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Leprosy

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

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 Phylum Order Suborder Family Genus Species Bacteria Actinobacteria Actinomycetales Corynebacterineae Mycobacteriaceae Mycobacterium M. leprae

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

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

Symptoms
Tuberculoid Borderline Tuberculoid Borderline Lepromatous Borderline Lepromatous
Skin
Infiltrated lesions Macular lesions
Defined plaques, irregular plaques, healing centers Single, small Polymorphic, partially raised edges, satellites Several, any size Papules, nodules, punched-out centers Multiple, all sizes, bizarre Many nerves involved symmetrical patterns Diffuse thickening Diffuse thickening

Innumerable, small Late neural thickening, asymmetrical anaesthesia and paresis

Innumerable, confluent Slow, symmetrical glove-andstocking anaesthesia

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
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

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

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/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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