Leprosy

Learning objectives
At the end of the session, the students will be able to understand:

▰ Clinical manifestations, classification, complications, lab diagnosis and

treatment of M.leprae.

▰ Differences between lepromatous leprosy and tuberculoid leprosy.

▰ Prevention of leprosy

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Essentials of Medical Microbiology
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 6
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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 Madrid classification Indian classification

classification (1966) (1953) (1981)
Lepromatous leprosy (LL) Lepromatous type Lepromatous type

Borderline Lepromatous Borderline Borderline

leprosy (BL)
Borderline leprosy (BB) Indeterminate type Indeterminate type

Borderline tuberculoid Tuberculoid type Pure neuritic type

leprosy (BT)
Tuberculoid leprosy (TT) — Tuberculoid type

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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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Differences between lepromatous leprosy and
tuberculoid leprosy
Characters Lepromatous leprosy (ll) Tuberculoid leprosy (TT)

Bacillary load Multibacillary Paucibacillary

Bacteriological index 4–6+ 0–1+

Skin lesions Many, symmetrical Margin One or few, asymmetrical Margin is sharp
is irregular Lesions appear Lesions appear as: Hypopigmented,
as: annular macules with elevated borders
 Multiple nodules Tendency towards central clearing
(lepromata)
 Plaques and
xanthoma-like
papules
Leonine facies and
eyebrow alopecia

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Differences between lepromatous leprosy and
tuberculoid leprosy (Cont..)
Characters Lepromatous leprosy (ll) Tuberculoid leprosy (tt)

Nerve lesion Nerve lesions appear late Early anesthetic skin lesion,
Hypoesthesia is a late sign Enlarged thickened nerves,
Variable nerve Nerve abscess seen
palsies (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). 14
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Other Categories of Leprosy
▰ Borderline type

▰ Indeterminate type

▰ Pure neuritic type

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IMMUNE
RESPONSE
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IMMUNE RESPONSE
▰ Innate immunity: High degree – to lepra bacilli - minority of those
infected develop clinical disease

▰ Cell-mediated immune response: Plays a vital role in the control of the

disease.
 People with low CMI - develop LL type of lesions
 People with intact CMI develop TT type lesions.

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IMMUNE RESPONSE (Cont..)

▰ Humoral immune response:

▰ Antibodies – minor role in disease control - M. leprae is

intracellular.
▰ In LL patients - exaggerated TH2 response - releases cytokines that
cause polyclonal B cell activation producing high titer of antibodies
—both specific and nonspecific antibodies. 18
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COMPLICATIONS
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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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Lepra Reactions

Characters Lepra reaction type I Lepra reaction type II

Hyper- sensitivity Type IV (delayed hypersensitivity) Type III (immune

complex-mediated)
Seen with Borderline leprosy Lepromatous variety (BL,
LL)
Manifests as Inflammation of previous lesions, new Crops of painful erythematous
skin lesions and neuritis 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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Lepra Reactions (Cont..)

Characters Lepra reaction type I Lepra reaction type II

T-helper response TH1 predominates leads to TH2 predominates-leads to ­

­IFN-g and IL-2 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
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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 inoculationEssentials

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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

▰ 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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LABORATORY
DIAGNOSIS
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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.
 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 Essentials

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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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Grading of the Smear (Cont..)

▰ SFG percentage (solid, fragmented granular rod percentage): gives better

picture of bacterial morphology and is a more sensitive indicator of
monitoring treatment response than MI

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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 45
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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
LEPROSYEssentials of Medical Microbiology
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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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