Tuberculosis (TB)

Overview

Tuberculosis (TB) is a potentially serious infectious disease caused by the bacterium Mycobacterium tuberculosis. While it primarily affects the lungs (pulmonary TB), it can also affect other parts of the body including the kidneys, spine, brain, and lymph nodes (extrapulmonary TB). Despite being preventable and curable, TB remains one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent.

TB has plagued humanity for millennia, with evidence of the disease found in ancient Egyptian mummies. Once called "consumption" due to the way it seemed to consume people from within, TB was responsible for countless deaths throughout history. The development of effective antibiotics in the 1940s transformed TB from a death sentence to a curable disease, yet it continues to pose significant health challenges globally.

The World Health Organization estimates that about one-quarter of the world's population has latent TB infection, meaning they carry the bacteria but are not ill and cannot transmit the disease. However, people with latent TB have a 5-10% lifetime risk of developing active TB disease, with the risk being much higher for those with compromised immune systems.

Understanding the distinction between latent TB infection and active TB disease is crucial. While latent TB is asymptomatic and non-contagious, active TB causes symptoms and can spread to others. Modern TB control relies on identifying and treating both forms to prevent transmission and reduce the global burden of disease.

Types of TB

Tuberculosis can be classified in several ways based on its activity, location, and drug sensitivity:

By Disease Activity

By Location

• Pulmonary TB: Affects the lungs (most common, about 80% of cases)
  • Primary progressive TB
  • Reactivation TB
  • Cavitary TB
  • Miliary TB (disseminated)
• Extrapulmonary TB: Affects other organs (20% of cases)
  • TB lymphadenitis (lymph nodes)
  • TB meningitis (brain and spinal cord)
  • Bone and joint TB
  • Genitourinary TB
  • Gastrointestinal TB
  • TB pericarditis (heart lining)

By Drug Sensitivity

• Drug-sensitive TB: Responds to standard first-line drugs
• Multidrug-resistant TB (MDR-TB): Resistant to isoniazid and rifampin
• Extensively drug-resistant TB (XDR-TB): Resistant to additional drugs
• Totally drug-resistant TB (TDR-TB): Resistant to all tested drugs

Symptoms

TB symptoms vary depending on which part of the body is affected. Latent TB has no symptoms, while active TB disease causes various symptoms that often develop gradually.

Extrapulmonary TB Symptoms

Symptoms depend on the affected organ:

• TB lymphadenitis: Swollen, painless lymph nodes, often in the neck
• TB meningitis: Headache, stiff neck, confusion, sensitivity to light
• Bone/joint TB: Pain and swelling in affected area, limited movement
• Genitourinary TB: Blood in urine, frequent urination, pelvic pain
• Gastrointestinal TB: Abdominal pain, diarrhea, blood in stool

Causes

Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex, with M. tuberculosis being the most common causative agent in humans.

The Causative Organism

• Mycobacterium tuberculosis: A slow-growing, acid-fast bacillus
• Unique characteristics:
  • Waxy cell wall resistant to many disinfectants
  • Can survive in dried sputum for weeks
  • Grows very slowly (doubling time 12-24 hours)
  • Aerobic organism requiring oxygen
• Other mycobacteria: M. bovis (from cattle), M. africanum (regional variant)

Pathogenesis

The development of TB follows a complex process:

1. Initial infection: Bacteria inhaled into lungs
2. Alveolar deposition: Bacteria reach air sacs in lungs
3. Macrophage ingestion: Immune cells attempt to destroy bacteria
4. Bacterial survival: Some bacteria survive within macrophages
5. Granuloma formation: Immune system walls off infection
6. Latency or progression: Infection controlled (latent) or progresses (active)

Factors Influencing Disease Development

• Bacterial factors: Strain virulence, bacterial load
• Host immunity: Strength of immune response
• Environmental factors: Nutrition, living conditions
• Genetic susceptibility: Some people more prone to active disease

Transmission

Understanding how TB spreads is crucial for prevention and control efforts.

How TB Spreads

• Airborne transmission: Primary route of spread
• Infectious droplets: Released when person with active pulmonary TB:
  • Coughs
  • Sneezes
  • Speaks
  • Sings
  • Laughs
• Droplet nuclei: Tiny particles (1-5 microns) remain airborne for hours
• Inhalation: Others breathe in bacteria-containing particles

Factors Affecting Transmission

Who Cannot Spread TB

• People with latent TB infection
• People with extrapulmonary TB only
• Children with TB (usually less infectious)
• People on effective treatment for 2+ weeks

Risk Factors

Certain factors increase the risk of TB infection and progression from latent to active disease.

High-Risk Groups

• People experiencing homelessness
• Incarcerated individuals
• Immigrants from high-burden countries
• Healthcare workers
• People living with HIV/AIDS
• Close contacts of TB patients

Diagnosis

TB diagnosis involves multiple tests to detect infection and determine if disease is active.

Tests for TB Infection

Tests for Active TB Disease

1. Chest X-ray:
   • Upper lobe infiltrates
   • Cavities
   • Lymphadenopathy
   • Pleural effusion
2. Sputum tests:
   • Acid-fast bacilli (AFB) smear
   • TB culture (gold standard)
   • Molecular tests (GeneXpert MTB/RIF)
3. Other specimens: For extrapulmonary TB
   • Tissue biopsy
   • Fluid analysis (pleural, CSF)
   • Urine testing

Advanced Diagnostics

• Drug susceptibility testing: Identifies resistant strains
• Molecular line probe assays: Rapid resistance detection
• Whole genome sequencing: Comprehensive resistance profile
• CT scan: Better detail than X-ray
• PET scan: For complex cases

Diagnostic Challenges

• Distinguishing latent from active TB
• Diagnosis in children (paucibacillary disease)
• HIV co-infection (atypical presentation)
• Extrapulmonary TB (varied presentations)
• Drug-resistant TB identification

Treatment

TB treatment requires combination therapy with multiple drugs taken for extended periods to cure the disease and prevent resistance.

Treatment of Latent TB

Preventive therapy reduces risk of developing active disease by 60-90%:

• Isoniazid (INH):
  • 9 months daily (standard)
  • 6 months daily (alternative)
• Rifampin (RIF): 4 months daily
• Isoniazid + Rifapentine: 12 weekly doses (3HP regimen)
• Isoniazid + Rifampin: 3 months daily

Treatment of Active TB

Directly Observed Therapy (DOT)

• Healthcare worker watches patient take medications
• Ensures adherence and completion
• Reduces treatment failure and resistance
• Can be in-person or video-observed (VDOT)

Special Situations

• TB meningitis: 12 months treatment with corticosteroids
• Bone/joint TB: 6-9 months treatment
• HIV co-infection: ART coordination, longer treatment
• Pregnancy: Modified regimen (avoid streptomycin)
• Children: Weight-based dosing, different formulations

Side Effects Management

• Hepatotoxicity: Monitor liver enzymes
• Peripheral neuropathy: Vitamin B6 supplementation
• Visual changes: Eye exams with ethambutol
• GI upset: Take with food
• Drug interactions: Especially with rifampin

Drug-Resistant TB

Drug-resistant TB is a growing global threat requiring specialized treatment approaches.

Types of Resistance

Monoresistance

Resistance to one first-line anti-TB drug

Polyresistance

Resistance to more than one drug (not both INH and RIF)

Multidrug-resistant TB (MDR-TB)

Resistance to at least isoniazid and rifampin

Extensively drug-resistant TB (XDR-TB)

MDR-TB plus resistance to fluoroquinolones and injectable agents

Totally drug-resistant TB (TDR-TB)

Resistant to all tested drugs (not officially defined)

Causes of Drug Resistance

• Inadequate treatment regimens
• Poor adherence to treatment
• Poor quality medications
• Interrupted drug supply
• Transmission of resistant strains
• Previous TB treatment

MDR-TB Treatment

• Duration: 18-24 months (shorter regimens available)
• Drugs: Second-line agents including:
  • Bedaquiline
  • Linezolid
  • Fluoroquinolones
  • Clofazimine
  • Cycloserine
• Monitoring: Monthly sputum cultures, adverse effects
• Success rate: 50-70% globally

Prevention of Resistance

• Appropriate initial treatment
• DOT implementation
• Drug susceptibility testing
• Quality-assured medications
• Patient education and support
• Infection control measures

Prevention

TB prevention involves multiple strategies targeting different stages of the disease process.

Primary Prevention

• BCG vaccination:
  • Given to infants in high-burden countries
  • Protects against severe childhood TB
  • Variable protection against adult pulmonary TB
  • Not used routinely in low-burden countries
• Infection control:
  • Administrative controls
  • Environmental controls (ventilation, UV lights)
  • Personal protective equipment (N95 respirators)

Secondary Prevention

• Contact investigation: Testing exposed individuals
• Preventive treatment: For latent TB infection
• Targeted testing: High-risk groups
• Immigration screening: In low-burden countries

Infection Control Measures

Personal Prevention

• Avoid close contact with active TB patients
• Ensure good ventilation in living spaces
• Cover mouth when coughing/sneezing
• Seek prompt medical care for symptoms
• Complete preventive treatment if prescribed
• Maintain good overall health and nutrition

When to See a Doctor

Early detection and treatment of TB is crucial for individual health and preventing transmission.

Seek Medical Evaluation For

• Cough lasting more than 3 weeks
• Coughing up blood or blood-tinged sputum
• Unexplained weight loss (>10% body weight)
• Persistent fever without obvious cause
• Drenching night sweats
• Extreme fatigue or weakness
• Chest pain with breathing or coughing

Get TB Testing If You

• Had close contact with someone with active TB
• Have HIV or other immune suppression
• Recently traveled to high TB burden areas
• Live or work in high-risk settings
• Have medical conditions increasing TB risk
• Are starting immunosuppressive therapy

Follow-up Care

• Keep all medical appointments
• Take medications exactly as prescribed
• Report side effects promptly
• Complete the full treatment course
• Inform close contacts about exposure

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