Introduction

Tuberculosis (TB) is one of the oldest and most persistent infectious diseases in human history, caused by the bacterium Mycobacterium tuberculosis. Despite advances in medicine, TB remains a significant global health challenge, particularly in low- and middle-income countries. It primarily affects the lungs (pulmonary TB) but can also affect other parts of the body (extrapulmonary TB). TB is an airborne disease, spread through inhalation of respiratory droplets from infected individuals, and it poses a dual threat as it often coexists with HIV/AIDS and is exacerbated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains.

This document provides an in-depth examination of TB, covering its epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, prevention, and global impact.


Epidemiology

Global Burden

  • TB is one of the top 10 causes of death worldwide and the leading cause from a single infectious agent, ranking above HIV/AIDS.
  • In 2021, the World Health Organization (WHO) estimated 10.6 million new TB cases globally, with 1.6 million deaths, including 187,000 among people living with HIV.
  • The highest burden regions include South-East Asia, Africa, and the Western Pacific.

Risk Factors

  1. Poverty and Overcrowding:
    • Poor living conditions and overcrowding facilitate TB transmission.
  2. HIV Coinfection:
    • HIV suppresses the immune system, significantly increasing the risk of TB.
  3. Malnutrition:
    • Weakens immunity, making individuals more susceptible to infection.
  4. Smoking and Air Pollution:
    • Damage the lungs, increasing vulnerability to TB.
  5. Diabetes Mellitus:
    • Triples the risk of developing active TB.

Transmission

  • TB spreads through airborne droplets expelled when an infected person coughs, sneezes, or speaks.
  • Close, prolonged contact with an infected individual is often required for transmission.

Pathogenesis

The Causative Agent

  • Mycobacterium tuberculosis is a slow-growing, acid-fast bacillus that is highly aerobic and thrives in oxygen-rich environments like the lungs.

Stages of Infection

  1. Primary Infection:
    • Occurs when M. tuberculosis enters the lungs and is engulfed by alveolar macrophages.
    • The bacteria can either be destroyed or replicate within the macrophages, spreading to regional lymph nodes and possibly other parts of the body.
  2. Latent TB Infection (LTBI):
    • The immune system walls off the infection within granulomas, leading to a dormant state where the bacteria remain alive but inactive.
    • Individuals with LTBI are asymptomatic and non-infectious but have a 5-10% lifetime risk of developing active TB.
  3. Active TB Disease:
    • Develops when the immune system fails to contain the bacteria, leading to bacterial replication and tissue destruction.
    • Active TB is contagious and presents with clinical symptoms.

Clinical Manifestations

Pulmonary TB

The majority of TB cases involve the lungs. Symptoms include:

  • Persistent cough lasting more than two weeks, often with sputum production.
  • Hemoptysis (coughing up blood).
  • Chest pain.
  • Fever and night sweats.
  • Unexplained weight loss and fatigue.

Extrapulmonary TB

TB can affect virtually any organ, leading to diverse clinical presentations:

  1. Lymph Node TB (Tuberculous Lymphadenitis):
    • Enlarged, painless lymph nodes, often in the neck.
  2. Skeletal TB:
    • Involves the spine (Pott’s disease) or long bones, causing pain, swelling, and deformities.
  3. Meningeal TB:
    • Affects the meninges, leading to headaches, confusion, and neurological deficits.
  4. Genitourinary TB:
    • Causes symptoms like pelvic pain, dysuria, and hematuria.
  5. Miliary TB:
    • A disseminated form with widespread small lesions visible on imaging.

Diagnosis

Clinical Evaluation

  • A thorough medical history, including risk factors (e.g., HIV status, prior TB exposure), and physical examination guide initial suspicion.

Laboratory Tests

  1. Microscopy:
    • Ziehl-Neelsen stain detects acid-fast bacilli in sputum or other samples.
    • Fluorescent microscopy (Auramine stain) is more sensitive.
  2. Culture:
    • Gold standard for TB diagnosis.
    • Requires 4–8 weeks for results on Lowenstein-Jensen media or shorter time with liquid culture systems (e.g., MGIT).
  3. Nucleic Acid Amplification Tests (NAATs):
    • Rapid, sensitive diagnostic tools, such as GeneXpert MTB/RIF, which also detect rifampicin resistance.
  4. Interferon-Gamma Release Assays (IGRAs):
    • Measure immune response to TB antigens, useful for latent TB detection.
  5. Tuberculin Skin Test (TST):
    • Indicates prior exposure to TB but has limitations due to cross-reactivity with BCG vaccine and other mycobacteria.

Imaging Studies

  • Chest X-Ray:
    • Shows infiltrates, cavitation, or miliary patterns in pulmonary TB.
  • CT or MRI:
    • Useful for extrapulmonary TB, especially in detecting skeletal, abdominal, or CNS involvement.

Treatment

Standard Drug Therapy

The treatment of TB involves a combination of antibiotics to prevent resistance and ensure complete eradication of the bacteria.

  1. First-Line Drugs (for drug-susceptible TB):
    • Rifampicin (RIF): Bactericidal, inhibits RNA synthesis.
    • Isoniazid (INH): Bactericidal, inhibits mycolic acid synthesis.
    • Pyrazinamide (PZA): Effective in acidic environments, targets dormant bacteria.
    • Ethambutol (EMB): Bacteriostatic, inhibits cell wall synthesis.
    Standard Regimen:
    • Intensive Phase: 4 drugs (RIF, INH, PZA, EMB) for 2 months.
    • Continuation Phase: 2 drugs (RIF, INH) for 4 months.
  2. Second-Line Drugs:
    • For drug-resistant TB, medications like fluoroquinolones (levofloxacin, moxifloxacin) and injectable agents (amikacin, kanamycin) are used.
  3. Shorter Regimens:
    • For MDR-TB, shorter regimens (e.g., BPaL: Bedaquiline, Pretomanid, and Linezolid) are showing promise.

Adjunctive Therapy

  • Corticosteroids: Used in TB meningitis or pericarditis to reduce inflammation.
  • Nutritional support to improve recovery.

Drug Resistance

Types of Drug Resistance

  1. Multidrug-Resistant TB (MDR-TB):
    • Resistant to at least rifampicin and isoniazid.
  2. Extensively Drug-Resistant TB (XDR-TB):
    • MDR-TB with additional resistance to fluoroquinolones and at least one second-line injectable drug.
  3. Totally Drug-Resistant TB (TDR-TB):
    • Rare cases where TB is resistant to all available drugs.

Causes

  • Incomplete or inconsistent treatment.
  • Poor drug quality or supply chain issues.
  • Spontaneous mutations in bacterial DNA.

Prevention

Vaccination

  • BCG Vaccine:
    • Provides partial protection against severe forms of TB in children (e.g., meningitis, miliary TB).
    • Limited efficacy in preventing pulmonary TB in adults.

Infection Control

  1. Public Health Measures:
    • Early diagnosis and treatment to reduce transmission.
    • Contact tracing and screening in high-risk populations.
  2. Personal Protective Measures:
    • Use of masks and improving ventilation in healthcare and communal settings.

Latent TB Management

  • Preventive therapy with INH or rifapentine reduces the risk of progression to active TB.

Global Impact and Challenges

Economic and Social Costs

  • TB disproportionately affects the poor, exacerbating cycles of poverty.
  • Stigma associated with TB can lead to social isolation and reduced quality of life.

Impact of COVID-19

  • The COVID-19 pandemic disrupted TB services, leading to delays in diagnosis and treatment, with an estimated increase in TB deaths.

Research and Innovations

  • Development of new vaccines, diagnostic tools, and shorter treatment regimens are critical for achieving TB elimination.

Conclusion

Tuberculosis remains a formidable global health challenge despite being curable and preventable. Its complex interplay with social determinants of health, drug resistance, and comorbidities such as HIV/AIDS highlights the need for a multifaceted approach to control. Strengthening health systems, investing in research, and addressing socioeconomic inequities are crucial to achieving the WHO’s End TB Strategy, which aims to reduce TB incidence by 90% and deaths by 95% by 2035.

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Last Update: January 26, 2025