Leprosy Mailing List Blog: November 2010

Tuesday, November 9, 2010

Perforation of the palate in leprosy

Leprosy Mailing List – November 6^th, 2010

Ref.: Perforation of the palate in leprosy

From: Noto S., Genoa , Italy

Dear Dr Krishna Bdr Tamang,

Thank you very much for your message (LML Nov. 5^th, 2010). Two more cases of perforation of the palate in advanced lepromatous leprosy were presented by Drs Manimozhi and Barminus to the LML in 2009. Herewith are the links:

Manimozhi N.; LML 02.03.09 Perforation of the hard palate in leprosy ;

http://www.aifo.it/english/resources/online/lml-archives/2009/020309.htm

2.
Barminus A. G.; LML 12.02.09 Hoarse voice and perforation of the palate in leprosy,

http://www.aifo.it/english/resources/online/lml-archives/2009/120209.htm

Best regards,

S. Noto

Case presentation (Perforation of the palate in leprosy)

From: Theuvenet, J. Willem, Apeldoorn, The Netherlands

Dear Dr. Krishna Bdr Tamang, Namasté!

Thank you for sharing the problems of this patient (LML Nov. 5^th, 2010). The perforation in his palate is the result of the chronic inflammation of the mucosa of his nose as often seen in multibacillary leprosy. Is he not also having an erosion of his nasal septum?

The problems in eating and drinking can be partially elevated by a dentist/orthodontist who can make a removable palatal inlay for him that will cover his palate and should facilitate his eating and drinking. It will take a while after finishing his MDT and before the nasal inflammation has completely subsided. Only then it may be safe to make an attempt to reconstruct the palatal defect. Depending on the condition of his palate and the size of the defect the solution may be in a reconstruction according to Langenbeck or coverage with a dorsal tongue flap.

As you now have an excellent hospital for reconstructive surgery in the Kathmandu valley, with plastic surgeons skilled in cleft lip and palate repair, I would suggest that your patient seeks their advice in due time!

Wih kind regards,

Dr. Willem J.Theuvenet,

Plastic Surgeon

Case presentation

Leprosy Mailing List – November 5thr, 2010

Ref.: Case presentation

From: Tamang Krishna, Dhanusa , Nepal

Dear Dr Noto,

I am Dr. Krishna working at Lalgadh Hospital , Nepal . About 2 months ago we diagnosed a 52 years male with multibacillary (MB) leprosy. On diagnosis he was presenting with diffuse infiltration on face and type two reaction. We screened for diabetes and hypertension before starting prednisolone. We started MB multi-drug therapy (MDT) and prednisolone with standard protocol with 40mg 2 weeks and taper down 30mg.

He was complaining headache and faintness. We admitted him for screening; his blood sugar was high about 250 mg. He was sent home with oral hypoglycaemic drug (glibencamide 5 mg once daily) again after two days he complained sudden loss of vision in his left eye with ptosis. We immediately referred to ophthalmologists who diagnosed central retinal artery occlusion. He was again taken to physician and started human insulin and admitted in hospital about 10 days. At this point, during the course of treatment he developed ulcer on the soft palate and get perforated. They did biopsy and found fungus.

This is my bitter experience. The patient deteriorated very fast; ct scan of head was done and every thing was normal. Now he is on MB-MDT and oral hypoglycaemic drug. His blood sugar is under control, but he has perforation of palate. He severe difficulty in drinking and eating; it will regurgitate from nose.

Could you please comment? Have anyone faced such problem?

Thank you,

Dr. Krishna Bdr Tamang (lama)

Lalgadh Hospital

Dhanusa

Nepal

Rifampicin, ofloxacin and minocycline (ROM) in leprosy

Leprosy Mailing List – November 5^th, 2010

Ref.: Rifampicin, ofloxacin and minocycline (ROM) in leprosy

From: Soutar D., London , UK

Dear Salvatore,

The regimen of single dose Rifampicin + Ofloxacin +Minocycline (ROM) for single lesion paucibacillary leprosy was a recommendation of the WHO 7^th Expert Committee on Leprosy which met in 1997. For some time ROM was available in blister packs in India ,Bangladesh , Nepal and Brazil and used quite widely, particularly in India where at the time, the 7^th Expert Committee reported that more than 50% of newly detected cases were classified as single lesion PB leprosy. I do not know if ROM is still being produced in blister packs but certainly in the WHO Global Strategy 2006-2010 and the WHO Enhanced Global Strategy 2011-2015, no recommendation is made regarding the use of ROM and it is not included in the recommended regimens in the operational guidelines of both those strategies.

The WHO HQ-based website pages dedicated to leprosyhttp://www.who.int/lep/mdt/regimens/en/index.html still indicate that ROM is part of the recommended regimens. This, I assume, is why the leprosy section of Wikipedia http://en.wikipedia.org/wiki/Leprosy still makes reference to it and also why in a recent new publication on Ocular Leprosy there is also a reference to this as a WHO recommended regimen http://www.cehjournal.org/files/tsno9/ts09.html#06 . This highlights the fact that websites do need to be updated on a regular basis to avoid out of date technical advice and references being perpetuated.

The 8^th WHO Technical Advisory Group meeting in Aberdeen 2006 reported the following in regard to ROM:

http://www.searo.who.int/LinkFiles/Reports_2-8th_MtngWTAG_Leprosy_Control_Aberdeen_Scotland.pdf

6. Clinical trials for treatment of PB leprosy patients with single dose of rifampicin, ofloxacin and minocycline (ROM)

Final report

These WHO-sponsored trials address two issues: (i) Effectiveness of single dose ROM in paucibacillary leprosy patients with two to five skin lesions carried out in India as a randomized double-blind trial, and (ii) Relapse rates in single-lesion paucibacillary leprosy cases treated with single dose ROM.

(i) Effectiveness of single dose ROM in paucibacillary leprosy patients with 2-5 skin lesions

The study was carried out in India to evaluate the effectiveness of single-dose ROM compared to standard, six-monthly doses of MDT regimen for PB leprosy patients with two to five skin lesions, under programme conditions. PB leprosy cases that were smear-negative presenting with two to five lesions were included in the study. These patients were recruited from five centres in

India

. All patients were treated for six months, with appropriate pre-coded drugs and identical looking placebo. The primary outcome was complete clearance of skin lesions. The initial plan was for six months each for intake and treatment phase followed by periodic post-treatment assessments for 36 months. The post-treatment follow-up period was extended for another 12 months in two centres that recruited the majority of the patients in this study. Data were analysed for these two centres with multivariate longitudinal regression analysis using Generalized Estimating Equations (GEE).

A total of 1,082 paucibacillary (PB) cases were randomly allocated to ROM (n= 539) or WHO PB-MDT (n= 543). Baseline characteristics were similar at intake. The total number of patients at the final follow-up was 468 (87%) in the ROM group and 477 (88%) in the WHO PB-MDT group. Complete clearance was observed in 71% (332 out of 468) in the ROM group and 75% of (358 out of 477) in the WHO PB-MDT group. Relapse rate was more than two times higher among patients treated with ROM as compared to WHO PB-MDT (Rate ratio: 2.31; 95% confidence Interval 1.00-5.35). GEE analysis indicated that patients’ age and time of follow-up were statistically significant after adjustment for factors included in the model. The clinical score was not statistically significant between the two treatment groups (Model coefficient: -0.045; 95% CI: -0.27-0.17)

(ii) Relapse rates in single-lesion paucibacillary leprosy cases treated with single dose ROM

The objective of the study was to evaluate the effectiveness of ROM for the treatment of skin smear negative single-lesion PB leprosy patients and to determine the occurrence of relapses over a period of 54 months. Four leprosy control units in the Chittoor and Cuddapah districts of Andhra Pradesh were selected for this trial. PB leprosy patients with only a single lesion who were untreated were enrolled for this study. Patients were examined at the time of intake, and then every six months from the date of inclusion. The rate of relapse was calculated using survival analysis.

A total of 1,262 patients were enrolled for this study out of which 35% (n=440) were children and 49% (n=619) were males. The study observed 126 special events. These were suspected relapse patients (n=19), confirmed relapse patients (n=7), migrations (n=84), deaths unrelated to leprosy (n=22) and misclassification (n=1). At the end of 54 months, 88% (n=988) patients had complete clearance of skin lesions. The improvement and deterioration scores of patients show that 0.1% had deterioration compared to their clinical status at intake, 2% had static clinical condition and the rest showed varying degrees of improvement. The incidence rate of suspected relapse was 3 per 1000 person- years.

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

Rifampicin, ofloxacin and minocycline (ROM) in leprosy

Leprosy Mailing List – November 3^rd, 2010

Ref.: Rifampicin, ofloxacin and minocycline (ROM) in leprosy

From: Frankel Richard I., Hawai'i, USA

Dear Salvatore and Dr Ahmad,

I refer to Dr Ahmad’s message dated LML Nov. 2nd, 2010. Three pertinent references are:

Single-Lesion Multicentre Trial Group. Efficacy of single-dose multidrug therapy for the treatment of single-lesion paucibacillary leprosy. Indian J. Lepr. 69:121-129 (1997)

Revankar, C.R., Bulchand, H.O., Pai, V.V., et al. Relapse rate in paucibacillary leprosy treated with single dose. Int. J. Lepr. 69:S131 (2001)

Lockwood, D. N. J. Rifampicin/Minocycline and ofloxacin for single lesions—what is the evidence? Lepr Rev 68:299-300 (1997)

This treatment is discussed briefly in the chapter on Leprosy by Dr. Scollard and myself in the Fourth Edition of "Bacterial Infections of Humans", edited by Drs. Brachman and Abrutyn, published by Springer in 2009.

Sincerely,

Richard I. Frankel, M.D., M.P.H., F.A.C.P.

Emeritus Professor of Medicine

University of Hawai'i

Rifampicine, ofloxacin and minocycline (ROM) in leprosy

Leprosy Mailing List – November 3^rd, 2010

Ref.: Rifampicine, ofloxacin and minocycline (ROM) in leprosy

From: Kar H K, New Delhi , India

Dear Dr Latif,

Greeting from India . I refer to your message dated LML Nov. 3^rd, 2010.

ROM trial was conducted by WHO in India (a multi-centric randomized, double blind controlled clinical trial) to compare the efficacy of ROM with that of the WHO paucibacillary multidrug therapy (PB-MDT) in 1483 patients with one skin lesion and no peripheral nerve trunk involvement. At 18 months follow up of 1381 patients who completed the study, marked improvement was was observed in 51.7% in ROM as against 57.3% in WHO group while complete cure was observed in 46.95 of ROM group as compared to 54.7% in WHO group. Six treatment failure in each group. (Indian J Lepr 1997;69:121-29).

In another study in Bangladesh, in 6.3 years follow up among 310 single skin lesion (SSL) PB cases treated during 1998-2000, 765 had complete clearance of lesions with relapse in 6 cases (3.6%). The authors concluded that higher rates of relapse possibility should be kept in mind. (Lep Rev 2007;78:160).

WHO later initiated another clinical trial with intermittent drug regimens ROM in both multibacillary (MB) and PB cases with monthly once supervised doses for 3 or 6 doses for PB (1800 cases) and 12 or 24 doses for MB cases (1500 cases) in a multi-centric study in three countries (Guinea, Myanmar, Senegal). The long term results are awaited.

Regards,

Dr (Prof.) H K Kar
Consultant & HOD
Department of Dermatology, STD & Leprosy
P.G.I.M.E.R. and Dr Ram Manohar Lohia Hospital
Baba Kharag Singh Marg
New Delhi-110001

Single dose treatment for single lesion leprosy

Leprosy Mailing List – November 2^nd, 2010

Ref.: Single dose treatment for single lesion leprosy (?)

From: Ahmad L., Karachi , Pakistan .

Dear Dr Salvatore ,

I am referring to LML October 30, 2010 by Dr Al Aboud Khalid from Mekkah.

A single dose treatment with rifampicin, ofloxacin and minocyclin for a single lesion leprosy which has been mentioned in Wikipedia is a new information for me. I would like to know its background, research and place where it is in practise. Could somebody please help me on this. I shall be grateful.

With regards,

Dr Latif Ahmad

Dermatologist

Karachi , Pakistan

Looking for Doctor with experience in leprosy in (or near) Vancouver , British Colombia, Canada

Leprosy Mailing List – November 2^nd, 2010

Ref.: Looking for Doctor with experience in leprosy in (or near) Vancouver , British Colombia, Canada .

From: Legault Maryse, Montréal, Québec , Canada

Dear Dr Noto,

It is with great interest that I often read you emails from the Leprosy Blog. I now come to you with a question.

I was contacted by a Canadian man living in Vancouver British Colombia. An International traveller, he has had various medical problems in the last year. He is looking for a doctor who could recognize leprosy in western

Canada

. His own doctor does not believe it is leprosy. He told me he has some facial changes, his fingers are curling, his eyes are sensitive to light. He would like to meet a leprologist or at least a doctor specialized in tropical diseases with some experience with leprosy.

Do you know of a leprologist near Vancouver BC ?

Thank you for your precious help.

Maryse Legault, MBA

Secours aux Lépreux - Leprosy Relief Canada

maryse.legault(at)slc-lr.ca

1-866-744-3199

Leprosy in Wikipedia

Leprosy Mailing List – October 30^th, 2010

Ref.: Leprosy in Wikipedia

From: Al Aboud Khalid M., Makkah ,

Saudi Arabia

Sir,

Online Resources are very convenient and effective tool for helping the physicians in their practice and also for patient health education. Wikipedia is a free, web-based, multilingual encyclopaedia project supported by the non-profit Wikimedia Foundation [1]. It was launched in 2001 by Jimmy Wales and Larry Sanger and is currently the largest and most popular general reference work on the Internet [1]. Its 16 million articles (over 3.4 million in English), have been written collaboratively by volunteers around the world, and almost all of its articles can be edited by anyone with access to the site [1].

On looking to the leprosy page in Wikipedia (kindly, see the link in reference 2), one can see a comprehensive information about the disease. The article is available in 63 languages. The above status about the multilingual availability about the topic is good, if we compare it with other common diseases like vitiligo or psoriasis (37 languages for each). However, few remarks need to be mentioned.

The Contents about leprosy in other languages (other than English and French), are limited. One can expect that the contents are more in the languages of the countries most affected about the disease.

Secondly, one can observe that there is a difference in the details among different languages and also the external links in the leprosy pages are not the same. I could not find a link to our LML in the Wikipedia leprosy page.

There is a need to supplement the articles in each language by good figures and images. Workers in leprosy elimination or rehabilitation of leprosy patients or in any other different leprosy programmes, may enhance their works by utilizing this important resource because the disease exist in many communities with different languages. It is particularly, more profitable if those with interest per language group try to upgrade the leprosy chapter. Before they can do this they have to register to Wikipedia.

I may conclude by saying that, we may need to initiate a task force among LML group with an aim to review and improve the leprosy pages in Wikipedia as it is a very important resource for the physicians and patients alike.

Khalid M. Al Aboud, MD

Medical Director and Consultant Dermatologist

King Faisal Hospital

Makkah ,

Saudi Arabia

Address for correspondence:

Khalid Al Aboud

M.D, Medical Director

King Faisal, P.O Box 5440

Makkah, Postal Code 21955 ,

Saudi Arabia

Tel 00966 2 5566411, Fax 00966 2 5563523/5574350, E-mail amoa65(at)hotmail.com

Pharmacogenetic studies of response to treatment erythema nodosum leprosum

Leprosy Mailing List – October 9^th, 2010

Ref.: Pharmacogenetic studies of response to treatment erythema nodosum leprosumFrom: Lavinia Schuler Faccini, Porto Alegre, RS, Brazil

Dear Salvatore,

Can you send this message about a project we are initiating in

Brazil

Thanks,
Lavinia

PHARMACOGENETIC STUDIES OF RESPONSE TO TREATMENT

ERYTHEMA NODOSUM LEPROSUM

The most used drugs in the Brazilian practice for the treatment of erythema nodosum leprosum (ENL) are thalidomide and prednisone. Clinical trials show that thalidomide besides being more effective in reducing symptoms also generates a faster response. However, it is not widely used because of teratogenicity and peripheral neuropathy. The treatment with prednisone is the best known and always used in cases of neural involvement, but has the disadvantage of very long treatment with significant adverse effects.
Based on the limitations of both treatments, we are developing a pharmacogenetic study in which we are testing genetic polymorphisms involved in the thalidomide and prednisone's metabolic pathway. Our goal is to evaluate if there is genetic differences between individuals in the response to treatment of ENL with these two drugs (both with respect to clinical response as adverse effects). In that way, we aim in the future to be able to predict which patients might benefit more with each medication or, on the other side, be more prone to adverse effects. Thus, we are asking Brazilian centers with patients undergoing treatment for ENL using some of these drugs to collaborate in this research. For those interested we ask to write to:

fslvianna(at)gmail.com
Fernanda Sales Luiz Vianna

lavinia.faccini(at)ufrgs.br
Dr. Lavinia Schüler-Faccini
UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL

Combined clofazimine and dapsone resistant leprosy: a case report

Leprosy Mailing List – October 9^th, 2010

Ref.: “Combined clofazimine and dapsone resistant leprosy: a case report”

From: H K Kar, New Delhi , India

Dear Sir,

I refer to Dr Kawuma's message (LML Oct. 2nd, 2010). The second report about clofazimine resistance was published by us from "Central leprosy teaching and research institute", Chingleput, Tamil Nadu , India . "Combined clofazimine and dapsone resistant leprosy: a case report by Kar H K, Bhatia V N, and Harikrishnan S. International J leprosy, 1986, 54:389-391."

Regards,

Dr (Prof.) H K Kar
Consultant & HOD
Department of Dermatology, STD & Leprosy
P.G.I.M.E.R. and Dr Ram Manohar Lohia Hospital
Baba Kharag Singh Marg
New Delhi-110001

The concept of “elimination” is confusing, indeed

Leprosy Mailing List – October 9^th, 2010

Ref.: The concept of “elimination” is confusing, indeed.

From: N. Modi, Thane, Maharashtra , India "

Dear Dr Noto,

I would like to thank Dr. Grace Warren for her valuable input. Indeed, the concept of "elimination" is confusing and often not well understood by government officials. In the Thane district in India , where I work, I recently diagnosed 3 children less than 6 years old with full blown lepromatous leprosy.

Dr Warren mentions that she often sees relapses. May I ask her how she makes this diagnosis?

Regards,

Dr Navin Modi
Medical Officer

Muktajeevan Leprosy Rehabilitation Center

Thane, Maharashtra , India

Clofazimine

Leprosy Mailing List – October 7^th, 2010

Ref.: Clofazimine

From: H Joseph Kawuma, Jinja , Uganda

Dear Salvatore,

While the search for the original paper* continues, I would like to add some detail to my statement regarding "clinical evidence" (LML – Oct. 2^nd, 2010). The tools: slit skin smears and histopathology were of course available to support the clinical diagnosis but they I suppose cannot be used as conclusive evidence of resistance to Clofazimine.

I wonder if there will be any "Yes" answer to Grace Warren's question in its new form. I am aware of a publication in the Indian Journal of leprosy by Ebenezer and others (2002) describing cases of primary and secondary clofazimine resistance from a series of biopsies before 1997. Again one would need to study the paper in order to obtain information about the patients.

Has the mode of action of clofazimine been fully understood now? Do we now have a reliable technique for testing Clofazimine resistance?

H Joseph Kawuma

*
Titia Warndorff-van Dieden, "Clofazimine-resistant leprosy, a case report" International journal of leprosy and other mycobacterial diseases, volume 50, number 2 June 1982."

I would like to back up Prof Ryan’s request

Leprosy Mailing List – October 5^th, 2010

Ref.: “I would like to back up Prof Ryan’s request”

From: G. Warren, Sydney , Australia

Dear Salvatore,

I would like to back up Prof Ryan’s request (LML – Sept. 25th, 2010). I know from letters, from workers in several countries, that the majority of the Government agencies are accepting that leprosy is Eliminated and that means eradicated! I am so sorry THAT THAT TERM ELIMINATION EVER GOT CONNECTED TO LEPROSY. It has made our task much harder.

From personal experience I know that most fully developed LL patients need for more than the 12 months of multi-drug therapy (MDT) as recommended by WHO. Many workers do not realise that the bacteria can survive in the nerves for many years of full MDT and certainly may not be eradicated, and once the MDT ceases the disease may return in a year or two. This may result in registration as a new patient because the name was removed from the original “affected“ list so the patient cannot relapse! No wonder WHO has such small “relapse” rates!

I have heard that in large areas of some counties, once they think elimination has occurred, the previous regular surveys have all ceased and the patients are left to voluntarily report if they suspect leprosy. Of course anyone who had had the disease "Eliminated” would not think of it coming back! Yes, the neglected tropical diseaseliterature needs to be well aware of this and promote more funding to continue surveys and teaching of the true facts in many countries. This would include the Medical personnel in developed countries, who need to be taught and to remember that anyone who has been to an endemic country as a tourist could develop the disease in the next say 10 years and, of course refugees from those countries. I have seen some horrible mistakes where patients have been missed till deformity is gross. World travel is becoming so frequent we do not need to work in an endemic country to see leprosy. IF we look for it.

Thank you Prof Ryan for voicing the problem. Has anyone got some answers? I now work in Australia after 50 years all over Asia and some other areas and get very depressed at the “relapses” I see who have been told “eliminated”. One patient is now on his third bout of leprosy, having completed MDT twice before (in two other countries!) and told: cured!

Yours sincerely,

Grace Warren

Previously Adviser in Leprosy and Reconstructive surgery for the Leprosy Mission in Asia( 1975-94)

Research groups discussing on future priority researches

Leprosy Mailing List – October 5^th, 2010

Ref.: Research groups discussing on future priority researches

From: Francesca C. Gajete, Manila , The Philippines

Dear Prof Ryan,

Thank you for tackling this issue (leprosy mailing list – Sept. 25th, 2010) as these are the same challenges I am experiencing in the Philippines as the national programme manager. I do agree with you particularly with your issue with the Neglected Tropical Diseases (NTD) wherein in my country, with WHO NTD/Stop Tuberculosis and Leprosy Programme, leprosy is just an attachment or appendage of a title.

For example, in the recently held meeting of the Disease Reference Group (DRG) for Research on Tuberculosis (TB), Leprosy and Buruli Ulcer, leprosy group was invited to a one day activity in a 3-day meeting wherein TB had the full agenda. We are just lucky that Dr Diana Lockwood was there, otherwise, no other leprosy expert was around to discuss with us. I do appreciate though the support I am getting from Dr Steve Lyons as far as multi-drug therapy drug supply is concerned but even if there is a Global NTD meetings, leprosy programme is not equally represented, from our end it is the Filaria programme which is given priority and called upon on these meetings.

As for government, I am assisted by the coordinators from the local government units in advocating to the Local chief executives ownership of the programme especially stressing the fact that sustaining the elimination level, decreasing the disease burden and addressing the stigma and human rights dimension is more challenging and more costly. However, you are right we need reference materials and more frequent dialogues with policymakers to strengthen this advocacy.

Lastly, local NTD people consider leprosy as a disease of the poorest of the poor. You and I know that the Mycobacterium leprae cannot and does not recognize economic status, but we are also aware why leprosy is considered so.

Best regards,

Francesca C. Gajete, MD; MHA

National Leprosy Control Program Manager

Department of Health, Manila , Philippines

as clofazimine resistance seen to develop in a patient?

Leprosy Mailing List – October 2^nd, 2010

Ref.: Has clofazimine resistance seen to develop in a patient?

From: H J Kawuma, Jinja, Uganda

Dear Dr Noto,

I refer to Dr Warren’s message dated LML Sept. 29th, 2010. I am not aware of any other report of clofazimine resistant leprosy in a patient apart from the one published by Titia Warndorff in an Ethiopian patient in 1982. This was published as a case report in the International Journal of Leprosy:- “Titia Warndorff-van Dieden, “Clofazimine-resistant leprosy, a case report” International journal of leprosy and other mycobacterial diseases, volume 50, number 2 June 1982.”

In that case (which I was privileged to see), there was only the clinical evidence to go by.

Best regards,

H Joseph Kawuma

GLRA, Uganda

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Tuesday, November 9, 2010