Viewpoint: Leprosy after the year 2000

This issue of TM & IH features a review on the epidemiology of leprosy and on leprosy control as well as recommendations for future actions ( Visschedijk et al. 2000 ) – with the present drive to have leprosy ‘eliminated’ after the year 2000 a timely paper. A number of authors have commented on the bacteriological soundness of the new WHO-advised treatment regimens ( Lockwood 1997; Katoch 1998; Waters 1998; Lynch 1999; Van Brakel 1999), focusing specifically on relapse rates ( Visschedijk et al. 2000 ). However, we should be more concerned with the prevention of disabilities ( Pönnighaus & Boerrigter 1995). Through the centuries leprosy has remained a feared disease with severe social repercussions for sufferers. Until World War II, no effective treatment was known and health authorities had to resort to segregation to prevent spread of the disease ( First International Leprosy Congress 1897; Rogers & Muir 1940). In 1941, Faget in the USA was the first to use a dapsone derivative (Promin®) intravenously to treat leprosy. Prior to this, dapsone derivatives had been shown to be partially effective against M. avium and M. tuberculosis infections. Cochrane used it intramuscularly in India in 1946, and in 1947 the mother substance dapsone (DDS, diaminodiphenylsulphone) was used orally by Lowe in Nigeria. From 1950 this drug, which had already been synthesized in 1908 by Fromm and Whittmann in Germany, became the mainstay of leprosy treatment ( Naafs 1988). It was hoped that patients would be cured and leprosy could be eradicated. However, this proved not to be the case. In 1960 it became clear that relapses occurred even after regular and prolonged treatment ( Bushby 1964), and in the 1970s dapsone resistance became a real problem ( Shepard et al. 1969 ). In the meantime, new drugs had become available, notably clofazimine (LamprenR) and rifampicin. The latter in particular proved to be extremely effective, killing 99.9% of M. leprae with a single dose of 600 mg. However, a leprosy patient may harbour as many as 1012–1013M. leprae. Under the auspices of the international league of donor organizations in the field of leprosy (ILEP), and later the WHO, experts designed a new drug regimen: Multiple Drug Treatment (MDT) was introduced in 1982 ( WHO 1982). For paucibacillary (PB) patients, this comprised 600 mg rifampicin once a month under supervision and 100 mg dapsone daily unsupervised for 6 months. For multibacillary (MB) patients, a supervised dose of 300 mg clofazimine was added to the rifampicin once a month and 50 mg clofazimine unsupervised daily was added to the dapsone. This treatment was to be given for at least 24 months or until the bacteriological index (BI) was negative. PB patients were defined as I, TT and BT leprosy patients with a BI < 2 at all sites, the others together with BB, BL and LL patients as MB. Due to the number of relapses among PB patients, the definition of PB had to be changed later to ‘a leprosy patient without detectable M. leprae in a smear or a biopsy’. Since a considerable number of patients was unable to comply with the duration of treatment specified by Release From Treatment (RFT) requirements, its length was changed to 6 monthly doses within 9 months for BP patients and to 24 monthly doses within 36 months for MB patients ( WHO 1985). These regimens proved to be extremely effective, relapses were unexpectedly rare: 1.09% in PB patients and 0.74% in MB patients over a 9-year period, giving an overall rate of < 0.1% per year ( Noordeen 1993; WHO 1994). Health authorities also noticed the regimens' success. The number of registered leprosy cases declined from 4 to 5 million in the mid-1980s to a little more than 800 000 to date ( Visschedijk et al. 2000 ), a reduction of 85%. For the first time both patients and health workers began to believe that leprosy might be cured. This resulted in more effort by health workers to detect and treat patients, whereas those afflicted with leprosy came forward earlier, often before developing severe nerve damage. Encouraged by the efficacy of these treatment regimens, in 1991 the 44th World Health Assembly established the goal of eliminating the disease by the year 2000, defined as a prevalence (patients on treatment) of less than 1 : 10000. The WHO goal has been achieved in many countries, but certainly not in those where 85% of all known leprosy patients live, notably India, Brazil, Nigeria, Myanmar and Indonesia. Although the treatments turned out to be very effective, problems were encountered ( Waters 1993). Leprosy workers had to classify patients into PB and MB, which proved rather difficult for them. Operationally, it was not always possible to reach all patients regularly and in time and not all patients were able to finish the prescribed treatment within the allocated time and therefore could not be released from treatment. Some patients objected to the clofazimine colour showing in their skin, some became anaemic from dapsone and a few developed ‘flu-reaction’, a feared side-effect of intermittent rifampicin therapy. However, the treatment proved acceptable and safe overall ( Naafs 1988; Waters 1993). But nerve-damaging reactions, similar to those encountered during dapsone monotherapy, remained a problem. Reversal Reaction (RR), a delayed-hypersensitivity reaction (type-IV Gell and Coombs) directed against M. leprae antigenic determinants, and the less understood erythema nodosum-leprosum (ENL)-type reaction, probably immune complex-mediated (type-III Gell and Coombs), continued to occur ( Prabhavolkar & Ansari 1997), although the number of ENL-type reactions in MB patients had markedly diminished thanks to the suppressive effect of clofazimine used in MDT ( Post et al. 1994 ). An alarming new phenomenon was encountered. Many patients developed reactions after RFT when they were considered cured. RR after RFT, unknown during dapsone monotherapy due to the length of treatment, often is indistinguishable from relapse ( Waters 1993). This so-called ‘late reversal reaction’ is probably triggered by the discontinuation of dapsone, which suppresses RR ( Naafs et al. 1986 ). Late RR occurs in 5–10% of PB and MB patients ( Post et al. 1994 ). ENL-type reactions also became more frequent and severe in MB patients after RFT ( Post et al. 1994 ), probably due to the discontinuation of clofazimine. Obviously leprosy is not only a bacteriological but also an immunological disease, a fact which often seems to be forgotten. Over the past decade the diminishing stigma associated with leprosy has resulted in a better outlook for the patients. Public understanding has increased considerably, benefiting from WHO's goal of eliminating leprosy as a public health problem by the year 2000. Unfortunately, this goal has led many to believe that leprosy has been or will be eradicated soon. This will certainly not happen in the near future. Despite the fall in the number of registered patients, the incidence of the disease changed little and remained constant at about 500000–600000 cases worldwide until 1995 ( Visschedijk et al. 2000 ). Thereafter, numbers steadily increased to 800000 cases detected in 1998. History should have taught us that the eradication of a bacterial infectious disease such as leprosy is unlikely with chemotherapy alone ( Jacobson & Krahenbuhl 1999). The number of patients under treatment in leprosy programmes declined so markedly that their cost-effectiveness became jeopardized. This and the authorities' belief that leprosy is nearly eradicated led to dismantling of leprosy services. Some are combined for practical purposes such as drug delivery with tuberculosis control, others are integrated in the general health services ( Naafs 1998). In 1998 the WHO Expert Committee on Leprosy convened to review the global situation and available technology to identify the remaining obstacles on the way of achieving the goal of eliminating leprosy as a public health problem and to recommend appropriate measures on technical and operational matters. On the basis of field trials and clinical studies, the committee concluded that a single dose of a combination of rifampicin, ofloxacin and minocycline (ROM) is an acceptable and cost-effective regimen for the treatment of single-lesion PB leprosy and that the duration of the current MDT regimen for MB leprosy could be shortened to 12 months ( WHO 1998). These new recommendations will certainly help to achieve the goal set by the World Health Assembly. By shortening the duration of MDT for MB patients from 24 to 12 months, the number of registrations will halve, thus improving statistics especially in countries such as Brazil and Indonesia, which have a high percentage of MB patients. ROM therapy for single-lesion leprosy will improve statistics in India, a country with a high proportion of single-lesion patients. Therefore the recommendations will satisfy the politicians ( Naafs 1998). However, are they beneficial to the individual patient or leprosy control programmes? A major problem in leprosy is the occurrence of nerve-damaging reactions. Two are known, the RR and the ENL-type. Data on leprosy patients treated between 1970 and 1991 (> 500) in The Netherlands show that during 24 months of MDT treatment, 9% of the patients develop RR and 14% severe ENL (mild ENL was not recorded). Following RFT, after 24 months of MDT, 9% developed RR and 5% severe ENL ( Post et al. 1994 ). In terms of 12 months of MDT, at least 14% of patients can be expected to develop RR and 12% severe ENL after RFT. This implies that one-quarter of patients is at risk of becoming more disabled after being considered cured! Nonclinicians often do not realize that leprosy is not merely a bacteriological infection which is cured as soon as the bacilli are killed. It is foremost an immunological disease in which the immune response of the patients continues to cause tissue damage, particularly of the nerves, long after the bacilli are dead. Moreover, whether or not 12 months of treatment will be effective in inducing lasting remission in highly bacilliferous MB patients still remains to be demonstrated. Single-lesion leprosy is often indeterminate leprosy and self-heals in more than 80% of patients ( Ekambaram & Sithambaram 1977; Browne 1984). Thus there is a case for not treating and wait-and-see. This, however, requires supervision by an experienced leprosy worker. Since such a person is unlikely to be available especially in integrated programmes, many for that reason will treat all single-lesion patients. It is still too early to answer the question whether those 20% of patients who eventually develop classifiable leprosy will benefit from a single ROM treatment. Most likely, treatment will only delay the onset of frank leprosy and may cure some of the patients. However, it is known that single lesions persist, especially at the polar tuberculoid side of the spectrum (SK Noordeen, personal communication). A patient may wonder whether he or she is actually cured thus discrediting the programme. From the financial point of view the programme's running costs will decline because the patient burden will decrease further. A complication mostly neither realized nor taken into account is that the quality of care provided by the leprosy worker must improve due to the difficulty of diagnosing single-lesion leprosy, and that the worker must also be able to classify PB and MB leprosy correctly. Moreover, since some leprologists are reluctant to treat highly bacilliferous patients for only one year, the worker must decide whether a patient is pauci-MB or a multi-MB. Also, the number of complicated cases due to reactions will very likely increase. Vertical leprosy services with more or less experienced workers are presently being dismantled and integrated in other services, partly due to the ‘success’ of MDT. The overburdened tuberculosis/leprosy worker has not the time to deal with complicated cases and probably is also not well equipped to do so, being geared to supplying drugs, keeping registers and collecting sputum. Moreover, the leprosy knowledge of a peripheral health worker or a clinic attendant in a general community health programme is inadequate to handle such problems. After the year 2000, leprosy may no longer be a public health problem in many countries, at least according to the WHO definition of 1991. However, the number of patients disabled because of leprosy will probably grow, as it is unlikely that the knowledge and experience on diagnosis and treatment of leprosy and its complications will survive in an integrated health service where leprosy constitutes but a small part of the programme. Thus leprosy remains a problem for the afflicted, even more so after the year 2000, and we need to design new strategies to deal with it ( Visschedijk et al. 2000 ). I think that a dermatological service within the general services is a viable solution. Since leprosy is a neural disease with expression in the skin, workers used to inspection of the skin are the best equipped to detect early cases, relapses and reactions. In Vietnam, Laos, China, Malawi and Brazil this is already being done. For anglophone Africa, students at the Regional Dermatological Training Centre in Moshi, Tanzania are being trained to provide such services. Dr B. Tank advised on the use of the English language.