Leprosy Mailing List – May 15, 2021
Ref.: (LML) Leprosy Cure
From: Diana Lockwood, London, UK
Dear Pieter,
I thank Dr L Laila de Laquiche for her question about leprosy cure (LML, May 7, 2021). She has asked a complicated question that has generated some thoughtful responses. Henk Eggens captured the problems of leprosy patients with neuropathic complications who do not feel cured (LML 8.5.21).
For the key point with treating leprosy patients is that this is both a mycobacterial and an immunological disease. Cure means having treated both aspects of the disease, the infection and the immune response. Leprosy is further complicated by individual responses that patients have in terms of the bacterial load that develops which ranges from the low in tuberculoid to very high in lepromatous leprosy patients. Superimposed on this are leprosy reactions and nerve damage which affect people mainly in the borderline part of the spectrum except for ENL which affects patients with LL disease.
I would like to add the following parameters to the ones mentioned by Dr Narasimha Rao's posting 12 may 2021:
1. Completed treatment for reactions and complications requiring immune-suppressive therapy
2. Stable neuropathic complications
3. Psychological ease post leprosy
This would give us a 6 point assessment for cure and takes in the different aspects of leprosy. Narasimha Rao's first 3 points were 1. clinical cure 2. Bacteriological cure, 3. Histopathological cure. Point 4, Serological cure, was rightly discarded.
The real problem is that patients with nerve damage and reactions have on going inflammation and do not feel cured when they have completed their MDT. About 50% of MB patients will have significant inflammation requiring steroids.(1) Patients who have reactions in their skin and nerves or ENL reactions require long courses of steroids which makes them anxious and depressed and they do not feel "cured". Patients with ENL sometimes commit suicide. I have discussed these chronic aspects of leprosy.(2)
The neuropathic complications of leprosy take in many different aspects of disease management and need multidisciplinary teamwork.
Psychological peace. Many patients are anxious and depressed during and after their treatment. This contributes to the feeling of stigma. One needs to assess this part of their being to assess a cure post leprosy.
Narasimha Rao discussed the different aspects and shortcomings of bacteriological cure that we can measure. Since having acid fast bacilli in slit skin smears are one of the cardinal signs of leprosy it is a great shame that many programmes stopped doing slit skin smears. This means that one cannot encourage patients by telling them that their skin smears are improved. It is difficult to assess possible relapse cases without having access to slit skin smear services. I agree with him that we should be doing all we can to promote the availability of slit skins smears through national programmes.
Butlin et al did a prospective observational study of patients in Bangladesh given 6 months or 12 months MDT. (4) Of the patients who were smear positive at the beginning of the study the proportion becoming smear negative was 21% at 24 months, 80% at 60 months and 100% at 96 months post treatment.
Clinical improvement of skin lesions is variable. This is partly due to the ongoing inflammation in the lesions which is part of the clinical disease. Some patients' skin lesions resolve completely, others often with borderline tuberculoid leprosy can have persisting lesions with hypopigmentation. The lesions in lepromatous leprosy patients may take years to improve. These variations in patient skin lesions improvement have been documented by Manickam (5) in their prospective open study of Uniform Multidrug therapy (U-MDT) 6 months of standard triple therapy (dapsone and clofazimine daily and rifampicin monthly) regimens in India and China (2091 PB and 1298 MB patients). They classified skin lesions using a scale into inactive, improved and static and followed up for five years, the rates for the MB patients were 10.4%. 84.9%, and 4.7% at treatment completion; 72.4%, 26.8%, and 0.8% at three years; and 80.7%, 18.2%, and 1.1% at five years. Patients can be reassured that their skin lesions will improve over 4 years, but some will have persisting lesions. This is an important clinical message and patients can be given hope that their skin will improve. The relapse rate was low, four MB patients relapsed giving a rate of 0.07/100 person years.
We should work to formalise the scale that was used by Manickam in their study so we have a better scale for measuring improvement.
The challenge is that new leprosy patients need to be given a message of hope but this has to be tempered with a message that they may have complications requiring further treatment with steroids. This is a difficult concept to transmit.
These factors also feed into the stigma associated with leprosy.
I told my patients that were bacteriologically cured once they had completed their multidrug therapy. I think this helped them even when they were having reactions because they knew that that at least part of the disease was treated.
The cure needs to embrace these different aspects of leprosy management. One needs a long time frame for leprosy cure.
Diana NJ Lockwood
Emeritus professor of Tropical Medicine
London School of Hygiene & Tropical Medicine
Keppel St
London WC1E 7HT
1. Walker S, L. Leprosy Reactions. The International Textbook of Leprosy American leprosy Mission; 2019.
2. Lockwood DNJ. Chronic aspects of leprosy-neglected but important. Trans R Soc Trop Med Hyg. 2019;113(12):813-7.
3. Lasry-Levy E, Hietaharju A, Pai V, Ganapati R, Rice AS, Haanpaa M, et al. Neuropathic pain and psychological morbidity in patients with treated leprosy: a cross-sectional prevalence study in Mumbai. PLoS Negl Trop Dis. 2011;5(3):e981.
4. Butlin CR, Pahan D, Maug AKJ, Withington S, Nicholls P, Alam K, et al. Outcome of 6 months MBMDT in MB patients in Bangladesh- preliminary results. Leprosy Review. 2016;87(2):171-82.
5. Manickam P, Mehendale SM, Nagaraju B, Katoch K, Jamesh A, Kutaiyan R, et al. International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes. Indian J Med Res. 2016;144(4):525-35.
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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