Leprosy Mailing List – February 10th, 2010
Ref.: Alternative antibiotic regimens in leprosy
From: T. H. Rea, USA
Dear Salvatore,
Those interested in alternative antibiotic regimens might find my trials helpful, even if prohibitively expensive. IJL 68: 129-135, 2000. "Trials of daily, long-term minocycline and rifampin or clarithromycin and minocycline in the treatment of borderlilne lepromatous and lepromatous leprosy."
Thank you,
Ref.: C
Ref.: Alternative regimens for multi-drug therapy (MDT) in leprosy
From: Ben Naafs, Munnekeburen, The Netherlands
Dear Salvatore,
Concerning alternatives for MDT.
Resistance is not often seen, though it was expected, with the known dapsone resistance and the widespread use of Rifampicine. It is however important to be aware that this may occur, and that one should have possibilities to prove it. Some surveillance system therefore should be in place.
Diane Lockwood mentions (LML Jan. 27th, 2010) scores of side-effects up to 50% quoting a paper of Patricia Deps from
Dapsone
Yes, haemolytic anaemia may occur on dapsone, independent of the G6PD status. I have seen this mainly in patients with Nordic or Celtic Caucasian background. I hardly saw it in Africans or Ethiopians. When it occurred it was usually because of the dose; 100 mg dapsone standard in MDT may be to high for people below 70kg bodyweight and a lower dose should be considered. The haemolysis is dose dependent. This lower dose could replace an other drug with more or not yet known side effects. Do not forget that dapsone is an immuno-modulator and may prevent type 1 leprosy reactions.
Allergic reactions may occur and the dapsone syndrome as well. But those are rare. Liver function disturbances are often wrongly attributed to dapsone. Methaemoglobinaemia is common but dose dependent and mostly does not interfere with the patients daily life. Gastrointestinal problems are also diagnosed, but mostly by people who look for it and are biased. Psychological problems are rare but sleeplessness may occur, but a lower dose and early morning intake may take care of this.
Rifampicine
Rifampicine side effects occur nearly only with a daily dose and than may cause infaust reactions. The flu-syndrome is hardly ever seen and if seen it is seen in patients who take their rifampicine irregular.
Clofazimine
Clofazimine has gastro-abdominal side effects, especially when one focuses on it. But again, this is in general, dose dependent, as is the discoloration. Minocycline is a good alternative, but it also has a number of side effects, in my experience more than clofazimine. I have not been able to confirm the protective effect of minocycline on type 2 reactions as suggested by Gelber.
Rifampicin, ofloxacine and minocycline (ROM)
Indeed ROM is a possibility, but one misses than the inhibitory effect of dapsone for type 1 and clofazimine for type 2 reactions. Little is yet known about the effectivity in daily use.
Rifampicine resistance
I have treated a few rifampicine resistant patients with either clarithromycine or ofloxacin or both. I have seen good results and no side effects. But I use both drugs also for other conditions and than see side effects. Resistance to components or side-effects attributable to components of MDT may occur, but I wonder whether alternatives have less.
In the past 25 years I have noticed one big problem, which makes me weary: often when an problem with a drug or treatment is emphasized, an alternative is in the pipeline, which is usually more expensive. People other than the patient benefit from the advertised problem, researchers, politicians or manufactures.
With kind regards,
Dr Ben Naafs
PS
The last remark is definitely not directed against Dr Gilead's question which was genuine and needed a proper and honest answer as is given by the other responders. The remark is a “cri de coeur” which occurred to me writing my comments.
Leprosy Mailing List – February 10th, 2010
Ref.: New multi authored text book of Leprosy
From: P. Narasimha Rao,
Dear Salvatore,
I am happy to inform our LML members that a new multi authored "IAL text book of leprosy' edited by Dr HK Kar and Dr Bhushan Kumar, was released at the national conference of Indian Association of Leprologists (IAL) in October 2009. Now the same is available for purchase for all, published by Jaypee bothers medical publishers of
It is a multi authored comprehensive text book of leprosy of about 600 glossy pages with coloured illustrations and detailed model charts for recording patients details etc. It has 9 sections and a total of 47 chapters with references at end of each chapter.
http://www.jaypeebrothers.com/pgDetails.aspx?cat=s&book_id=978-81-8448-852-4#
If we recollect, we had a discussion whether there is a need for a comprehensive text book of leprosy about two to three years back on this forum. I hope this text book would fill the lack of such a comprehensive text book on leprosy with latest details which was felt by few of us. I am happy to state that I was a part of this endeavor.
I would recommend this book for all who are teaching leprosy and also as a reference book for medical colleges and other institutes working on leprosy.
With best regards,
P. Narasimha Rao
Leprosy Mailing List – February 7th, 2010
Ref.: Alternative Antibiotic Regimens for Leprosy
From: R Ganapati,
Dear Dr Noto,
Though some interesting views have been exchanged on reactions following MDT and the role of clofazimine etc in response to the question on the above subject by Dr Leon Gilead of
Combinations based on Moxifloxacin, the most powerful anti-bacterial agent against M leprae have been recommended by recognized authorities:
1.
Pre Congress Workshop of the 17th International Leprosy Congress,
2.
WHO Technical advisory Group Report of the Ninth meeting on Leprosy Control in 2008
We reported our preliminary observations on a limited sample of 54 patients treated with monthly supervised doses of moxifloxacin, rifampicin and minocycline (Ganapati R, Pai VV, Khanolkar S and Shinde M, Revista de Leprologia, 27, 49-55, 2009). Remarkable clinical regression demonstrable within 2 to 3 months was noticed in all types of leprosy.
On-going and unpublished studies on 98 leprosy cases treated with the same regimen ie. moxifoxacin, rifampicin and minocycline followed for periods ranging from 6 to 18 months indicate that about 28% of BB, BL and LL patients had reactions. Trials using clofazimine as a component of the this regimen are in progress.
With regards,
Dr R Ganapati,
Director Emeritus,
Leprosy Mailing List – February 7th, 2010
Ref.: Relapse and reaction after patients have been released from treatment (RFT). (see attachment)
From: Norihisa ISHII,
Dear Prof Das and Dr van Brakel,
Please find herewith in attachment the PDF file of our paper about relapse and reaction after RFT.
Best regards,
Norihisa ISHII MD, PhD
Director-General, Leprosy Research Center,
National Institute of Infectious Diseases (NIID)
4-2-1 Aobacho, Higashimurayama,
Tokyo 189-0002, JAPAN
Tel: (81)42-391-8211 FAX: (81)42-391-8210 E-mail: norishii(at)nih.go.jp
Leprosy Mailing List – February 7th, 2010
Ref.: Clarithromycin as alternative drug for DDS resistant/DDS hypersensitive patients.
From: Francesca Gajete, City of
Dear Dr Noto,
I refer to Dr Gilead’s (LML Jan. 27th , 2010) and Dr van Brakel’s (LML Feb. 2nd , 2010) messages.
In the
Warm regards,
Francesca Gajete,
Dr Francesca Gajete
National Manager
National Leprosy Control Programme
The
Leprosy Mailing List – February 7th, 2010
Ref.: Clofazimine in the
From: Francesca Gajete, City of
Dear Dr Noto,
A prominent side effect of clofazimine is reversible coloration of the skin. It produces an initial redness of the skin due to an accumulation of the drug. Later with prolonged treatment a pink to brownish-black colour develops and this is most noticeable in lesional areas (1, 2).
In the
Best regards,
F. Gajete
Dr Francesca Gajete
National Manager
National Leprosy Control Programme
The
1.
Rook … Textbook of dermatology 6th Ed. 1998
2.
Leprosy for medical practitioners and paramedical workers, S J Yawalkar 2nd Ed. 2002
3.
Leprosy, Robert C. Hastings, 1985
Leprosy Mailing List – February 7th, 2010
Ref.: VIIIth cranial nerve toxicity caused by minocycline
From: Richard I.
Dear Salvatore,
While I have found minocycline a useful alternative drug, I would caution practitioners that VIIIth cranial nerve toxicity manifest by dizziness is not an uncommon adverse effect. This may be debilitating and is more common in smaller individuals. Patients may not report this unless they are specifically asked about it.
Kind regards,
Richard
Richard I. Frankel, M.D., M.P.H., F.A.C.P.
Emeritus Professor of Medicine
Leprosy Mailing List – February 3rd, 2010
Ref.: Web links to key WHO Global Leprosy documents
From: Doug Soutar,
Dear Dr Noto,
I would be grateful if you would be prepared to post this message to the LML concerning the improved access to key WHO leprosy documents via the SEARO / Global Leprosy Programme website.
Many thanks,
Doug Soutar
Dear Colleagues,
In recent years I have regularly heard people complain that it is difficult to find the most up-to-date WHO Leprosy Strategy documents on the WHO Website. Many have told me they prefer to use the ILEP website http://www.ilep.org.uk/library-resources/who-publications/ to find the most recent WHO materials on leprosy. Certainly the leprosy section of the WHO International website (updated in
The WHO Global Leprosy Programme is of course situated within the WHO’s South East Asia Regional Office (SEARO) in
http://www.searo.who.int/EN/Section980/Section2572.htm
In
With best regards,
Douglas Soutar
Douglas Soutar
General Secretary
International Federation of Anti-Leprosy Associations
Tel: 44 (0) 207 602 69 25 – Fax: 44 (0) 207 371 16 21 – Website: www.ilep.org.uk
E-mail: doug.soutar(at)ilep.org.uk
Leprosy Mailing List – February 2nd, 2010
Ref.: Leprosy patients developing erythema nodosum leprosum (ENL) reactions after stopping multi-drug therapy (MDT)
From: Wim H. van Brakel,
Dear Prof. Das,
I refer to your message dated LML Jan. 23rd, 2010 regarding leprosy patients developing ENL reactions after stopping MDT.
I am very sure about this observation, but realise that this does not constitute 'evidence' in itself. I have tried to encourage people in many countries to collect such information systematically. Unfortunately I do not know of a single (published) study with adequate design that has done this. There was one paper from the
With kind regards,
Wim van Brakel
Wim H. van Brakel
Royal Tropical Institute
Leprosy Unit
and
Athena Institute
Faculty of Earth and Life Sciences
VU University
Correspondence address:
Wibautstraat 137k
1097DN
tel +3120 6939297
fax +3120 6680823
w.v.brakel(at)kit.nl
wim.van.brakel(at)falw.vu.nl
Leprosy Mailing List – February 2nd, 2010
Ref.: Alternative antibiotic regimens for leprosy
From: Wim H. van Brakel,
Dear Dr. Gilead,
Thank you for your response (LML Jan. 27th, 2010).
If patients are also unable to take dapsone or are dapsone resistant, that of course changes matters considerably. Such patients should be given at least one alternative effective antibiotic. I would fully support the combination suggested by Prof. Diana Lockwood in an earlier contribution (LML Jan. 27th, 2010). I do not have personal experience with moxifloxacin or clarithromycin. There is (some) evidence of their efficacy, but they are very likely much more expensive than ofloxacin or minocyclin.
I do not see why Ethiopian patients should have a higher rate of dapsone resistance than patients from elsewhere.
I hope this helps!
With kind regards,
Wim
Wim H. van Brakel
Royal Tropical Institute
Leprosy Unit
and
Athena Institute
Faculty of Earth and Life Sciences
VU University
Correspondence address:
Wibautstraat 137k
1097DN
tel +3120 6939297
fax +3120 6680823
w.v.brakel(at)kit.nl
wim.van.brakel(at)falw.vu.nl
Leprosy Mailing List – February 2nd, 2010
Ref.: Alternative antileprosy regimens
From: Navin Modi, Shahad, Thane,
Respected Sir,
I practice in Thane district,
I give daily rifampicin 600, ofloxacilin 400 and minicycline 100mg for adult patients who are sensitive to dapsone and also to patients of lepromatous (LL) leprosy who clinically seems to need treatment more than 1 year. For example looking at signs like their infiltrated skin, persisting ear nodules, new lesions. I use this for periods ranging from two to ten months.
Regards,
Dr Navin Modi
Dermatologist/sexologist
Secretary: National Human Rights centre, Thane District
Leprosy Mailing List – February 1st, 2010
Ref.: Axillary block anaesthesia
From: Latif Ahmad,
Dear Salvatore,
I agree with Dr Brandsma LML Jan 27th 2010 but, if I may add, all 3 patients had failure of axillary block anaesthesia. Such a skilled procedure by an unskilled operator is likely to cause damage to nerve trunks especially when repeated attempts are made.
Dr Latif Ahmad
Dermatologist and
Ex
Leprosy Mailing List – February 1st, 2010
Ref.: In leprosy axillary and cervical nerve blocks are not recommended
From: Grace Warren,
Dear Salvatore,
I note with interest the various responses to the letter from Angelika (LML Jan. 23rd Jan. 2010). I am fascinated by the many suggestions and yes I understand that the tight tourniquet could be a problem and has caused many problems but, I would be grateful if this paper of mine could be included to show workers that they do not need to inject the nerves directly and in a patient with marked nerve damage the extra needle damage may well be the last straw and produce the paralysis. I have seen it in non-leprosy people with otherwise normal nerve function, sometime producing severe lasting pain sometime producing paralysis.
In Leprosy we can never be sure exactly how much of a nerve has been damaged or completely destroyed and/or if we have got rid of all the infection that is destroying or has destroyed that group of nerve fibres, and hence if there is ever likely to be a further neural deficit in the future.
For good rehabilitation as soon as diagnosis is made, we should strengthen every muscle in the limb to its maximum and assess the detailed function of all nerves affected. Some nerve may have been damaged and yet may recover with time and good medication. Every patient with nerve damage in the arm, ought to be taught full hand exercises. Details of these exercises, are given in my book “The care of the neuropathic limb” (Parthenon – 1999). I will ask Dr Noto to publish a revision of those exercises in the LML. The idea is to help physiotherapists and other involved health workers in restore fuction in weak intrinsics etc.
After the disease is controlled and the muscle function has plateaued we can then assess what measures, surgical or otherwise can assist that person to rehabilitation.
In leprosy the nerves are involved very early in the disease but may not show a deficit for a prolonged period of time. When the nerve is damaged it does not show obvious deficient function until about 10% (some say 15%) of the nerve fibres of any one modality are damaged, so palpating a nerve may suggest it is OK but in fact some 6-8-10% of its fibres may be NON functioning and yet there is no obvious sign of the functional deficit.
Even skilled technicians cannot detect the functional deficit, initially, and may say ”No obvious deficit”- so when assessing a hand with a weakness of thumb opposition for example, one must assume that there is a weakness of the other medially innervated intrinsic muscles and even if not detectable at present there will be some deficit of the other modalities of that nerve in the future or there will be some sensory abnormality even if one cannot record anything definite. All the nerves in the arm are likely to be affected to some degree even if we cannot record it.
It is also wise to remember that in lepromatous leprosy the nerve damage is not obvious early and I have had patients who were initially “ cured” of the active infection before 1960, and recorded as “No neural deficit” and developed a neural deficit in the 1970s! Was this just that the continuation of the “healing” fibrosis in the nerves from the disease has eventually squeezed the life out of the remaining fibres or was it relapse? It was not obviously relapse as no other lesions were found just a progressive (usually ulnar) palsy! So One should bear this in mind when planning surgery so that one selects muscles for transfer carefully so that there are possibilities available if something further is needed in future.
The basic treatment of the patient is important in the long term rehabilitation of the patient. If the patient has any other disease like tuberculosis, typhoid or just a septic foot, anaemia, some intercurrent disease. Is he malnourished? We cannot expect good recovery for the malnourished!
When a nerve block is put in it is aimed at defunctioning some of the nerves, albeit temporarily. However in most nerve blocks one manages to damage some nerves permanently! I assume just by the needle hitting the nerve and I realised this to my disgust many years ago (in the i960s!). When I had two patients, within a few months, who developed radial nerve palsy from brachial plexus anaesthesia. As a medical student I had discovered that a cervical plexus block was more likely to produce problems and it is also much more difficult to put in for people who are not yet fully experienced. When I have to use an arm block now I use an upper arm or brachial block, which is much easier to insert and just as good for anything below the elbow.
For operations on leprosy patients the use of general sedation and ketamine is usually more than adequate, supplemented by a little local at incision sites if needed. Most of them if they have a paralysis due to leprosy also do have reduced sensory perception, and a good sedative plus ketamine is usually effective. However for that, one needs a suitable assistant to give the anaesthetic as he may need respiratory assistance or other medication. In many situations there is not other “doctor” to help.
An excellent alternate method is a “Biers Block” using a tourniquet on the arm and then injecting local anaesthetic into the vessels distal to the tourniquet
The good old Karigiri Cocktail is excellent requiring NO injection of nerves and I still use that when a good anaesthetic doctor is not available. In many centres that I have visited teaching over the years, I have used Karigiri Cocktail by choice as I know it well and the patient has no post op discomfort from the anaesthetic! Again a good sedative with properly given preoperative sedation, seconal and phenergan and later morphine and scopolamine and Intravenous pethedine and largactil! (I wrote it up in Leprosy review in 1974!).
Second I note two of the hands used Palmaris tendon as the transferred tendon
The object of the operation is to improve function and many of our patients need a strong grip
We always have to take into consideration the possibility that there is further progression of the neural deficit and be prepared to deal with it! Patients may have multiple bouts of paralysis because of relapses and inadequate therapy in the initial stages. The MDT regimens as suggested by WHO may be inadequate.
Now, in the first case mentioned I see weak thumb muscles I wonder how weak? And I wonder if intensive exercises would have restored enough function to have eliminated the need for surgery.
I note he used fascia as graft would have been easier to use Flexor carpi radialis as motor and palmaris as graft! Sounds now as if he will need a full radial nerve reconstruction
Case two
I do not mind if you write then and say what muscles do function and their strength I use the 0-5 voluntary muscle test (VMT) scale
Case three is much the same. Do not try and rush. Remember the nerves re-grow at one inch per month! And from an axillary damage it is many inches to the muscle affected!
I hope this will warn THAT IN LEPROSY (and some other diseases) AXILLARY AND CERVICAL NERVE BLOCKS ARE NOT RECOMMENDED for reconstructive surgery
Dr Grace Warren
The
Adviser in Leprosy and Reconstructive Surgery for The Leprosy