Leprosy Mailing List – January 31, 2015
Ref.: (LML) How Efficacious is MDT
From: Dr. Grace Warren, Sidney, Australia
Dear Pieter,
Thank you for publishing these letters regarding relapse after routine WHO MDT. It is interesting to note that several people are stating similar things. One wonders how many more patients do not really have the bacteria eliminated by the now 12 months, originally 2 year recommendation, of WHO as treatment for MB Leprosy.
I started treating leprosy in 1959 and at our hospital we had an excellent lab tech who did slit skin smears from 6 sites every 2 months while they were in our institution. We showed that true LL required a year to drop the BI by one point i.e. it took 5 years to go from 6 down to 1 and then after that it may take another year or two to negativity. That was with Dapsone alone. When other drugs came available, we added them and found that they really did not increase the rate of negativity by any significant degree, but certainly made a difference in patients in whom we suspected dapsone resistance. When we did the drug trials with Clofazamine we found the BI did fall a bit quicker, but not much more so, but there was far less ENL
In those days we gave Dapsone for life. Even so we did occasionally see relapse of skin lesions, a return of positive skin smear, or more neuritic symptoms, quite a long time after the patient was smear negative. This was usually after discharge and one wonders if the patient was always regular with his medication. Of course he said he was, but we would usually treat as if he had dapsone resistance.
Interestingly, in the letter from Dr Shetty in Mumbai in which he quotes several who relapsed after DDS monotherapy (one only given for twelve years). It was always stated to be needed for life!!!! One of them is florid lepromatous in the picture that sure would need far more than a terminated course of DDS only.
However, in the 1960s I had contact with a research institution who showed that the bacilli were able to resist even daily supervised Rifampicin and hide in nerves for several years while the patient was on daily Rifampicin supervised. Even after 5 years of the daily supervised Rifampicin live fully sensitive bacilli could be isolated in testicular nerves!! So one wonders if this type of record has been considered. Is it that the bacilli do hide in nerves and can come out and restart the disease when the routine MDT is stopped?
There is no way that one can check on the regularity of the patient taking their drugs and there is no way we can check on the presence of viable bacilli in a patient. In the 1980s we did see some relapses in those in whom we stopped MDT after 2 years as recommended. So a number of us continued, others thought cessation of medication was acceptable. Often I would continue with Clofazamine alone for a couple of years with a satisfaction in seeing a reduction in relapse and/or reaction in the many patients across Asia that I supervised.
One important point is that steroids are so often given for reaction. It has been shown that the number of bacilli do not fall significantly while on Steroids. On steroids the bacilli run for cover probably deep in the nerves where they cannot easily be got. So one should not include the length of time on steroids as part of the MDT duration. It is advised by many good leprologists that the duration of MDT after the steroids are stopped should be long enough to ensure that the patient has at least the recommended duration of MDT without steroids. I feel the use of Prednisolone has produced many problems that are often unrecognised at the time.
For all LL and BL patients I would give 24 months at least. Not only 12 months and as I have already stated. Often continue for a prolonged period as we do not want relapse. It is also important to arrange for follow up visits - I would say for all MB patients at least 5 years.
So for the query in the attached letter I do not think it is a re-infection. I think it is just that the disease was not eliminated initially and/or the patient does not have enough good natural resistance or else has other medical problems like poor nutrition or intercurrent disease.
Leprosy is far from eliminated. I have been fascinated with the number of patients that we have diagnosed who do not present with classical signs. As Leprosy does not receive any preference in Medical teaching schools, many clinicians are never really taught to look for leprosy. In my work in Asia in the 1980s/90s I was surprised - I could say horrified - to find that when I was invited to go to a Medical school to lecture on Leprosy I was often informed it was first time that that school had had such a lecture for many years, some for ever - and that in endemic countries.
One of my favourite statements is along this line "What one does not look for one never sees and what one does not think about, one will never recognise!” If people do not look for it they will never find it and if they do not take it seriously then the disease will often return! We need to ensure we find the disease early and treat it adequately.
May you really treat it fully- never try and hurry up the course of treatment, overtreat is better than undertreat. I love Clofazamine. It is effective, resistance has not yet been seen to develop in a patient and it has virtually no undesirable side effects except perhaps the pigmentation that does go when the drug is stopped. If I could only have one drug for leprosy treatment please let me have Clofazamine.,
Best wishes,
Grace Warren,
Previously Advisor in Leprosy and Reconstructive Surgery for The Leprosy Mission International in Asia ( 1975-1995)- She did leprosy work in 26 countries for over 50 years.
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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