Leprosy Mailing List – February 16, 2015
Ref.: (LML) “Completed treatment, not cured”
From: B. Naafs, S. Noto, P. Schreuder, the Netherlands and Italy
Dear LML readers,
We agree with most of the writers involved in the recent LML discussion regarding relapses “How Efficacious is MDT “. We agree particularly with the last writer (LML February 6, 2015) who brings an interesting point of view. That stimulated us to write our own opinion.
Leprosy is an immunological disease initiated by M. leprae. Its clinical symptoms and signs are due to the dividing bacilli and the host’s response. The disease may progress after treatment completion for different reasons such as host response, reactions, relapse, sequelae and inadequate short treatment.
Host response, reactions
Leprosy reactions continue even after the bacilli are killed. In this case progression is caused by immunological events, either immune reactions to M. leprae antigens and antigenic determinants or induced autoimmunity. Antigenic determinants can be either on remnant antigens or on host cells. The antigenic determinants stimulate both the innate (a.o. complement system) and the adaptive immune system. Even contact of cells (Schwann cells) with these antigens (LAM - a major cell wall antigen of M.leprae lipoarabinomannan) may induce damage, in particular, neural damage. After multi-drug therapy (MDT) many multibacillary (MB) patients, we estimate more than 30% develop further damage. Particularly after stopping dapsone, patients are prone to Type I reaction and after stopping clofazimine to Type II reaction. Systematic follow-up policies would help in prevention, diagnosis and treatment of these complications.
Relapse
Relapse is due to dividing bacilli. It is well established that after MDT multibacillary leprosy patients still harbour viable bacilli, so called persisters. Under favourable conditions these can multiply again (e.g. Immunosuppression due to HIV, malnutrition, pregnancy, old age, inoculation in susceptible animals). Infectiologists, epidemiologist and public health officials consider 10% relapse rate acceptable for infectious diseases. For leprosy MDT the observed relapse rate is even lower, except most likely for patients with a high bacterial load.
Sequelae
Sequelae of leprosy are permanent and aggravate with time. Worsening is a consequence of increasing or permanent nerve functions loss in the eyes, face, hands and feet.
Inadequate short treatment
The one year MB MDT protocol is too short for forms of leprosy with high bacillary load. Borderline lepromatous or lepromatous patients with bacteriological index of 3+ or higher will benefit of longer protocols. For some PB patients diagnosed on clinical criteria only (no skin smear for example) the treatment may be too short as well and MB treatment would have been more appropriate.
“Completed treatment” versus “cured”
Too many patients deteriorate after the MDT has stopped. One cannot say that leprosy is cured after completing a course of MDT. We assume that the misunderstanding about “being cured” has its origin in the different disciplines involved and the stake the WHO, the subsidizing industries and some NGO’s have in the success of “leprosy elimination”.
Summarizing
It is M. leprae that brings about the disease leprosy. Even after killing of the M. leprae the immunological reaction remains and thus the disease. Damage after completion of MDT may be caused by a relapse or inadequate short treatment, but is usually due to induced autoimmunity or innate or adaptive immune system reaction against remnant antigenic determinants or sequelae of previous nerve damage. Multibacillary leprosy may be bacteriological in remission; the immunological remission is slow and may take years. Most paucibacillary leprosy may be cured, however one is never sure. One cannot claim that a patient is cured after completing his course of MDT. Patients deserve adequate follow-up and care after MDT completion. Not so much for the risk of a relapse but for preventing further nerve and tissue damage. Not acknowledging this is questionable medicine.
Ben Naafs, Salvatore Noto, Pieter Schreuder
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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