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Leprosy

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Title: Leprosy


1
Leprosy
2
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

3
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
4
A little taxonomy .
Kingdom Bacteria
Phylum Actinobacteria
Order Actinomycetales
Suborder Corynebacterineae
Family Mycobacteriaceae
Genus Mycobacterium
Species M. leprae
5
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

6
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

7
Symptoms
Tuberculoid Borderline Tuberculoid Borderline Lepromatous Borderline Lepromatous
Skin
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
Peripheral Nerve lesions Solitary, enlarged nerves Irregular enlargement of several large nerves, asymmetrical patterns Many nerves involved symmetrical patterns Late neural thickening, asymmetrical anaesthesia and paresis Slow, symmetrical glove-and-stocking anaesthesia
Note Contrary to popular belief leprosy does not
cause body parts to simply fall off
8
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

9
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

10
Geographic Rage For Leprosy
11
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
12
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

13
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

14
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.
15
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

16
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

17
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/tr
    itzid/leprosy.htm

18
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?

19
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
20
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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