Transcript Leprosy - Biol 448B: Fundamentals of Tropical Disease

Leprosy
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Leprosy (Hansen’s 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 …
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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
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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
Tuberculoid
Borderline
Lepromatous
Borderline
Lepromatous
Infiltrated
lesions
Defined plaques,
irregular plaques,
healing centers
Polymorphic,
partially raised
edges, satellites
Papules, nodules,
punched-out
centers
Diffuse
thickening
Diffuse thickening
Macular
lesions
Single, small
Several, any
size
Multiple, all sizes,
bizarre
Innumerable,
small
Innumerable,
confluent
Many nerves
involved
symmetrical
patterns
Late neural
thickening,
asymmetrical
anaesthesia
and paresis
Slow, symmetrical
‘glove-andstocking’
anaesthesia
Skin
Peripheral Solitary, enlarged Irregular
nerves
enlargement of
Nerve
several large
lesions
nerves,
asymmetrical
patterns
Note: Contrary to popular belief leprosy does not cause body parts to simply fall off
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Immunology
• Tuberculoid leprosy
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Patient’s 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-γ
These strong cell-mediated responses clear antigens, but cause local tissue
destruction
• Lepromatous leprosy
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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-γ
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”
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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 1960’s 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
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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)
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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
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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
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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 isn’t 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 let’s 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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