Leprosy
Dr. Roumi Ghosh
Assistant Professor
Microbiology
ESI PGIMSR, Joka
INTRODUCTION
▰ Mycobacterium leprae - causative agent of leprosy; a disease of antiquity,
having been recognized since long time :
 Vedic times in India (described as Kushta Roga in Sushruta Samhita, 600
BC)
 Biblical times in the Middle East
 Hippocrates, 460 BC.
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INTRODUCTION (Cont..)
▰ G. H. Armauer Hansen (1873) - discovery of lepra bacilli
▰ Shepard (1960) – multiplying lepra bacilli in footpads of mice kept at a low
temperature (20°C).
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CLINICAL MANIFESTATIONS
▰ Chronic granulomatous disease of humans - involving cooler parts of the body
(skin, peripheral nerves, upper respiratory tract, eyes, and testes, etc.).
▰ Capable of affecting any tissue or organs causing bony deformities and
disfigurements in untreated cases.
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CLINICAL MANIFESTATIONS
▰ Incubation period: long incubation period - 5–7 years (vary between 2 and 40
years)
▰ Attributed to longer generation time of lepra bacilli - 12–13 days as compared
to 14 hours for tubercle bacillus.
▰ Lepromatous cases - longer incubation period than tuberculoid cases.
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Classification of Leprosy
Ridley-Jopling classification
Madrid classification (1953)
Indian classification (1981)
Lepromatous leprosy (LL)
Lepromatous type
Lepromatous type
Borderline Lepromatous leprosy
Borderline
Borderline
Borderline leprosy (BB)
Indeterminate type
Indeterminate type
Borderline tuberculoid leprosy (BT)
Tuberculoid type
Pure neuritic type
Tuberculoid leprosy (TT)
—
Tuberculoid type
(1966)
(BL)
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Clinical Classification
▰ Paucibacillary (PB) leprosy: A case of leprosy which fulfills all the criteria—
 (i) 1 to 5 skin lesions,
 (ii) no nerve involvement, and
 (iii) slit-skin smear negative for lepra bacilli
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Clinical Classification (Cont..)
▰ Multibacillary (MB) leprosy: A case of leprosy which fulfills any one of the
criteria—
 (i) >5 skin lesions; or
 (ii) nerve involvement (neuritis); or
 (iii) slit-skin smear positive for lepra bacilli.
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Characters
Lepromatous leprosy (ll)
Tuberculoid leprosy (TT)
Differences between
lepromatous leprosy
and
Multibacillary
Paucibacillary
tuberculoid leprosy
Bacillary load
Bacteriological index
4–6+
0–1+
Skin lesions
Many, symmetrical Margin
is irregular Lesions appear
as:

Multiple nodules
(lepromata)

Plaques and
xanthoma-like papules
Leonine facies and
eyebrow alopecia
One or few, asymmetrical Margin is sharp
Lesions appear as: Hypopigmented,
annular macules with elevated borders
Tendency towards central clearing
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Characters
Lepromatous leprosy (ll)
Tuberculoid leprosy (tt)
Differences between lepromatous leprosy and
Nerve lesion
Nerve lesions appear late
Early anesthetic skin lesion,
tuberculoid leprosy
(Cont..)
Hypoesthesia is a late sign Enlarged thickened nerves,
Variable nerve
palsies
Nerve abscess seen
(common in BT)
CMI
Low
Normal
Lepromin test
Negative
Positive
Humoral immunity
Exaggerated
Normal
Macrophages
Foamy type (lipid- laden)
Epithelioid type
Langhans giant cells
Not seen
Found
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Differences between lepromatous leprosy and
tuberculoid leprosy (Cont..)
A
B
A. Nodular lesions of lepromatous leprosy; B. Hypopigmented
skin lesions of tuberculoid leprosy (arrow showing).
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COMPLICATIONS
▰ Complications in leprosy patients may be of two types—
 Deformities and
 Allergic response (called lepra reactions).
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Deformities
▰ 25% of untreated cases develop deformities - may arise due to—
 (1) nerve injury - muscle weakness or paralysis, or
 (2) disease process (facial deformities or loss of eyebrow), or
 (3) infection or injury (ulcers).
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Deformities (Cont..)
Common deformities include:
▰ Face: Leonine facies, sagging face, loss of eyebrow/eye lashes, saddle nose
and corneal opacity and ulcers
▰ Hands: Claw hand and wrist drop
▰ Feet: Foot drop, clawing of toes, inversion of foot, and plantar ulcers.
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Deformities (Cont..)
Deformities seen in untreated lepromatous leprosy:
A. Saddle nose deformity; B. Bony deformity; C. Corneal opacity.
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Characters
Lepra reaction type I
Lepra reaction typeII
Hyper- sensitivity
Type IV (delayed hypersensitivity)
Lepra Reactions
Type III (immune complexmediated)
Seen with
Borderline leprosy
Lepromatous variety (BL, LL)
Manifests as
Inflammation of previous lesions, new
skin lesions and neuritis
Crops of painful erythematous
papules which become
nodular called ENL
Progresses as
If occurs before treatment
It usually occurs following
—progresses towards LL (down grading the start of chemotherapy
reaction) If occurs after treatment—
progresses towards TT (reversal
reaction)
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Characters
Lepra reaction type I
T-helper
TH1 predominates
leads to
Lepraresponse
Reactions
(Cont..)
IFN-g and IL-2
Lepra reaction typeII
TH2 predominates-leads to
IL-6, IL-8.
TNF-α plays a central role
Other organs
Usually not affected
Eyes, testes and kidney are
affected
Treatment
Glucocorticoid
Glucocorticoid, thalidomide,
clofazimine and antipyretics
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EPIDEMIOLOGY
Source of infection:
▰ Multibacillary (LL and BL) cases - most important sources of infection.
▰ Asymptomatic cases - have a role in transmission.
▰ Tuberculoid leprosy - do not transmit infection efficiently
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EPIDEMIOLOGY (Cont..)
Mode of transmission:
▰ Nasal droplet infection (aerosols containing M. leprae) - most common mode.
▰ Contact transmission (skin):
 Direct contact from person to person
 Indirect contact with infected soil, fomites - clothes and linens.
▰ Direct dermal inoculation during tattooing.
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EPIDEMIOLOGY (Cont..)
▰ Communicability: Leprosy - not highly communicable - Intimate and prolonged
contact - necessary for transmission.
▰ Environmental factors - people of rural areas, moist soil, humidity and
overcrowding.
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Leprosy Elimination
▰ In 1992 - WHO launched a campaign to eliminate leprosy as a public health
problem by year 2000.
▰ Goal - <1 case per 10,000 population.
▰ India: Achieved the elimination status by December 200.
▰ Global Leprosy Strategy (2016-20): Launched by WHO in 2016 - aims at
reducing disability among children by 2020
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Geographical Distribution
▰ Once leprosy was worldwide in distribution – now almost exclusively confined
to the developing nations like India Africa , Latin America etc.
▰ India:
▰ As of 31st March 2018 - 90,709 cases are on record in India.
▰ Five states/UTs reported prevalence above elimination cut-off of >1/10,000
population as on 31st March.
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1. Smear Microscopy
▰ Smear microscopy - done to demonstrate the acid-fast bacilli in the lesions.
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Specimen Collection
Total six samples are collected:
▰ Four from skin (forehead, cheek, chin and buttock),
▰ One from ear lobe and nasal mucosa by nasal blow/scraping.
Click to add text
 Slit skin smear - collect skin and ear lobe specimens .
 Nasal specimens:
 Nasal blow - early morning mucus material
 Nasal scraping - mucosal scraper to scrape the nasal septum
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Appearance
▰ Less acid-fast - stained by Ziehl–Neelsen
technique - 5% sulfuric acid for decolorization.
▰ Under oil immersion - red acid-fast bacilli,
arranged singly or in groups (cigar like
bundles).
▰ Virchow’s lepra cells or foamy cells
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Appearance (Cont..)
▰ Live bacilli - uniformly stained with parallel sides and round ends and length is
five times the width
▰ Dead bacilli - less uniformly stained and have fragmented and granular
appearance.
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Grading of the Smear
▰ 1–10 bacilli in 100 OIF =1+
▰ 1–10 bacilli in 10 OIF = 2+
▰ 1–10 bacilli per OIF = 3+
▰ 10–100 bacilli per OIF = 4+
▰ 100–1000 bacilli per OIF = 5+
▰ >1000 bacilli or bacilli in clumps and globi in each OIF = 6+
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Grading of the Smear (Cont..)
▰ Bacteriological index (BI): Total number of bacilli (live and dead) per oil
immersion field
▰ Morphological index (MI): Percentage of uniformly stained bacilli out of the
total number of bacilli counted
 MI is a better marker to monitor the treatment response
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2. Mouse Foot Pad Cultivation
▰ Not cultivable either in artificial culture media or in tissue culture.
▰ Only certain way - by inoculating the specimens into foot pad of mice and
keeping at 20°C for 6–9 months.
▰ Other animals - nine banded armadillo (Dasypus novemcinctus) - also used.
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2. Mouse Foot Pad Cultivation (Cont..)
▰ Advantages:
 10 times more sensitive than microscopy
 Detecting drug resistance & Evaluating potency of drugs
 detects viability of bacilli
▰ Disadvantages: Time-consuming (6–9 months) & ethical issues
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3. Antibody Detection
▰ FLA-ABS (Fluorescent leprosy antibody absorption test):
 To identify subclinical cases
 Antibodies detected irrespective of duration and stage of the disease
 92% sensitive and 100% specific
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3. Antibody Detection (Cont..)
▰ ELISA detecting IgM antibodies to PGL-1 (phenolic glycolipid-1) antigen of M.
Leprae - found in 95% of patients with untreated LL patients & titre decreases
with effective therapy
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4. Test for Detecting CMI (Lepromin Test)
▰ Demonstrates delayed hypersensitivity reaction against the lepra antigen.
▰ Also indicates an intact host’s CMI.
▰ Procedure: Lepromin antigen - injected intradermally to forearm and reading is
taken at two occasions.
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4. Test for Detecting CMI (Lepromin Test)
(Cont..)
▰ At 48hr (Early or Fernandez reaction): Induration (>10 mm) - corresponds to
DTH reaction to lepra antigen and indicates past exposure to lepra bacilli.
▰ At 21 days (Late or Mitsuda reaction): A nodule of >5 mm – subsequently
ulcerates
 If positive - patient’s CMI is intact
 If negative - absence of CMI
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Treatment of Leprosy
▰ Recommended drugs: Dapsone, rifampicin and clofazimine
▰ Alternate drugs: Ethionamide, quinolones (ofloxacin), minocycline and
clarithromycin.
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Treatment of Leprosy (Cont..)
▰ WHO Regimen (2018)
▰ 3-drug regimen: WHO recommends a 3-drug regimen of rifampicin, dapsone
and clofazimine for all leprosy patients.
 Dapsone (100 mg) - daily, self-administered
 Rifampicin (600 mg) - once a month under supervision
 Clofazimine (300 mg) - once a month under supervision, and by 50 mg
daily, self-administered
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Treatment of Leprosy (Cont..)
▰ Duration of treatment—6 months for paucibacillary leprosy and 12 months for
multibacillary leprosy
▰ Follow-up - annually for 2 years for paucibacillary leprosy and for five years for
multibacillary leprosy.
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PREVENTION OF LEPROSY
▰ Active case finding and effective treatment of cases.
▰ BCG vaccine: No effective vaccine available so far.
▰ MIP vaccine: Killed leprosy vaccine - developed in India in 2018, using
Mycobacterium indicus pranii (MIP).
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PREVENTION OF LEPROSY (Cont..)
▰ Chemoprophylaxis: Dapsone – to high-risk household contacts of tuberculoid
patients, but not for lepromatous patients; hence not recommended
▰ Hospitalized patients need not be isolated as transmission requires prolonged
contact.
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Questions:
▰ Q1. The generation time of lepra bacilli is:
a.
20 minutes
b.
2 hours
c.
20 hours
d.
12-13 days
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Questions:
▰ Q2. Correct about lepromatous leprosy:
a.
Multibacillary
b.
CMI is normal
c.
Langerhans cells are found
d.
Positive lepromin test
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