LEPROSY

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.

EPIDEMIOLOGY More prevalent in tropical and subtropical areas of Africa, Southeast Asia and Latin America. More susceptible - childhood Adults are less susceptible. Peak at 10 -14 ys./ 34 - 44 ys Both sexes - affected, More common among men.

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

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

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).

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.

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

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.

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)

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.

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

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,

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.

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.

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.

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.

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.

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.

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.

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.

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

THANK YOU -PHARMA STREET