Wednesday, July 11, 2018

(LML) Manifest against the implementation of MDT-U


Leprosy Mailing List – July 11,  2018


Ref.:    (LML) Manifest against the implementation of MDT-U

From:  Ben Naafs and Pieter Schreuder, the Netherlands; Salvatore Noto, Italy


Dear colleagues,

Although not as eloquent as the colleagues Salgado and Rao, we like to add our voice. The well written manifestos by Claudio Salgado and Narasimha Rao, make it clear: Do not start U-MDT as yet!

There is enough evidence that U-MDT works as good as WHO MDT within the treatment period.  But does it during follow-up? Are there the same number of relapses, reactions and or disabilities? A follow-up for a maximum of five years may seem a long time to bacteriologists, who are used to bacteria dividing within seconds or minutes, but not to leprologists who are used to thinking in longer time periods. M.leprae divides only once in 12-14 days and may survive in dormant or persisting forms, which start to divide again when the circumstances for the bacilli improve (i.e. immunosuppression). Leprologists have experience with relapses after 10 and more years after releasing from treatment (RFT), after WHO-MDT or any other treatment. Will it be the same with U-MDT or even worse? Thus a follow-up of 5 years is not sufficient. Particularly when only basic clinical symptoms are taken into account and different regimens are not compared at the same time at the same place.

For most infections, infectiologists accept a relapse rate of 10% or even more. They are able to diagnose a relapse soon, start treatment again and prevent spreading of the disease. But leprosy relapses are not that easy to diagnose. One of the problems in diagnosing relapses, particularly in multibacillary cases (the infectious ones), is that they often downgrade and clinical symptoms may be short lasting and may not be noticeable at the moment of control.

Thus, patients may go on undiagnosed for years, may infect many others, since leprosy is highly infective. and spread disease unknowingly.  Relapses jeopardize the control of leprosy and may be important in maintaining the disease endemic.

It may not be possible to test for live bacilli in every patient on RFT with PCR or NASBA, but it is possible to do skin smears, which, when properly taken and stained, may herald a relapse showing a positive morphological index (MI) or a rising bacteriological index (BI). Also rising anti-PGL-1, or LID1 antibody titres may support this. That the latter approach is feasible Salvatore and Ben experienced using PGL-1 in the Zimbabwean leprosy program in the eighties.

Leprosy is an infectious disease which leads to an immunologic disease and may last as long there are M.leprae antigenic determinants present. It may take up to 6-8 years for these determinants to diminish under the level that elicits "reaction".  In the WHO-MDT there are 2 drugs which diminish the severity of these immunological events. Dapsone which diminishes the severity of the Type I reaction and Clofazimine which diminishes the type II reaction. So, an early discontinuation of treatment will harm some patients.

It is not well established that Clofazimine also prevents or diminish type I reaction.  So why give it to paucibacillary patients who only develop this reaction? Just because we do not want to classify? Each active working drug has side effects. Do you indeed need the drug? Remember: "primum non nocere"

A good clinical trial should take in account the patient's benefit in its conclusion: "Ten years after RFT, are the patients treated with U-MDT more or, less handicapped compared with those treated with WHO-MDT or any other treatment?  Was the better result achieved with or without interventions?".  In most trials involving U-MDT there was no proper follow-up of sensation, voluntary muscle testing (VMT), let alone more sophistic parameters like Nerve Conduction Velocity and there was no proper comparison with other types of treatment particular regular MDT.

There are too many imperfections in most studies, in particular in those done with WHO support. In these studies, there is no proper differentiation among the patients. Differentiation does not comply with uniform treatment. Moreover, the health workers who were able to make this differentiation are not available anymore since they had to look for other employment when leprosy was "eliminated".

In conclusion, what is the argument of the supporters of U-MDT? We do not know, but one is: "Today there are no clinicians to classify patients."  Specialised clinicians have quitted work in leprosy since leprosy control has been too much simplified and money for more than simple care is not available. They can no longer be proud of their work. Worse, leprosy teaching has disappeared from most curricula. So, look for alternatives, "a self-fulfilling prophecy"?




Ben, Pieter and Salvatore

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link:

Contact: Dr Pieter Schreuder <<


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