Leprosy

Hansens disease

It is known in Germany as ,Aussatz

and as Prokaza in Russia and as
Lepre in French and as
Lepra in Spanish and as
Mafung Chinese and as
Raibyo in Japanese and as
Kushtha In Hindi and in most
Sengalese languages , it is known as
The great disease

Introduction

Leprosy is a chronic granulomatous infection of

the skin and the peripheral nerves, with an
intracellular bacterium Mycobacterium Lepra.

Leprosy was recognized in the ancient

civilization of China, Egypt, and India. The first
known written mention of leprosy is dated
600BC.

Introduction
Leprosy shows a wide range of clinical

presentation from:

Tuberculoid leprosy (TT)

Borderline leprosy:
borderline tuberculoid (BT),
midborderline (BB),
borderline lepromatous (BL).

Lepromatous leprosy (LL).

(Classified by Ridley & Jopling 1966)

A simpler field classifications depending on the

number of skin lesions:

Single skin lesion (one patch).

Paucibacillary ( 2-5 patchs).

Multibacillary more than 5 patchs)

Etiologic agent

Mycobacterium Leprae,
discovered in 1873 by
G.A. Hansen.

Intracellular parasite with

tropism for macrophages
and Schwann cells.

Viable bacilli stained with

carbol-fuchsin appear as
solid rods with rounded
ends, while those is
irregular stain are dead.

Etiologic agent

M. leprae is an acid &

alcohol fast (Ziehl-Neelsen),
gram positive bacilli.

Prefer to grow in cooler

regions of the body <
37c.

It has never been

cultivated extracellularly,
but organism can
replicate in mouse
footpad & 9-banded
armadillo

Etiologic agent

Genome include 1605 genes encoding proteins

& 50 genes for stable RNA molecule.

More than half of the functional genes are

replaced by inactive or pseudogenes, retaining
the genes essential for Mycobacterial cell wall
formation.

Thus M. leprae depend on host metabolic

products, and this explain its slow rate of
replication and inability to grow in culture.
(Shin Y,et al. 2000)

Etiologic agent
Mycobacterial cell wall contain several

targets for host immune response:

Phenolic glycolipid I (PGL-I).

Lipoarabinomannan.

Other cell wall proteins purified from

glycolipid component of cell wall.

 Phenolic glycolipid I (PGL-I).

Prominent surface lipid specific for M. leprae.
Best characterized virulent factor:

Binds to C3, phagocytosis of the bacterium by mononuclear

phagocytes.
Protect against oxidative killing by hydroxyl radicals and
superoxide anions.

Phenolic glycolipid I (PGL-I).

Specific tropism for Schwann cells:

Trisaccharide terminal of PGL-I G domain of 2

chain of laminin 2, a basal component of lamina of
Schwann cells restricted to peripheral nerves.

Stimulates host immune response:

Potent IgM antibody response, that is proportional to

bacterial load and fall with therapy.
(Sridharan, et al. 2005)

Lipoarabinomannan:

Modulates macrophages phagocytic activity, & proteins

involved in cell wall synthesis.

Other cell wall proteins purified from glycolipid

component of cell wall:

Act as potent T-cell antigens, stimulate protective

immunity in murine M. leprae infection.
(Britton & Lockwood, 2004)

Epidemiology
Prevalence:

In the past 20 years more than 14 million

patients have been cured.

In 1985 12/10 000, dropped in 2000 >

1/10 000, with a 20% annual decrease in new
cases detected globally since 2001.

Leprosy is eliminated from 113 countries of 122

where leprosy was considered a public health
problem in 1985.

Epidemiology

In 9 countries in Africa, Asia & Latin America more

than 1/10 000
Eighty three % of cases are present in 6 countries: India,
Brazil, Burma, Indonesia, Madagascar & Nepal.
India account for 64% of cases world wide.
(WHO, 2005)

WHO African region leprosy elimination program

meeting in 2003

Epidemiology

Primary host is human. Naturally occurring

infection is also reported armadillos in America &
African chimpanzee.

Sex: Male more affected than females (M/F ratio

1.5-2 to 1) except in some areas of Africa.

Age: All ages, about 20% of cases occur in

children below 10 years, but it is extremely rare
in infants.

Transmission

Aerosol spread of nasal secretion, & uptake

through nasal or respiratory mucosa.

M. Leprae in nasal secretion can survive up to 36

hours, or as much as nine days in tropical areas.

Proximity is an important determinant of

transmission, & incidence among houses hold
contacts:
8-10 for lepromatous leprosy.
2-4 for tuberculoid leprosy
(Sridharan, et al. 2005)

Incubation Period

Varies widely from months to 30 years

With a mean of 4 years for TT and 10 years for LL.

Subclinical infection is reported in areas of high

prevalence, as M. leprae DNA was detected in 5% of
nasal swabs from normal individuals.
(Britton & Lockwood, 2004)

Host susceptibility

Genetic factors can affect both the development

and the pattern of the disease:

susceptibility loci on chromosomes 10 & 6 Indian

patients.
Polymorphism TNF- promoter genes multibacillary
leprosy in Brazilian patients.
HLA DR2 & DR3 tuberculoid diseases, while HLA
DQ1with lepromatous form
Mutation in toll-like receptor-2 gene lepromatous
leprosy in Koreans.
(Britton & Lockwood, 2004)

Pathogenesis

Clinical forms of the diseases depend on the ability to

mount a cell mediated immune response.
One pole (TT) vigorous CMI lesions infiltrated with
Th1-like Tcell IFN , TNF , IL-2 and IL-15 well
demarcated granulomas with few mycobacteria found in
the lesions.
Diseases is limited to few well defined skin patchs or
nerve trunks.

Other pole (LL):

Absent specific cellular immunity, uncontrolled

proliferation of bacilli with many lesions and extensive
infiltration of the skin and nerves.
There is no organized granuloma, foamy macrophages,
and high antibody titer to PGL-I.
Deviation of CD4+ve T cells, with Th2 like cytokines IL-4
and IL-10, deletion of T cells, or suppressor T cells

Pathogenesis

Most of the patients have the intermediate form (BT,BB,

and BL).
They are unstable and either progress:

Slowly toward lepromatous pole, or

Type 1 leprosy reaction (reversal reaction)

Spontaneous increased T cell reactivity & in cytokines IFN , TNF

Type 2 reaction (erythema nodosum leprosum)

Systemic inflammatory immune response extravascular immune
complexes neutrophil infiltration, complement activation and high
concentration of TNF

Clinical features

Skin involvement:

Commonly macules or plaques rarely papules or nodules

are seen.
In tuberculoid and BT, lesions are few, hypopigmented with
raised edges, and with reduced sensation

Clinical features

Lepromatous form, many skin lesion,

symmetrical, confluent in some cases, and many
of them are not hypoaesthetic.

Clinical features

Clinical features

Nerve damage:

Peripheral nerve trunk

damage:

Posterior tibial, ulnar, median,

lateral popliteal and facial.
Involved nerves are enlarged, and
with regional sensory and
motor loss.
Small dermal sensory &

autonomic nerves:

Hypoaesthesia TT and BT.

Glove & stocking lepromatous
form.
Pure neuritic leprosy:

Clinical features

Eye involvement:

Blindness nerve damage &

direct invasion

Lagophthalmus orbicularis
oculi zygomatic & temporal
branches of facial nerve.

Corneal ulceration
anaesthesia ophthalmic branch
of trigeminal nerve.

Clinical features

Systemic features:

Nasal mucosa
cartilage saddle
shape.

Bone destruction
osteomyelitis.

Testicular atrophy
loss of testosterone .

Renal involvement and

amyloidosis

Diagnosis

Lepromin test:

Intradermal inoculation of killed M leprae.

Early reactions (48 h, Fernandez)
Late reactions (3-4 wk, Mitsuda)
strongly positive responses (>5 mm) in TT or BT, while patients
with LL do not respond.

Diagnosis
Slit smear technique:

Skin incision in 6 sites ( ear lobes, elbow, knee and a

lesion)
Slit is smeared on a slide and stained with ZiehlNeelsen.
Microscopic score (1+ to 6+), reflect number of bacilli
by HPF
Useful to quantitate bacterial load
High specificity but low sensitivity 70%

Diagnosis
Serology:

ELISA: to detect antibodies against carbohydrate

portion of the PGL-I.
Postive in lepromatous but not the tuberculoid form.
Antibody titer decreases with effective therapy.

Polymarase chain reaction (PCR):

Amplify the DNA of M leprae

Low bacterial loads (<10 bacilli) can be detected.
60-75% of smear -ve patients with TT leprosy have
positive results on PCR.

Diagnosis

Histologic diagnosis:

In TT: Noncaseating
granuloma, bacilli are few
or absent, dermal nerve
involvement, with normal
skin organs.
In LL: Diffuse
granulomatous reaction,
foamy macrophages, more
common around blood
vessels and nerves

Treatment

Chemotherapy:

All patient should receive multi-drug therapy (MDT).

First line drugs: Rifampicin, Clofazimine, and Dapsone.

Treatment
Second line therapy: Minocycline, clarithromycin, and
ofloxacin, are highly effective against M. leprae.

Reversal reaction:
Peak time: during the first 2 month of therapy, even up 12
months, and after (MDT) is completed.
Corticosteroids 40-60mg daily, taper 5 mg every 2-4 weeks,
duration of therapy 3-4 months.
Recovery rate for nerve function 60-70%, less with preexisting nerve damage or recurrent reaction.

Treatment
Type 2 reaction (ENL):
Develop during 1st or 2nd year of MDT, and can relapse over
several years.
Anti- inflammatory: Clofazimine 300mg daily. Or
Drug that target overproduction of TNF-,Thalidomide
400mg daily, or pentoxifylline. Or
Neutralization of TNF- with monoclonal antibodies, or
soluble inhibitors.

Prophylaxis

Immunoprophylaxis:

BCG offer variable protection against leprosy (34-80%) in different

countries, adding heat killed M. leprae increases the protective
effect to 64%.

Endemicity of leprosy, background saprophytic mycobacterial flora,

and the age at vaccine may affect the response to vaccination.

Vaccination may precipitate TT leprosy in apparently healthy

contacts, thus immunoprophylaxis is best carried out at an early
age.

Chemoprophylaxis:

Rifampicin, to close contact of a case, and can be give to children

under the age 12 years (15mg/kg monthly for 6 months)

Pregnancy & leprosy

Little evidence that pregnancy can cause new diseases

or relapse.

However, pregnant BL patients may experience type 1

reaction in the post partum period.

Also lepromatous leprosy patients can experience ENL

during pregnancy and lactation, with early loss of nerve
function than non-pregnant patients.

MDT (Rifampicin, Clofazimine, and Dapsone) is safe.

HIV infection & leprosy

Unlike tuberculosis, leprosy is not significantly

associated with HIV infection.

HIV-associated neuropathy might be confused with

leprosy neuritis, also neuropathy due to antiretroviral
chemotherapy might be confused with leprosy.

There is difference in treatment strategy for patients with

leprosy and HIV, icluding treatment of reactions.

Mycobacterium leprae Causes

Leprosy

Source: Tropical Medicine and Parasitology, 1995

Mycobacterium leprae Causes

Leprosy

Severe bone destruction in advanced leprosy

Source: Diagnostic Pictures in Infectious Diseases, 1995

Thank you