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See all Premium member Presentation Transcript CURRENT UPDATE ON DRUGS AGAINST LEPROSY : CURRENT UPDATE ON DRUGS AGAINST LEPROSY DR.NATASHA INTRODUCTION : Chronic disease Mycobacterium leprae Incubation period 2-4 years Culture not possible No primary prevention INTRODUCTION SOCIAL STIGMA : SOCIAL STIGMA HISTORY : Sushrutha samhita,manu smrithi,atharva veda Vat rakta,vat shonita,kushta Chaulmoogra oil-Rx till 1940 HISTORY Oldest Evidence Of Leprosy Found In India : Oldest Evidence Of Leprosy Found In India This skeleton represents both the earliest archaeological evidence for human infection with Mycobacterium leprae in the world and the first evidence for the disease in prehistoric India. Leper colonies : Calcutta,varanasi 1875-chamba(HP) BELRA 1 million cases estimated at that time Leper colonies Gandhi with a leper : Gandhi with a leper Gandhi tending to Parchure shastri,a sanskrit scholar who was Shunned by family GOVT NODAL AGENCIES : 1954-NLCP early detection and dapsone monotherapy 1983-NLEP early detection,MDT,disability prevention 1991-WHO eliminate leprosy by 2000 1998-importance of dermatologist in reporting and treatment 2003-endemic in BIHAR,UP,WB,ORISSA,DELHI Dec 2005-elimination in india achieved GOVT NODAL AGENCIES Slide 9: Trend of Leprosy Prevalence & Annual New Case Detection (ANCDR) Rates Slide 10: As on Mar.2001 PR: 3.74/10,000 As on Mar.2007 PR: 0.72/10,000 As on 1981 PR: 57.60/10,000 Elimination achieved in 28 out of 35 States/Union Territories STATEWISE PREVALENCE Slide 11: WE HAVE COME A LONG WAY… Definition of a case of leprosy : WHO 1998 definition(one or more of these signs) Anesthetic hypopigmented patch Thickened nerves SSS positive for AFB 2002-Revised definition (at least 2 of the signs) Definition of a case of leprosy Status of SSS : 100% specific, not sensitive WHO-not mandatory in NLEP Requires experience Microscopy Mere 15% new cases test positive with SSS Risk of HIV,HB with skin prick Status of SSS Clinical classification : Clinical classification Clinical spectrum of Leprosy : Clinical spectrum of Leprosy LL BL BB BT TT IL Healthycontact MB Leprosy PB Leprosy Resistance to M. leprae Tuberculoid leprosy : Single or 2 - 3 Erythematous or coppery Dry surface, hairless Raised well defined edge with sharp outer margin Tuberculoid leprosy Lepromatous leprosy : B/l symmetrical innumerable macules indistinct margin Infiltrative stage follows papules, plaques and nodules Lepromatous leprosy Variants in LL : Histoid leprosy waxy, shiny, firm nodules/plaques Lucio leprosy non-nodular occurring in Mexico and Central America Variants in LL SLPB : Definition-one hypopigmented,anaesthetic lesion,no involvement of nerve trunk Incorporated in NLEP-1997 Treatment with Rifampicin,ofloxacin,minocycline(ROM) Surveillance for 2 years Not mentioned under WHO-2003 onwards SLPB classification : classification Sulfone-dapsone,acedapsone Phenazine-clofazimine Anti-TB drugs-rifampicin,ethionamide Dapsone -1940’s : Dapsone -1940’s Diamine diphenyl sulfone (DDS) synthesised in 1908 Structure-sulfonamide like Inhibition of PABA incorporation in folic acid Leprostatic Resistance-primary/secondary Oral absorbtion ,wide distribution(esp skin) Acetylated/sulfated in liver Dose-100mg/day Slide 22: Adverse effects- mild hemolytic anaemia,agranulocytosis GIT intolerance Headache Parasthesia Fever Dizziness Cutaneous reaction Contraindicated-severe anaemia,G6PD deficiency,hypersensitivity reaction clofazimine : clofazimine Leprostatic and anti-inflammatory MOA-interfere with DNA in myc.leprae Resistance develops in 1-3 years Half life-70 days Used in lepra reaction Adverse reaction-red black discoloration skin,hair and body secretion GIT-loose stools,nausea,abdominal pain Rifampin and ethionamide : Rifampin and ethionamide Kills myco leprae (99.99%) in 1 week Added in MDT-shortens duration of treatment Oral 600mg/month Ethionamide-causes hepatotoxicity Alternative to clofazamine Dose-250mg/day Newer drugs : Flouroquinolone-Moxifloxacin,sparfloxacin,pefloxacin Rifapentin Telithromycin Minocycline Pefloxacin Macrolides-clarithromycin,erythromycin Newer drugs MDR : Monotherapy and treatment discontinuation 1964-dapsone 1976-rifampicin 1996-ofloxacin Dapsone resistance-3 mutations in folp1 gene Rifampicin resistance-rPO –B gene Ofloxacin resistance- gyrA gene MDR MDT and modifications : Same schedule followed -1982 Duration -2years -24 month 1998-12 month fixed duration based on 7th WHO expert committee BI >2 no of hypopigmented patches MDT and modifications MDT : MDT 12 months for multibacillary RDC 6 month for paucibacillary RD Effective in dapsone resistant cases Prevents emergence of dapsone resistance Quick symptomatic relief and renders cases noncontagious Reduces duration of treatment WHO MDT treatment : WHO MDT treatment DRUG REGIMENS : DRUG REGIMENS Ongoing trial regimens : MBL ROM treatment -12 to 24 months (myanmar) 4 weeks of oflox 400 mg daily +WHO MDT PBL ROM treatment-3 to 6 months Rifampicin 600 mg+oflox 400 mg-4 weeks Ongoing trial regimens UNIFORM MDT : 2002-WHO technical advisory Due to low relapse ,resistant strains Proposal for a common 6 month treatment Applicable for MBL and PBL Not implemented as yet in india-feasibility? UNIFORM MDT Accompanied MDT : Proposal to increase compliance and reduce defaulters Mobile patients Remote areas Civil strife areas 1st visit-treatment along with information regarding disease to patient and a relative who accompanies him CONTROVERSIAL Accompanied MDT Leprosy Reactions : Leprosy Reactions immunologically mediated episodes of acute or subacute inflammation affecting the skin, nerves, mucous membrane and\or other sites which interrupt the chronic course of leprosy. Unless promptly and adequately treated, can result in deformity and disability. Lepra reaction : Type 1/reversal reaction Prednisolone-30-40 mg daily Later 15-20 mg daily (3 months) Extend to 6 months? Lepra reaction Slide 37: Type 2/ENL analgesics, Prednisolone-1mg/kg/day (12 weeks) Clofazimine 300 md/day thalidomide Role of thalidomide : Serendipitious discovery-sheskin USFDA -1998 Inhibits chemotaxis,TNF alfa,inflammatory mediators and fibroblast growth factor Dose-300mg/day ,tapered by 100 mg every 2-4 weeks Maintainance dose-50-100 mg (6 months) Analogues-revimid,actimid Role of thalidomide Treatment with thalidomide : Treatment with thalidomide Role of vaccines : First vaccine considered BCG-fernandez in 1939 1965-experimental model in footpad of mouse 4 large scale trials-india,burma,Papua guinea,uganda Range of protection-20-80% Exposure to one species of mycobacterium-confers protection against another Cross reacting antigens between M.leprae and BCG Role of vaccines Future of subunit vaccines : Cancer research institute,mumbai PP-1glycoprotein dominant immunogen of ICRC bacillus Phase II and III trials ongoing Cell wall core (CWC) fraction Mixed polyvalent vaccine-BCG+ICRC Future of subunit vaccines THANK YOU : THANK YOU You do not have the permission to view this presentation. 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