Leprosy

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 Leprosy (Hansens Disease)
A chronic infectious disease caused by the bacterium Mycobacterium
leprae
It is mainly a Granulomatous disease affecting: peripheral nerves and
mucosa of the upper-respiratory tract
Granulomatous - refers to granulomas which are lesions of epithelioid
macrophages

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 A Little History
Gerhard Henrik Armauer Hansen was
a physician which first identified
Mycobacterium leprae as the cause of
leprosy in 1873

FYI

7/29/1841-2/12/1912
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 A little taxonomy .
Kingdom Bacteria

Phylum Actinobacteria

Order Actinomycetales

Suborder Corynebacterineae

Family Mycobacteriaceae

Genus Mycobacterium

Species M. leprae

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 Pathology
Gram-positive
Intracellular
Aerobic rod-shaped bacillus
With a waxy coating
M. leprae is unable to grow in vitro
This is thought to be due to the fact that it no longer has the genes
needed for independent growth
Because of its inability to grow on agar, nude mice and nine-banded
armadillos are used as animal models

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 Clinical Features
Skin lesions, typically anaesthetic at the tuberculoid end of
the spectrum
Thickened peripheral nerves
Acid-fast bacilli on skin smears or biopsy
Acid-fast is a property of Mycobacteria in which they a
resistant to decolorization by acids during staining
This is a helpful diagnostic tool for M. tuberculosis and M.
leprae

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 Symptoms
Tuberculoid Borderline Borderline Borderline Lepromatous
Tuberculoid Lepromatous

Skin

Infiltrated Defined plaques, Polymorphic, Papules, nodules, Diffuse Diffuse thickening

lesions irregular plaques, partially raised punched-out thickening
healing centers edges, satellites centers

Macular Single, small Several, any Multiple, all sizes, Innumerable, Innumerable,
lesions size bizarre small confluent

Peripheral Solitary, enlarged Irregular Many nerves Late neural Slow, symmetrical
Nerve nerves enlargement of involved thickening, glove-and-
lesions several large symmetrical asymmetrical stocking
nerves, patterns anaesthesia anaesthesia
asymmetrical and paresis
patterns

Note: Contrary to popular belief leprosy does not cause body parts to simply fall off

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 Immunology
Tuberculoid leprosy
- Patients lymphocytes respond to M. leprae in vitro
- Skin tests with lepromin elicit a strong positive response
- They also have a Th1- type response producing interleukin-2 and intergerons-
- These strong cell-mediated responses clear antigens, but cause local tissue
destruction
Lepromatous leprosy
- Patients in this case do not mount a normal cell mediated response to M.
leprae, and in fact their lymphocytes do not respond to M. leprae in vitro
- They are also unresponsive to lepromin
- They have specific T cell failure and macrophage dysfunction, and
problems producing interleukin-2 and intergerons-
- But they do produce Th2-type cytokins

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 Social Aspect
WHO reported that at the start of 2007 there were 224,717 reported
cases (from 109 countries and territories)
In comparison with the number of new cases detected in 2006 which
was 259,017, the number of new cases fell by more than 40,019 cases
(a 13.4% decrease)
In the last five years, the global number of new cases has dropped on
average by 20% per year.
Also Leprosy has been around since about 300BC

FYI

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Geographic Rage For Leprosy

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 Transmission
The transmission of leprosy is thought to occur through the respiratory
track
Infected individuals discharge bacilli through their nose and a healthy
individual breaths them in
But it is important to note that the extract mechanism is not known
The main reservoir is humans
Risk group: children, people living in endemic areas, in poor
conditions, with insufficient diet, or have a disease that compromises
their immunity (ie HIV)

In the 19th century leprosy was believed to be a hereditary ailment 11

 Diagnosis
Is clinical, by finding signs of leprosy and supported with the use of
acid-fast bacilli smear or skin biopsy
But this is contingent on experienced histopathologist
What doctors typically look for include: anaesthesia of skin lesions,
and peripheral nerve thickening and tenderness
There is no serological test

Note: The genome has been sequenced

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 Treatment & Management
Chemotherapy
- First line drugs are rifampicin, dapsone, and clofazimine
- The WHO recommends that if a patient test positive in an acid-fast
skin smear they should be treated for multibacillary disease
- The patients bacterial load decides length of treatment (6-24 months)
- Patients tend to improve quickly with minimal side-effects
- Second line drugs are ofloxacin and minocycline
- Triple drug combinations have been used in cases where a patient has
only a single lesion
- Leprosy is combated with multidrug therapy to reduce the chance of
developing resistance
- Since in the 1960s resistance to dapsone developed

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Multibacillary (MB or lepromatous) is a 24-month treatment of rifampicin, clofazimine, and dapsone.
Paucibacillary (PB or tuberculoid) is a six-month treatment of rifampicin and dapsone.

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 Treatment & Management
New Nerve Damage
- Patients with motor or sensory loss of 6 moths or less should receive a 6 month treatment of
corticosteroids (a treatment for type 1 reactions)

Patient Education
- It is very important since within a few days of starting chemotherapy since patients will no
longer be infectious and can live a normal life
- Currently there are few leper colonies left
- Also care of limbs is very important

Preventing Disability
- Nerve damage produces anaesthesia, dryness and muscle weakness which in turn causes
misuse of affected limbs causing ulceration and infection, leading to deformity
- Dryness can lead to skin cracking and ultimately infection
- Treatment involves soaking and applying oil- based creams to affected areas, also
physiotherapy can help prevent contractures, muscle atrophy and over stretching of muscles

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 Treatment & Management
Immune-Mediated Reactions
- Type 1 reactions occur in borderline leprosy
- Type 1 reaction delayed hypersensitivity occurring at site of localized M. leprae antigens
- Skin lesions appear and are erythematous, and peripheral nerves become tender and painful
- Loss of nerve function can be sudden (ie foot-drop)
- Type 2 reactions occur in borderline lepromatous and lepromatous cases
- Type 2 reaction erythema nodosum leprosum (ENL) results from immune complex
deposition
- The main symptoms are malaise, fever, and crops of small, pink nodules on face and limbs,
and ENL may continue for years
- Management procedures include : control inflammation, pain, treat neuritis, and halt eye
damage

Vaccines
there currently isnt a vaccine against leprosy, but there are trials investigating the
effectiveness of the BCG vaccine

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 Discussion
Thalidomide (Thalomid). This drug was originally developed as a sedative and morning-
sickness pill but was subsequently found to cause severe birth defects; the Food and Drug
Administration then banned it. Under the new regulations there are a number of restrictions
on its use:
1. It can be used only for the treatment of erythema nodosum leprosum.
2. Doctors who prescribe the drug and pharmacists who dispense it must register with
Celgene, the company that produces it.
3. Women must have a negative pregnancy test 24 hours before taking the drug.
4. Women must get weekly pregnancy tests during the first month of treatment. Thereafter
they
must get once-a-month pregnancy tests.
5. All thalidomide users must enroll in a registry at Boston University that will record any
pregnancies that occur and their outcomes.
6. All male patients must use condoms during sexual intercourse because the drug is
found in
semen.
http://www.kcom.edu/faculty/chamberlain/Website/tritzid/leprosy.htm

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 Discussion
1) First of all lets assume that areas with high
concentrations of Leprosy could afford
Thalidomide in addition to their basic
treatment. What are the moral problems
with its prescription? What are some of the
additional problems that might arise if the
above regulations aren't followed?

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 Discussion
2) What could explain such a drop in new Leprosy cases? Considering
the expense and length of treatment, not knowing the mode of
transitions and the fact that most areas that are affected are still
developing.

Free MDT,
Reducing disease burden,
Preventing disability, Changing
the negative image, Working
with local governments and
agencies

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I got this off the net, I hope it helps, if anyone has any questions please email me.

Can leprosy cause limbs to fall off?

Leprosy does not cause flesh to rot and fingers and toes to drop off. In the past, limbs that have been
damaged because the person cannot feel pain have sometimes had to be amputated. Now that the
disease can be detected early and cured completely, the need to amputate is very rare.

Who can get leprosy?

Susceptibility: About 90% of the population is not susceptible to infection. Children are more
susceptible than adults. Immunologic and epidemiologic studies suggest that only 10-20% of those
exposed to M. leprae will develop signs of indeterminate Hansen's disease; only 50% of those with
indeterminate disease will develop full-blown clinical leprosy. Spontaneous healing also has been
reported in tuberculoid leprosy.
Host immunity: Where host cell-mediated immunity functions perfectly, organisms are routed and
no disease develops. If the individual has good immunity, organisms are contained and TT disease
occurs. In subjects with moderate immunity, a battle occurs and results in borderline types of leprosy.

In persons with poor immunity, LL occurs.

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