BCG Vaccination

History

(1) Aim

(2) Vaccine

• BCG is the only widely used live bacterial vaccine.
• Consists of living attenuated bovine strain of tubercle bacilli.
• Derived from the original Calmette strain.
• Many substrains have evolved due to different production methods.
• WHO recommended strain: "Danish 1331" (used at BCG Laboratory, Guindy, Chennai since January 1967).
• Quality control: International Reference Centre at Copenhagen.

(3) Types of Vaccine

1. Liquid (fresh) vaccine
2. Freeze-dried vaccine - more stable, superior keeping quality; present-day vaccines are distributed in this form.

• Stable for several weeks at ambient tropical temperature.
• Up to 1 year if kept away from direct light and refrigerated at below 10°C.
• Must be protected from light during storage (wrapped in double layer of red or black cloth).
• Normal saline is the recommended diluent (distilled water may cause irritation).
• Reconstituted vaccine must be used within 3 hours; leftover vaccine must be discarded.

(4) Dosage

(5) Administration

• Route: Strictly intradermal using a "Tuberculin" syringe (Omega microstat syringe with 1 cm, 26-gauge intradermal needle).
• Syringe-and-needle technique is the most precise method.
• Other methods (bifurcated needle, dermo-jet) are less accurate.
• Subcutaneous injection increases risk of abscess formation.
• Site: Just above the insertion of the left deltoid muscle (left upper arm).
• Skin must not be contaminated with antiseptic/detergent; if alcohol is used, it must evaporate before injection.
• No other injection should be given into the BCG-vaccinated arm for at least 6 months.

(6) Age Policy

• India (high-TB prevalence countries): BCG given very early in infancy:
  • At birth (for institutional deliveries), OR
  • At 6 weeks simultaneously with DPT and polio
• BCG given early in life provides high protection, especially against:
  • Severe forms of childhood tuberculosis
  • Tuberculous meningitis
• Low-prevalence countries: Restriction to high-risk groups (hospital personnel, tuberculin-negative contacts of TB cases especially MDR-TB).

(7) Normal Phenomena After Vaccination

(8) Complications

1. First: Aspiration
2. If unsuccessful: Incision + local applications of PAS or INH powder (daily)
3. No systemic INH needed
4. Patient should be reassured of harmless nature

(9) Protective Value

• Duration of protection: 15 to 20 years.
• Mechanism: Local BCG infection generates immunity associated with tuberculin hypersensitivity.
• First prospective controlled trial: 80% effectiveness over 20 years.
• Range of protection in various trials worldwide: 0 to 80% (highly variable).
• South India trial found poor protection, possibly due to prior exposure to non-tuberculous environmental mycobacteria (e.g., M. vaccae, M. non-chromogenicum) conferring partial immunity and masking BCG benefit. M. kansasii and M. scrofulaceus have an antagonistic action against BCG.
• Infants and young children vaccinated before contact with environmental mycobacteria do derive protection.
• WHO holds it unreasonable to stop current BCG vaccination programmes.

(10) Revaccination

• Duration of protection is still disputed even 90 years after vaccine development.
• BCG revaccination is NOT included in India's official EPI (Expanded Programme on Immunization) schedule.
• Booster doses are not routinely indicated.

(11) Contraindications

• Generalized eczema or infective dermatosis
• Hypogammaglobulinaemia
• Known/suspected congenital immunodeficiency
• Leukaemia, lymphoma, or generalized malignant diseases
• Patients under immunosuppressive treatment (corticosteroids, alkylating agents, antimetabolites, radiation)
• Symptomatic HIV infection
• Pregnancy

(12) Direct BCG Vaccination

• Direct BCG vaccination (without prior tuberculin test) is India's national policy.
• Allows faster, more complete coverage at lower cost.
• No adverse effects reported in tuberculin-positive reactors.
• Best practice: administer BCG during infancy before contact with environmental mycobacteria.

(13) Impact

• BCG is less effective than active case-finding and chemotherapy.
• Offers only partial protection.
• A 1982 WHO Expert Committee concluded BCG can prevent tuberculosis in uninfected individuals but has only relatively small epidemiological effect on overall risk of infection in the community.

(14) BCG Vaccination and HIV Infection

• Previous WHO recommendation: In high TB-burden countries, BCG should be given to all healthy infants at birth unless the child had symptomatic HIV infection.
• Revised recommendation (GACVS): Children known to be HIV-infected, even if asymptomatic, should NOT be immunized with BCG vaccine, because:
  • HIV-infected children vaccinated at birth who later developed AIDS were at increased risk of disseminated BCG disease.
  • Benefits of preventing severe TB are outweighed by risks.
• However: Most infants born to HIV-infected mothers are themselves uninfected (due to PMTCT interventions) and would benefit from BCG.
• Accurate HIV diagnosis in the first year of life is technically challenging and expensive; WHO recommends HIV testing at around 6 weeks of age, but this is often after BCG has already been given.

(15) Combined Vaccination

• BCG may be given simultaneously with:
  • Oral polio vaccine
  • DPT vaccine (in a different arm) - without reducing immune responses or increasing complications
• Mixed vaccines containing BCG have not yet been introduced.

Criteria for Switching from General to Selective BCG Vaccination ("Low Endemicity" Criteria)

• (a) Average annual notification rate of smear-positive pulmonary TB < 5 per 100,000
• (b) Average annual notification rate of tubercular meningitis in children under 5 years < 1 per 10 million population over previous 5 years
• (c) Average annual risk of TB infection < 0.1%

Summary

BCG vaccination is a fundamental component of a national tuberculosis programme. Despite contradictory trial evidence, BCG plays a valuable role in preventing severe forms of childhood tuberculosis - especially meningitis and miliary tuberculosis. BCG is part of WHO's Expanded Programme on Immunization (EPI). The greatest need remains in developing countries where TB is still a major health problem.

• Park's Textbook of Preventive and Social Medicine, pp. 231-232

Recent Clinical Guidelines: BCG Vaccination in HIV-Positive Infants

Overview of the Core Problem

WHO / GACVS Current Recommendations (Updated December 2025)

Rationale Behind These Recommendations

1. Disseminated BCG disease risk approaches 1% in HIV-positive infants - data from Argentina and South Africa. This is enormously higher than the <1 per million risk in immunocompetent infants.
2. HIV severely impairs BCG-specific T-cell responses in the first year of life - meaning BCG may provide little or no protection against TB in these infants, removing the benefit side of the risk-benefit equation.
3. HAART/ART may reduce dBCG disease rate and immune reconstitution inflammatory syndrome (IRIS) risk, supporting the "delay-until-stable-on-ART" strategy.
4. Early virological testing (recommended by WHO at ~6 weeks of age) is often technically demanding and expensive in high-burden settings, and is frequently done after BCG has already been administered.

The Practical Dilemma in Low-Resource Settings

• BCG vaccination should continue at birth for all infants regardless of HIV exposure, given the high TB endemicity in such populations.
• Close follow-up of infants known to be born to HIV-infected mothers is mandatory to detect and treat any BCG-related complications early.
• Where adequate HIV services exist (early virological testing + rapid ART initiation), BCG should be deferred until HIV status is confirmed.

Recent PubMed Evidence

Comparison: Park's Textbook vs. Current Guidelines

Summary

• Known HIV-infected infant = BCG contraindicated, even if asymptomatic
• Unknown status in a high-burden setting = vaccinate at birth, follow up closely
• HIV-exposed but confirmed uninfected = vaccinate normally
• HIV-infected but stable on ART (CD4% >25%) = BCG can be given

Cardinal Symptoms of Tuberculosis

Respiratory (Pulmonary) Symptoms

1. Cough

• The most common and earliest symptom
• Initially dry and non-productive, progressing to productive (purulent or mucoid sputum) as cavitation develops
• Chronic cough lasting >2-3 weeks is the key screening threshold
• Cough may develop late in primary TB, usually only after tubercle cavitation

2. Hemoptysis (Blood in Sputum)

• Ranges from blood-streaked sputum to frank hemoptysis
• Indicates cavitation or erosion of a blood vessel by the TB lesion
• One of the most specific "alarm" symptoms that should trigger immediate TB workup
• Described across all major textbooks as a cardinal feature

3. Chest Pain

• Usually pleuritic in nature - sharp, worsening on breathing/coughing
• Suggests pleural involvement (pleuritis or pleural effusion)
• May also arise from extensive parenchymal disease

4. Dyspnea (Breathlessness)

• Occurs with extensive lung disease, pleural effusion, or miliary TB
• Usually a later feature in the course of disease

Constitutional (Systemic) Symptoms

5. Fever

• Characteristically low-grade with an evening rise in temperature (pyrexia of insidious onset)
• Often described as a "diurnal fever" - temperature peaks in the late afternoon/evening
• The patient may be unaware of fever, only noticing the associated night sweats

6. Night Sweats

• Drenching night sweats - the patient wakes soaked
• Caused by the evening fever and its subsequent defervescence overnight
• Highly characteristic of TB and other chronic granulomatous/infectious diseases

7. Weight Loss and Anorexia

• Progressive, unexplained weight loss
• Anorexia (loss of appetite) typically precedes the weight loss
• In advanced disease, leads to frank cachexia (wasting)
• Caused by cytokine-driven catabolism (TNF-α, IL-1, IL-6) and reduced caloric intake

8. Fatigue and Malaise

• Generalized weakness, lassitude, and easy fatigability
• Often the earliest and most subtle constitutional complaint
• Patients frequently attribute it to overwork or stress, delaying presentation

Summary Table

Primary vs. Reactivation TB - Symptom Differences

• Tintinalli's Emergency Medicine, p. 796

Classic "Alarm" Triad for TB Screening

Hemoptysis + Night sweats + Weight loss

• Tintinalli's Emergency Medicine: "Clues that suggest tuberculosis include hemoptysis, night sweats, and weight loss."
• Textbook of Family Medicine: "Cough, hemoptysis, night sweats, fever, and weight loss suggest the need to investigate for tuberculosis."

Extrapulmonary TB - Additional Cardinal Features by Site

A Note on Atypical Presentations

• Tietz Textbook of Laboratory Medicine: "Typical signs and symptoms of tuberculosis may be absent in individuals with advanced AIDS, resulting in a delay in diagnosis."

• Dose: 0.1 ml standard / 0.05 ml for newborns <4 weeks
• Scar: 4-8 mm, appears by 6-12 weeks
• Mantoux positive: by 8 weeks (max 14 weeks)
• Complications: Lymphadenitis 1-10%, disseminated <1/million
• Duration: 15-20 years protection
• Efficacy: 0-80% (variable) - first trial showed 80%