2. INTRODUCTION
Chronic granulomatous infectious disease.
Caused by Mycobacterium leprae
Mainly involves the peripheral nerves and skin
Other organs may involve:
Mucosa of mouth
Upper respiratory tract
Eyes
Bones & Muscles.
Testes etc.
Commonly involves every organ except :
CNS, Ovary and Lungs.
4. Distribution
Prevalence
Worldwide distribution but essentially a disease of developing
countries.
The prevalence rate has dropped by 90 percent from
21.1cases/10000 in 1985 to <1/10000 in 2000.
To date there has been no resistance to antileprosy medicines
when used as MDT.
6. Leprosy Situation in India
The goal of leprosy elimination at National level (i.e. PR of <1 case/10,000
population) as set by National Health Policy 2002 had been achieved in the month
of December 2005.
7. associated with poverty and rural residence
not associated with AIDS, perhaps because of
leprosy's long incubation period
time of peak onset is in the second and third
decades of life
India and Africa, 90% of cases are tuberculoid
most severe lepromatous form of leprosy is
twice as common among men as among women
and is rarely encountered in children
9. Lepra bacilli
Gram positive Obligate intracellular bacillus - due to its large
pool of non functional genes.
Acid fast stained with modified Fite stain or ZN stain
Occurs characteristically in clumps or bundles( “globi”)
Affinity for Schwann cells & cells of R-E system .
M. leprae grows best in cooler tissues (the skin, peripheral
nerves, anterior chamber of the eye, upper respiratory tract,
and testes), sparing warmer areas of the skin (the axilla, groin,
scalp, and midline of the back).
Optimal temp. for growth is 30-33 centigrade
10. M. leprae remains one of the few bacterial species
that still has not been cultivated on artificial
medium or tissue culture and produces no known
toxins, but can grow in
Nude mouse
Nine banded armadillos(best)
12. Reservoir of infection
Main reservoir : Human being
Lepromatous case> Non lepromatous cases
Animal reservoirs
9-banded armadillos
Chimpanzees
Mangabey monkeys
Sphagnum moss
13. Portal of exit
Major portal of exit : Nasal Mucosa
LL cases harbour millions of M. leprae in their nasal
mucosa discharged when they sneeze or blow nose.
Ulcerated or broken skin of bacteriologically
positive cases
14. Mode of transmission
Transmission by inhalation
Droplet infection(most common)
Transmission by contact
Skin to skin contact with infectious cases
Contact with soil or fomites
Other Routes
Insect Vectors e.g.. Mosquito, Bedbugs
Tattooing needles
NB : Breast feeding and Transplacental infection do not
occur.
15. Incubation period
Long incubation period
Ranged: 2 to 40 years or more
Average: 3-5 years
Generation time : 12 days(1 day and 20 min for M.
tuberculosis and Escherichia coli, respectively)
Infectivity : Leprosy is a highly infectious disease with low
pathogenicity. Among household contacts of lepromatous
cases about 5 to 12 percent is expected to show signs of
leprosy within 5 yrs.
16. VIRULENCE FACTOR
The bacterium's complex cell wall contains large
amounts of an M. leprae–specific phenolic glycolipid
(PGL-1), which is detected in serologic tests.
The unique trisaccharide of M. leprae binds to the basal
lamina of Schwann cells; this interaction is probably
relevant to the fact that M. leprae is the only bacterium
to invade peripheral nerves.
17. Host Factors
Leprosy affects all age groups but incidence generally
rises to a peak between 10 to 20 years of age and then
fall.
Higher incidence is seen in males, more marked among
adults, more marked among lepromatous cases.
Cell Mediated Immunity is responsible for resistance to
infection with M.leprae. In lepromatous leprosy there is
complete breakdown of CMI.
19. Various Classifications
Indian Classification : clinicobacteriological
Madrid Classification : clinicobacteriological
Ridley Jopling classification : immunohistological
Classification by WHO Study Group on Chemotherapy
of Leprosy : clinicobacteriological.
20. Ridley- Jopling 1966
(Research purposes)
Most widely accepted
Divides Leprosy cases into five groups according
to their position on an immunohistological scale.
It can be used only when full research facilities
are available :
Tuberculoid (TT)
Borderline Tuberculoid (BT)
Borderline Borderline (BB)
Borderline Lepromatous (BL)
Lepromatous (LL)
22. Immunity in leprosy
(-)
(+)
LLHD BLHD BBHD BTHD TTHD
TT -paucibacillary
state, few lesions due
to high immune
response
LL - multibacillary state with
multiple lesions due to low
immune response
23. Contd..
Borderline forms (BB, BT and BL) lie between these
two poles and are immunologically unstable, tending
to move towards one of the polar forms
25. Clinical Feature on
Skin Lesion
Paucibacillary
Leprosy
PB
Multi Bacillary
Leprosy
MB
Including macular flat
lesion, papules & nodules
1 to 5 lesion
Asymmetrical
distribution
Definite loss of
sensation
BI <2 at all sites in the
initial skin smear
More than 5 lesion
Symmetrical distribution
Loss of sensation
may or may not be present
BI >= 2 at any site in the
initial skin smear
WHO
Classification(1981,87,93)
26. W H O classification
(For chemotherapy – M. leprae)
Paucibacillary
Indeterminate - I
Tuberculoid – TT
Borderline Tuberculoid – BT
If any of these have positive
bacterial index they should be
classified as multibacillary
for multidrug therapy
Multibacillary
Mid borderline – BB
Borderline Lepromatous –
BL
Lepromatous – LL
All smear positive cases
29. Indeterminate Leprosy
If untreated may progress towards tuberculoid,
borderline or lepromatous leprosy
Spontaneous regression may occur
Bacteriologically Negative
30. Tuberculoid Leprosy
less severe end of the spectrum
encompasses TT and BT disease
symptoms confined to the skin and peripheral
nerves
most commonly affected are the ulnar, posterior
auricular, peroneal, and posterior tibial nerves
TT leprosy is the most common form of the
disease encountered in India
31. TT
Single or a few lesions
Asymmetrically distributed on trunk and limbs
Sharply defined, dry, flat or raised, erythematous or
hypopigmented, and are anesthetic.
One or two nerves may be enlarged near the skin
lesion
SS for AFB: Negative
Lepromin test may be strongly positive
33. Borderline Tuberculoid
Four or more lesions, asymmetrically distributed
Macules or plaques of variable sizes with well or ill-
defined margins & satellite lesions
Peripheral nerves enlarged asymmetrically
Sensation: hypoesthesia
SS for AFB: may or may not be positive.
Lepromin test may be weakly positive
35. Borderline Leprosy
BB, BL
Intermediate between BT- and LL-type lesions;
ill-defined plaques with an occasional sharp
margin; few or many in number
Hypesthetic or anesthetic skin lesions; nerve
trunk palsies, at times symmetric
36. Borderline Borderline
Multiple erythematous macules & plaques
Various sizes and shapes with punched out center and
ill defined slopping outer margin
Tend to be symmetrical
Nerves may be asymmetrically enlarged
Sensation:+/-
SS for AFB: seen +/-
Lepromin test-usually negative, may be doubtful
38. Borderline Lepromatous
Numerous, symmetrically distributed lesions
Hypopigmented or erythematous irregularly shaped
maculopapular, infiltrative nodules, or plaques, with
smooth surfaces & ill defined borders, sloping outwards
Nerves may be symmetrically or asymmetrically enlarged
Sensation:+/-
SS for AFB: numerous seen
Lepromin test -negative
40. Lepromatous Leprosy
Numerous macules, plaques, nodules or diffusely
infiltrated lesions, shiny, smooth, symmetrically
distributed on face (leonine facies), trunk and
extremities with ill-defined margin which may be
slightly hypopigmented or erythematous
Symmetrical nerve enlargement is seen
Sensation: normal
SS for AFB: numerous seen
Lepromin test - negative
43. Diffuse thickening of the skin, with loss of hair
(eyebrows and eyelashes) : madarosis.
Saddle nose deformity
Leonine facies
44. Clinical, Bacteriologic, Pathologic, and Immunologic
Spectrum of Leprosy
Feature Tuberculoid (TT, BT) Leprosy Borderline (BB, BL) Leprosy Lepromatous (LL) Leprosy
Skin lesion One or a few sharply defined
annular asymmetric macules or
plaques with a tendency toward
central clearing, elevated borders
Intermediate between BT- and
LL-type lesions; ill-defined
plaques with an occasional sharp
margin; few or many in number
Symmetric, poorly marginated,
multiple infiltrated nodules and
plaques or diffuse infiltration;
xanthoma-like or dermatofibroma
papules; leonine facies and
eyebrow alopecia
Nerve lesion Skin lesions anesthetic early; nerve
near lesions sometimes enlarged;
nerve abscesses most common in
BT
Hypoesthetic or anesthetic skin
lesions; nerve trunk palsies, at
times symmetric
Hypoesthesia a late sign; nerve
palsies variable; acral, distal,
symmetric anesthesia common
BI(Bacteriological index) 0-1+ 3-5+ 4-6+
lymphocytes 2+ 1+ 0-1+
Macrophage differentiation Epitheloid Epitheloid in BB,usually undiff
but may have foamy changes in
BL
Foamy change is the rule,may be
undifferentiated in early lesions
Langhans giant cells 1-3+ - -
Lepromin skin test +++ - -
Lymphocyte transformation test Generally positive 1 to 10 1 to 2
CD4 : CD8 ratio 1.2 BB(NT),BL:0.48 0.50
PGL1 antibodies 60 85 95
45. General Findings
Eye : The anterior chamber can be invaded in LL with
resultant glaucoma and cataract formation.
Iritis/Iridocyclitis
Testes : May be involved in LL with resultant
hypogonadism.
Systemic involvement – Respiratory, Bones, Kidneys,
Lymph glands, etc.
48. M. Leprae : superficial nerve involvement
W Britton
49. Nerve Involvement
Neural involvement leads to muscle weakness, muscle
atrophy, severe neuritic pain, and contractures of the
hands and feet.
Ulnar nerve at elbow is most commonly involved , least
common is radial.
Most common cranial nerve involved is Trigeminal.
>30 percent neural loss required for loss of sensation.
First sensation to go is thermal (cold>fine touch).
Proprioception is usually preserved.
58. DIAGNOSIS
HISTORY
CLINICAL EXAMINATION
BACTERIOLOGICAL EXAMINATIONS
FOOT-PAD CULTURE
HISTAMINE TEST
BIOPSY
IMMUNOLOGICAL TEST
59. DIAGNOSIS
HISTORY
History should include the following points :
Patients Bio data : name, age, sex, address
Presenting complaints
Family history of leprosy
Contact with leprosy cases
Previous history of treatment for leprosy, if any
60. DIAGNOSIS
CLINICAL EXAMINATION
Physical examination should include :
A thorough inspection of the body surface(skin).
Palpation of commonly involved superficial nerves:
1. Ulnar N. near the medial epicondyle.
2. Greater Auricular N as it turns over SCM muscle.
3. Lateral Popliteal N.
4. Dorsal branch of Radial N.
Testing for :
1. Loss of sensation : heat, cold, pain, touch .
2. Paresis or paralysis of muscles of hands and feet.
64. DIAGNOSIS
BACTERIAL INDEX
Bacterial index is the only objective way of monitoring
benefit of treatment.
According To Ridley’ Logarithmic Scale It Ranges
From 0 To 6+ and is based on the no. of bacilli seen in
an average microscopic field.
B 0 stands for no bacilli in any of 100 oil immersion
field.
68. DIAGNOSIS
MORPHOLOGICAL INDEX
The MI is calculated after examining 200 pink-stained
free standing bacilli.
The percentage of solid staining bacilli in a stained
smear is referred to as MI.
It is a valuable indicator of the patient’s response to
treatment during the first few months and helps to
signal drug resistance.
SOLID FRAGMENTED GRANULAR(SFG)
PERCENTAGE : similar to MI but a more sensitive
indicator of the patient’s response to treatment.
69. DIAGNOSIS
FOOT-PAD CULTURE
Only certain way of identifying M. Leprae.
10 times more sensitive at detecting the bacilli than slit
skin smear.
Time consuming : requires 6 to 9 months.
Used for :
1. Detecting drug resistance.
2. Evaluating the potency of anti-leprosy drugs.
3. Detecting the viability of bacilli during treatment.
Newer in vitro macrophage culture which takes only 3 –
4 weeks.
70. DIAGNOSIS
HISTAMINE TEST
Reliable test for detecting at an early stage peripheral
nerve damage due to leprosy.
Method : carried out by injecting 0.1ml of a 1:1000
solution of histamine phosphate into hypopigmented
patches or in areas of anesthesia.
Result : in normal person it gives rise to a wheal
surrounded by erythematous flare(Lewis triple
response). In case of leprosy where the nerve supply is
destroyed, flare response is lost.
Particularly useful in cases of indeterminate leprosy.
71. DIAGNOSIS
BIOPSY
Usually resorted to when there is high clinical
suspicion but the other test are unyielding. It also
gives information about the bacterial content of
skin.
72. DIAGNOSIS
IMMUNOLOGICAL TESTS
Tests for cell mediated immunity(CMI)
LEPROMIN TEST
Tests for humoral antibodies(serological tests)
FLA-ABS test : used for detecting subclinical infections. 92.3
percent sensitive and 100 percent specific in detecting specific
antibodies in all types leprosy irrespective of type and duration of
disease.
Monoclonal antibodies
Others : RIA, ELISA.
73. DIAGNOSIS
LEPROMIN TEST
Method : it is performed by injecting 0.1ml of lepromin
into inner aspect of the forearm. The reaction is read at 48
hours and 21 days. Two types of reaction have been
described :
EARLY REACTION(FERNANDEZ REACTION) :
an inflammatory reaction develops within 24 to 48 hours and this
tends to disappear in 3 to 4 days. If the diameter of the red area is
more than 10mm the test is considered positive. It is a delayed type
hypersensitivity reaction to soluble constituents of lepra bacilli and
indicates whether or not a person has been sensitized by exposure
to and infection by lepra bacilli.
74. DIAGNOSIS
LEPROMIN TEST
LATE REACTION(MITSUDA REACTION) : It is
characterized by the appearance of a nodule which
becomes apparent in 7 to 10 days and reaches its
maximum in 3 to 4 weeks. The test is read at 21 days. If
the nodule is more than 5 mm it is considered positive. It
is induced by the bacillary component and indicates cell
mediated immunity.
In the first six months of life most children are
lepromin negative
BCG vaccination is capable of converting lepra reaction
from negative to positive.
75. DIAGNOSIS
LEPROMIN TEST
VALUE OF LEPROMIN TEST :
Useful tool for evaluating the immune status of leprosy patients.
Aid to classify the type of disease.
Estimating the prognosis
Strongly positive in a typical tuberculoid case and getting weaker
towards the lepromatous end, the typical lepromatous case being
lepromin negative indicating failure of CMI.
The greatest drawback being high false positive and false negative
cases hence not used as a diagnostic test.
OTHER TESTS FOR CMI :
Lymphocyte transformation test(LTT)
Leucocyte migration inhibition test(LMIT)
76. TREATMENT
MULTIDRUG CHEMOTHERAPY
In the absence of effective primary prevention by a
leprosy vaccine leprosy control is based on effective
multidrug chemotherapy(secondary prevention).
OBJECTIVES :
To interrupt transmission of infection
Early detection and treatment of cases to prevent deformities
To prevent drug resistance
77. TREATMENT
MULTIDRUG CHEMOTHERAPY
First line drugs : rifampicin, dapsone, clofazimine,
ethionamide and prothionamide.
Second line drugs : quinolones, minocycline,
clarithromycin, aminoglycosides
78. TREATMENT
MULTIDRUG CHEMOTHERAPY
WHO RECOMMENDED REGIMENS OF
CHEMOTHERAPY :
MULTIBACILLARY LEPROSY
Rifampicin : 600mg once monthly under supervision
Dapsone : 100mg daily self administered
clofazimine : 300mg once monthly under supervision
50mg daily self-administered
Where clofazimine is unacceptable due skin coloration it may
be substituted by 250 to 375mg daily dose of ethionamide or
prothionamide.
The above regimen needs to taken for 12 months within 18
months
81. TREATMENT
MULTIDRUG CHEMOTHERAPY
Important points :
MDT is not contraindicated in patients with HIV
infection.
MDT is safe during pregnancy.
Drugs are excreted in breast milk but no reports of
adverse reaction except for mild discoloration of infants
skin by clofazimine
Leprosy is exacerbated during pregnancy, it is
important that MDT is continued
82. TREATMENT
MULTIDRUG CHEMOTHERAPY
Drugs
Rifampicin : highly bactericidal, a single 1500mg dose
kills 99 percent of viable organisms
Toxic effects includes anorexia, nausea, vomiting,
abdominal discomfort and orange discoloration of body
secretions. It is hepatotoxic
Dapsone : weakly bactericidal.
Adverse effects include hemolytic anemia,
methemoglobinemia, agranulocytosis, hepatitis,
neuropathy, psychosis and rarely…
83. TREATMENT
MULTIDRUG CHEMOTHERAPY
DDS syndrome ch. by fever, maculopapular rash,
enlarged lymph nodes, hepatitis and exfoliative dermatitis.
Clofazimine : was originally synthesized for TB. Less
effective than dapsone but has added advantage of
preventing lepra reaction. More expensive but less toxic
which includes dark red discoloration of skin, mucus
membranes, sweat and urine.
85. LEPRA REACTIONS
During the course of leprosy, immunological mediated
episodes of acute or subacute inflammation known as
reaction may occur.
There are two types of reactions :
Type 1 or Reversal reaction
Type 2 or erythema nodosum leprosum
Both types can occur before the start of MDT, during
treatment or after completion of treatment.
86. REVERSAL/DOWNGRADING
REACTION
occur in almost half of patients with borderline
forms of leprosy but not in patients with pure
lepromatous disease
Manifestations include classic signs of
inflammation within previously involved
macules, papules, and plaques and, on occasion,
the appearance of new skin lesions
87. nerve trunk most commonly involved in this
process is the ulnar nerve at the elbow, which
may be painful and exquisitely tender
most dramatic manifestation is footdrop, which
occurs when the peroneal nerve is involved.
(less commonly) fever—generally low-grade
88. type 1 lepra reactions precede the initiation of
appropriate antimicrobial therapy, they are
termed downgrading reactions, and the case
becomes histologically more lepromatous
when they occur after the initiation of therapy,
they are termed reversal reactions, and the case
becomes more tuberculoid
often occur in the first months or years after the
initiation of therapy
89. LEPRA REACTIONS
ERYTHEMA NODOSUM LEPROSUM
In ENL new inflamed, red nodules appear under the
skin, while the original lesions remain same. Commonly
on face, arm and legs & bilaterally symmetrical. They
appear in crops and subside within few days even
without treatment
It is antigen antibody reaction.
Seen in MB cases only.
Nerves may be affected but is uncommon
Other organs like testis, eye, kidney may be affected
General symptoms of fever, joint pain, red eyes and
watering may be associated.
90. ERYTHEMA NODOSUM
LEPROSUM
occurs exclusively in patients near the
lepromatous end of the leprosy spectrum (BL-
LL)
90% of cases it follows the institution of
chemotherapy, generally within 2 years
most common features of ENL are crops of
painful erythematous papules that resolve
spontaneously in a few days to a week but may
recur; malaise; and fever
91. may also experience symptoms of neuritis,
lymphadenitis, uveitis, orchitis, and
glomerulonephritis and may develop anemia,
leukocytosis, and abnormal liver function tests
Elevated levels of circulating tumor necrosis
factor (TNF) have been demonstrated in ENL;
thus, TNF may play a central role in the
pathobiology of this syndrome
thought to be a consequence of immune
complex deposition
92. LEPRA REACTIONS
TREATMENT
Because of high risk of permanent nerve damage
reversal reaction needs to be promptly diagnosed and
treated adequately
Standard 12 wk. regimen of prednisolone is the
treatment of choice.
ENL varies in severity, duration and organ
involvement, and can be treated with prednisolone as
reversal reaction.
Treatment includes bed rest, splinting of affected
nerves, analgesics and prednisolone.
93. LEPRA REACTIONS
TREATMENT
Prednisolone regimen Add clofazimine in ENL
40mg daily for first 2 weeks
30mg daily or week 3 and 4
100mg tds x 4 weeks
20mg daily for week 5 and 6
15mg daily for week 7 and 8
100mg bd x 4weeks
10mg daily for week 9 and 10
5mg daily for week 11 and 12
100mg od x 4 weeks
For neuritis, treatment with prednisolone
20mg onwards
Should be prolonged to four weeks from
94. LEPRA REACTIONS
TREATMENT
For pregnant women prednisolone should be started at
30mg dose instead of 40mg and limit the course for
10weeks in PB cases and 20 weeks for MB cases.
For children dose should be started at 1mg/kg of body
wt. per day.
Thalidomide : was reintroduced for the treatment of ENL,
mainly because of its antipyretic action. WHO does not
recommend the use of thalidomide in leprosy. Prednisolone is
more effective in controlling ENL and associated neuritis,
clofazimine is the drug of choice for the management of
chronic, recurrent ENL reactions. Another drug claimed to be
useful in ENL is pentoxyfylline.