This document discusses leprosy (Hansen's disease), including its epidemiology, clinical manifestations, bacteriological classification, and chemotherapy. It is caused by Mycobacterium leprae. The main drugs used to treat leprosy are dapsone, clofazimine, rifampin, ofloxacin, clarithromycin, and minocycline. The World Health Organization recommends either a 6-month multi-drug regimen for paucibacillary leprosy or a 2-year multi-drug regimen for multibacillary leprosy. The document reviews the mechanisms of action, pharmacokinetics, indications, and adverse effects of the main antileprotic drugs.

1. CHEMOTHERAPY OF LEPROSY

2. EPIDEMIOLOGY OF LEPROSY
• Leprosy is a chronic granulomatous infection
• Agent
– Mycobacterium Leprae -1873-Armauer
• Large number of person may be infected but
only few suffer chemically
• Source of Infection
– Nasal secretion
– Discharged from superficial ulcers

3. Clinical Manifestation
Cardinal features…
–
–
–
–
Hypo pigmented patches (T)
Loss of coetaneous sensation in affected areas.
Thickened nerves
M. Leprae in skin or nasal passage.
Signs of advanced disease…
–
–
–
–
–
–
Nodules / lumps in skin of face & ears.
Planter ulcers
Loss of fingers / toes
Nasal depression
Foot drop
Claw hand and toes.

4. BACTERIOLOGICAL CLASSIFICATION
PAUCIBACILLARY
MULTIBACILLARY
• NON INFECTIOUS
• INFECTIOUS
• TUBERCULOID
• LEPROMATOUS
• Incubation period 2-5yr
• Incubation period 8-12y
• < 5 LESIONS
• NORMAL CMI/ partially deficient
• +ve LEPROMIN
• FEW BACILLI
• > 5 LESIONS
• DEFICIENT CMI
• -ve LEPROMIN
• NUMEROUS BACILLI

5. Classification of Leprosy
– Indeterminate Type/Borderline Type
– Which ultimately progresses to either
tuberculoid or lepromatous

6. ANTILEPROTIC DRUGS
– SULFONE
:
DAPSONE, SULFOXONE, ACEDAPSONE
– PHENAZINE
:
CLOFAZIMINE
– ANTITUBERCULAR
:
RIFAMPIN
– ANTIBIOTICS
:
FQ: OFLOXACIN
Tetra: MINOCYCLIN
Macrolids: CLARITHROMYCIN

7. DAPSONE
– Diamino Diphenyl Sulfone (DDS) -1940
– Oldest, cheapest, most active, most commonly used
MOA :
Inhibition of PABA
Inhibit Bacterial Folic Acid Synthesis
Leprostatic
RESISTANCE : 1964
–
–
–
–
More in lepromatous leprosy patients if used monotherapy
Primary- harbouring from resistant bacilli
Secondary- during treatment
Combined with Rifampicin

8. Pharmacokinetics of DAPSONE
– p. o. absorbed
– Distributed to all body compartment
– Retains in skin & organs upto 3 wks.
– Metabolised by
– acetylation
– glucuronid conjugation
– half life > 24 hrs.
– Dose is cumulative
– excretion through kidney (1-2 wks)

9. ADVERSE EFFECTS OF DAPSONE
– HAEMOLYTIC ANAEMIA
– METHAEMOGLOBINEMIA
– GASTRIC INTOLERANCE –decrease later
– CUTANEOUS REACTIONS
–
–
–
–
ALLERGIC RASHES
FIXED DRUG ERUPTION
HYPERMELANOSIS
PHOTOTOXICITY
– LEPRA REACTIONS
– SULFONE SYNDROME

10. ADVERSE EFFECTS OF DAPSONE
Type 2
Type 1
• Delayed hypersensitivity
• Erythema nodosum leprosum
• IV
• Humoral antibody response
• Reversal reaction
•
Reactions to M. Leprae antigens
• Characterized by cutanoeus
ulceration, multiple nerve
involvement
• Prevented by corticosteroids
•
III
•
Response to dead bacteria
• Characterized lesions enlarge,
become red, inflamed, painful
• Treated by
clofazamine/corticosteriods

11. SULFONE SYNDROME
• If lepra reactions develops after 1-2months c/s sulfone syndrome
• Characterized by
–
–
–
–
–
Fever
Lymphnode enlargement
general malaise
Jaundice
anaemia

12. INDICATIONS OF DAPSONE
– WELL TOLERATED
– CHEAP
– TABLET : 100 mg OD
– I.M. DEPOT : Acedapsone
– BOTH TYPE OF LEPROSY
– CI in Hb% below 7g
– OTHER –
– PNEUMOCYSTIS CARINII PNEUMONIA(100mg)
– DERMATITIS HERPETIFORMIS (first 50mg, slow 300mg)

13. CLOFAZIMINE
• MOA :
– BINDS TO DNA 
 INTERFERES TEMPLATE FUNCTION of DNA
 INHIBITS GROWTH
– LEPROSTATIC
– ANTI-INFLAMMATORY

14. KINETICS OF CLOFAZIMINE
– P. O. INCOMPLETE ABSORPTION
– WIDELY DISTRIBUTED IN TISSUES : PHAGOCYTES
– HALF LIFE : 60 – 70 hrs.
– Elimination through FAECES

15. ADVERSE EFFECTS OF CLOFAZIMINE
– REDDISH-BROWN DISCOLORATION
• SKIN ; HAIR ; SECRETIONS
– CONJUNCTIVAL PIGMENTATION
– ACNEFORM ERRUPTIONS
– PHOTOTOXICITY
– GASTRIC INTOLERANCE
• ABDOMINAL PAIN
• LOOSE STOOL
PRECAUTION
:
PREGNANCY/Liver/Kidney damage

16. INDICATIONS OF CLOFAZIMINE
– DAPSONE RESISTANT LEPROSY
– PREFERED IN MDT OF LEPROSY
– LEPRA REACTION
– ULCERATIVE LESIONS : M. ulcerans

17. RIFAMPIN
– INHIBIT DNA DEPENDENT RNA SYNTHESIS
– BACTERIOCIDAL
– KILLS 99.9 % M. leprae : NONCONTAGIOUS
– RESISTANCE : MONOTHERAPY
– USE IN MDT :
DURATION OF T/t
– DOSE 600 mg MONTHLY

18. OFLOXACIN
– KILLS 99.9 % BACILLI
: 22 Day MONOTHERAPY
– HASTEN BACTERIOLOGICAL & CLINICAL RESPONSE
– SHORTEN DURATION OF THERAPY
– ALTERNATIVE DRUG
– RIFAMPIN INTOLERANCE / RESISTANCE
– DOSE : 400 mg/day

19. CLARITHROMYCIN
– MACROLIDE ANTIBIOTIC
– BACTERICIDAL < RIFAMPIN
– KILLS 99.9 % BACILLI IN 8 wks
– DOSE : 500 mg/day
– ALTERNATIVE DRUG

20. MINOCYCLINE
– TETRACYCLIN
– RIFAMPIN > MINOCYCLINE >
CLARITHROMYCIN
– ALTERNATIVE TO CLOFAZIMINE
– DOSE : 100 mg/day

21. WHO REGIMEN
• PAUCIBACILLARY LEPROSY
DAPSONE
RIFAMPIN
100 mg OD
600 mg MONTHLY
DURATION
6 MONTHS
• MULTIBACILLARY LEPROSY
DAPSONE
100 mg OD
RIFAMPIN
600 mg MONTHLY
CLOFAZIMINE 300 mg MONTHLY
50 mg DAILY
DURATION
2 YEARS