenstein-Jensen medium; takes 4–8 weeks)
• CBNAAT (Cartridge-Based Nucleic Acid Amplification Test) like GeneXpert (rapid and detects rifampicin resistance)
• Line Probe Assay (LPA) for drug resistance

9.3 Radiological Imaging

• Chest X-ray: shows cavitations, infiltrates, or consolidation
• CT/MRI for extrapulmonary TB

9.4 Immunological Tests

• Tuberculin skin test (TST/Mantoux test)
• Interferon-gamma release assays (IGRAs): e.g., QuantiFERON-TB Gold

10. Treatment of Tuberculosis

10.1 First-Line Anti-TB Drugs (for Drug-Sensitive TB)

Intensive Phase (2 months):

• Isoniazid (H)
• Rifampicin (R)
• Pyrazinamide (Z)
• Ethambutol (E)

Continuation Phase (4 months):

• Isoniazid (H)
• Rifampicin (R)

Total duration: 6 months

10.2 Drug-Resistant TB Regimens

• MDR-TB requires longer treatment (18–24 months) with:
  • Second-line drugs: fluoroquinolones (levofloxacin, moxifloxacin), injectable agents (amikacin, kanamycin), linezolid, clofazimine, cycloserine, etc.
• Shorter MDR-TB regimens (9–11 months) are recommended under specific conditions.

10.3 Newer Drugs

• Bedaquiline
• Delamanid
• Used in drug-resistant TB cases under special programs.

10.4 Treatment of Latent TB

• Isoniazid for 6–9 months
• Or rifampicin +/- isoniazid for 3–4 months

10.5 DOTS Strategy

• Directly Observed Treatment, Short-course (DOTS) ensures compliance.
• Endorsed by WHO.
• Implemented under National TB Elimination Program (NTEP) in India.

11. TB and HIV Co-infection

• TB is the leading cause of death among people living with HIV/AIDS.
• Co-infected patients require integrated care:
  • Antiretroviral therapy (ART)
  • Cotrimoxazole preventive therapy
  • Early TB treatment

12. Prevention and Control

12.1 BCG Vaccination

• Bacillus Calmette-Guérin (BCG) vaccine is administered at birth in endemic areas.
• Offers protection mainly against severe childhood TB (e.g., TB meningitis, miliary TB).

12.2 Infection Control

• Cough etiquette, masks, proper ventilation.
• Isolation of infectious patients.

12.3 Screening and Surveillance

• Contact tracing and screening of high-risk groups.
• Community-level awareness programs.

12.4 Public Health Strategies

• WHO End TB Strategy targets a 90% reduction in TB deaths and an 80% reduction in incidence by 2030.
• India aims to eliminate TB by 2025 through its NTEP.

13. Challenges in TB Control

• Drug resistance
• Poor treatment adherence
• HIV co-infection
• Social stigma
• Healthcare access inequities
• Inadequate diagnostics in rural areas

Conclusion

Tuberculosis continues to be a formidable public health challenge, despite being preventable and curable. A comprehensive approach involving early detection, standardized treatment, contact tracing, vaccination, and public awareness is imperative for successful control and eventual eradication.

New advances in molecular diagnostics, shorter and more effective drug regimens, and vaccine research offer promising avenues. However, achieving the goal of TB elimination requires political commitment, adequate funding, international collaboration, and community involvement.