Treatment of leprosy in India
Netherlands Leprosy Relief-India, B-38, Panchsheel Enclave, New Delhi - 110017, India
V P Gautam
Netherlands Leprosy Relief-India, B-38, Panchsheel Enclave, New Delhi - 110017
Introduction of multi-drug therapy (MDT) into the National Leprosy Eradication Program (NLEP) of India has brought a decline in both the burden of the disease and the detection of new cases in the country. Despite this success, MDT has had many problems like remarkable relapse rate, non-adherence to the MDT and the emergence of drug resistance associated with it. Moreover, there is no new MDT regimen at present, which could solve all these problems. The current situation suggests that we should look for alternative solutions in the delivery of leprosy-related services. With the introduction of Accredited Social Health Activists under the National Rural Health Mission, there is an opportunity to control some of these problems associated with MDT. Besides, District Nucleus should take initiatives and actively participate in establishment of coordination between departments of Health, Social welfare and justice, education and various non-governmental agencies working in the field of leprosy and disability in order to deliver the best of services to the persons affected by leprosy.
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Gautam V P. Treatment of leprosy in India.J Postgrad Med 2009;55:220-224
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Gautam V P. Treatment of leprosy in India. J Postgrad Med [serial online] 2009 [cited 2020 Apr 5 ];55:220-224
Available from: http://www.jpgmonline.com/text.asp?2009/55/3/220/57410
Until now, in the fight against leprosy, "multi-drug therapy (MDT)" has proved to be an efficacious and the most cost-effective weapon in the armamentarium of leprosy control programs across the world. Since 1985, the load of leprosy cases globally has reduced from more than 10 million to less than 0.2 million by 31 December 2007 and more than 14.5 million patients have been declared cured of leprosy through MDT. , MDT emerged as a winner in the battle against the disease by the end of 2000, when the elimination of leprosy was declared at the global level. By the beginning of 2008, 119 of 122 endemic countries achieved the goal of elimination of leprosy i.e. less than one case per 10,000 population; however, three countries viz. Brazil, Nepal and Timor Leste have yet to eliminate leprosy.  In the year 2007, five countries including India contributed more than 80% of the newly detected cases worldwide [Table 1]. 
MDT was included in the National Leprosy Eradication Program (NLEP) of India in 1982. Initially, MDT drugs were purchased by the Government of India (GOI) till World Health Organization (WHO) started supplying them. By 1989, 45 out of 201 highly endemic (prevalence > 50/10,000) districts were covered by MDT, and by 1992 all such districts were covered. However, from 1985 onwards MDT was also supplied on demand to all those districts that were not covered by MDT, through the state government. By 1995, all districts of India were covered by MDT.
The importance of MDT can be gauged from the fact that before the introduction of MDT, the number of registered leprosy cases in India was 3.9 million, which fell to 3.4 million in 1986 and, by the beginning of 2008 it was further reduced to 87,228. Accordingly, the prevalence rate (PR) has declined from 5.7 cases per 10,000 population in 1983 to 0.74 per 10,000 in March 2008. Since the time of achievement of elimination of leprosy as a public health problem, the Annual New Case Detection Rate (ANCDR) has reduced by 50%, which has an effect on the PR also. As of 31 March 2009, 32 States/Union Territories (UTs) have achieved the level of elimination and Bihar has a PR between 1 and 2 per 10,000 population [Table 2]  Two States/UTs viz. Chhattisgarh and Dadra and Nagar Haveli have a PR more than 2 i.e. 2.30 and 2.21 per 10,000 population, respectively [Table 2].  Furthermore, 519 of 630 districts have achieved elimination by March 2009. 
Though the current MDT of 12 months for multibacillary (MB) leprosy and six months for paucibacillary (PB) leprosy has shown good response it is riddled with problems like poor compliance due to long duration of the current MDT and threat of development/emergence of rifampicin-resistant leprae bacilli. ,,
Practice of using chaulmoogra oil (also called Hydnocarpus oil) for treatment of leprosy in India can be traced back to as early as 600 BC in Sushruta Samhita. It was extracted from the nut of a tree native to India and used to be administered as an ointment or by injection or by mouth. In the early 1870s, another remedy called "gurjon oil" was developed by Surgeon Dougall of the Madras Medical Service for treatment of leprosy. Dougall began prescribing the oil after reports of its successful use in leprosy patients in Venezuela. Gurjon oil was derived from the wood of a tree native to Andaman and Nicobar Islands and was rubbed on the skin. However, the use of gurjon oil was abandoned because patients reported that reaction with chaulmoogra oil were milder and left the skin softer as compared to gurjon oil. Despite the fact that there was little evidence to support the effectiveness of chaulmoogra oil, it continued to be the treatment of choice for leprosy in India until 1946 when Robert Cochrane started using dapsone. ,
Guy Faget used dapsone in leprosy patients on a pilot basis in 1941 at the National Leprosarium, Carville, USA.  Two years later, Faget and colleagues reported that intravenous administration of sodium salt of diamino-diphenyl-sulfone (DDS) could arrest the progress of leprosy. Their findings introduced great hope for leprosy patients and marked the decline of use of chaulmoogra oil. Robert Cochrane and John Lowe started using dapsone in India and Nigeria, respectively. , Later it was proved that DDS was the most active, least toxic form of sulfones against leprae bacilli, and it could be used in field conditions. , The review of the literature suggests that the duration of dapsone monotherapy was not fixed and the patients were treated for a period varying from one to more than 20 years. ,
Thus, introduction of dapsone simplified the treatment by paving the way for ambulatory treatment and changed the face of leprosy dramatically. Unfortunately, the reports of dapsone resistance started surfacing in the early 1960s.  The first report of primary dapsone resistance was documented in 1977.  This was followed by, footpad-proven secondary resistance being reported from an increasing number of countries worldwide with a frequency ranging from about 2-3%.  With the realization of worldwide increase in dapsone resistance in M. leprae in the late '70s, dapsone monotherapy was no longer considered adequate for treatment of leprosy. ,, The surveys sponsored by "Therapeutic leprosy" (THELEP) and others also proved that the epidemic of dapsone resistance was sabotaging the entire leprosy control efforts.  Thus, there was a clear and urgent need for safe and practicable combined drug regimens effective in curing leprosy and preventing drug resistance under field conditions.
Era of Newer Drugs
The 1960s and 1970s witnessed the discovery of various drugs including clofazimine and rifampicin for treatment of leprosy. The concept of MDT in leprosy arose after the availability of clofazimine and rifampicin and from the experience of rifampicin use in the therapy of tuberculosis. ,, Based on the theoretical considerations, leprologists worldwide started using combined drug regimens for the treatment of leprosy on an experimental basis. ,,,,,, Although, by late 1970, many countries including India had realized the importance of combined therapy as a definitive treatment of leprosy they included it in their national leprosy programs only in 1982 or later at the initiative of WHO. Since 1981, Moxafloxacin, macrolides and rifapentine have emerged as potential candidates for wonder drugs against leprae bacilli. ,,,,,,,,,
Multi-drug Therapy Era
In 1981, WHO took a monumental decision and recommended MDT for leprosy in the absence of systematic reviews, randomized control trials, cohort studies with comparators, or case control studies, which would support the use of WHO MDT over dapsone monotherapy.  The development of the 1981 Study Group regimens was conceptually a product of THELEP work and discussions. , Later, six case series assessing the effects of WHO MDT (monthly supervised rifampicin 600 mg and clofazimine 300 mg, plus daily unsupervised dapsone 100 mg and clofazimine 50 mg) for 24 months supported the WHO recommendations (1981). The original WHO recommendation was to treat the MB patients for two years or until skin smear negativity and to treat the PB patients with rifampicin and dapsone for six months.  By 1985, these recommendations were adopted by almost all countries.
At the global level, the treatment of leprosy has not undergone much change since 1982, except for changes in the duration of the therapy. But in India, standard schedule of MDT has gone through many changes both in the duration of therapy and the criteria for classification of patients into paucibacillary and multibacillary for the purpose of therapy.
Immunotherapy and Immunoprophylaxis
The role of vaccine in primary prevention of leprosy is limited because various trials have shown variable protective efficacy ranging from 20% in Burma to 80% in Uganda. ,,,,,, Trials of other vaccines based on cultivable mycobacteria such as Indian Cancer Research Centre (ICRC), mycobacterium 'W' and M. habana as immunoprophylactic agents have also not shown encouraging results.  Under these circumstances, MDT remains the only effective option available. However, vaccine therapy in combination with MDT may be considered for treatment of highly bacilliferrous cases with Erythema Nodosum Leprosum lesions to clear the dead bacilli from the tissues, which would help in preventing the relapse of leprosy. 
Role of Surgery
After having achieved the goal of elimination, it is felt that prevention of deformities and disabilities should be given importance so as to facilitate the social and psychological rehabilitation of persons affected by leprosy. Under the Disability Prevention and Medical Rehabilitation (DPMR) plan, a number of hospitals have been identified in India to provide reconstructive surgery (RCS) to the needy ones. It has been envisaged that the cases will be first screened by the medical officer at the Primary Health Centre and also by a Dermatologist/Medical Specialist at a district hospital to assess the suitability of the surgery. At the RCS unit of a tertiary level hospital, the surgeon and physiotherapy technician would further examine these cases in order to decide who would benefit from the surgeries. Also, there is a provision of cash incentive of Rs. 5000/- to be paid to patients below the poverty line for major RCS.  However, what is lacking in the DPMR plan is the constitution of a team of specialists from orthopedics, plastic surgery, physical medical rehabilitation and ophthalmology specialties at each of these hospitals. This issue needs to be addressed so as to ensure effective delivery of quality services.
Changes in Multi-Drug Therapy Schedule in National Leprosy Eradication Program (India) Since Multi-Drug Therapy Introduction
Initially, in India, on the basis of the recommendations of the "Indian Association of Leprologists", the GOI made slight modifications to the WHO MDT regimen for MB patients by adding an optional two-week of daily rifampicin at the start of treatment. However, this recommendation was withdrawn in 1990.
The results of the trials conducted by UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases through its Scientific Working Group on the Chemotherapy of Mycobacterial Diseases (previously THELEP) indicated that the rate of relapse was less than one per 1000 person years irrespective of the duration of treatment i.e. less or more than 24 months. On the basis of these findings, duration of MDT was reduced to a fixed duration of 24 months in 1992.  This was further shortened to 12 months in 1998 on WHO recommendations, which were based on the results mentioned below of the research work conducted across the world. 
The combined effect of clofazimine, rifampicin and dapsone is greater than the bactericidal effect of rifampicin alone. Furthermore, addition of clofazimine and dapsone help in the elimination of rifampicin-resistant mutants in untreated MB patients.Less than 24 monthly doses of MDT were as good as 24 or more doses of MDT in terms of efficacy.A fixed 12-month MDT was effective in preventing relapse.
Rifamapicin-Ofloxacin-Minocycline (ROM) regimen: A single-dose regimen comprising rifampicin (600 mg), ofloxacin (400 mg) and minocycline (100 mg) for single-lesion cases was also introduced around this time following the WHO recommendations. 
Changes in Criteria for Classification in National Leprosy Eradication Program (India) Since MDT Introduction
Till 1988, patients with bacterial index two or greater were categorized as MB and those with BI less than two were categorized as PB cases.  From 1988 to 1995, all smear-negative patients were classified as PB on the basis of the recommendations of the WHO Expert Committee on Leprosy, and leprosy cases with more than 10 lesions (skin and nerve lesions involved) were classified as MB.  However, all cases with positive skin-smear test were classified as MB, irrespective of the number of skin and nerve lesions. Since 1996, patients with more than five skin lesions are being classified as MB patients and patients with less than five skin lesions are considered as PB patients, for field conditions.  However, there is provision for a slit-skin smear wherever facilities are available, and all smear-positive patients are included in the MB group.
At present, standard 12 months' fixed duration therapy for MB patients is being followed all over India and the duration of treatment of PB remains unchanged since its introduction.
In 2006 the DPMR plan was launched by the NLEP after realizing the burden of disabilities in leprosy-affected persons in India, which is estimated to be approximately 1 million and the fact that not all impairments or deformities are preventable through early detection and treatment with MDT drugs.  This plan will be implemented in a three-tier system of healthcare delivery. Although prevention of disability was part of NLEP earlier too, lately stress has also been put on the rehabilitation of the patients through coordination between various government agencies and non-government organizations. The following components are part of the DPMR plan so as to facilitate the uniformity and quality of services across India:
A step-by-step approach to the persons affected by leprosy is described, which includes assessment of disability, management of lepra reactions, and management of impairments and disabilities through medical care, self-care and surgeries.Recording and reporting related to reactions, disability, referrals and surgeries, which would further help in guiding the formulation of a project implementation plan in future.
In addition, guidelines related to the referral system, other cases, and absentee retrieval etc. have also been developed.
Conclusion and Recommendations
Since the introduction of MDT, the treatment of leprosy has been a subject of debate and has seen a lot of changes in terms of duration of treatment and the criteria for classification of leprosy. Nevertheless, the fall in PR and new case detection - an indicator of disease transmission - may be attributed to MDT and some operational factors. The 50% reduction in ANCDR since 2005 may be an early sign of decrease in the intensity of Information Education and Counseling activities and stopping of active search of cases. Now that the active search for cases is not recommended, the role of Accredited Social Health Activists (ASHAs) becomes more important.  Furthermore, program managers at the district level must also ensure that Inter-Personal Communication activity is given due importance.
As MDT has been associated with the below-mentioned problems it calls for another MDT regimen, which is of short duration, effective, free of side-effects and free from the fear of emergence of resistant leprae bacilli.
Poor compliance, which often has been attributed to the low socioeconomic status, gender differences, residence and long duration of treatment. , Furthermore, the minor and serious known side-effects of MDT drugs like discoloration of urine/skin, gastrointestinal upsets, itchy skin rashes, urticaria, and jaundice etc, may also be responsible for non-adherence to MDT.Emergence of rifampicin and/or multidrug resistance, which is usually attributed to irregular intake of MDT.High relapse rates varying from 0.65 to 3.0% for PB and 4 to 7% for MB, using person years of observation. , Considering the number of cases contributed by India, it has serious implications.
Over the past two decades, a number of drugs have been tested to be effective against M. leprae under laboratory conditions and a number of trials of various combinations are going on under field conditions. So far, the scientific community has not yet reached a consensus as to which combination of drugs would be most suitable.
However, there are other avenues to improve the treatment completion, prevent the irregularity of treatment intake, and also for early detection and referral of the patients for treatment, which may be helpful in overcoming some of the problems associated with the current MDT. For instance, ASHAs who are introduced in the healthcare delivery system of India under the National Rural Health Mission (NRHM) may be involved in the referral of suspected cases, monitoring the drug intake by the patients, and advice on self-care to the patients. They may also be successful in reducing the stigma associated with the disease in the community because they are selected from the community to which they belong. Under NLEP, it is envisaged that ASHAs may be given Rs. 300 and 400 for PB and MB cases, respectively, if she is involved in patient care from the point of the referral of a case of suspected leprosy till completion of treatment.  Thus, there is an excellent opportunity to improve the compliance to current MDT by ensuring regular intake of MDT amongst leprosy-affected persons through ASHAs at the field level.
The counseling of the patients by the healthcare staff in relation to the disease and its management such as course of the disease, transmissibility of infection, side-effects of the drugs and self-care advice at the time of registration, during treatment and discharge from the treatment should also be stressed upon.
Finally, the "District Nucleus", which is the nodal authority at the district level in NLEP, should be strengthened in result-based approach in planning and management; so that they could plan and manage the programme related activities effectively and efficiently in order to ensure quality services to the persons affected by leprosy.
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