Tuesday, July 30, 2019

FW: (LML) Drug costs and impact of post-MDT chemoprophylaxis for LL patients

Leprosy Mailing List – July 30,  2019

Ref.:   (LML)  Drug costs and impact of post-MDT chemoprophylaxis for LL patients

From:  Joel Almeida, Mumbai and London

Dear Pieter,


Thanks to Dr. Gelber (LML, July 26, 2019) for sharing his well-informed understanding on this topic. He has been responsible for major advances in chemotherapy, including the introduction of minocycline. We can be grateful to be standing on the shoulders of giants. Prof. Isabela Goulart (Brazil) had earlier provided detailed research findings and well-reasoned suggestions. Dr. Kawuma (Uganda) and several others had earlier also shared their well-reasoned views. All people of goodwill from across the world have been coming together to fight our common enemy: the potentially devastating bacilli. Thanks to LML, we have an open platform for building rapidly on one another's insights. "How can you get the best ideas and have the ideas, and not the hierarchies, win?" asked Dr. Vas Narasimhan in an interview. LML fosters such a healthy community of science, enabling constructive and rapid progress. Anybody can put their shoulder to the wheel and advance our common cause. The validity and utility of ideas matters much more than the identity of those making contributions.


Those from a non-biological background might find an analogy useful in understanding post-MDT chemoprophylaxis. Imagine Hansen's Disease (HD) as a fire. Imagine polar LL (LLp) patients as perspiring kerosene during their whole life, owing to genetically-determined anergy. Would we send these inflammable individuals unprotected to face fire again? Of course not. We would ensure their protection before sending them out again.


That's why it is necessary to provide post-MDT chemoprophylaxis to LLp patients in endemic areas. It is like "fire-proofing" for innately "inflammable" individuals. Our challenge is to ensure that one highly "inflammable" LLp patient never "sets fire" to another such patient, directly or indirectly. That can be powerfully effective. That's how the "fire" starts to die out. In epidemiological terms, that can reduce the reproductive ratio of infected LLp patients to below one. That's how Shandong wiped out the disease, achieving near-zero transmission. 


Evidence keeps mounting that progressive forms of HD are like a distinct disease. They differ from self-limiting forms in terms of genetics and pathophysiology. (1-4) Our efforts need constantly to be updated in the light of such accumulating evidence. 


Further, untreated LLp patients are also the most likely to shed high concentrations of viable bacilli, as many as a billion bacilli per day including tens of millions of viable bacilli. (5) Without post-MDT chemoprophylaxis, they are forced unknowingly to spread the "fire" once they suffer relapse or re-infection. No other untreated sources, apart from armadillos, develop such high concentrations of viable bacilli.


LL patients are also the most likely to have suffered visible deformity, and they remain at greatest risk of further nerve damage. Competent case management for them involves not just post-MDT chemoprophylaxis but also comprehensive services for nerve protection, rehabilitation and inclusion. These patients have a huge job in addition to contributing their individual gifts to society. That job is to fight the bacilli on everyone's behalf. They might not realise how important that job is. We realise, because we understand the underlying biology. With proper epidemiological understanding, these persons can be recognised and treated as VIPs. Monthly chemoprophylaxis, as part of comprehensive case management services, is useful because it facilitates regular ingestion of drugs. Monthly contact with a designated helper can help affected persons with visible deformity also to access services for nerve protection, rehabilitation and inclusion. 


What about BL patients? They too can have post-MDT chemoprophylaxis and comprehensive case management services, although they tend to shed far fewer viable bacilli than do LLp patients. (5)


What about endemic areas where skin smear and lab services have been neglected or shut down? While we work to restore those services, we could rely on physical signs.  All those with widely and symmetrically distributed signs of HD could be regarded as eligible for post-MDT chemoprophylaxis. It is better to be cautious. Eventually, as investment increases, we can restore quality-controlled laboratory services in all endemic areas.


We need no longer abandon LLp patients to the bacilli, after MDT. We now know that recurrence of disease allows concentrated bacilli to spread despite all our other worthy efforts. Post-MDT chemoprophylaxis, for all LL patients in endemic areas, can reduce the cumulative recurrence rate of disease among LLp patients from as high as 75% to near 0%. Otherwise, all our good work with other interventions can be undone. Neglect of LL patients after MDT carries a heavy price not only for the individuals but also for society. 


Post-MDT chemoprophylaxis for LL patients is the only intervention, apart from MDT itself, which interrupts transmission at source. Once we add post-MDT chemoprophylaxis for all LL patients in endemic areas, and prevent stock-outs of MDT in peripheral health centres, we have a realistic chance of wiping out this devastating disease (at least from continents without armadillos). It is our best hope of matching Shandong's demonstrable victory. A 20%/year decline in incidence rate, leading to zero transmission, would transform endemic countries. Think of billions of children, generations to come, freed from the threat of this devastating disease. We can achieve this if we act before multiple-drug resistant (MDR) bacilli take over.


Let's act before it's too late.


Joel Almeida



वे लोग जो जीवविज्ञानी नहीं हैं, वे एक सादृश्य उपयोगी पा सकते हैं। आग के रूप में हैनसेन की बीमारी की कल्पना करें। कल्पना कीजिए कि एलएल रोगियों को जीवन भर केरोसिन पसीना आता है। क्या हम इन ज्वलनशील व्यक्तियों को असुरक्षित रूप से आग में भेज देंगे? बिलकूल नही। आग में लौटने से पहले हम उन्हें सुरक्षा उपकरण देंगे।


इसलिए नए रोगियों की अधिक संख्या वाले क्षेत्रों में एलएल रोगियों को पोस्ट-एमडीटी केमोप्रोफिलैक्सिस प्रदान करना आवश्यक है। यह "ज्वलनशील" लोगों के लिए "फायर-प्रूफिंग" जैसा है।


यह सुरक्षा शांडोंग की जीत की बराबरी करने का हमारा सबसे अच्छा मौका है। इसके बिना, रोग में गिरावट 20% प्रति वर्ष के बजाय प्रति वर्ष 10% से कम होने की संभावना है। दवा प्रतिरोधी बेसिली हर जगह फैलने से पहले, शून्य संचरण प्राप्त करना आवश्यक है। हमें जल्दी से काम करने की जरूरत है।



Aquelas pessoas que não são biólogos podem ser ajudadas por uma analogia. Imagine a hanseníase como um incêndio. Imagine pacientes com LL suando querosene devido à sua genética. Será que vamos enviar essas pessoas inflamáveis desprotegidas para o fogo? Claro que não. Nós lhes daremos equipamentos de segurança antes que retornem ao fogo.

Portanto, a quimioprofilaxia pós-PQT deve ser fornecida a pacientes com LL em áreas endêmicas. Isto é como "prova de fogo" para pessoas "inflamáveis".

A quimioprofilaxia pós-PQT fecha a lacuna principal em nossa abordagem e nos permite alcançar uma transmissão quase zero como Shandong. Sem isso, o declínio da doença provavelmente será inferior a 10% ao ano, em vez de 20% ao ano. Antes que os bacilos resistentes aos medicamentos se espalhem por toda parte, precisamos interromper a transmissão. Precisamos agir rapidamente.



Les personnes qui ne sont pas biologistes peuvent être aidées par une analogie. Imaginez Hanseniasis comme un feu. Imaginez des patients LL transpirant du kérosène en raison de leur génétique. Allons-nous envoyer ces personnes inflammables non protégées dans le feu? Bien sûr que non. Nous leur donnerons du matériel de sécurité avant leur retour au feu.

Par conséquent, une chimioprophylaxie post-PCT doit être fournie aux patients LL des zones d'endémie. Cela ressemble à une "résistance au feu" pour des personnes "inflammables".

La chimioprophylaxie post-PCT comble le principal problème de notre approche et nous permet d'obtenir une transmission presque nulle, comme dans le Shandong. Sans cela, le recul de la maladie serait probablement inférieur à 10% par an au lieu de 20% par an. Avant que le bacille pharmacorésistant ne se répande partout, nous devons interrompre la transmission. Nous devons agir rapidement.



Aquellas personas que no son biólogos pueden ser ayudadas por una analogía. Imagina la Hanseniasis como un fuego. Imagina a los pacientes con LL sudando queroseno debido a su genética. ¿Enviaremos a estas personas inflamables desprotegidas al fuego? Por supuesto no. Les daremos equipo de seguridad antes de que vuelvan al fuego.

Por lo tanto, debe proporcionarse quimioprofilaxis post-PCT a pacientes con LL en áreas endémicas. Esto es como "prueba de fuego" para personas "inflamables".

La quimioprofilaxis después de PCT cierra la brecha principal en nuestro enfoque y nos permite lograr una transmisión de casi cero como Shandong. Sin ella, es probable que la disminución de la enfermedad sea inferior al 10% anual en lugar del 20% anual. Antes de que los bacilos resistentes a los medicamentos se diseminen por todas partes, debemos interrumpir la transmisión. Tenemos que actuar con rapidez.





1) Andrade PR,  Mehta M, Lu J et al. The cell fate regulator NUPR1 is induced by Mycobacterium leprae via type I interferon in human leprosy.  PLOS NTD, July 25, 2019 https://doi.org/10.1371/journal.pntd.0007589


2) Gaschignard J, Grant AV, Thuc NV et al. Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases. PLoS Negl Trop Dis. 2016 May 24;10(5):e0004345. doi: 10.1371/journal.pntd.0004345

3) Wang N, Wang Z, Wang C et al. Prediction of leprosy in the Chinese population based on a weighted genetic risk score. PLoS Negl Trop Dis. 2018 Sep 19;12(9):e0006789. doi: 10.1371/journal.pntd.0006789.

4) Palermo ML, Pagliari C, Trindade MA et al. Increased expression of regulatory T cells and down-regulatory molecules in lepromatous leprosy. Am J Trop Med Hyg. 2012 May;86(5):878-83. doi: 10.4269/ajtmh.2012.12-0088.


5) Davey TF, Rees RJ. The nasal dicharge in leprosy: clinical and bacteriological aspects. Lepr Rev. 1974 Jun;45(2):121-34.

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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Saturday, July 27, 2019

FW: (LML) Confronting multiple-drug resistant (MDR) bacilli


Leprosy Mailing List – July 27,  2019


Ref.:   (LML)  Confronting multiple-drug resistant (MDR) bacilli

From:  Pieter Schreuder, Maastricht, the Netherlands

Dear colleagues, 



Last week (July 20, 2019), Joel Almeida wrote in LML about "Confronting multiple-drug resistant (MDR) bacilli" and referred to the following article: "Emergence and transmission of drug/multidrug-resistant Mycobacterium leprae in a former leprosy colony in the Brazilian Amazon". By Rosa PS, et al. In: Clin Infect Dis. 2019 Jul 1. pii: ciz570. doi: 10.1093/cid/ciz570.


May be not everyone was able to download and read this article. Here follows the abstract:


Leprosy has been treated with multidrug therapy (MDT) distributed for free across the globe and regarded as highly efficient. However, the impossibility to grow M. leprae in axenic media has historically impaired assessment of M. leprae resistance, a parameter only recently detectable through molecular methods.


A systematic, population-based search for M. leprae resistance in suspected leprosy relapse cases and contacts was performed in Prata Village, an isolated, hyper-endemic former leprosy colony located in Pará state, the Brazilian Amazon. Results led to an extended active search involving the entire Prata population. Confirmed leprosy cases were investigated for bacterial resistance using a combination of in vivo testing and direct sequencing of resistance genes folP1, rpoB and gyrA. Molecular epidemiology analysis was performed using data from 17 variable number tandem repeats (VNTR).


M. leprae was obtained from biopsies of 37 leprosy cases (18 relapses and 19 new); 16 (43.24%) displayed drug-resistance variants. Multi-drug resistance to rifampicin and dapsone was observed in 8 relapses and 4 new cases. Single resistance to rifampicin was detected in one new case. Resistance to dapsone was present in two relapses and one new case. Combined molecular resistance and VNTR data revealed evidence of intra-familial primary transmission of resistant M. leprae.


A comprehensive, population-based systematic approach to investigate M. leprae resistance in a unique population revealed an alarming scenario of emergence and transmission of resistant strains. These findings may be used for the development of new strategies for surveillance of drug resistance in other populations.


LML is always prepared to publish abstracts of articles of interest. It had been proposed to set up a small working group for this purpose, but there was not sufficient interest and willingness to participate in such an exercise.

For copies of articles which can not be found on the internet contact Jiske Erlings, INFOLEP, Amsterdam, the Netherlands: Infolep@leprastichting.nl


Best wishes,


Pieter AM 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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Friday, July 26, 2019

FW: (LML) Drug costs and impact of post-MDT chemoprophylaxis for LL patients


Leprosy Mailing List – July 26,  2019

Ref.:    (LML)  Drug costs and impact of post-MDT chemoprophylaxis for LL patients

From:  Robert Gelber, San Francisco, USA

Dear Pieter,

First I want to express my gratitude to Joel Almeida for his scholarship, vision and tenacity in advocating for antimicrobial therapy after the completion of MB MDT.   I never was convinced that finite therapy for MB leprosy could with conscience be recommended on the time-honored principal that therapeutic recommendations must first require convincing clinical trials of efficacy.   In fact, the MB MDT regimen was recommended without any prior clinical trial.   Currently there are several convincing studies and others of which I am aware but as yet unpublished demonstrating that after MB MDT clinical and bacteriologic leprosy recurred in a substantial number of patients, most commonly many years after treatment and in those with a high BI.


In the dapsone monotherapy era it was observed that MB patients often relapsed if dapsone was discontinued (1).   Rather than WHO MDT between 1979 and 1995 I treated in San Francisco 125 previously untreated BL/LL patients with dapsone 100mg daily and rifampin 600mg daily for a minimum of 2 years followed by dapsone alone 100 mg daily indefinitely.   In that cohort followed-up at least annually both clinically and bacteriologically an average of 9.7 years and an average of 4.1 years after smear negativity, none developed new skin lesions or became smear positive (2).   Though a longer follow-up period would be optimal, such data is encouraging that prolonged chemoprophylaxis is effective in preventing relapse/reinfection.


In San Francisco at that time we regularly checked for dapsone sensitivity in the mouse model and found that in 101 patients all were prior to therapy dapsone sensitive (3).   Also, in the 23 MB Cebu, Philippines patients who relapsed after 2 year MDT all were sensitive in mice to rifampin and clofazimine and only one dapsone resistant (4,5).  Since in Cebu drug sensitivity was not assessed prior to MDT the single dapsone resistant relapsed patient might have been been dapsone resistant prior to MDT.   These findings from the dapsone mono- therapy era, San Francisco and Cebu suggest monotherapy dapsone has reason to be effective as chemoprophylaxis after MDT. 


The regimen I had used in San Francisco I had consistently recommended in the literature (1), and in several editions of the Merck Manual, several standard infectious and tropical disease textbooks and in the leprosy chapter in Harrison's Principals and Practice of Internal Medicine from 2001, edition 15 to the most recent one 2018 edition 20.   Whether the chemoprophylactic regimen I recommended or the one of Dr Almeida of monthly moxifoxicin/minocycline/rifampin or yet another one should be evaluated and implemented. 


In Cebu (4,5) it was noteworthy that following 2 year MB MDT new lesions and increasing BI was not confined to polar LL patients (11) but a similar number of BL patients (12).   There recurrent leprosy did not occur in TT, BT or BB patients and in smear negative patients and in all but one patient with an average BI (4 to 6 sites) of 2.7 or more.


It thus appears that low tech skin smears and biopsies can both reliably predict those MB patients treated with MDT who are at risk for recurrence and would benefit from chemoprophylaxis and those where it would not be needed.


MDT promised reliable cure. Implementing chemoprophylaxis for those MB patients who are easily identified to be at risk for leprosy recurrence after MDT might well make that reliable cure a reality.




1. The chemotherapy of leprosy: An interpretive history, Lepr. Rev., 2012, vol.83:221-240

2.  Our experience with another multidrug therapy regimen  for leprosy, Int. J Lepr, 1998, vol. 66:9a-10a. 

3.  Primary dapsone-resistant Hansen's disease in California. Experience with over 100 Mycobacterium leprae isolates, Arch. Dermatol,1990, vol.126:1584-1586.

4.  The relapse rate in MB leprosy patients treated with 2 years of WHO-MDT is not low, Int J.Lepr, 2012, vol.72:493-500.

5.  Long-term relapse risk of multibacillary leprosy after completion of 2 years of Multiple drug therapy (WHO-MDT) in Cebu, Philippines.  Am.J.Trop.Med Hyg.,2009,vol.81: 895-899.

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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Thursday, July 25, 2019

FW: (LML) Leprosy Mailing List




Leprosy Mailing List – July 25,  2019

Ref.:    (LML) Leprosy Mailing List

From:  Pieter AM Schreuder, Maastricht, the Netherlands

Dear colleagues,



The leprosy mailing list (LML) is an e-mail-based list for sharing information among people working in the field of leprosy worldwide (Editorial Leprosy Review 2012). The first part of this letter is to welcome the newcomers to LML of the past year. The second part of this letter is of interest to all LML readers.


LML was started in February 2001 at the Centre for Training and Research in Public Health (Cefpas) in Caltanissetta, Italy; from 2005 – 2013 held at the National Leprosy Referral Centre, Department of Dermatology, at San Martino University Hospital, in Genoa, Italy; and since 2013 run by Pieter AM Schreuder, Maastricht, the Netherlands. Contact: Dr Pieter Schreuder <editorlml@gmail.com>


LML is independent and has no financial ties to any governmental or non-governmental organization or the World Health Organization (WHO). The LML blog  (LML blog link: http://leprosymailinglist.blogspot.it/) is hosted by courtesy of AIFO, Bologna, Italy. The editorial Board consists of Sunil Deepak, Ben Naafs, Salvatore Noto and Pieter Schreuder. All information passes its editorial board before being distributed. However, opinions expressed are those of the contributors and not necessarily shared by the editorial board.


LML accepts all contributions as long as they are relevant to leprosy. For a good understanding: LML contributions are not considered publications as a publication in a recognised scientific journal. They can (and are) however be cited because represent professional opinions.


A good example of the impartiality of LML was the discussion about 'elimination.'

Although the feelings about 'elimination' on both sides of the battle ground run high, and this issue absorbed many people in the field, there did and does not exists a stated LML opinion. However, LML editors can on personal title contribute to the discussion as long as it is clear that they do not claim to express an "official" LML opinion.


LML is an open forum which brings you in contact with almost 600 persons engaged in leprosy related work (from scientists to leprosy field workers, government officials to non-governmental organisations) in more than 50 countries. We like to hear the voices of all LML subscribers. Although not many people contribute actively to the discussions, many LML readers appreciate our efforts to show different opinions as was the case with the "elimination" discussion.


Over the past few years, we have seen a kind of turn-around in leprosy control: from attention to prevalence (elimination as a public health problem) to incidence (reducing transmission), from only passive case-reporting to providing funds for active case-finding activities to promote early detection and prevent nerve damage, renewed attention to detection and treatment of silent neuritis, treatment of reactions and prevention of further disability, upgrading skin smear services, attention to possible drug and multidrug resistance in leprosy, importance of post-MDT chemoprophylaxis in the case of LL patients, promoting respect for human rights etc. LML provided a widely-read platform for important discussions on such topics.


Recently, suggestions have been made to transform LML into an online Community of Practice (CoPs). Community of Practice is a vehicle for capturing knowledge to ensure public health preparedness, managing information more effectively, enabling global health professionals to work collaboratively in a virtual environment, and improving effectiveness in the face of dwindling resources. Online CoPs provide a virtual space for people who share a common interest and are working towards a shared goal.  https://www.globalhealthlearning.org/course/online-communities-practice-cops-global-health  For those interested, examples of such CoPs you will find in: https://knowledge-gateway.org/ 


Those of the editorial board who participated in such online fora were of the opinion that we should not go this direction. The fear is that  even with CoPs only a small percentage of those health professionals and stakeholders will be active participants in those discussions. However, make up your own mind and visit those mentioned websites. CoPs could be of interest for your situation!


Nevertheless, we would like to appeal to our readers to take up the challenge and contribute to ongoing discussions or bring new items. LML makes a difference.



Best wishes,



Editorial Board LML

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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Tuesday, July 23, 2019

(LML) Fundação para o Controle da Hanseníase no Amazonas

Leprosy Mailing List – July 23,  2019

Ref.:   (LML)  Fundação para o Controle da Hanseníase no Amazonas

From:  Maria Leide W Oliveira, Rio de Janeiro, Brazil

Dear Pieter,  

I would like to reinforce the words from Dr Maroja (LML, 20-07-2019) regarding the power abuse, which is quite common from the government Institutional leaderships, nowadays in Brazil.

The Amazon state and also the country received strong support from DAHW through FundHans and it allowed the impact observed in Hansen´s Disease activities in the state, formally the most endemic in the Country. In addition, the reference center-Alfredo da Matta - improvement (for North region, Country and Latin America) was possible due to FUNDHANS administration.  

I am sure that the history will show how devastating it will be and its legacy is already recognized.  To all ex-team, donators, health personnel and also patients reached by the Foundation my acknowledgment and eternal gratitude.  

Kind regards,

Prof. Maria Leide W. Oliveira

Federal University of Rio de Janeiro

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

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com