Bacilliferous household contacts adversely influence leprosy reactions

Leprosy Mailing List – March 17th, 2011

Ref: Bacilliferous household contacts adversely influence leprosy reactions.

From: Barreto J A, Bauru, SP, Brazil

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Dear Dr Salvatore,

Thank you very much to Dr Ganapati for his comments (LML, March 13^th 2011).  He refers to my observation that patients with “intractable” recurrent erythema nodosum leprosum (ENL) reaction improve after treating their household contacts for lepromatous leprosy.  What could be the basis of this phenomenon?  He states that there should be a strong scientific reason to conclude that the bacilliferous household contacts will influence the reaction adversely and that the treatment of the contacts will help in any way.  Dr Ganapati asked if some light could be thrown on this hypothesis?

Herewith I am sending some references to support my opinion:
- Martins AC, Miranda A, Oliveira ML, Bührer-Sékula S, Martinez A. Nasal mucosa study of leprosy contacts with positive serology for the phenolic glycolipid 1antigen.Braz J Otorhinolaryngol. 2010;76(5):579-87.
- Job CK, Jayakumar J, Kearney M, Gillis TP. Transmission of leprosy: a study of skin and nasal secretions of household contacts of leprosy patients using PCR. Am J Trop Med Hyg. 2008;78(3):518-21.
- Hatta M, van Beers SM, Madjid B, Djumadi A, de Wit MY, Klatser PR. Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia. Trans R Soc Trop Med Hyg. 1995;89(4):381-5.

These papers shine some lights on the likely causes of association between re-exposition and reactions. In the paper of Martins et al., there are many reports (from several authors) which suggest that the reaction (presentation of antigen leading to Th2 DTH and production of IgM antibodies) can start in nasal mucosa, even in not sick individuals.  This same paper shows that there was strong correlation between DNA of M. leprae in nasal mucosa and the levels of anti PGL-1 antibodies in serum.

In the others 2 papers it is suggested that nasal mucosa is the likely main important route of entry of bacilli.  We all know that type 1 or type 2 reactions begin after presentation of antigen, and that the outcome depends on the balance between genetic determined immunity of host and the bacilli load. Similarly to all other diseases caused by intracellular microorganisms.  After initial Th0 reaction, high amounts of antigens cause a shift towards Th2 reaction, while low levels lead to Th1.  This could explain several cases of BL patients developing ENL even before treatment or just after the start of anti-leprosy treatment.

Some (after 1year of treatment or later) present type 1 reaction, probably by the natural decreasing of antigens and consequent recovering of immune-cellular response, mimicking the IRIS phenomenon observed in AIDS.  By analogy with several other diseases, in which hypersensitivity (humoral or cellular) is observed after re-exposure to the same antigen, like rheumatic fever, acute glomerulonephritis, cutaneous tuberculosis, or even in other immunological diseases, like Wegener granulomatosis, Behçet's disease, Erythema Nodosum not related to leprosy, Sweet's syndrome (this latter shows histopathological features almost identical to ENL).  Where antigens of bacteria are implicated on the appearance of manifestations, it is nice to suggest that the same could occur with leprosy, isn't it?

Whether the triggering factors for reactions could be due to dormant bacilli multiplication, re-infection or re-exposure to M. leprae in a previous sensitized patient must be proved, but I think that none of these assumptions can be ruled out.  What I have commonly seen is:

1.cases of treated asymptomatic lepromatous leprosy patients developing ENL just after travelling to hyperendemic areas and;

2. improvement of patients with intractable reactions after diagnosis and treatment of their multibacillary (MB) household contacts.

Best regards,

Jaison A. Barreto
Instituto Lauro de Souza Lima
Bauru SP - Brazil

Can the BI of a BL or LL patient clear in a few months?

Leprosy Mailing List – March 15^th, 2011

Ref.:   Can the BI of a BL or LL patient clear in a few months?

From: Dr. Grace Warren, Australia

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Dear Salvatore,

These are my comments about Dr Salafia’s request of information about the use of cyclosporine in erythema nodosum leprosum (ENL) reaction not responding to treatment.

One young teenager had chronic ENL we could not control till we discovered that a year before he has been diagnosed with typhoid fever and only given ten days antibiotics.  On checking his blood, levels for typhoid factor were very high.  We gave him a 6 weeks course of  the current anti-typhoid drug (I think it was Chloramphenicol). After that his blood picture cleared completely and he never had another ENL spot.

Also his skin smear bacteriological index (BI) cleared within a few months.  He had been  under treatment for BL/LL leprosy for several years and his BI would not fall as expected. We have found often that a chronic disease like TB or parasites (eg amoebae) interfere with the bodies ability to eliminate the leprosy bacilli.  The body goes for the “ BUGS”  or problems that are most life threatening.  In his case it was the Typhoid that could have killed him and once we cleared the Typhoid the body got rid of the leprosy!

Just realized that perhaps we ought to add that in patients with chronic ENL who are given steroids to control the ENL often do not show any fall in BI on steroids, even though they are on full MDT.  Then once the steroids stop the BI rapidly falls.  I have seen the same in those with chronic ENL in whom the worst of the reaction is controlled  by other means but without steroids.  The BI stays stable but there are no solid bacilli (negative morphological index [MI]).  The ENL continues to simmer on until the intercurrent disease is controlled and then bang the BI falls.

Please note that if the patient is on steroids  we really need to continue the MDT for an extended period.  We found back in the 1960/70s that if a patient was on double or triple (pre-MDT) anti-leprosy medication but on steroids the skin smear did not really fall till the steroids ceased.  I would recommend where WHO recommends only 12 months MDT, that MDT should be continued for at least as many extra months as the patient has received steroids.  I am seeing many patients who "relapse'  after being given steroids during the standard MDT course.

I thought these comments may help Dr Salafia and his patient.  We must not forget we need to treat the whole patient to enable him to adequately fight this infection, without causing more medical problems.

Grace Warren

Previously adviser in Leprosy and reconstructive surgery for The Leprosy Mission in Asia ( 1975-1995)

Laboratory diagnostic tools for leprosy

Leprosy Mailing List –  March 15th, 2011

Ref:    Laboratory diagnostic tools for leprosy. 

From: Das P K, Amsterdam, The Netherlands

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Dear Leon Gilead,

Thank you for your message dated LML March 8^th, 2011.

Lepromin reagents are still produced by Dr. Esther at the Institute Lauro Souza Lima, inBauru , Brazil .  Among the laboratory tests still the IgM titre to PGL-1 (high bacilli laden forms of leprosy only) is the golden standard. 

In addition, IgG and IgM to gel purified 29/33 KDa doublet and IgG and IgM titre to gel purified 65KDa antigen will diagnose LL /BL and TT/BT cases respectively (kindly, see the publication J. Clin Microbiol by Das PK et al 1990). 

One can, therefore also perform ELISA using gel purified 29Kd/33Kd doublet and 64-65 KD singlet antigens, in parallel to lepromin test and IgM -PGL-1 by ELISA.  These antigens are prepared easily by first electrophoresing the BCG homoheganates in reducing SDS gel;followed by cutting out the bands of 29/33KD doublet and /^4-65 KD singlet and then eluted with distilled water.  By combining the ELISA measurement of IG/IGM titre with 29/33KD doublet and 64-65KD singlet with the western blotting pattern showing 29/33KD doublet bands and strong band of 64-65 singlet band will confirm lepromatous side (LL/BL) and diagnose BT/TT of the spectrum respectively.  In this latter test, true BB cannot be diagnosed.

Further, serum cytokine and chemokine profiling is advisable for monitoring the patients (see the publications by de Silva E et al, Lyer et al etc.).  Recently IDEAL group strongly advise cell based assay like that of quantiferon for TB also for leprosy using post genomic antigens.

A combination of serum anti-PGL-1 Ab test positive plus lepromin skin test negative will be consistent with diagnosis of leprosy on the lepromatous side of the spectrum.  While a combination of serum anti-PGL-1 Ab test negative plus lepromin skin test positive will be consistent with diagnosis of leprosy at the tuberculoid side of the spectrum.  So far this is the best laboratory diagnostic tool that we have got.  It matches with the clinical diagnosis and is robust enough to diagnose >90% of the patients.

Hope that this information is useful.

Pranab

Table. Laboratory diagnostic tools in leprosy: anti-PGL-1 Ab and lepromin tests
serum anti-PGL-1 Ab test positive	+	lepromin skin test negative	consistent with diagnosis of	leprosy at the lepromatous side of the spectrum
serum anti-PGL-1 Ab test negative	+	lepromin skin test positive	consistent with diagnosis of	leprosy at the tuberculoid side of the spectrum

Management of “Intractable” recurrent erythema nodosum leprosum (ENL) reaction

Leprosy Mailing List –  March 13^th, 2011

Ref: Management of “Intractable” recurrent erythema nodosum leprosum (ENL) reaction.
From:  Ganapati R., Bombay , India  

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Dear Dr Noto

I refer to Dr Jaison A. Barreto’s observation (LML February 26th, 2011) that after treating the household contacts for lepromatous leprosy the index case responded to “intractable recurrent“ ENL.  I cannot understand the basis of this assumption.  It is well established that in leprosy, the host parasite relationship in relation to immunity decides the out came of the disease.  The occurrence of events like reactions in a mild, moderate or “intractable” form is also related to immune mechanisms of the host as well as the adverse effect of antigens derived from M. leprae.

There should be a strong scientific reason to conclude that the bacilliferous household contacts will influence the reaction adversely and the treatment of the contacts will help in any way. 

Can any of the readers throw some light on this hypothesis?

With regards,

R Ganapati

Director Emeritus

Bombay Leprosy Project Vidnyan Bhavan, 11, V.N.Purav Marg

Sion-Chunabharri

Bombay - 400 022 India

Leprosy without visible skin lesions

Leprosy Mailing List –  March 13^th, 2011

Ref:     Leprosy without visible skin lesions   

From:  Ganapati R., Bombay, India 

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Dear Dr Noto,

I refer to the recent LMLs dealing with the occurrence of areas of anaesthesia caused by leprosy without visible skin lesions.  I would like to bring the following references to the knowledge of the readers: -

1)
 “A study of Mono-Neuritic Lesions  in A Leprosy Clinic”, Dongre V.V., Ganapati R., Chulawala R.G. (1976), Leprosy in India, 48 ; 132-137.  An analysis of 11,581 leprosy patients registered at the Acworth Leprosy Hospital clinic showed that 494 cases (4.3%) had primary polyneuritic leprosy and 143 (1.2%) localised cutaneous anaesthetic lesions (or non-visible anaesthetic lesions), accounting for 5.5% who had  no evidence of obvious skin lesions.

2)
 “Epidemiology of (Poly) Neuritic type of leprosy”, Noordeen SK (1972), Leprosy in India, 44: 90-96.  Noordeen prefers the term “neuritic” leprosy to denote involvement of peripheral nerve trunks as well as cutaneous nerves, if skin lesions are not clinically obvious.  His observations on the epidemiology of this type of leprosy reveal that this condition is much more common that what is generally believed and may contribute up to one-sixth (13.6%) of all cases.  Majority of the neuritic cases were found to occur over the age of 40, the 50 to 60 age group accounting for 41.9%.

Indeed it has been rightly observed by Jopling (1971)* that a prolonged polyneuritic phase may precede the appearance of skin lesions in borderlines leprosy.

*Jopling, W.H. 01(1971). In “Handbook of Leprosy”, William Hinemann Medical Books Ltd.,London , pp. 30-31.

With Regards,

Dr R Ganapati,

Director Emeritus, Bombay Leprosy Project

VN Purav Marg,

Sion-Chunabhatti, 400 022

Bombay , India  

Clinical indications for PCR and serum anti phenolic glycolipid (PGL) -1 Ab test?

Leprosy Mailing List –  March 13^th, 2011

Ref:   Clinical indications for PCR and serum anti phenolic glycolipid (PGL) -1 Ab test?

From:  Burdick A E., Miami , Florida , USA

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Dear Dr. Ishii,

Thank you very much for your message about laboratory tests in leprosy in Japan dated LML March 12^th 2011.  I am interested to learn the clinical situations when you use PCR and the serum anti-PGL-1 Ab test?  At the Miami Hansen's Disease Program, we use slit-smear examination and rarely PCR; never lepromin.

I am presenting the lecture "Leprosy in 2011" at the American Academy of Dermatology Summer 2011 meeting and I would like to include information on the use of antibody testing in special clinical cases.

Regards,

Anne E. Burdick, MD, MPH
Medical Director, University of Miami/Jackson Memorial Hospital Hansen's Disease Program
Professor of Dermatology
Associate Dean for TeleHealth and Clinical Outreach
University of Miami Miller School of Medicine
1150 NW 14th Street , Room 206 (R-350)
Miami , Florida 33136 , USA

A case of ENL complicated by a severe form of chicken pox

Leprosy Mailing List –  March 12^th, 2011

Ref:     A case of ENL complicated by a severe form of chicken pox.

From:  Salafia A, Mumbai , India

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Dear Salvatore,

I am really very grateful to all for the many (and prompt) suggestions. These are my update on my patient and a few further comments.

1.
Prof. Frankel: the patient is on a monthly dose of rifampicin.  The steroids given by us, where as 2mg/Kg/daily....

2.

Prof. Fine: yes, small pox was just a suspicion.  I repeat that about two months ago there was a news in the paper that in a remote village - somewhere in India - they had found a case of small pox; this is shocking because according to the Government of India small pox has been eradicated.

3.
The child, is still at Kasturba Hospital which is a Government hospital specialized in infectious diseases.

4.
The Doctor in charge confirmed, a few days ago, that it is a case of ENL but, complicated by a severe form of chicken pox; the child had developed signs of encephalitis (mentioned by Ben Naafs in his case).  She is now recovering.  The ENL reaction is under control too.

5.

They have administered to her some new antiviral drugs (very costly) but when she was admitted she was given lyophilised vaccine containing attenuated oka strain of varicella-zoster virus.  She is still in the hospital but she is recovering well.  

When she will come back to us, for continuing the management of ENL, I will have more news.

Thanks to you and to all.

Best wishes,

Antonio

IDEA newsletter Vol. 14, No. 1, 2010

Leprosy Mailing List –  March 12^th, 2011

Ref:     IDEA newsletter Vol. 14, No. 1, 2010

From:  Erlings J, Amsterdam, The Netherlands

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Dear Dr Noto;

In attachement is the above mentioned newsletter (PDF).

With kind regards,

Jiske Erlings

Information Officer

Infolep Leprosy Information Services

Postbus / P.O. Box 95005

1090 HA Amsterdam

The Netherlands

Tel: +31 20 5950530

Fax: +31 20 6680823

E-mail: J.Erlings(at)Leprastichting.NL

Web: www.leprosy-information.org

Infoleps Choice of new (e) publications on leprosy (7 March 2011)

Leprosy Mailing List –  March 12^th, 2011

Ref:     Infoleps Choice of new (e) publications on leprosy 2011 03 07

From:  Erlings J, Amsterdam, The Netherlands

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Dear Dr Noto;

Greetings from Infolep!  Below you will find a selection of new publications on leprosy.  Please contact me for full text versions.  Do you have publications on leprosy to share? Please let me know! 

With kind regards,

Jiske Erlings

Information Officer

Infolep Leprosy Information Services

Postbus / P.O. Box 95005

1090 HA Amsterdam

The Netherlands

Tel: +31 20 5950530

Fax: +31 20 6680823

E-mail: J.Erlings@Leprastichting.NL

Web: www.leprosy-information.org

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Articles

1: Atas M, Citirik M, Sönmez K. [Visual outcome of cataract surgery in leprosy patients.] Turkiye Klinikleri J Ophthalmol . 2011;20(1):26-30. (Turkish)

2: Borg J, Lindström A, Larsson S.
Assistive technology in developing countries: a review from the perspective of the Convention on the Rights of Persons with Disabilities. Prosthet Orthot Int. 2011;35(1):20-9 p.

Free full text online: http://www.leprosy-information.org/resource/assistive-technology-developing-countries-review-perspective-convention-rights-persons-disa

3: Contreras-Steyls M, López-Navarro N, Herrera-Acosta E, Castillo R, Ruiz del Portal G, Bosch RJ, et al.
The current challenge of imported leprosy in Spain : a study of 7 cases. Actas dermo-sifiliograficas. 2011.
Free full text online: http://www.leprosy-information.org/resource/current-challenge-imported-leprosy-spain-study-7-cases

4: Costa RD , Mendonça VA , Penido RA, Lyon S, Costa AM, Costa MD, et al.
Study of the profile of the neurotrophin BDNF in new leprosy cases before, during and after multidrug therapy. Arq Neuropsiquiatr. 2011;69(1):100-4.

Free full text online: http://www.leprosy-information.org/resource/study-profile-neurotrophin-bdnf-new-leprosy-cases-during-and-after-multidrug-therapy

5: Crawford CL, Hardwicke
PM. Experimental leprosy: a model of epithelioid cell granuloma. Int J Dermatol. 2011;50(3):255-61.

6: Mastrangelo G, da Silva Neto J, da Silva GV, Scoizzato L, Fadda E, Dallapicola M, et al.
Leprosy reactions: the effect of gender and household contacts. Mem Inst Oswaldo Cruz. 2011;106(1):92-6.
Free full text online: http://www.leprosy-information.org/resource/leprosy-reactions-effect-gender-and-household-contacts

7: Melão S, Blanco LF, Mounzer N, Veronezi CC, de Simões PW.[Epidemiological profile of leprosy patients in the extreme south of Santa Catarina between 2001 and 2007]. Revista da Sociedade Brasileira de Medicina Tropical. 2011;44(1):79-84. (Portuguese)

8: NSAGHA D, BISSEK A, NSAGHA S, NJUNDA A, ASSOB J, TABAH E, et al.Social stigma as an epidemiological determinant for leprosy elimination in Cameroon . Journal of Public Health in Africa . 2011.

Free full text online: http://www.leprosy-information.org/resource/social-stigma-epidemiological-determinant-leprosy-elimination-cameroon

9: Pinheiro RO, de Souza Salles J, Sarno EN, Sampaio EP.Mycobacterium leprae-host-cell interactions and genetic determinants in leprosy: an overview. Future Microbiol. 2011;6:217-30.

10: Ponte CM, Gurgel MH, Ponte GA, Ramos AV, Montenegro Júnior RM.
[Metabolic disorders in emerging and neglected infectious diseases.]. Arquivos brasileiros de endocrinologia e metabologia. 2010;54(9):785-92. (Portuguese)

Free full text online: http://www.leprosy-information.org/resource/metabolic-disorders-emerging-and-neglected-infectious-diseases

11: Shannon EJ, Sandoval FG, Morales MJ.In vitro thalidomide does not interfere with the activation of complement by M. leprae. J Drugs Dermatol. 2011;10(3):274-8.

12: Teixeira Junior GJ, Silva CE, Magalhães V.[Application of the diagnostic criteria for systemic lupus erythematosus to patients with multibacillary leprosy.]. Revista da Sociedade Brasileira de Medicina Tropical. 2011;44(1):85-90. (Portuguese).

Free full text online: http://www.leprosy-information.org/resource/application-diagnostic-criteria-systemic-lupus-erythematosus-patients-multibacillary-lepros

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Newsletters, Journals

IDEA Newsletter: issue 1.
Stigma Research & Action:  1^st issue! http://stigmaj.org/

WHO newsletter on Disability and Rehabilitation: issue 12.http://www.who.int/disabilities/publications/newsletter/dar_newsletter_issue12.pdf 

Laboratory tests in leprosy in Japan

Leprosy Mailing List –  March 12^th, 2011

Ref:    Laboratory tests in leprosy in Japan

From: Ishii N, Tokyo, Japan

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Dear Dr Noto;

I refer to Dr Gilead’s message dated LML March 8^th, 2011.  In Japan , we do not use Lepromin reagent.  We do not produce it.  We use slit-skin smear examination, polymerase chain reaction (PCR), and sometimes serum anti-PGL-1 Ab test.

We have only few new leprosy patients (2009: 2 foreigners,  2010: 4 foreigners).  Laboratory test is covered at Leprosy Research Center NIID, Tokyo .

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

Infolep choice of new (e-)publications on leprosy (21 Feb 2011)

Leprosy Mailing List –  March 8^th, 2011

Ref.:   Infolep choice of new (e-)publications on leprosy 2011 02 21

From: Erlings J., Amsterdam , Netherlands

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Dear Dr Noto,

Greetings from Infolep!  Below you will find a selection of new publications on leprosy.  Please contact me for full text versions.  Do you have publications on leprosy to share? Please let me know! 

With kind regards,

Jiske Erlings

INFOLEP

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Articles

1: Antunes SL, Medeiros MF, Corte-Real S, Jardim MR, da Nery JC, Hacker MA, et al.Microfasciculation: a morphological pattern in leprosy nerve damage. Histopathology. 2011;58(2):304-11.

2: Awofeso N.
Leprosy control, public health paradigms and stigma. Aust N Z J Public Health. 2011;35(1):9-11.

Free full text online: http://onlinelibrary.wiley.com/doi/10.1111/j.1753-6405.2010.00662.x/pdf

3: Falus O.
[Leprosy - a stigmata in the 21st century.]. Orvosi hetilap. 2011;152(7):246-51. (Hungarian).

4: Iwata M.
[Clinical Aspects of Leprous Neuropathy.]. Brain and nerve = Shinkei kenkyu no shinpo. 2011;63(2):157-64. (Japanese).

5: Kai M, Nguyen Phuc NH, Nguyen HA, Pham TH, Nguyen KH, Miyamoto Y, et al.
Analysis of drug-resistant strains of mycobacterium leprae in an endemic area of Vietnam. Clin Infect Dis. 2011;52(5):e127-32.
Free full text online: http://cid.oxfordjournals.org/content/52/5/e127.full.pdf+html

6: Luna IT, Beserra EP, Alves MD, da Pinheiro PN.
[Adhesion to Leprosy treatment: inherent difficulties of the patients.]. Revista brasileira de enfermagem. 2010;63(6):983-90. (Portuguese).

Free full text online: http://www.scielo.br/pdf/reben/v63n6/18.pdf

7: Mastrangelo G, da Neto JS, da Silva GV, Scoizzato L, Fadda E, Dallapicol M.
Leprosy reactions: the effect of gender and household contacts. Mem Inst Oswaldo Cruz. 2011;106(1):92-96.

Free full text online: http://memorias.ioc.fiocruz.br/106(1)/106_1_2272.pdf

8: Matsuo C, Talhari C, Nogueira L, Rabelo RF, Santos MN, Talhari S.
[Borderline lepromatous leprosy.]. Anais brasileiros de dermatologia. 2010;85(6):921-2. (Portuguese)

Free full text online: http://www.scielo.br/pdf/abd/v85n6/en_v85n6a26.pdf

9: Ofosu AA, Bonsu G.
Case control study to determine the factors associated with leprosy in the sene district, brong ahafo region of ghana . Ghana Med J. 2010;44(3):93-7.

Free full text online:http://www.ghanamedj.org/articles/September2010/Final%20Leprosy%20case%20control%20study.pdf

10: Proto RS, Machado Filho CD, Rehder JR, Paixão MP, Angelucci RI.[Quality of life in leprosy: a comparative analysis between patients in the Amazon region and patients in Santo André in the ABC region of São Paulo , Brazil. ].Anais brasileiros de dermatologia. 2010;85(6):939-41.  (Portuguese)
Free full text online: http://www.scielo.br/pdf/abd/v85n6/en_v85n6a30.pdf

11: Rada E, Aranzazu N, Rodríguez V, Borges R, Convit J.[Serological and cellular reactivity to mycobacterial proteins in Hansen's disease]. Invest Clin. 2010;51(3):325-40. (Spanish)
Free full text online: http://www.scielo.org.ve/pdf/ic/v51n3/art04.pdf

12: Rodrigues MM, de Ximenes RA, da Dantas MM, Batista TD, de Freire AL.[UVB susceptibility as a risk factor to the development of lepromatous leprosy.]. Anais brasileiros de dermatologia. 2010;85(6):839-42. (Portuguese)

Free full text online: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962010000600009&lng=en&nrm=iso&tlng=en

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Other Publication(s)

Moran M, Guzman G, Henderson K, Abela-Oversteegen
L. G-finder 2010: Neglected disease research and development: is the global financial crisis changing R&D?. Sydney ; London : Policy Cures; 2011.

http://www.policycures.org/downloads/g-finder_2010.pdf