1. LEPROSY

2. LEPROSY (HANSEN’S DISEASE)
A chronic, systemic infectious disease
Primarily affecting the peripheral nerves
Secondarily the skin, mucous membranes, the eyes, bones and viscera.
ETIOLOGY
Causative agent - Mycobacterium leprae.

3. EPIDEMIOLOGY
More prevalent in tropical and subtropical areas of Africa, Southeast Asia and Latin America.
More susceptible - childhood
Adults are less susceptible.
Peak at ys./ ys
Both sexes - affected,
More common among men.

4. MODE OF INFECTION Prolonged close contact of susceptible individuals.
Main source of infection:-
Nasal discharge from the highly infectious patients (droplet infection),
Blood sucking insects
Infected soil mat

5. 2-5 years for tuberculoid leprosy 8-12 years for lepromatous leprosy
CLASSIFICATION
Based on the clinical, bacteriologic, immunologic and histopathologic features
Classified into 5 types:
Tuberculoid leprosy (TT).
Borderline tuberculoid leprosy (BT).
Mid-borderline leprosy (BB).
Borderline lepromatous leprosy (BL).
Lepromatous leprosy (LL).
INCUBATION PERIOD
2-5 years for tuberculoid leprosy
8-12 years for lepromatous leprosy

6. According to the results of slit – skin smears
Classified into two types:
Paucibacillary,(PBL) (Non-infectious)
With scanty or absent bacilli (TT, BT).
Multibacillary,(MBL) (infectious)
With numerous bacilli (BB, BL, LL).

7. SYMPTOMS AND SIGNS Lesions involve the cooler body tissues:
Skin, superficial nerves, nose, pharynx, larynx, eyes, and testicles.
Skin lesions
May occur as pale
Anesthetic lesions
1 – 10 cm in diameter
Neurologic disturbances:-
By nerve infiltration and thickening
resultant anesthesia, neuritis.

8. PHENAZINE DERIVATIVE: ANTITUBERCULAR DRUGS:
CLASSIFICATION
SULFONE:
Dapsone (DDS)
PHENAZINE DERIVATIVE:
Clofazimine
ANTITUBERCULAR DRUGS:
Rifampin,
Ethionamide
OTHER ANTIBIOTICS:
Ofloxacin,
Minocycline,
Clarithromycin

9. DAPSONE Diamino diphenyl sulfone (DDS) ACTIVITY AND MECHANISM:-
Dapsone like the sulfonamides
Inhibits folate synthesis (PABA antagonist).
Bacteriostatic
Specificity for M. Leprae :- Due to difference in the affinity of its folate synthase.
Doses of dapsone needed for the treatment of acute infections are too toxic,
So not used.
Resistance can emerge if very low doses are given.
Combination of dapsone, rifampin and clofazimine is recommended for initial therapy.

10. ADVERSE EFFECTS
Haemolysis in patients having G6PD deficiency.(lysis of erythrocytes)
Methemoglobenemmia (Presence of a higher level of methemoglobin in the blood.)
GI intolerance
Fever, Headache
Pruritus (Severe itching of the skin) and rashes
Paresthesias ( An abnormal sensation, typically pricking ),
Mental symptoms
Cutaneous reactions include
Allergic rashes, Phototoxicity and rarely Exfoliative dermatitis
Hepatitis
Agranulocytosis (A deficiency of granulocytes in the blood)
Lepra reaction (one of the acute episodes of chills and fever, and skin eruption occurring in the chronic course of leprosy )
Sulfone syndrome (A hypersensitivity reaction to sulfone)

11. CONTRAINDICATIONS 1. Leprosy:
Dapsone should not be used :
In patients with severe anaemia
G-6-PD deficiency and
In those showing hypersensitivity reactions.
Clinical uses :
1. Leprosy:
Tuberculoid leprosy: with rifampin
Lempromatous leprosy: with rifampin and clofazimine
2. Prevention and treatment of pneumocystis jiroveci pneumonia in AIDS patients.
3. In combination with pyrimethamine, dapsone can be used for chloroquine-resistant malaria.

12. RIFAMPIN Highly effective in lepromatous leprosy. Because of resistant
The drug is given in combination with dapsone or another anti leprosy drug.

13. CLOFAZIMINE Mechanism of action : A phenazine dye
Used as an alternative to dapsone.
Mechanism of action :
Unknown
But may involve DNA binding.
Clofazimine binds to DNA & inhibits template function.
Its redox properties may lead to generation of cytotoxic oxygen radicals that are also toxic to the bacteria.
Bactericidal
When used alone, resistance develops in 1-3 years.
Dapsone-resistant M. leprae respond to clofazimine,

14. Orally active (40-70% absorbed).
PHARMACOKINETICS :
Orally active (40-70% absorbed).
It accumulates in many tissues, especially in fat, in crystalline form.
Entry in CSF is poor.
T1/2 is 70 days
USES:
Used as a component of multidrug therapy of leprosy.
It is valuable in lepra reaction.
Occasionally, it is used as a component of MDT for MAC.

15. ADVERSE EFFECTS 1. Skin :(major disadvantage) 2. GI symptoms
Reddish-black discolouration of skin
Discolouration of hair and body secretions may also occur.
Dryness of skin and itching.
Acneform eruptions and phototoxicity.
Conjunctival pigmentation.
2. GI symptoms
Enteritis with loose stools, nausea, abdominal pain, anorexia and weight loss can occur.
Clofazimine is to be avoided during early pregnancy and in patients with liver or kidney damage.

16. An antitubercular drug Has significant antileprotic activity
ETHIONAMIDE
An antitubercular drug
Has significant antileprotic activity
But causes hepatotoxicity in - 10% patients.
Used as an alternative to clofazimine
Should be used (250 mg/ day) only when absolutely necessary.

17. Ciprofloxacin is not active against M. leprae,
OTHER ANTIBIOTICS
Ciprofloxacin is not active against M. leprae,
But ofloxacin, pefloxacin, gatifloxacin and sparfloxacin are highly active.
Ofloxacin
Used in alternative regimens
In case rifampin cannot be used, or
Shorten the duration of treatment.

18. Active against M. leprae Because of its high lipophilicity
MINOCYCLINE
Active against M. leprae
Because of its high lipophilicity
Its activity is much less than that of rifampin, but greater than that of clarithromycin.
It is being tried in alternative MDT regimens.

19. Less bactericidal than rifampin.
CLARITHROMYCIN
It is the only macrolide antibiotic with significant activity against M. leprae.
Less bactericidal than rifampin.
It is being included in alternative MDT regimens.

20. TREATMENT OF LEPROSY
Many patients exploit it for begging and do not come forward for treatment.
In India, the National Leprosy Control Programme was launched in 1955,
Was changed to National Leprosy Eradication Programme (NLEP) in 1982.
With the use of multidrug therapy (MDT)
India has achieved elimination of leprosy as a public health problem though some states still have leprosy patients.

21. MULTIDRUG THERAPY (MDT) OF LEPROSY
Multidrug therapy with rifampin, dapsone and clofazimine was introduced by the WHO in 1981.
This was implemented under the NLEP.
The MDT is the regimen of choice for all cases of leprosy.
Advantages are:
• Effective in cases with primary dapsone resistance.
• Prevents emergence of dapsone resistance.
• Affords quick symptom relief and renders MBL cases noncontagious.
• Reduces total duration of therapy.

22. Initially under standard MDT
The PBL cases were treated with
Dapsone + Rifampin for 6 months
While the MBL cases were treated with
Dapsone + rifampin + clofazimine for a minimum of 2 years or till disease inactivity/ skin smear negativity was achieved.
The MBL cases were kept under surveillance without treatment for the next 5 years.
WHO (1994) recommended a 'fixed duration therapy' (FDT) of 2 years for MBL and 6 month for PBL

23. THANK YOU -PHARMA STREET