Control and prevention of TB

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Control and Prevention of Tuberculosis

Overview

TB prevention operates on four pillars: (1) prompt diagnosis and effective treatment, (2) infection control measures, (3) treatment of latent TB infection (LTBI), and (4) BCG vaccination. - Murray & Nadel's Textbook of Respiratory Medicine

1. Prompt Diagnosis and Effective Treatment

Early diagnosis and treatment remain the most powerful TB control tools because they rapidly reduce the infectious burden in the community.

Case finding approaches:

Passive case finding - patients present to health services with symptoms; historically the dominant approach under DOTS (Directly Observed Therapy, Short-course)
Active case finding / contact tracing - systematic surveillance of household contacts with symptom screening, physical examination, and chest X-ray at baseline and follow-up. A cluster-randomized trial in Vietnam showed active surveillance identified 2.5-fold more cases than passive case finding
Community-wide screening - A study using Xpert TB/RIF on sputum of community members regardless of symptoms showed a 44% reduction in TB prevalence in screened communities vs controls (126 vs 226 per 100,000), and a 50% lower TB infection rate in children 3-10 years old - Murray & Nadel's Textbook of Respiratory Medicine

DOTS Strategy: In the 1990s, the WHO and World Bank promoted DOTS as the cornerstone of global TB control. DOTS relies on:

Short-course chemotherapy with isoniazid and rifampin
Direct observation of medication intake
Uninterrupted drug supply
Passive smear-based case finding
Recording and reporting

DOTS was effective for uncomplicated drug-susceptible TB but had limitations: sputum smear microscopy misses extrapulmonary cases, pediatric cases, and many pulmonary cases; passive case finding requires health service availability; and it did not address MDR-TB. This led to DOTS-Plus, which adds the diagnostics and drugs needed to manage drug-resistant disease. - Harrison's Principles of Internal Medicine 22E

2. Infection Control Measures

Transmission of M. tuberculosis occurs via airborne droplet nuclei. Control measures fall into four categories:

a) Clinician Awareness

Maintaining a high index of suspicion, especially in settings where TB may be uncommon, and using rapid molecular tests (e.g., Xpert MTB/RIF) for early diagnosis. Prompt and specific diagnosis minimizes unnecessary isolation time and reduces the infectious period.

b) Administrative Controls (Policies)

Prompt respiratory isolation of suspected or confirmed pulmonary TB cases
Cohorting of confirmed cases
Triage protocols to identify potentially infectious patients quickly
Training of health care workers
Enablers and incentives to maintain treatment adherence (e.g., transportation vouchers, food stamps, convenient clinic hours, DOT outreach workers) - Textbook of Family Medicine 9e

c) Environmental Controls

Negative-pressure isolation rooms (air flows into the room, preventing contaminated air from escaping)
Upper-room ultraviolet germicidal irradiation (UVGI)
High-efficiency particulate air (HEPA) filtration
Adequate ventilation with sufficient air changes per hour

d) Personal Protective Equipment

Health care workers should wear N95 respirators (not simple surgical masks) when entering rooms of suspected/confirmed TB patients
Patients should wear surgical masks when outside isolation rooms

Together these measures protect both health care workers and other patients. - Murray & Nadel's Textbook of Respiratory Medicine

3. Treatment of Latent TB Infection (LTBI)

Who has LTBI? Persons infected with M. tuberculosis who have a positive tuberculin skin test (TST) or IGRA, a normal chest X-ray, no symptoms, and no sputum positivity. Without treatment, 5-10% will develop active TB over their lifetime; about half of those will do so within the first 2 years. The risk is substantially higher in HIV-positive individuals.

Who should be treated? Not everyone with LTBI needs treatment. High-priority target groups include:

Recent contacts of infectious pulmonary TB cases
HIV-infected persons
Persons with silicosis
Immigrants from high-burden to low-burden countries
Prisoners and the homeless
Illicit drug users
Persons with diabetes mellitus, chronic renal failure, or other immunocompromising conditions
In high-burden countries: HIV-positive individuals and household contacts (especially children under 5)
Park's Textbook of Preventive and Social Medicine

LTBI Treatment Regimens (current preferred options)

Regimen	Duration	Interval	Min. Doses
Isoniazid + Rifapentine (3HP)	3 months	Once weekly (DOT)	12
Rifampin alone	4 months	Daily	120
Isoniazid + Rifampin (3HR)	3 months	Daily	90
Isoniazid alone (alternative)	6 months	Daily	180
Isoniazid alone (alternative)	9 months	Daily	270

The 3HP (isoniazid + rifapentine weekly for 12 doses) is non-inferior to 9-month isoniazid with substantially higher treatment completion rates. Rifampin for 4 months is preferred for HIV-negative patients and is likely the safest option in terms of adverse events. The 9-month isoniazid regimen is conditionally recommended for both HIV-positive and HIV-negative patients. - Murray & Nadel's Textbook of Respiratory Medicine; Park's Textbook of Preventive and Social Medicine

Contraindications/cautions: Active liver disease is a contraindication. Extra monitoring is needed for persons >35 years, those on interacting medications (phenytoin, disulfiram, antiretrovirals), and those with alcoholism, diabetes, or renal insufficiency. Pregnancy is not an absolute contraindication to isoniazid. If infected with MDR-TB or XDR-TB strains, preventive treatment may not be possible.

4. BCG Vaccination

History and mechanism: BCG (Bacille Calmette-Guérin) is derived from an attenuated bovine strain of M. bovis. First given orally (1921-1925), then by intradermal route (from 1927). The aim is to induce a benign primary infection that stimulates acquired resistance to virulent tubercle bacilli, reducing morbidity and mortality from primary TB.

Efficacy:

Protection estimated at approximately 50% (meta-analysis data)
Most consistent protective effect is against severe childhood forms: TB meningitis and miliary TB
Protection in adults is inconsistent - varies widely across trials worldwide (including the TB Prevention Trial in South India, which showed minimal protection)
BCG vaccination can reduce childhood TB infection rates by up to 50% in highly endemic settings

Current recommendations:

BCG is part of the WHO Expanded Programme on Immunization (EPI)
Given to neonates/infants at birth in high-burden countries (single intradermal dose)
Not routinely used in low-burden countries (e.g., the United States) where risk is low; instead, limited use in specific high-risk groups
Infant BCG vaccination does not prevent subsequent use of TST for LTBI diagnosis (though it may cause a false positive)

New TB vaccines: Two recent clinical trials have shown optimism for vaccines more efficacious than BCG. A novel "prevention of infection" trial and intravenous BCG immunization (in macaques) have shown promising results, and the M72/AS01E vaccine candidate reduced progression from LTBI to active TB in a 2019 NEJM trial. - Murray & Nadel's Textbook of Respiratory Medicine; Park's Textbook of Preventive and Social Medicine

5. Drug Resistance: A Major Challenge to TB Control

All anti-TB drugs can produce resistant strains through two mechanisms:

Primary (pre-treatment) resistance - patient infected with resistant bacteria
Acquired (secondary) resistance - emerges during inadequate treatment (irregular drug intake, inadequate regimens)

Classification:

MDR-TB - resistant to at least isoniazid and rifampin
XDR-TB - resistant to isoniazid, rifampin, any fluoroquinolone, and at least one injectable agent

Globally (as of 2021), ~4% of new TB cases and ~18% of previously treated cases involve rifampin-resistant or MDR strains. Poor infection control in hospitals, combined with delayed effective therapy, drove explosive lethal outbreaks of MDR/XDR strains. - Harrison's Principles of Internal Medicine 22E; Park's Textbook of Preventive and Social Medicine

The End TB Strategy (WHO 2015-2030) aims to reduce TB deaths by 95% and new cases by 90% by 2030 vs 2015 baseline, built on three pillars: integrated patient-centered care, bold policies, and intensified research.

6. Surveillance and Public Health Infrastructure

Surveillance is an integral part of any TB control programme, covering:

Measuring annual TB infection rates (epidemiological surveillance)
Monitoring control measures (BCG coverage, treatment outcomes)
Sputum culture and drug sensitivity testing - increasingly important to detect and contain MDR-TB
Maintaining an effective public health infrastructure including TB surveillance, screening, and contact tracing

Hospitalization is reserved for emergencies (massive haemoptysis, pneumothorax), surgical treatment, severe forms (TB meningitis), and specific social indications. Domiciliary (home-based) treatment is standard for uncomplicated cases. - Park's Textbook of Preventive and Social Medicine

Summary Table: Four Pillars of TB Prevention

Pillar	Key Interventions
Prompt diagnosis & treatment	Active case finding, Xpert testing, contact tracing, DOTS/DOTS-Plus
Infection control	Clinician awareness, administrative controls, negative-pressure rooms, HEPA filters, N95 respirators
LTBI treatment	Target high-risk groups; 3HP (12 doses), 4-month rifampin, or 6-9 month isoniazid
BCG vaccination	Neonatal BCG in high-burden countries; protects against severe childhood TB

Recent reviews confirm these strategies remain current (Tuberculosis, Lancet 2025; TB prevention strategies, Clin Microbiol Infect 2024).

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