Immunotherapy in Leprosy
Immunotherapy with mycobacterial vaccines, particularly Mycobacterium w and BCG, serves as an effective adjunct to multidrug therapy (MDT) in multibacillary leprosy patients with high bacterial loads, accelerating bacterial clearance and reducing treatment duration.
Role and Mechanism
Immunotherapy in leprosy aims to correct the defective cell-mediated immune response characteristic of lepromatous and borderline lepromatous disease 1. The approach involves administering mycobacterial vaccines alongside standard MDT to enhance bacterial killing and clearance, particularly in patients with high bacterial indices who harbor viable persisters even after completing standard therapy 2.
Primary Immunotherapeutic Agents
Mycobacterium w (Mw)
- Dosing regimen: Initial dose of 1 × 10⁸ killed bacilli, followed by 0.5 × 10⁸ bacilli per subsequent dose, administered intradermally every 3 months for 4 doses 2
- Superior bacterial clearance: Achieves complete smear negativity by 36 months in bacilliferous BL/LL patients, with a mean BI reduction from 4.75+ to 0 3
- Viable bacilli elimination: No detectable viable bacilli by mouse foot pad or ATP measurement after 6 months of combined therapy 3
BCG Vaccine
- Dosing regimen: 0.1 mg (10⁵ live bacilli) administered intradermally, repeated every 3-6 months 2, 3
- Bacterial clearance rate: BI declines by 2.40 units/year compared to 0.85 units/year in controls 2
- Time to negativity: All patients achieve smear negativity by 42 months 3
Comparative Efficacy
Mycobacterium w demonstrates slightly faster bacterial clearance than BCG, achieving complete smear negativity 6 months earlier (36 vs 42 months), though both are significantly superior to MDT alone 3. BCG shows marginally better clinical improvement scores in the first 12-24 months, but histopathological improvements are comparable between the two vaccines 2.
Clinical Benefits Beyond Bacterial Clearance
- Reduced type 2 reactions: Lower incidence of erythema nodosum leprosum compared to MDT-only controls 2
- Decreased neuritis: Fewer episodes of nerve inflammation and new deformity development 2
- Faster clinical improvement: Significantly greater reduction in clinical scores (Ramu's score) at all time points compared to controls 2
Important Caveats and Adverse Effects
Reversal Reactions (Type 1)
- Increased incidence: Marginally higher in immunotherapy groups (22.6% with Mw vs 15% in controls) 4
- Timing: 50% of reversal reactions occur within the first 3 months of therapy 4
- Risk factors: All patients with prior downgrading reactions will develop reversal reactions during therapy 4
Cutaneous Reactions
- Local reactions: Typically limited to injection site 5
- Rare generalized reactions: Generalized granulomatous dermatitis can occur, requiring high clinical suspicion to distinguish from relapse or leprosy reactions 5
Optimal Candidate Selection
Immunotherapy should be prioritized for:
- Borderline lepromatous (BL) or lepromatous (LL) patients with initial BI ≥ 4+ 2, 3
- Patients requiring shortened MDT regimens (12 months instead of 24 months) 2
- Cases at high risk for relapse due to persistent viable bacilli 1
Treatment Protocol
- Initiate standard WHO MDT-MB regimen (rifampin monthly, clofazimine and dapsone daily) 3
- Add immunotherapy with either Mycobacterium w or BCG at treatment onset 2
- Administer vaccines every 3-6 months for a total of 4 doses 2, 3
- Monitor closely in first 3 months for reversal reactions 4
- Continue follow-up for 12 months post-MDT to assess for late reactions and relapse 2
Monitoring Parameters
- Clinical assessment: Ramu's score every 6 months 2
- Bacteriological monitoring: Slit-skin smear BI every 6 months 2
- Histopathological evaluation: Skin biopsy at baseline and periodically 2
- Viability testing: Mouse foot pad or ATP measurement in research settings 3
Both vaccines are well-tolerated, with the primary concern being an increased but manageable incidence of reversal reactions that require prompt recognition and treatment 2, 4.