Leprosy

1. LEPROSY

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.

3. Epidemiology
WORLDWIDE AND INDIA

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.

5. WORLDWIDE PREVALENCE
AT THE TURN OF CENTURY

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 lepromatousform of leprosy is
twice as common among men as among women
and is rarely encountered in children

8. Bacteriology

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. lepraegrows 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. lepraeremains one of the few bacterial species
that still has not been cultivated on artificial
medium or tissue culture andproduces no known
toxins, but can grow in
Nude mouse
Nine banded armadillos(best)

11. The Leprosy Bacteria

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.
tuberculosisand 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. lepraebinds to the basal
lamina of Schwann cells; this interaction is probably
relevant to the fact that M. lepraeis 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.

18. CLASSIFICATION OF
LEPROSY

19. Various Classifications
Indian Classification : clinicobacteriological
Madrid Classification : clinicobacteriological
Ridley Jopling classification: immunohistological
Classification by WHO Study Groupon 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)
 BorderlineTuberculoid(BT)
 Borderline Borderline (BB)
 BorderlineLepromatous(BL)
 Lepromatous(LL)

21. Indian classification
Indeterminate type
Tuberculoid type
Borderline type
Lepromatous type
Pure neuritic type

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

24. Immunology & bacteriology in
leprosy (spectrum)
Bacilli
Bacilli
(-)
(+)
(++)
(+++)
(+++)
(++)
(+)
(-)
Immunity
Immunity
LLHD BLHD BBHD BTHD TTHD

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

27. Clinical Feature

28. Indeterminate Leprosy
Earliest & transitory stage
One or two vague hypopigmented macule with definite
sensory impairment.

29. Indeterminate Leprosy
If untreated may progress towards tuberculoid,
borderline or lepromatous leprosy
Spontaneous regression may occur
Bacteriologically Negative

30. TuberculoidLeprosy
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 tibialnerves
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

32. Tuberculoid Leprosy

33. Borderline Tuberculoid
Fourormorelesions,asymmetricallydistributed
Maculesorplaquesofvariablesizeswithwellorill-
definedmargins&satellitelesions
Peripheralnervesenlargedasymmetrically
Sensation:hypoesthesia
SSforAFB:mayormaynotbepositive.
Lepromintestmaybeweaklypositive

34. Borderline Tuberculoid

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
Hypestheticor anestheticskin lesions; nerve
trunk palsies, at times symmetric

36. Borderline Borderline
Multipleerythematousmacules&plaques
Varioussizesandshapeswithpunchedoutcenterand
illdefinedsloppingoutermargin
Tendtobesymmetrical
Nervesmaybeasymmetricallyenlarged
Sensation:+/-
SSforAFB:seen+/-
Lepromintest-usuallynegative,maybedoubtful

37. Borderline Borderline

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

39. Borderline Lepromatous

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
SSforAFB:numerousseen
Lepromintest-negative

41. Lepromatous Leprosy

42. Ear lobes involvement

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) LeprosyBorderline (BB, BL) LeprosyLepromatous (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 differentiationEpitheloid Epitheloid in BB,usually undiff
but may have foamy changes in
BL
Foamy change is the rule,maybe
undifferentiated in early lesions
Langhans giant cells 1-3+ - -
Lepromin skin test +++ - -
Lymphocyte transformation testGenerally 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.

47. Nerve involvement in
Leprosy

48. M. Leprae : superficialnerve 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.

50. Face
Facial Nerve
 Lagophthalmos
 Facial droop
Trigeminal Nerve
 Corneal anesthesia

51. NERVE DAMAGE
UPPER LIMB

52. UlnarS Anesthesia medial 1/3 palm
MClaw ring and little fingers
A Dryness medial 1/3 palm

53. MedianSAnesthesia lateral 2/3 palm
MClaw mid + index + loss Opposition
ADryness lateral 2/3 palm

54. RadialSAnesthesia dorsum hand
MWrist drop

55. NERVE DAMAGE
LOWER LIMB

56. Lateral (common) Popliteal
Foot drop

57. Posterior Tibial
SSole anesthesia
MClaw Toes
ADryness in sole

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.

61. Nerve palpation

63. DIAGNOSIS
BACTERIOLOGICAL EXAMINATION
This includes :
Skin Smears :
Nasal Smears or blows :
Nasal Scrapings :

64. DIAGNOSIS
BACTERIAL INDEX
Bacterial index is the only objective way of monitoring
benefit of treatment.
According To Ridley’ Logarithmic ScaleIt 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.

65. DIAGNOSIS
BACTERIAL INDEX

66. DIAGNOSIS
BACTERIAL INDEX

67. DIAGNOSIS
BACTERIAL INDEX

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 vitromacrophage 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 100percent 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 mmit 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

79. TREATMENT
MULTIDRUG CHEMOTHERAPY
WHO RECOMMENDED REGIMENS OF
CHEMOTHERAPY :
PAUCIBACILLARY LEPROSY :
The above regimen needs to be taken for 6months within 9
months

80. TREATMENT
MULTIDRUG CHEMOTHERAPY

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.

84. TREATMENT
MULTIDRUG CHEMOTHERAPY
Ethionamide and Prothionamide :highly bactericidal
killing 98 percent of viable bacilli in 3 to 4 days. Relatively
more expensive and more toxic.

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
lepromatousdisease
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 peronealnerve is involved.
(less commonly) fever—generally low-grade

88. type 1 leprareactions 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
lepromatousend 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 tumornecrosis
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
40mgdaily 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 week9 and 10
5mg daily for week 11 and 12
100mg od x 4 weeks
Forneuritis, 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.Prednisoloneis
more effective in controlling ENL and associated neuritis,
clofazimineis the drug of choice for the management of
chronic, recurrent ENL reactions. Another drug claimed to be
useful in ENL is pentoxyfylline.

95. Thank You