Leprosy — Epidemiology & Control
Community Medicine · Communicable Disease · lean revision notes
Leprosy — Epidemiology & Control
Leprosy (Hansen's disease) is a chronic granulomatous infection caused by Mycobacterium leprae, primarily affecting skin and peripheral nerves. For NEET PG, the heavily-tested zones are the Ridley-Jopling spectrum versus WHO operational classification, MDT regimens, lepra reactions, disability grading, and the NLEP elimination milestones.
Etiology & Microbiology
- Causative organism: Mycobacterium leprae — an obligate intracellular, acid-fast bacillus (weakly acid-fast, decolourised by 5% sulphuric acid, so a 5% H₂SO₄ is used instead of the 25% used for tubercle bacilli in modified Ziehl-Neelsen / Fite-Faraco stain).
- It is the only bacterium that infects peripheral nerves (Schwann cells) and has the longest generation time (~12–13 days).
- Cannot be cultured in artificial media (non-cultivable in vitro). Grown in the mouse footpad (Shepard's model) and the nine-banded armadillo (natural reservoir; armadillo also used to study lepromatous disease and as a source of bacilli for lepromin antigen).
- M. lepromatosis causes diffuse lepromatous leprosy (Lucio phenomenon), especially in Mexico.
- Optimum growth at cooler body temperatures (27–30°C) → explains predilection for skin, superficial nerves, nose, earlobes, testes, and anterior eye.
High-yield: M. leprae is non-cultivable, is the slowest-multiplying human bacterium (generation time ~12 days), and is studied in the mouse footpad and nine-banded armadillo.
Epidemiology
- Reservoir: Humans are the principal reservoir; armadillos are a natural animal reservoir.
- Source of infection: Untreated multibacillary (lepromatous) cases — the nasal mucosa discharge is the most important source (a single sneeze of an LL patient can shed millions of bacilli).
- Portal of exit: Nasal secretions (main), ulcerated skin.
- Portal of entry: Nasal mucosa (upper respiratory route) and broken skin.
- Mode of transmission: Mainly droplet/respiratory; prolonged close contact matters. Not highly contagious — most exposed adults are naturally immune.
- Incubation period: Long and variable — average 3–5 years (tuberculoid can be 2–5 yrs; lepromatous up to 8–12 yrs). One of the longest incubation periods among infectious diseases.
- Host factors: Affects all ages; M > F (~2:1). Genetic susceptibility (HLA-DR2, DR3 with tuberculoid; HLA-DQ1 with lepromatous).
High-yield: The most infectious clinical type is lepromatous leprosy (LL), and the most important exit route is nasal discharge, not skin.
Immunology & Lepromin Test
The clinical type depends on the host's cell-mediated immunity (CMI):
- Strong CMI → tuberculoid pole (paucibacillary, localised, lepromin positive).
- Weak/absent CMI → lepromatous pole (multibacillary, disseminated, lepromin negative).
Lepromin (Mitsuda) test — a test of CMI/host resistance, NOT diagnostic of leprosy (it is positive in many healthy individuals):
- Early (Fernandez) reaction: read at 24–48 h — delayed hypersensitivity to soluble antigen.
- Late (Mitsuda) reaction: read at 21 days (3–4 weeks) — nodule formation, indicates granuloma-forming capacity; used for classification & prognosis.
| Pole | CMI | Lepromin test | Bacillary load |
|---|---|---|---|
| Tuberculoid (TT) | Strong (Th1) | Positive | Few/absent (PB) |
| Lepromatous (LL) | Absent (Th2) | Negative | Heavy (MB) |
Classification — Ridley-Jopling vs WHO
Ridley-Jopling (immunological/histological spectrum, 1966)
Five groups along the immunity spectrum:
TT → BT → BB → BL → LL
- TT (Tuberculoid): few well-defined anaesthetic plaques, asymmetric, thickened nerve; lepromin +; AFB absent.
- BT (Borderline tuberculoid): more lesions, satellite lesions.
- BB (Mid-borderline): most unstable, "punched-out"/inverted-saucer lesions.
- BL (Borderline lepromatous): numerous lesions, some symmetry.
- LL (Lepromatous): numerous symmetric lesions, leonine facies, madarosis (loss of eyebrows—lateral first), saddle nose, gynaecomastia, glove-and-stocking anaesthesia, abundant AFB (globi/lepra cells = Virchow cells); lepromin negative.
- I (Indeterminate): earliest, single hypopigmented macule; may heal or progress.
| Feature | Tuberculoid (TT) | Lepromatous (LL) |
|---|---|---|
| Number of lesions | Single/few (≤5) | Numerous |
| Symmetry | Asymmetric | Symmetric |
| Sensation in lesion | Markedly lost (early) | Late loss |
| Nerve involvement | Few, asymmetric, marked | Many, symmetric, late |
| AFB in lesion | Absent / scanty | Abundant (globi) |
| Lepromin test | Positive | Negative |
| Infectivity | Low | High |
| Bacterial Index | 0 | 5–6 |
| Natural course | May self-heal | Progressive |
WHO Operational Classification (field/treatment-based)
Because slit-skin smears are not always available, WHO uses lesion (and nerve) count:
| WHO class | Skin lesions | Nerves involved | Slit-skin smear |
|---|---|---|---|
| Paucibacillary (PB) | 1–5 lesions | Only one nerve trunk | Negative |
| Multibacillary (MB) | >5 (≥6) lesions | >1 (more than one) nerve trunk | Positive |
High-yield: Any patient with a positive slit-skin smear is classified as MB regardless of lesion count. Single-lesion = PB; ≥6 lesions or smear-positive = MB.
Clinical Features
- Cardinal signs (WHO — any one is diagnostic):
- Hypopigmented/reddish patch with definite loss of sensation.
- Thickened peripheral nerve (with sensory/motor loss).
- Positive slit-skin smear (AFB).
- Earliest sensation lost: temperature → pain (touch) → fine touch (temperature first).
- Commonly thickened nerves: ulnar (most common, at elbow), median, radial cutaneous, common peroneal (lateral popliteal), posterior tibial, greater auricular (visibly enlarged), facial.
- Deformities: claw hand (ulnar+median), wrist drop (radial), foot drop (common peroneal), lagophthalmos & corneal anaesthesia (facial + trigeminal), trophic ulcers, absorption of digits.
Lepra Reactions (very high-yield)
Acute immunological episodes during the chronic course; common causes of nerve damage and emergencies.
| Feature | Type 1 (Reversal) reaction | Type 2 (ENL) reaction |
|---|---|---|
| Type of hypersensitivity | Type IV (delayed, cell-mediated) | Type III (immune complex) |
| Seen in | Borderline (BT, BB, BL) | LL & BL (multibacillary) |
| Immunity shift | Upgrading (↑CMI) or downgrading | — |
| Skin | Existing lesions become red, swollen, painful | New crops of tender erythematous nodules (erythema nodosum leprosum) |
| Nerve involvement | Acute neuritis prominent (sudden palsy) | Less, but possible |
| Systemic features | Usually absent | Fever, malaise, iridocyclitis, arthritis, orchitis, lymphadenitis |
| Drug of choice | Corticosteroids (prednisolone) | Thalidomide (DOC); clofazimine; steroids |
High-yield: Type 1 (reversal) = Type IV hypersensitivity, treated with steroids. Type 2 (ENL) = Type III (immune-complex), DOC = thalidomide (avoid in pregnancy — teratogenic). Do NOT stop MDT during a reaction.
- Lucio phenomenon: severe necrotising reaction in diffuse non-nodular LL (M. lepromatosis).
Diagnosis & Investigation of Choice
Stepwise approach: Clinical cardinal signs → Slit-skin smear (SSS) → Skin biopsy (confirmatory) → ancillary tests.
- Slit-skin smear (SSS): Sites = both earlobes, and lesion edges. Stained with modified ZN (Fite). Reported as:
- Bacterial Index (BI): Ridley's logarithmic scale 0 to 6+ — measures total (live + dead) bacilli density.
- Morphological Index (MI): % of uniformly stained (solid/viable) bacilli — measures viability and monitors treatment/infectivity.
- Skin biopsy: Most definitive; tuberculoid shows epithelioid granuloma around nerves; lepromatous shows foamy macrophages (lepra/Virchow cells) with globi and a clear subepidermal "grenz zone".
- Investigation of choice (confirmatory): slit-skin smear + skin biopsy; PCR used in difficult/paucibacillary cases.
- Lepromin test is for classification/prognosis, not diagnosis.
High-yield: Morphological Index (MI) falls rapidly with effective treatment (reflects viable bacilli); Bacterial Index (BI) falls slowly (~1 log/year) as dead bacilli are cleared.
Management — WHO MDT (Drug of Choice)
Multidrug therapy (MDT) since 1981 prevents resistance. WHO supplies it free worldwide. The 2018 WHO guideline now uses a uniform 3-drug regimen for all (adding clofazimine to PB), though the classical scheme is the most tested.
| Type | Drugs | Doses | Duration |
|---|---|---|---|
| Paucibacillary (PB) | Rifampicin + Dapsone (± Clofazimine per 2018) | Rifampicin 600 mg monthly (supervised); Dapsone 100 mg daily | 6 months |
| Multibacillary (MB) | Rifampicin + Dapsone + Clofazimine | Rifampicin 600 mg monthly; Clofazimine 300 mg monthly + 50 mg daily; Dapsone 100 mg daily | 12 months |
| Single-lesion PB (older ROM) | Rifampicin + Ofloxacin + Minocycline | Single dose | Single dose |
- Mnemonic for MB drugs — "R-D-C" (Rifampicin, Dapsone, Clofazimine).
- Rifampicin = most potent bactericidal drug (renders patient non-infectious within days).
- Dapsone = bacteriostatic; side effect = haemolysis (esp. G6PD deficiency), methaemoglobinaemia, dapsone-hypersensitivity syndrome.
- Clofazimine = bacteriostatic + anti-inflammatory; side effect = reddish-black skin discolouration, ichthyosis, GI cramps.
High-yield: MB = 3 drugs for 12 months; PB = 2 drugs for 6 months. Rifampicin is given monthly and supervised. WHO now recommends counting the fixed number of monthly blister packs rather than relying on smear negativity to stop therapy.
Disability / Deformity Grading (WHO)
Graded separately for eyes, hands, and feet:
| Grade | Eyes | Hands & Feet |
|---|---|---|
| Grade 0 | No eye problem due to leprosy; no visual loss | No anaesthesia, no visible deformity |
| Grade 1 | Eye problem present but vision not severely affected (≥6/60) | Anaesthesia present, but no visible deformity |
| Grade 2 | Severe visual impairment (<6/60), lagophthalmos, iridocyclitis, corneal opacity | Visible deformity (clawing, ulcer, shortening, wrist/foot drop) |
High-yield: Grade 1 = sensory loss only (anaesthesia, no visible deformity); Grade 2 = visible deformity/severe visual impairment. Grade-2 disability (G2D) rate is a key NLEP indicator.
Complications
- Deformities: claw hand, foot drop, lagophthalmos, trophic ulcers, resorption of digits, saddle nose, leonine facies, madarosis.
- Ocular: iridocyclitis, corneal anaesthesia/ulcer → blindness.
- Neuritis → permanent palsies (Type 1 reaction is the main culprit).
- ENL with chronic iritis, orchitis (sterility), amyloidosis (chronic LL).
- Social stigma and psychological morbidity.
Prevention & National Programme (NLEP)
- NLEP launched 1955 as National Leprosy Control Programme; renamed National Leprosy Eradication Programme (NLEP) in 1983 when MDT was introduced.
- Elimination defined as prevalence <1 case per 10,000 population. India achieved this at the national level in December 2005.
- Chemoprophylaxis: Single-Dose Rifampicin (SDR) to contacts of newly diagnosed cases (post-exposure prophylaxis).
- Vaccine: BCG offers partial protection (variable); Mycobacterium indicus pranii (MIP / Mw vaccine) is an Indian immunotherapeutic vaccine.
- Key strategies: early case detection, free MDT, disability prevention & rehabilitation, IEC to reduce stigma, ASHA-based active surveillance (LCDC — Leprosy Case Detection Campaigns).
High-yield: Elimination = <1 per 10,000 population (a prevalence target, not eradication). India reached national-level elimination in 2005.
Key Differentials (hypopigmented patch)
- Pityriasis versicolor — fine scaling, KOH positive, sensation intact.
- Pityriasis alba — children, ill-defined, sensation intact.
- Vitiligo — depigmented (not hypopigmented), sensation intact, no nerve thickening.
- Tinea corporis — active scaly raised margin, itchy.
- Post-inflammatory hypopigmentation, nevus anaemicus/depigmentosus.
The clincher distinguishing leprosy from all of these = definite loss of sensation in the patch ± thickened nerve.
Recently asked / exam angle
- MDT composition & duration: "Which is NOT a component of MB-MDT?" / "Duration of PB regimen?" (Answer cues: MB = R+D+C × 12 mo; PB = R+D × 6 mo).
- Lepra reactions: matching Type 1 ↔ Type IV ↔ steroids, and Type 2 (ENL) ↔ Type III ↔ thalidomide. Frequently a single best answer.
- WHO classification cut-off: ≤5 vs ≥6 lesions; smear positive = MB.
- Disability grading: Grade 1 vs Grade 2 differentiation (anaesthesia only vs visible deformity).
- Indices: MI for viability/monitoring; BI on 0–6 log scale.
- Elimination definition (<1/10,000) and NLEP renaming year (1983).
- Microbiology one-liners: non-cultivable, mouse footpad/armadillo, longest generation time, Fite stain with 5% H₂SO₄.
- DOC for ENL not responding/contraindicated to thalidomide = clofazimine/steroids; thalidomide contraindicated in pregnancy.
Rapid revision
- M. leprae — non-cultivable, intracellular acid-fast bacillus; mouse footpad & armadillo; generation time ~12 days.
- Most infectious type = lepromatous (LL); main exit = nasal discharge; entry = nasal mucosa/skin.
- Cardinal signs: hypopigmented anaesthetic patch, thickened nerve, positive slit-skin smear (any one diagnostic).
- Earliest sensation lost in a patch = temperature.
- Ridley-Jopling spectrum: TT–BT–BB–BL–LL (BB most unstable); plus Indeterminate.
- WHO: PB = 1–5 lesions; MB = ≥6 lesions or any smear-positive case.
- PB-MDT = Rifampicin + Dapsone × 6 months; MB-MDT = Rifampicin + Dapsone + Clofazimine × 12 months. Rifampicin monthly & supervised.
- Type 1 (reversal) = Type IV HS, borderline, steroids; nerve damage prominent.
- Type 2 (ENL) = Type III HS, LL/BL, thalidomide (DOC); fever + tender nodules + iridocyclitis. Never stop MDT in reactions.
- Disability: Grade 1 = anaesthesia only; Grade 2 = visible deformity / <6/60 vision.
- BI (0–6 log scale) falls slowly; MI (% solid bacilli) falls fast and tracks viability/infectivity.
- Elimination = <1 case/10,000 population; India achieved nationally in 2005; NLEP since 1983; chemoprophylaxis = single-dose rifampicin to contacts; lepromin test = prognosis/classification, not diagnosis.