Leprosy

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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 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
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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
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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 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/tr
  itzid/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.