2. ๏ LEPROSY IS A CHRONIC GRANULOMATOUS INFECTION
CAUSED BY MYCOBACTRIUM LEPRAE (By G.A.Hansen 1873)
๏ SKIN
๏ PERIPHERAL NERVOUS SYSTEM
๏ UPPER RESPIRATORY TRACT
๏ EYES
๏ TESTES
๏ M.Leprae has uniqe tropism for peiphral nerves
๏ Reactional state responsible for morbidity &
disease if not treated leads to charecterstic deformity & profound social
stigma
3. ๏ First bacterium to be identified as causing disease in
humans.
๏ Obligate intracellular bacilli
๏ Acid-fast
๏ Reductive evolution
๏ Cell wall contains PGL-1, Trisaccharides
๏ Grows in cooler tissues
๏ Doubling time 14 days
๏ Culture
๏ Incubation period
4. EPIDEMIOLOGY
๏ Disease of developing world
๏ Endemic among 10 to 15 million people living in poor
tropical countries.
๏ Prevalence rate decreased from 21 cases/ 10000
population in 1985 to <1 per 10000 in 2000.
๏ Leprosy has been eliminated from 119 of 122 countries
where it was considered as a public health problem.
๏ 2005 - Elimination of Leprosy at National Level
5. ๏ M.leprae replicates intracellularly in the skin histocytes and
nerve cells and has two forms.
๏ Tuberculoid, which induces a cell-mediated response that
limits its growth. M.leprae multiplies at the site of entry,
(skin), invading and colonizing Schwann cells.
๏ The microbe then induces T-helper lymphocytes, epitheloid
cells, and giant cell infiltration of the skin, causing infected
individuals to exhibit large flattened patches with raised and
elevated red edges on their skin.
๏ These patches have dry, pale, hairless centers, accompanied
by a loss of sensation on the skin.
๏ The loss of sensation may develop as a result of invasion of
the peripheral sensory nerves.
6. ๏ The second form is the lepromatous form.
๏ This form of the microbe proliferates within the
macrophages at the site of entry.
๏ It also grows within the epithelial tissues of the face and
ear lobes.
๏ With cell mediated immunity impaired, large numbers
of M.leprae appear in the macrophages and the infected
patients develop papules at the entry site, marked by a
folding of the skin.
๏ Gradual destruction of cutaneous nerves lead to what is
referred to as "classic leonine facies." Extensive
penetration of this microbe may lead to severe body
damage; for example the loss of bones, fingers, and toes.
11. ๏ Early reaction: (Fernandez)
๏ An inflammatory response develops within 24 to 48
hrs. & tends to disappear after 3 to 4 days.
๏ +ve test if the diameter of red area is more than 10mm
at the end of 48 hrs.
๏ It indicates whether person has previously sensitized
by exposure to & infection by leprosy.
12. ๏ Late Reaction: (Mitsuda)
This reaction becomes apparent in 7-10days and
reaching its maximum in 3 or 4 weeks. Test is read at
21 days and at the end, if nodule is more than 5mm in
diameter reaction is said to be (+)ve. The nodule may
even ulcerate & heal with scarring.
13. ๏ Leprosy reactions are the acute episodes of
inflammation occurring during the chronic course of
disease.
๏ They pose a challenging problem because they
increase morbidity due to nerve damage even after the
completion of treatment.
18. ๏ Hemolysis in patients with G6PD deficiency.
๏ nervousness, insomnia, blurred vision, paresthesias,
drug fever, pruritus, psychosis, and a variety of skin
rashes.
19. ๏ Fat soluble Riminophenazine dye.
๏ MOA - Bind to DNA of M. leprae, membrane disruption,
inhibition of mycobacterial phospholipase A2, inhibition of
microbial K+ transport, generation of hydrogen peroxide,
interference with the bacterial electron transport chain.
๏ Variable oral bioavailability.
๏ Hydrolytic dehalogenation, hydrolytic deamination,
glucuronidation, and hydroxylation.
20. ๏ AE โ Acute abdominal symptoms, Skin discolouration.
๏ Anti-inflammatory effects via inhibition of
macrophages, T cells, neutrophils, and complement.
๏ Interaction
21. ๏ Semisynthetic derivative of macrocyclic antibiotic rifamycin.
๏ Rapidly bactericidal against M. leprae.
๏ ฮฒ subunit of DNA-dependent RNA polymerase - RNA transcription.
๏ It is readily absorbed with an elimination half-life of ~3 hours.
๏ Excreted mainly through liver into bile and undergoes enterohepatic
circulation.
๏ Enzyme inducer โ Auto enzyme induction, Ocpโs, warfarin.
๏ Resistance
22. Adverse Effects
๏ Rash, fever, and nausea and vomiting. Hepatitis,
Hemolysis, hemoglobinuria,
๏ Flu like syndrome
๏ Orange-tan discoloration of skin, urine, feces, saliva,
tears.
23. ๏ Patients with intolerance, resistance, or clinical failure
to primary therapy(rifampicin).
๏ Inhibits DNA gyrase - DNA replication and
transcription.
๏ 400mg on first day followed by 200mg/day.
24. ๏ Intolerance to Clofazimine.
๏ 30S ribosomal subunit.
๏ 100mg/day.
๏ Deposit in tooth enamel and discolor teeth.
25. ๏ Multi drug therapy (MDT) is a key element for cure.
๏ MDT is available free of charge from WHO
๏ The drugs used in WHO-MDT are a combination of
Rifampicin,clofazimine and Dapsone for MB leprosy
patients
๏ Rifampicin and Dapsone for PB leprosy patients.
๏ Treatment of leprosy with only one anti leprosy drug
will always result in development of drug resistance.
๏ Treatment with Dapsone or any other anti leprosy
drug used as monotherapy should be considered as
unethical practice.
26.
27.
28. ๏ Type 1 reaction: Clofazimine 200 mg daily
Corticosteroids
๏ Loss of sensation or other peripheral nerve symptoms,
corticosteroids should be started immediately to
prevent permanent damage.
๏ Type 2 reactions may not respond to corticosteroids
alone, and the addition of drugs such as thalidomide.
29. ๏ 40 mg (8 tablets) every morning for 14 days
๏ 30 mg (6 tablets) every morning for 14 days
๏ 20 mg (4 tablets) every morning for 14 days
๏ 15 mg (3 tablets) every morning for 14 days
๏ 10 mg (2 tablets) every morning for 14 days
๏ 5 mg (1 tablets) every morning for 14 days
Aspirin or paracetamol as required
๏ Examine the patient every 14 days before reducing the
dose
๏ Continue MDT
30. ๏ Reduce systemic concentrations of TNF-ฮฑ, IL-2,
Interferon
๏ 100โ300 mg/day
๏ Avoided in pregnancy and during lactation.
31. ๏ Care of hands-avoid direct skin contact with hot objects.
While working reducing pressure prevents injuries. Gentle
massage keeps fingers mobile. Exercise to keep hands
mobile. Use clothes or canvas gloves for protection.
๏ Care of feet-clean & soak in salt water for 15 min. Rub off
hard skin with water. Rest the swollen foot by elevation.
Regular dressing helps to heal simple ulcer. Use MCR
(micro-cellular rubber insole) footwear to prevent injuries.