Leprosy is caused by Mycobacterium leprae, an obligate intracellular bacterium. It primarily affects the skin and peripheral nerves, causing disfiguring skin sores and nerve damage that can lead to loss of feeling or muscle weakness. There are three main types of leprosy - tuberculoid, lepromatous, and borderline. Treatment involves multidrug therapy with antibiotics, antileprotic drugs like dapsone, and corticosteroids to treat potential reactions.
CALL ON ➥8923113531 🔝Call Girls Husainganj Lucknow best Female service 🧳
Leprosy or Hansen's Disease Explained
1.
2. Leprosy or Hansen’s Disease
• Leprosy is caused mainly by Mycobacterium leprae, a rod shaped bacillus
that is an obligate intracellular (only grows inside of certain human and
animal cells) bacterium.
• Means Living culture media is required for growth of this bacterium eg of
culture media- Rat- Whole animal (Like virus and Reckettsia)
• It is a Gram positive bacteria.
• M. lepraeis termed an "acid fast" bacterium. When special stains ( eg. The
Ziehl-Neelsen stain) are used for microscopic analysis, it stains red on a blue
background due to mycolic acid content in its cell walls.
• The bacteria take an extremely long time to reproduce inside of cells
(about 12-14 days as compared to minutes to hours for most bacteria)
• The bacteria grow very well in the body's macrophages (a type of immune
system cell) and Schwann cells (cells that cover and protect nerve
axons). M. leprae is genetically related to M. tuberculosis (the type of
bacteria that cause tuberculosis) and other mycobacteria that infect
humans.
Note- Artificial culture media- M. lepraeis do not show growth. This
character is different in it from other bacteria.
3. Risk factors for leprosy
• People at highest risk are those who live in the areas where
leprosy is endemic (parts of India, China, Japan, Nepal, Egypt,
and other areas) and especially those people in constant
physical contact with infected people.
• There is some evidence that genetic defects in the immune
system may cause certain people to be more likely to become
infected (region q25 on chromosome 6).
• People who handle certain animals that are known to carry
the bacteria (for example, armadillos, African chimpanzee,
sooty mangabey, and cynomolgus macaque) are at risk of
getting the bacteria from the animals, especially if they do
not wear gloves while handling the animals.
4. Transmission
Droplets and other secretions can contain the bacteria that cause Hansen’s disease.
Disease can spread from person to person when someone with the disease coughs
or sneezes. This can release droplets into the air.
Symptoms of Leprosy
Leprosy primarily affects the skin and the nerves outside the brain and spinal cord,
called the peripheral nerves. It may also strike the eyes and the thin tissue lining the
inside of the nose.
The main symptom of leprosy is disfiguring skin sores, lumps, or bumps that do not go
away after several weeks or months. The skin sores are pale-colored.
Nerve damage can lead to:
Loss of feeling in the arms and legs
Muscle weakness
It usually takes about 3 to 5 years for symptoms to appear after coming into contact
with the leprosy-causing bacteria. Some people do not develop symptoms until 20
years later. The time between contact with the bacteria and the appearance of
symptoms is called the incubation period. Leprosy's long incubation period makes it
very difficult for doctors to determine when and where a person with leprosy got
infected.
5. Type of Leprosy
• A mild, less severe form of
leprosy.
• People with this type have only
one or a few patches of flat,
pale-colored skin (paucibacillary
leprosy).
• The affected area of skin may
feel numb because of nerve
damage underneath.
• Tuberculoid leprosy is less
contagious than other forms.
Treatment depend on the type of leprosy.
Tuberculoide Lepromatous
•A more severe form of the disease.
It has widespread skin bumps
and rashes (multibacillary leprosy),
numbness, and muscle weakness.
•The nose, kidneys, and male
reproductive organs may also be
affected.
•It is more contagious than
tuberculoid leprosy.
People with this type of leprosy have symptoms of both
the tuberculoid and lepromatous forms.
Borderline
6. Diagnostic test
• Skin biopsy -Docter remove a small sample of
the abnormal skin and send it to a lab to be
examined.
• Skin smear test
• Result of test-In paucibacillary leprosy, no bacteria
will be detected. In contrast, bacteria are expected
to be found on a skin smear test from a person with
multibacillary leprosy.
7. Anti leprosy drugs
A Antileprosy drugs is a drug that interferes with proliferation of the bacterium that
causes leprosy
Sulfone
• Dapsone (Primary Antileprotic Drugs)
Phenazine dye
• Clofazimine
Antibiotics
• Minocycline,
• Ofloxacin
Anti-TB drugs
• Rifampine
• Ethionamide
8. SULFONE
Dapsone
IUPAC Name-
4-[(4-aminobenzene)sulfonyl]aniline
Dapsone, also known as diaminodiphenyl
sulfone (DDS),is an antibiotic commonly
used in combination with rifampicin and
clofazimine for the treatment of leprosy.
Dapsone is the most widely used sulfone for the long-term therapy of leprosy.
Although the sulfones are highly effective against most strains of M. leprae, a
small number of organisms, especially those found in lepromatous leprosy
patients, are less susceptible and can persist for many years, resulting in
relapse. Before the introduction of current multidrug regimens, resistance
rates were as high as 20% with dapsone monotherapy.
MOA The sulfones are structural analogues of PABA and are competitive
inhibitors of folic acid synthesis. Sulfones are bacteriostatic and
are used only in the treatment of leprosy.
9. • Sulfones, such as dapsone are well absorbed orally and are widely
distributed throughout body fluids and tissues.
• Peak concentrations of dapsone are reached within 1 to 3 hours of oral
administration and have a half-life of 21 to 44 hours; about 50% of
administered dapsone is bound to serum proteins.
• The sulfones tend to remain in the skin, muscle, kidney, and liver up to 3
weeks after therapy is stopped. The concentration in inflamed skin is 10 to
15 times higher than that found in normal skin.
• The sulfones are retained in the circulation for a long time (12–35 days)
because of hepatobiliary drug recirculation. The sulfones metabolism by
acetylation in the liver, and 70 to 80% of drug is excreted in the urine
as metabolites.
Pharmacokinetic
Dapsone, combined with other antileprotic agents like rifampicin and clofazimine, is
used in the treatment of both multibacillary and paucibacillary M. leprae infections.
Note- sulfoxone (Diasone) is other Sulphone that use as Anti leprotic
USE
10. Within a few weeks of therapy some patients may develop
acute skin lesions described as sulfone syndrome
ordapsone dermatitis. Some rare side effects include
fever, pruritus, paresthesia, reversible neuropathy,
and hepatotoxicity.
Adverse effects
Phototoxicity- patient should avoid direct sun light exposure
Acute Haemolytic anaemia - especially in those with (G-6-PD) glucose-
6-phosphate dehydrogenase deficiency (Genetic defect).
NOTE- This enzyme protect RBC from oxidizing agents
NOTE- Dapsone is contraindicated in = Severely anemic person Hb<7
Methemoglobinemia
11. Allergic reaction or lepra Reaction
• During the course of leprosy, immunologically
mediated episodes of acute or subacute
inflammation known as reactions may occur in
up to 25% of patients with paucibacillary
leprosy and as much as 40% in multibacillary
leprosy.
• Clinical indications of a reaction are nerve pain,
loss of sensation and loss of function. The
reactions may rapidly cause severe and
irreversible nerve damage and must always be
treated promptly. If a patient does not respond
to lepra reaction treatment within 4 weeks or
patient condition deteriorates at any time
during lepra reaction treatment, send that
patient immediately to the nearest specialist
centre.
• During a lepra reaction, do not interrupt leprosy
multidrug therapy. Treatment with multidrug
therapy reduces the frequency and severity of
lepra reactions.
LEPRA
REACTIONS
TYPE 1
Lepra Reactions
TYPE 2
Lepra Reactions
12. Type 1 lepra reactions or reversal reactions
• Type 1 lepra reactions or reversal reactions are associated with the
development of M. leprae antigenic determinants.
• They are delayed hypersensitivity reactions and may occur in both
paucibacillary leprosy and multibacillary leprosy.
• In type 1 lepra reactions, there is a high risk of permanent damage to the
peripheral nerve trunks.
• If the reaction is mild and there is no evidence of neuritis (pain, loss of
sensation or function), the reaction should be treated with analgesics, such
as acetylsalicylic acid or paracetamol.
• However, if there is nerve involvement, treat type 1 reactions with
analgesics and corticosteroids, such as oral prednisolone. The usual course
begins with 40 - 60 mg daily (up to a maximum of 1 mg/kg), and the
reaction is generally controlled within a few days. The dose is then gradually
reduced weekly or fortnightly and eventually stopped. Most reversal
reactions and neuritis can be treated successfully under field conditions
with a standard 12-week course of prednisolone but some authorities claim
that corticosteroids need to be continued for much longer periods of time.
13. Type 2 lepra reactions (erythema nodosum leprosum)
• Type 2 lepra reactions (erythema nodosum leprosum), are associated with
circulation and tissue deposition of immune complexes.
• They are an antibody response or immune complex response to M.
leprae antigenic determinants which occur only in multibacillary leprosy.
• Therapy for type 2 reactions may include analgesics, such as acetylsalicylic acid or
paracetamol, and corticosteroids, such as oral prednisolone.
• In patients with severe type 2 reactions, who do not respond to corticosteroids or in
whom corticosteroids are contraindicated, clofazimine at high doses or thalidomide
may be used under close medical supervision.
• Clofazimine often requires 4-6 weeks before an effect is seen, and therefore must
never be used as the sole drug for treatment of severe type 2 reactions. However, it
may be useful for reducing or withdrawing corticosteroids from patients who have
become dependent on corticosteroids.
• The clofazimine dose for treatment of severe type 2 reactions is 300 mg daily,
which should be given in 3 doses of 100 mg each. The total duration of this high
dose of clofazimine should not exceed 12 months.
• Thalidomide should be avoided in women of childbearing age since it is a proven
teratogen. If this is not possible, it is imperative that pregnancy is excluded before
this treatment is initiated. Effective contraception must be used during the 4 weeks
preceding and following treatment as well as during the treatment period. Should
pregnancy occur despite these precautions, there is a high risk of severe
malformation of the fetus.
14. Phenazine dye (Clofazimine)
• Clofazimine is a weakly bactericidal dye (Red color dye) that has activity against M.
leprae. It is not primary drug to treat leprosy.
• Clofazimine is given to treat sulfone-resistant leprosy or to patients who are
intolerant to sulfones.
IUPAC Name
N,5-bis(4-chlorophenyl)-3-(propan-2-
ylimino)-3,5-dihydrophenazin-2-amine
15. • This is a major advantage of clofazimine over other antileprosy drugs is
• Ulcerative lesions caused by Mycobacterium ulcerans respond well
to clofazimine.
• It also has some activity against M. tuberculosis and can be used as last
resort therapy for the treatment of MDR (Multi Drug Therapy)
tuberculosis.
• May involve binding with mycobacterial DNA – and interfer its
templet functions
• It also Increase generation of Reactive oxidants from Neutrophils and
exerts an antiinflammatory effect and prevents erythema nodosum
leprosum, which can interrupt treatment with dapsone.
Mechanism of action
USE
16. • The most disturbing adverse reaction to clofazimine is a red-brown
discoloration of the skin, especially in light-skinned persons.
• A rare but serious adverse reaction is acute abdominal pain significant
enough to warrant exploratory laparotomy or exploratory .
• Other infrequent side effects include splenic infarction, bowel obstruction,
paralytic ileus, and upper GI bleeding.
Adverse Effect
• Its oral absorption is quite variable, with 9 to 70% of the drug eliminated in
the feces.
• Clofazimine achieves significant concentrations in tissues, including
the phagocytic cells; it has a plasma half-life of 70 days.
• It is primarily excreted in bile, with less than 1% excretion in urine.
Pharmacokinetic