Leprosy Mailing List Blog: February 2015

Sunday, February 22, 2015

(LML) INFOLEP selection of recent publications on leprosy

Leprosy Mailing List – February 22, 2015

Ref.: (LML) INFOLEP selection of recent publications on leprosy

From: Jiske Erlings, Amsterdam, the Netherlands

Dear LML readers,

Greetings from Infolep!

Below you will find a selection of recent publications on leprosy. Feel free to contact me to receive the full text versions if a link to the full text is not included.

You might have heard that we are working on expanding the Infolep portal with publications on cross-cutting issues in Neglected Tropical Diseases. An overview of this rapidly growing collection can be found here: http://www.leprosy-information.org/category/collection/infontds-cross-cutting-issues

With kind regards,

Jiske Erlings

INFOLEP Information specialist

Follow Infolep on Facebook or Twitter

Infolep Leprosy Information Services

Postbus / P.O. Box 95005

1090 HA Amsterdam

The Netherlands

Tel:	+31 20 5950530
Mob:	-
Email:	J.Erlings@Leprastichting.NL
Web:	www.leprosy-information.org

Publications

Investing to overcome the global impact of neglected tropical diseases : Third WHO report on neglected tropical diseases / WHO, Department of control of neglected tropical diseases. 2015. Download full report

New Journal Articles

Andrade PR, Pinheiro RO, Sales AM, Illarramendi X, de Mattos Barbosa MG, Moraes MO, Jardim MR, da Costa Nery JA, Sampaio EP, Sarno EN. Type 1 reaction in leprosy: a model for a better understanding of tissue immunity under an immunopathological condition. Expert Rev Clin Immunol. 2015 Feb 10:1-17.
Free full text: http://www.leprosy-information.org/resource/t-regulatory-cells-treg-tcd4cd25foxp3-distribution-different-clinical-forms-leprosy-and

Arakkal GK, Damarla SV, Chanda GM. Immune reconstitution inflammatory syndrome unmasking erythema nodosum leprosum: a rare case report. Indian J Dermatol. 2015 Jan-Feb;60(1):106. Free full text: http://www.leprosy-information.org/resource/immune-reconstitution-inflammatory-syndrome-unmasking-erythema-nodosum-leprosum-rare-case

Berkowitz AL, Raibagkar P, Pritt BS, Mateen FJ. Neurologic manifestations of the neglected tropical diseases. J Neurol Sci. 2015 Feb 15;349(1-2):20-32. Abstract: http://www.leprosy-information.org/resource/neurologic-manifestations-neglected-tropical-diseases

Chhabra N, Grover C, Singal A, Bhattacharya SN, Kaur R. Leprosy Scenario at a Tertiary Level Hospital in Delhi: A 5-year Retrospective Study. Indian J Dermatol. 2015 Jan-Feb;60(1):55-9. Free full text: http://www.leprosy-information.org/resource/leprosy-scenario-tertiary-level-hospital-delhi-5-year-retrospective-study

Das J, Katyal A, Naunwaar D. Dapsone-induced Methemoglobinemia in a Patient of Leprosy. Indian J Dermatol. 2015 Jan-Feb;60(1):108. Free full text: http://www.leprosy-information.org/resource/dapsone-induced-methemoglobinemia-patient-leprosy

de Souza-Santana F, Marcos E, Nogueira M, Ura S, Tomimori J. Human leukocyte antigen class I and class II alleles are associated with susceptibility and resistance in borderline leprosy patients from Southeast Brazil. BMC Infect Dis. 2015 Jan 21;15(1):22. Free full text: http://www.leprosy-information.org/resource/human-leukocyte-antigen-class-i-and-class-ii-alleles-are-associated-susceptibility-and

Donoghue HD, Michael Taylor G, Marcsik A, Molnár E, Pálfi G, Pap I, Teschler-Nicola M, Pinhasi R, Erdal YS, Velemínsky P, Likovsky J, Belcastro MG, Mariotti V, Riga A, Rubini M, Zaio P, Besra GS, Lee OY, Wu HH, Minnikin DE, Bull ID, O'Grady J, Spigelman M. A migration-driven model for the historical spread of leprosy in medieval Eastern and Central Europe. Infect Genet Evol. 2015 Feb 10. pii: S1567-1348(15)00044-1.

Grauwin MY, Wavreille G, Fontaine C. Double tendon transfer for correction of drop-foot. Orthop Traumatol Surg Res. 2015 Feb;101(1):115-8. Abstract: http://www.leprosy-information.org/resource/double-tendon-transfer-correction-drop-foot

Jardim MR, Vital R, Hacker MA, Nascimento M, Balassiano SL, Sarno EN, Illarramendi X. Leprosy neuropathy evaluated by NCS is independent of the patient's infectious state. Clin Neurol Neurosurg. 2015 Jan 12;131C:5-10. Abstract: http://www.leprosy-information.org/resource/leprosy-neuropathy-evaluated-ncs-independent-patients-infectious-state

Kline L, Powers R, Defazio J. What is your diagnosis? lepromatous leprosy. Cutis. 2015 Jan;95(1):19;25;26. Free full text: http://www.leprosy-information.org/resource/what-your-diagnosis-lepromatous-leprosy

Kumaran SM, Bhat IP, Madhukara J, Rout P, Elizabeth J. Comparison of bacillary index on slit skin smear with bacillary index of granuloma in leprosy and its relevance to present therapeutic regimens. Indian J Dermatol. 2015 Jan-Feb;60(1):51-4. Free full text: http://www.leprosy-information.org/resource/comparison-bacillary-index-slit-skin-smear-bacillary-index-granuloma-leprosy-and-its

Lana-Peixoto MA, Campos WR, Reis PA, Campos CM, Rodrigues CA. Tonic pupil in leprosy. Arq Bras Oftalmol. 2014 Dec;77(6):395-6. Free full text: http://www.leprosy-information.org/resource/tonic-pupil-leprosy

Lanza FM, Vieira NF, Oliveira MM, Lana FC. Evaluation of the Primary Care in leprosy control: proposal of an instrument for users. Rev Esc Enferm USP. 2014 Dec;48(6):1054-61. Full text http://www.leprosy-information.org/resource/evaluation-primary-care-leprosy-control-proposal-instrument-users

Liegeon AL, Reigneau M, Rivail J, Bauvin O, Cuny JF, Schmutz JL. [Linear tuberculoid leprosy along the lines of Blaschko: A very rare presentation.]. Ann Dermatol Venereol. 2015 Feb 11. pii: S0151-9638(15)00009-5. Abstract: http://www.leprosy-information.org/resource/linear-tuberculoid-leprosy-along-lines-blaschko-very-rare-presentation

Liu H, Irwanto A, Fu X, Yu G, Yu Y, Sun Y, Wang C, Wang Z, Okada Y, Low H, Li Y, Liany H, Chen M, Bao F, Li J, You J, Zhang Q, Liu J, Chu T, Andiappan AK, Wang N, Niu G, Liu D, Yu X, Zhang L, Tian H, Zhou G, Rotzschke O, Chen S, Zhang X, Liu J, Zhang F. Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy. Nat Genet. 2015 Feb 2. Abstract: http://www.leprosy-information.org/resource/discovery-six-new-susceptibility-loci-and-analysis-pleiotropic-effects-leprosy

Malhotra K, Kulshreshtha D, Shukla S, Husain N. ENL Developing Ten Years After Leprosy Treatment Masquerading as Atypical-Mycobacterial infection. QJM. 2015 Feb 5. pii: hcv042. Free full text: http://www.leprosy-information.org/resource/enl-developing-ten-years-after-leprosy-treatment-masquerading-atypical-mycobacterial

Nisha J, Shanthi V. Computational Simulation Techniques to Understand Rifampicin Resistance Mutation (S425L) of rpoB in M. Leprae. J Cell Biochem. 2015 Feb 10. Abstract: http://www.leprosy-information.org/resource/computational-simulation-techniques-understand-rifampicin-resistance-mutation-s425l-rpob-m

Palácios VR, Gonçalves NV, Bichara CN, Fontelles MJ, Andriolo RB, Silva Junior JB, Póvoa MM. Leprosy and pregnancy: detection coefficient and proposal for a new index. Rev Soc Bras Med Trop. 2014 Dec;47(6):798-800. Free full text: http://www.leprosy-information.org/resource/leprosy-and-pregnancy-detection-coefficient-and-proposal-new-index

Parente JN, Talhari C, Schettini AP, Massone C. T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states. An Bras Dermatol. 2015 Jan-Feb;90(1):41-7. Free full text: http://www.leprosy-information.org/resource/t-regulatory-cells-tregtcd4cd25foxp3-distribution-different-clinical-forms-leprosy-and

Pires CA, Miranda MF, Bittencourt Mde J, Brito AC, Xavier MB. Comparison between histopathologic features of leprosy in reaction lesions in HIV coinfected and non-coinfected patients. An Bras Dermatol. 2015 Jan-Feb;90(1):27-34. Free full text: http://www.leprosy-information.org/resource/comparison-between-histopathologic-features-leprosy-reaction-lesions-hiv-coinfected-and-non

Rêgo JL, Oliveira JM, de Lima Santana N, Machado PR, Castellucci LC. The role of ERBB2 gene polymorphisms in leprosy susceptibility. Braz J Infect Dis. 2015 Jan 27. pii: S1413-8670(15)00030-6. Free full text: http://www.leprosy-information.org/resource/role-erbb2-gene-polymorphisms-leprosy-susceptibility

Shaikh I, Soomro F, Bhatti NS, Bhutto AM. Leprosy in Sukkur region: A series of 143 cases from 2001-2011 at leprosy centre Sukkur, Sindh. Journal of Pakistan Association of Dermatologists. 2014;24(4) 298-301. Free full text: http://www.jpad.org.pk/Oct%20Dec%202014/4.%20Original%20article%20Leprosy%20in%20Sukkur%20region.pdf

Silva GA, Ramasawmy R, Boechat AL, Morais AC, Carvalho BK, Sousa KB, Souza VC, Cunha MG, Barletta-Naveca RH, Santos MP, Naveca FG. Association of TNF -1031 C/C as a potential protection marker for leprosy development in Amazonas state patients, Brazil. Hum Immunol. 2015 Jan 27. pii: S0198-8859(15)00012-9.
Abstract: http://www.leprosy-information.org/resource/association-tnf-1031-cc-potential-protection-marker-leprosy-development-amazonas-state

Silva Junior GB, Daher Ede F, Pires Neto Rda J, Pereira ED, Meneses GC, Araújo SM, Barros EJ. Leprosy nephropathy: a review of clinical and histopathological features. Rev Inst Med Trop Sao Paulo. 2015 Feb;57(1):15-20. Free full text: http://www.leprosy-information.org/resource/leprosy-nephropathy-review-clinical-and-histopathological-features

Tang SF, Chen CP, Lin SC, Wu CK, Chen CK, Cheng SP. Reduction of plantar pressures in leprosy patients by using custom made shoes and total contact insoles. Clin Neurol Neurosurg. 2015 Feb;129 Suppl 1:S12-5. Abstract: http://www.leprosy-information.org/resource/reduction-plantar-pressures-leprosy-patients-using-custom-made-shoes-and-total-contact

Vashisht D, Das AL, Vaishampayan SS, Vashisht S, Joshi R. Nerve conduction studies in early tuberculoid leprosy. Indian Dermatol Online J. 2014 Dec;5(Suppl 2):S71-5. Free full text: http://www.leprosy-information.org/resource/nerve-conduction-studies-early-tuberculoid-leprosy

Yang YK. [Life Experiences of Korean Patients with Hansen's Disease in Sorok Island Hospital]. J Korean Acad Nurs. 2014 Dec 31;44(6):639-48. Korean. Abstract: http://www.leprosy-information.org/resource/life-experiences-korean-patients-hansens-disease-sorok-island-hospital

Journals & Newsletters

Clinics in Dermatology, Jan, Feb 2015, Special issue on leprosy: http://www.cidjournal.com/

Disability, CBR & Inclusive Development: http://dcidj.org/

Leprosy Review: http://www.lepra.org.uk/Pages/FAQs/Category/volume-85

Revista de Leprología: http://www.leprosy-information.org/resource/revista-de-leprologia

WHO Goodwill Ambassador’s Newsletter for the elimination of leprosy: http://www.leprosy-information.org/resource/who-goodwill-ambassador-s-newsletter-elimination-leprosy

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, February 21, 2015

(LML) NYTimes Feb. 16. 2015: Research Finds a Reason Leprosy Has Persisted

Leprosy Mailing List – February 21, 2015

Ref.: (LML) NYTimes Feb. 16. 2015: Research Finds a Reason Leprosy Has Persisted

From: Indropo Agusni, Surabaya, Indonesia

Dear Dr. Schreuder,

After reading the article about M.leprae can live in amoeba, I remember about our environmental studies we conducted some years ago in East Java. Our conclusion were:

1) M.leprae can be found inside the protozoa that live in the water of some ponds in leprosy endemic areas, proved by ZN staining and PCR test.

2) By genomic study of M.leprae using TTC repeats, the variation of TTC pattern in M.leprae isolates obtained from environmental samples were similar with those M.leprae isolates obtained from human leprosy patients.

The problem of this laboratory study was the different of replication speed between the protozoa / amoeba and M.leprae. The protozoa will easily replicate and became thousand cells in hours, while M.leprae will duplicate after 2 weeks. It was very difficult to monitor the survived M.leprae inside the protozoa’s in laboratory. That is why we could not continue the study on this matter. We need advice from experts; perhaps other centers could give us some recommendations. My email address is: indropo49@gmail.com

Regards,

Prof. Indropo Agusni MD-DV

Tropical Disease Center, Airlangga University

Surabaya - Indonesia.

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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(LML) How Efficacious is MDT

Leprosy Mailing List – February 21, 2015

Ref.: (LML) How Efficacious is MDT

From: Sunil D.Ghate, Mumbai, India

Dear all,

This mail from Dr Gelber is quite informative (LML February 18, 2015).

I worked at FMR, Mumbai with Dr Shetty who initiated this discussion. We saw quite a few patients of relapse & published those results. In my private practice, I don't differentiate between MB & PB for treatment. All cases of leprosy get 3 drugs. I have started giving daily Rifampicin over past few years to all the patients; I also dose Clofazimine at 100 mg daily and Dapsone is continued at 100 mg. PB patients receive minimum of 1 year of MDT while in MB, I give up to 3 years & beyond depending on patients initial status. I try & do biopsy at the completion of Rx to ascertain that there was no activity.

Many of my colleagues also prescribe MDT for a longer duration. I feel WHO MDT MB is outdated & revision is needed even for field programmes. I don't know whether we treat any other disease with monthly dose, given for 12/24 months.

Regards.

Dr Sunil D Ghate

MD,DNB,DDV,MNAMS

Consultant Dermatologist

Mumbai,India

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, February 20, 2015

(LML) NYTimes Feb. 16. 2015: Research Finds a Reason Leprosy Has Persisted

Leprosy Mailing List – February 20, 2015

Ref.: (LML) NYTimes Feb. 16. 2015: Research Finds a Reason Leprosy Has Persisted

From: Judith Justice, California, USA, and Pieter Schreuder and Ben Naafs, the Netherlands

Dear LML readers,

We receive the following article from Judith Justice, Berkeley, California. After this article the editors LML would like to give their comments.

“The following article ("Research Finds a Reason Leprosy has Persisted") appears in the New York TImes on February 17, 2015. This short article is based on a study published in December 2014 in PLOS Neglect Tropical Diseases.

With best wishes,

Judith Justice

Subject: NYTimes Feb. 16. 2015: Research Finds a Reason Leprosy Has Persisted

http://www.nytimes.com/2015/02/17/health/study-offers-explanation-for-leprosys-persistence.html?smid=nytcore-iphone-share&smprod=nytcore-iphone

Global Health

By DONALD G. McNEIL Jr.

The bacteria that cause leprosy can survive for months inside amoebae that are common in water and soil, and even in human eyes and noses, scientists at Colorado State University have found.

The discovery may help answer a question that has puzzled tropical disease experts for years: Why does the number of new leprosy cases around the world not decrease even though thousands of victims are now on drugs that make them less infectious and eventually will cure them?

There are about 200,000 new infections each year in Brazil, India, Angola, Madagascar, Myanmar, Indonesia, the Philippines and a few other countries.

The study was published in December in PLOS Neglected Tropical Diseases.

Leprosy is caused by Mycobacterium leprae, slow-growing bacteria related to tuberculosis that target nerve cells beneath the skin. They cannot be cultured in the laboratory, and exactly how they infect is unclear.

Because leprosy spreads in families and among people in prolonged contact, researchers have long assumed that it always moves between human hosts.

“But we do get novel cases that don’t seem to be related to others," said William H. Wheat, a microbiologist at Colorado State University and one of the study’s authors.

M. leprae are engulfed by five kinds of common amoebae, including some that can live in mucus and eye fluids and can resist being digested. When the amoebae form cysts to avoid drying out, the study found, the bacteria can survive inside them for months and then still infect laboratory mice.

That, Dr. Wheat said, may explain how the bacteria persist and turn up even where no infected humans are found.

A version of this article appears in print on February 17, 2015, on page D6 of the New York edition with the headline: Research Finds a Reason Leprosy Has Persisted.”

Comments editors LML, February 20, 2015

According to us, the New York Times goes too far, or better the scientist goes too far to sell their research as a solution. Too many of us are tempted to do the same or have already done.

We think and it needs to be discussed: amoebae’s are at present a band-wagon. One after another of the mycobacteria species are found to have a relation with amoebae.

Amoebae host mycobacteria in trophozoites and cysts. Experimental observations indicate that the majority of environmental, opportunistic mycobacteria but also obligate pathogens including Mycobacterium tuberculosis, Mycobacterium leprae and Mycobacterium ulcerans can be inter-amoebal organisms. Amoebae clearly protect opportunistic mycobacterial pathogens during their environmental life but their role for obligate mycobacterial infection remains to be established. (Drancourt M. Looking in amoebae as a source of mycobacteria. Microb. Pathog. 77:119-24. Epub 2014 Jul 10)

Water seemed to be the source for emerging, community-acquired and health care-associated infections with Mycobacterium avium, Mycobacterium abscesses and Mycobacterium fortuitum groups, among others.

Amoebae are organisms where mycobacteria can be found and, accordingly, amoeba co-culture can be used for the isolation of mycobacteria from environmental and clinical specimens. (Drancourt M.) M. leprae has been found to survive in many environments for shorter or longer time.

We like to know your comments on this issue.

Best regards,

Editors 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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(LML) "Completed treatment, not cured"

Leprosy Mailing List –February 20, 2015

Ref.: (LML) “Completed treatment, not cured”

From: Dinkar D. Palande, Poncherry, India

Dear Pieter,

I very much appreciate this brief and succinct comment (LML, February 16, 2015). I particularly stress the excellent approach in the following:

"One cannot claim that a patient is cured after completing his course of MDT. Patients deserve adequate follow-up and care after MDT completion. Not so much for the risk of a relapse but for preventing further nerve and tissue damage. Not acknowledging this is questionable medicine."

Regards

Dinkar D. Palande

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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(LML) Prednisone Blister Packs

Leprosy Mailing List – February 20, 2015

Ref.: (LML) Prednisone Blister Packs

From: Tine Demeulenaere, Brussels, Belgium

Dear Sir,

We are looking for pre-packed prednisone, like prednipack or prednicombi. However, it seems such standardised prednisone blister packs are not produced anymore as far as I know. In the past WHO provided such packets.

Such blister packs are especially helpful in integrated health programmes in areas where fieldworkers have only basic training. We realise of course that 12 weeks of prednisone in many cases is not sufficient to treat a patient in reaction or with neuritis.

Would the readers of LML know where we could buy such standardized prednisone blister packs? Please contact me by email: tine.demeulenaere@damien-foundation.be or stijn.sanders@damiaanactie.be

Thank you and kind regards,

Tine Demeulenaere

Damian Foundation

Belgium

tine.demeulenaere@damien-foundation.be

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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Wednesday, February 18, 2015

(LML) How Efficacious is MDT

Leprosy Mailing List – February 18, 2015

Ref.: (LML) How Efficacious is MDT

From: Robert Gelber, University of California, San Francisco, USA

Dear Pieter,

I have been following with great interest and firm applause the several contributions to these compelling dialogues. I too wish to weigh in here:

The preponderance of evidence suggests that MB relapse is a significant problem resulting in double digit relapse rates in a number of locales, particularly occurring in patients with a high BI, and results from the failure of chemotherapy to reduce the number of viable M leprae in the patients' tissue below a critical level, thereby enabling re-multiplication of M leprae. In fact this is not surprising as many years ago in Malaysia we found following a far more robust and bactericidal treatment than MB MDT, consisting of 5 years of daily rifampin, that M leprae grew in mice in 1 or more tissue samples (skin, peripheral nerves, dartos muscle and skeletal muscle) in 20 of 32 patients, these persisters being most likely the source of relapsed leprosy in MB patients.

Dr. Warren rightly makes the case for carefully following patients after completion of MDT. Unfortunately, the WHO has never recommended follow-up of patients after completion of MDT and conversely view that once therapy is complete the leprosy burden would be eliminated, those patients no longer considered a “case". Surely with the current reduction of leprosy and its resources follow- up after completion of MDT is rare. Importantly, we found in the Philippines that MB relapses were detected 3 times more frequently when conducted by seasoned leprologists rather than by the general health services. Certainly relapse detection cannot be expected to be robust in the integration era and when leprosy skills are on the wane.

Prior to the initiation of MDT for leprosy, painstaking short course chemotherapy trials for pulmonary tuberculosis, which ultimately resulted in the sequential and successful reduction of therapy from 2 years to 6 months, rejected regimens with relapse rates greater than 5%. Yet for leprosy policy makers appear unconcerned with relapse frequencies which are considerably higher. In fact success in leprosy treatment is measured by the number of patients completing MDT, and treatment recommendations have progressively reduced the duration of therapy and operational requirements to promote the elimination goal, while ignoring the considerable problem of MB relapse and in fact the reliable cure and well-being of leprosy patients, that relapse being a source of the spread of infection to others. Surely there are studies that have found MB relapse after MDT to be low but these are flawed owing to the follow- up duration being too short and the studies conducted in locales with but a few MB patients with a high BI.

Definition of MB relapse has varied considerably and included one or more of 3 features- new skin lesions, a rise in BI (generally of 2 + or more) and growth of M leprae from relapse sites in the mouse foot pad. In Cebu, Philippines where I was Scientific Director all 3 requirements were met in 22 patients. I wish to share a few more observations from that best documented relapse series:

1. The earliest relapse occurred 6 years after the completion of MB MDT and 2/3 of relapses 10 or more years thereafter.

2. All relapses occurred in BL (10) or LL (12) patients.

3. All but 1 of the relapses occurred in MB patients with an average BI (6 sites) of greater than or equal to 2.7.

As a consequence of claims of leprosy elimination the very tools to recognize MB relapse have been largely lost - skilled leprologists are rapidly disappearing, while more and more the general health services, largely untrained and inexperienced with leprosy are the primary providers of leprosy care, skin smears and biopsies are no longer required and rarely practiced, and mouse footpad facilities are close to non-existent.

My own experience with treating 125 BL and LL patients in San Francisco for 19 years found that the regimen used, daily dapsone and rifampin for an average of 5 years followed by daily dapsone alone indefinitely resulted in no relapses after an average follow up of 10 years which included annual clinical examination and skin smears. Perhaps for a subset of MB patients, particularly those with a high initial BI lifelong therapy could be the treatment of choice. In fact, if I had such leprosy that is what I would do. Though largely forgotten it should be remembered that the WHO regimens were first designated for Control Programmes and never considered to be the optimal therapy for leprosy. Of course lifetime therapy for a subset of MB patients surely will not promote elimination targets but may reliably cure patients which it is of course our goal. Many medical conditions require lifetime treatment, including diabetes, hypertension, gout, hypercholesterolemia and etc. Once we did this for certain forms of leprosy with great success. Why not again for some?

MB relapse following MDT with its potential to result in neuropathy and deformity as was reported by Dr. Shetty is not the only reason to advocate for alternative regimens. Patient intolerance and side effects to the 3 components of MDT is not uncommon, and yet alternative antimicrobials, when these occur, have not been addressed by policy makers. The current high MB relapse rate is surely a compelling cause to seek improved MDT. I believe a new generation of more bactericidal MDT composed of 2 other agents which have proved more active and bactericidal both in M leprae infected mice and in MB patients and superior to 2 of the 3 individual components of MDT, namely dapsone and clofazimine both of which are bacteriostatic. To replace dapsone and clofazimine candidate agents include the fluoroquinolones, particularly moxifloxicin which has been established in mice and MB patients to be the only agent to date which is similarly bactericidal as is rifampin, minocycline and clarithromicin. This prospect holds promise for the subset of leprosy patients prone to fail MDT as the short course of chemotherapy of tuberculosis was found to require 2 or more bactericidal agents, while current MDT for leprosy has but 1, rifampin.

The most recent WHO amendments to MDT, A-MDT and U-MDT, surely promote the elimination goal. A-MDT permits the distribution of the full complement of medication at the time of diagnosis, making a new patient no longer a considered "case", while U-MDT reduces the duration of leprosy treatment for MB patients from 1 year to 6 months. A-MDT compromises effective treatment by eliminating DOT which contains the most robust MDT component, rifampin, DOT being considered necessary and critical to successful treatment of active pulmonary tuberculosis. Furthermore, the reduction of treatment duration of MB leprosy provided by U-MDT is occurring in the context where 1 year MDT has not yet been shown to result in a reliable and convincing cure rate and adds clofazimine with its troublesome discoloration to the treatment of PB patients where cure rates without it are already exemplary.

In conclusion, those at risk for relapse after completion of MDT are a substantial percentage of the leprosy population, those previously classified as LL and BL. While the WHO advocates follow-up for relapse in patients completing treatment of active pulmonary tuberculosis, 90% of relapses occurring within the first year after completion of MDT, while no active follow up after completion of leprosy MDT has been advocated. Surely for not looking for relapse and in a systematic annual fashion it has been under reported. Also, the fact that MB relapse occurs very late and only in a subset of MB patients, it has not been universally evident. Nonetheless, it should no longer be ignored.

Selective references:

1. Baihong J, Does there exist a subgroup of BM patients at greater risk of relapse after MDT? Leprosy Review, 2001, 72, 3-7.

2. Gelber R H, Balagon VF, Cellona RV, The relapse of MB leprosy patients treated with 2 years WHO-MDT is not low Int, J, Lepr, 2004, 72, 493-500

3. Gelber R H, Grosset, J, The chemotherapy of leprosy: An interpretive history, Leprosy Review, 2012, 83, 221-240.

Robert Gelber

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

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

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Monday, February 16, 2015

(LML) "Completed treatment, not cured"

Leprosy Mailing List – February 16, 2015

Ref.: (LML) “Completed treatment, not cured”

From: B. Naafs, S. Noto, P. Schreuder, the Netherlands and Italy

Dear LML readers,

We agree with most of the writers involved in the recent LML discussion regarding relapses “How Efficacious is MDT “. We agree particularly with the last writer (LML February 6, 2015) who brings an interesting point of view. That stimulated us to write our own opinion.

Leprosy is an immunological disease initiated by M. leprae. Its clinical symptoms and signs are due to the dividing bacilli and the host’s response. The disease may progress after treatment completion for different reasons such as host response, reactions, relapse, sequelae and inadequate short treatment.

Host response, reactions

Leprosy reactions continue even after the bacilli are killed. In this case progression is caused by immunological events, either immune reactions to M. leprae antigens and antigenic determinants or induced autoimmunity. Antigenic determinants can be either on remnant antigens or on host cells. The antigenic determinants stimulate both the innate (a.o. complement system) and the adaptive immune system. Even contact of cells (Schwann cells) with these antigens (LAM - a major cell wall antigen of M.leprae lipoarabinomannan) may induce damage, in particular, neural damage. After multi-drug therapy (MDT) many multibacillary (MB) patients, we estimate more than 30% develop further damage. Particularly after stopping dapsone, patients are prone to Type I reaction and after stopping clofazimine to Type II reaction. Systematic follow-up policies would help in prevention, diagnosis and treatment of these complications.

Relapse

Relapse is due to dividing bacilli. It is well established that after MDT multibacillary leprosy patients still harbour viable bacilli, so called persisters. Under favourable conditions these can multiply again (e.g. Immunosuppression due to HIV, malnutrition, pregnancy, old age, inoculation in susceptible animals). Infectiologists, epidemiologist and public health officials consider 10% relapse rate acceptable for infectious diseases. For leprosy MDT the observed relapse rate is even lower, except most likely for patients with a high bacterial load.

Sequelae

Sequelae of leprosy are permanent and aggravate with time. Worsening is a consequence of increasing or permanent nerve functions loss in the eyes, face, hands and feet.

Inadequate short treatment

The one year MB MDT protocol is too short for forms of leprosy with high bacillary load. Borderline lepromatous or lepromatous patients with bacteriological index of 3+ or higher will benefit of longer protocols. For some PB patients diagnosed on clinical criteria only (no skin smear for example) the treatment may be too short as well and MB treatment would have been more appropriate.

“Completed treatment” versus “cured”

Too many patients deteriorate after the MDT has stopped. One cannot say that leprosy is cured after completing a course of MDT. We assume that the misunderstanding about “being cured” has its origin in the different disciplines involved and the stake the WHO, the subsidizing industries and some NGO’s have in the success of “leprosy elimination”.

Summarizing

It is M. leprae that brings about the disease leprosy. Even after killing of the M. leprae the immunological reaction remains and thus the disease. Damage after completion of MDT may be caused by a relapse or inadequate short treatment, but is usually due to induced autoimmunity or innate or adaptive immune system reaction against remnant antigenic determinants or sequelae of previous nerve damage. Multibacillary leprosy may be bacteriological in remission; the immunological remission is slow and may take years. Most paucibacillary leprosy may be cured, however one is never sure. One cannot claim that a patient is cured after completing his course of MDT. Patients deserve adequate follow-up and care after MDT completion. Not so much for the risk of a relapse but for preventing further nerve and tissue damage. Not acknowledging this is questionable medicine.

Ben Naafs, Salvatore Noto, Pieter 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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Monday, February 9, 2015

(LML) Burial customs of leprosy patients in past and present

Leprosy Mailing List – February 9, 2015

Ref.: (LML) Burial customs of leprosy patients in past and present

From: Jingquan Wang, Wukang,Deqing Zhejiang, China

Dear Pieter,

I would like to add more information for the tip of "burial customs of leprosy patients."

I have been engaged in leprosy control work for 25 years and have travelled many places in China.

There was a special burial custom in Haining City in Zhejiang, China, popular in the early 1920s. The alive leprosy patients were put into a big jar, only the head could raise from the jar head. In several years the patients slowly starved to death due to the poor provision of foods and bad living circumstances. Then the nearby people would dig more earth covering the jar to form a tomb.

In some places of the North China, people would use lime to cover the corpse of leprosy patients. They believed that the leprosy bacteria will be killed by the boiling lime.

I came to a southern province of China for supervising the leprosy control work in 2007 or so. Local residents told me that there was a leprosy patient living in a hut in the nearby mountain, who was burned to death in a dark night. It was suspected that someone intentionally lighted the hut to kill him. This miserable thing happened 20 years ago. I am sure it is very rare at present around China.

I have worked as a leprosy control worker in a eastern province of China from 1989-2002. During that period, I diagnosed a leprosy patient and gave her MDT. Unfortunately, the patient developed DDS syndrome. I treated her with dexamethasone 50 mg in her home. Her children were so scared for her leprosy that, eventually, she starved to death in bed as no one cared for her.

Off course, these are only extreme examples of leprosy patients in the past

I wish these will be helpful to her research.

Best regards,

Jingquan Wang,Bachelor of Medicine
Chief Physician and Deputy Director
Inpatient Department

Institute of Dermatology of Zhejiang Province,
China,313200
No. 61,Wuyuan Street,Wukang,Deqing,313200，Zhejiang,China.

Academic Secretary of China Leprosy Association since 2010
Science Communication Expert of Leprology of China Association for Science and Technology since 2013

Phone:86-572-8296002

Fax:86-572-8078115

E-mail:Jingquanwang.cn@hotmail.com, wjingquan@126.com

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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