Leprosy

Diana NJ Lockwood
London School of Hygiene & Tropical Medicine
Hospital for Tropical Diseases

Leprosy in 2006

Leprosy is an interesting disease

Interesting model of tissue damage
Important diagnosis not to miss
Readily treatable if diagnosed early
Particular problems of sensory and
visual loss
Global challenge
London School of Hygiene & Tropical Medicine

Leprosy- research
Pathogenesis of reactions and nerve damage
molecular mechanisms, using
immunohistochemistry
Effects of drugs on reactional pathology

Treating reactions
Established immunosuppresants
azathioprine, cyclosporin, methylprednisolone
New drugs

Using M.leprae genome

Strain typing

India, Nepal, Ethiopia, London

London School of Hygiene & Tropical Medicine

Blue Peter Research Centre,

Hyderabad, India

London School of Hygiene & Tropical Medicine

Leprosy is a disease
caused by infection with Mycobacterium
leprae
whose pathology is determined by the
immune response
that causes damage to peripheral nerves
and may result in disability and deformity

London School of Hygiene & Tropical Medicine

M.leprae
obligatory intra-cellular parasite
non-cultivable in vitro
genome sequenced in 2001,
40 unique proteins

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Leprosy - Case Definition

Cardinal Signs of Leprosy
Definite loss of sensation in a skin lesion
consistent with leprosy
Skin smears positive for acid fast bacilli
Thickening of one or more peripheral nerves

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CMI

Leprosy Spectrum

Ab

BI

TT

BT

BB

BL

LL
Type 2

Type 1
Reversal reactions

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Leprosy Classifications
Ridley-Jopling
TT - BT - BB - BL - LL
Skin lesions
Bacterial load
Histology
Referral centre/research

WHO Classification
Paucibacillary (2-5 skin lesions)
Multibacillary (>6 lesions)
Operational
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Tuberculoid Leprosy

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Lepromatous Leprosy (LL)

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Transmission
Human to human
M.leprae can survive in the
environment for up to 45 days
5% pop in leprosy endemic areas have M.leprae
DNA in their noses

Lepromatous patients shed M.leprae

from the nasal mucosa
minor routes- breast milk untreated LL

Entry also through nasal mucosa

No good evidence for transdermal entry

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M.leprae within the new host

Brief bacteraemic phase

Binds to skin macrophages and Schwann cells
Elicits immune response
development of host protective immunity or
progression to established leprosy
Long incubation times
2-5 years tuberculoid
8-11 lepromatous
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transmission of leprosy
climate
living conditions
genes
etc

%
environment

Early
% disease diagnosis
Treatment
% no disease

human host
genes
immunity
etc
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New case detection rates of leprosy

2004

>10 /100,000
1-10 /100,000
0.1-1/100,000

Leprosy 2006
83% of the worlds registered cases
are in 6 countries*
700,000 new cases are detected
annually
*India, Nepal, Tanzania, Brazil,
Madagascar, Mozambique
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Leprosy and HIV

No association between HIV and leprosy per se
(data from Malawi, Uganda, Mali, India)
Leprosy now reported as an Immune
Reconstitution Diseases in patients on HAART
HIV/Leprosy co-infected patients
increased risk of reactions and nerve damage
normal granuloma formation even with low CD4

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Leprosy Elimination Campaign

1985 Eradicate leprosy by 2000
1989 Eliminate leprosy by 2000
1991 Eliminate leprosy as a public health
problem by 2000
2003 Elimination declared
Jan 2006 India declared elimination
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Prevalence/new cases
per 10,000 population

Incidence vs Prevalence
of leprosy in India
40

35
30

prevalence

25
20
15
10

new cases

5
0
84

86

88

90

year

92

94

96

98

2000

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Was it possible to achieve

elimination?

Political imperatives
Suspect indicators
Changed the definition of disease
Leprosy a bad disease to pick for
elimination
Biology
long survival in environment
long incubation in host
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The fall out of non-elimination

Non-recognition of the problems of the
campaign
Many people believe that elimination
has occurred
Poor future provision for the long term
problems of leprosy patients
Off the research agenda
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Diagnosis of Leprosy
History
Clinical Examination
Skin lesions
Thickened nerves

Slit skin smears/histology

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Treatment of leprosy

Treat the infection

Treat reactions and nerve damage
Prevent neuropathic damage
Education
Psychological support
Reduce stigma
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Chemotherapy
Rifampicin/Clofazimine/Dapsone
MB cases
12 months

Rifampicin/dapsone
PB
6 months
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Cohort Study In Ethiopia

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MDT Success Story

Rapid clinical improvement

toxicity rare
time limited
11.2 million patients treated since
1982
low relapse rates so far
no evidence of drug resistance
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Prevention of Disability

Good management
Patients role in self help
Early detection
Lifelong prevention of secondary
disability
Good communication

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Nerve damage
Occurs across the spectrum
Occurs before diagnosis, during and
after treatment
Skin
Sensory and autonomic nerve fibres

Peripheral Nerve Trunks

Motor weakness
Regional sensory loss
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Thickened Nerve

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Prevalence of impairment among

new field patients (MB only)
grade 1
grade 2
total

Bangladesh (n=444)
Thailand (n=220)
Malawi (n=305)
West Nepal (n=1999)
Ethiopia (n=158)
0

20

40

60

80

100

% with impairment

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Incidence rates of impairment

during treatment
Thailand
(n=640)

PB
MB

West Nepal
(n=333)
Bangladesh
(n=2664)
0

10

20

30

40

50

incidence per 100 PYAR

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BT Reactional nerve

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Nerve impairment with secondary damage

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The eye in leprosy

Blinding complications

lagophthalmos
decreased corneal sensation
acute iritis
chronic iritis
cataract

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 London School of Hygiene & Tropical Medicine

Immunological Complications
Type 1 (reversal reactions)
Type 2 (Erythema Nodosum
Leprosum)
Neuritis
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Type 1(reversal) Reactions

Patients at risk
BT, BB & BL
first 6 months of anti-leprosy treatment
women after childbirth

Pathology
increased cell mediated immunity towards
M. leprae antigens
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Type 1 (reversal) reactions

Skin lesions
increased erythema, oedema
new lesions
Neuritis
tender/painful nerves
muscle weakness
loss of sensation

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Results of steroid treatment of

motor impairment
Full recovery
Same or worse
Improved

West Nepal
(n=125)
Bangladesh
(n=85)
Bangladesh
(n=83 nerves)
0

20

40

60

80

100

percentage

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Results of steroid treatment of

sensory impairment
West Nepal
(n=104)
Bangladesh
(n=65)
Bangladesh
(n=166 nerves)
0

20

40

60

80

100

percentage

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Treatment of Type 1 reactions

Mild reactions
aspirin
NSAID
usually require steroids - try low dose

Steroids
Prednisolone 40mg/day
reduce by 5mg/day every month

Continue regular neurological

assessment

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Effects of sensory loss

Sensory fibre
loss

Decreased
sensation

Patient may not feel

HEAT
PAIN
TOUCH
PRESSURE

Because NO PAIN patient

neglects injuries

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Effects of sensori-motor loss

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Involving Patients
How disabilities develop
prevention
importance of self care

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Involving Patients
help patients become competent
instruct and train patients and their families
training needs to be relevant
tackle one issue at a time

let patients talk, listen

help them discover their own solutions
practical, feasible solutions
local circumstances, resources, constraints

Be Positive
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Stigma
Occurs worldwide
May be subtle
often affects women more than men

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Leprosy 2006
Diagnosis often missed
Difficult to detect nerve damage
early
Feet, hands and eyes may all be
damaged
Stigma remains a huge problem
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