Tuesday, March 26, 2013

Epidemiology in the Leprosy Mailing List


Leprosy Mailing List – May 14th, 2012
Ref.:   Epidemiology in the Leprosy Mailing List (LML)
FromP. K. Das, Amsterdam, the Netherlands

Dear Salvatore,
I always look at the LML postings with interest.  Though I appreciate Dr. Lombardi's suggestion [LML May 13th, 2012] of having some veteran Epidemiologists to take part in these exchanges of opinion, he should be aware that as I recall that, these heavy weights had been engrossed in their own dogmatic views.  Nevertheless their participation in the discussion together with those who are engaged in the field and providing the firsthand knowledge, will surely be valuable.

Hope that the discussions become critical, non-biased, and fruitful in terms of stopping the slow but continuous transmission of this unfortunate disease.

Best regards,

Pran

Prof. P. K. Das

ENL or relapse in a BL/LL patient?


Leprosy Mailing List – May 3rd, 2012
Ref.:   ENL or relapse in a BL/LL patient?
From: G Warren, Sydney, Australia


Dear Salvatore,

I refer to the letter from Dr Kawuma in Uganda (LML May 3rd, 2012).

Yes, definitely down grading reaction can occur and it frequently did in the “old days” when a patient was receiving one drug only, when the patient developed resistance to that drug.  In the 1960s it was usually dapsone but, also downgrading reaction occurred to some of the other drugs in which initial improvement had appeared to occur and then the patients would down grade till we changed the antileprosy drug therapy.  It usually required several years for such resistance to show up.

It also occurred in patients who had been given multidrug therapy because they were not responding to dapsone and so were considered dapsone resistant; though there was no ability to test for resistance to dapsone.  After a period often a year or two the disease seemed under control and the patient stopped drug therapy (often just by dropping out himself but sometimes by completing the 12 months recommended for MDT).  But after several years the patient would reappear with what was said to be ENL; but on careful testing one would find the bacteriological index (BI) was higher than it had been at the last test.

It is fascinating how one can separate between new lesions of downgrading BL/LL and the lesions of ENL that look similar.  Restarting adequate anti-leprosy medication especially including the use of clofazamine, seemed to rapidly deal with the problem that was apparently resistance to dapsone and the multidrug therapy had not been given long enough.

I hope that will help.  When a patient returns with what is queried to be ENL or relapse in a BL/LL patient who has completed the recommended 12 months MDT it is wise to check the lesions for infiltration, by pressing a glass slide onto the lesions.  The pressure of a slide will define the edge of the lesion.  If it is ENL there will be a well localised small patch of infiltration but, if it is a new lesion ie true relapse, it will not be so definite and not so erythematous.

We need to be on the watch for such relapses!

Grace Warren
Previously Superintendent Hong Kong Leprosarium 1960-1975.

Epidemiology in the Leprosy Mailing List


Leprosy Mailing List – May 13th, 2012
Ref.:   Epidemiology in the Leprosy Mailing List (LML)
From: C Lombardi, São Paulo, Brasil

Dear leprosy specialists,
I have been following the LML closely for many years.  In the past few months, I have noticed that posts concerning clinical and therapeutical issues have become the great majority.  Indeed, these issues are crucial, but what worries me is that the epidemiological issues concerning leprosy are being approached, and usually very lightly, by professionals whose background is not mainly in epidemiology and public health.
I would like recall that epidemiology and statistics have methodologies and paradigms of their own.  According to these, the health/disease phenomena in a collectivity are not merely the sum of the individual phenomena related to health/disease.  Thus, a clinical and therapeutical approach to a disease cannot suffice to explain the epidemiology of the given disease.
Obviously, all opinions should be voiced and heard, as these exchanges are always fertile.  It is just as obvious that in the last few decades, the leprosy elimination process as a public health problem has eventually faced mistakes and deviations.  Nevertheless, I believe that only a broad, knowledgeable and experienced discussion could evaluate properly the impact of this process and to define perspectives for the future.
In this sense, I judge necessary a debate that would include renowned specialists in epidemiology of leprosy, such as Prof. M. F. Lechat, Dr. S. K. Noordeen, Prof. C. Smith, Dr. P. Feenstra, Dr. P. Fine, Prof. J. Ferreira, amongst many others.  Perhaps the adequate moment for such a discussion could be the next World Leprosy Congress to be held in Brussels, September 2013.
Sincerely,
Dr. Clovis Lombardi
São Paulo, Brasil

The leprosy burden – NCD or registered prevalence which is better?


Leprosy Mailing List – May 8th, 2012
Ref.:   The leprosy burden – NCD or registered prevalence which is better?
FromS Noto and S. Canata, Genoa, Italy


Dear All,

In attachment a PDF file about comparison between new case detection and registered global trends of leprosy from 1985 to 2010.
Best regards,

Salvatore Noto and Silvia Canata



NB
The original Excel file is available on request

The DiaLep study - Combining care interventions for people affected by either leprosy or diabetes


Leprosy Mailing List – May 5th, 2012

Ref.:    The DiaLep study - Combining care interventions for people affected by either leprosy or diabetes
FromW de Bruin, Amsterdam, The Netherlands


Dear Salvatore,

Some time ago a request to participate in the DiaLep study by filling in a questionnaire was posted in the LML.  We would kindly like to remind you to fill in this questionnaire.  With as many responses as possible we aim to achieve a large sample and a broad perspective of the opinions on this topic worldwide.

The DiaLep study aims to research  the possibility of combining care interventions for people affected by either leprosy or diabetes.  The questionnaire is available online at: https://www.surveymonkey.com/s/dialepstudy.

It will take approximately 15 minutes to complete the questionnaire.  We would appreciate if you could provide your input by 7 May 2012.  An offline version of the questionnaire is in attachment to this message; please only use it in case of a limited internet connection.

We encourage you to complete the questionnaire and to pass the link on to appropriate health-care workers, professionals and representatives of patient organisations active in the field of either leprosy or diabetes.

Many thanks!

Kind regards,

Willemijn de Bruin and Evelien Dijkkamp


Willemijn de Bruin
Leprastichting / Netherlands Leprosy Relief (NLR)
Postbus / P.O. Box 95005
1090 HA Amsterdam
The Netherlands
Tel:
Mob:
E-mail: W.d.Bruin(at)Leprastichting.NL

The downgrading reaction would only be an issue at first presentation


Leprosy Mailing List – May 3rd, 2012
Ref.:   The downgrading reaction would only be an issue at first presentation.
From: H J Kawuma, Buluba, Uganda


Dear Salvatore,
I am glad that this longstanding puzzle has come up for debate again.

Dr. Bryceson, as usual, has put the arguments clearly for many of us to appreciate [LML April 26th, 2012].  It appears the downgrading reaction would only be an issue at first presentation as we would not expect it in a person on treatment.  Might it also be a manifestation of treatment failure?

Dr. Bryceson must be aware of the reasons behind the shift to referring to type 1 reactions as "Reversal Reactions" at some stage.  Would he kindly remind the readers of those reasons as well?

Best wishes,
H Joseph Kawuma
GLRA, Uganda 

Ungrading and downgrading reactions; do these concepts help us?


Leprosy Mailing List – May 3rd, 2012
Ref.:   Ungrading and downgrading reactions; do these concepts help us?
From: J A da Costa Nery, Rio de Janeiro, Brazil

Dear Salvatore,

It´s always a pleasure to follow these reports, so we can think upon them.  In my whole life studying leprosy, these nomenclatures [upgrading and downgrading reactions] always bothered me.  I find them, as a clinician, very hard to distinguish on a daily basis.
I don’t really know if these concepts help us in the programme and, not all doctors know how to use that kind of nomenclature while treating reactional episodes.  The discussion on appearance of either upgrading or downgrading type 1 reaction [type 1 reaction is also commonly referred to as reversal reaction or RR] is very relevant to the knowledge on leprosy in the state of art.  Nevertheless, such a goal is more likely to be achieved by basic researchers, by means of immunologic tests; not by clinicians.  Moreover, it is not always possible, given that cellular proliferation and activation tests are not deemed as a golden standard assessment.  On the other hand, histopathology is also helpful for the definition of RR, although such examination is not very useful to evaluate the characteristic of such a reaction (either upgrading or downgrading). 

It’s always good to hear new opinions so we can discuss.  Lately I´ve been studying cases of relapse in leprosy, and I´ll watch out for these type 1 reactions, which are treated with long term corticosteroids,  can they be included in the downgrade?

We have a large experience with a number of RR cases per year, and our most relevant concern relates to the long-term use of corticosteroids and risk of disability. 
Best wishes,

Dr. José Augusto da Costa Nery
Fiocruz 

The leprosy burden – NCD trend of leprosy at Global, South East Asia Region and India


Leprosy Mailing List – May 1st, 2012
Ref.:   The leprosy burden – NCD trend of leprosy at Global, South East Asia Region and India (see attachment)
FromS Noto, S. Canata, P A M Schreuder; Genoa, Italy, Maastricht, The Netherlands


Dear All,

In attachment a PDF file about the new case detection (NCD) trend of leprosy at Global, South East Asia Region and India from 1991 to 2010.
Best regards,

Salvatore Noto




NB
The original Excel file is available on request

What would be the meaning of the downgrading type 1 reaction in terms of the management of the patient?


Leprosy Mailing List – May 1st, 2012
Ref.:   What would be the meaning of the downgrading type 1 reaction in terms of the management of the patient?
From: H K Kar, New Delhi, India

Dear Dr C Shumin,

Thanks for your message [LML April 23rd, 2012].  The term downgrading type 1 reaction is basically downgrading of the spectrum of the disease with some amount of inflammation over some of the lesions.  In those cases simply multi-drug therapy (MDT) has to be started immediately.  These patients need close watch, since they are likely to develop upgrading type 1 reaction.
Regards

Dr (Prof.) H K Kar
Dean, PGIMER, Dr R M L Hospital
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

In my opinion those hypothetic concepts of upgrading and downgrading reaction only confuse


Leprosy Mailing List – April 30th, 2012
Ref.:   In my opinion those hypothetic concepts of upgrading and downgrading reaction only confuse
FromP AM Schreuder, Maastricht, The Netherlands



Dear Salvatore,

I have problems with the explanation of Prof. Bryceson [LML April 26th, 2012]:
<< "Add more lymphocytes (as in upgrading) and the reaction, as measured by titrated thymidine incorporation, increases.  Add more antigen (as in downgrading) and the reaction increases." >>

What we, however, see is that most reactions happens the first six months after starting with MDT.  You would expect an enormous increase in antigen, while at the same time the patient has a so-called "upgrading" reaction.  In my opinion those hypothetic concepts of upgrading and downgrading reaction only confuse.
  
Kind regards,

Pieter AM Schreuder

The leprosy burden – Global NCD trend


Leprosy Mailing List – April 29th, 2012
Ref.:   The leprosy burden – Global NCD trend
FromS Noto and S. Canata, Genoa, Italy


Dear All,

In attachment two Excel files about the global new case detection trend of leprosy from 1985 to 2010 and the global new case detection trend excluding the South East Asia region from 1991 to 2010.

Best regards,

Salvatore Noto and Silvia Canata

Difference between Jopling’s downgrading and upgrading reactions.


Leprosy Mailing List – April 29th, 2012
Ref.:   Difference between Jopling’s downgrading and upgrading reactions.
FromJ A. Barreto, S Paulo, Brazil


Dear Dr Noto,

Many thanks for circulating our clinical case of about “Borderline leprosy in reaction in a boy from Brazil” (LML March 24th, 2012).  Herewith I would like to comment on the difference between Jopling’s downgrading reaction and upgrading reaction.

Initially, the most important feature is the presence of viable (“solid” or globi) bacilli.  In downgrading reaction, there are viable bacilli, despite the presence of a granulomatous epithelioid reaction; which is seen on the tuberculoid side of the leprosy spectrum.  Actually a “granulomatous epithelioid reaction” can be found on the following three distinct conditions: 

First condition
True TT leprosy (rare).  In this case, bacilloscopy in biopsy specimens ranges from 0 to 1+, and bacilli are usually found, when present, inside dermal nerve branches.

Second condition
BT leprosy (most common).  In this case, bacilloscopy in biopsy is positive, usually 2+ or 3+, inside dermal nerve branches, macrophages (less common), sub-epidermal area and smooth muscle of hair follicles.

Third condition
Type 1 reaction.  Borderline tuberculoid (BT) and mid borderline (BB) leprosy can show epithelioid cells, which in turn means that macrophage differentiation and antigen processing was done, due to IL2 plus IFN-gamma and TNF alfa functions.  What does it mean the presence of epithelioid cells together with viable (solid or globi) bacilli?  This is easy to understand: it means that the macrophage differentiation was not proper and bacilli are still multiplying.  This pattern is typical of the non-treated borderline group, where cellular immunity is partial, and is the reason why most BT patients downgrade to borderline lepromatous (BL), progressively or during reactions.  According to Ridley, indeed, most of BL patients results from downgraded BT.

Coming back to the clinical case we presented; the boy had globi under the epidermis, and it means that this is a downgrading reaction.  Upgrading reaction will never show globi, that is to say aggregations of viable (solid or well stained) bacilli.  This boy also did not receive antibiotics.  Clinicians in the past had already noticed that downgraded reaction occurred in untreated borderline patients [B Naafs personal communication]. 

Unfortunately, leprosy knowledge has been lost since the Ridley and Jopling (R&J) Classification was forgotten, and a new classification (W.H.O.) based only on the number of lesions is nowadays the rule. 

Best regards,

Jaison A. Barreto
Dermatologist and Dermatopathologist

More details can be found on the suggested bibliography.
(Ridley DS. Skin biopsy on leprosy. 2ed. 1987 and Hastings RC. Leprosy 2ed. 1994)

Downgrading and upgrading type 1 reactions. Do they exist?


Leprosy Mailing List – April 26th, 2012
Ref.:   Downgrading and upgrading type 1 reactions.  Do they exist?
FromA Bryceson, London, UK



Dear Salvatore,

I refer to Prof. Kar’s message << Downgrading type 1 reaction? >> [LML April 10th, 2012]

The problem in understanding type 1 reactions lies with the nomenclature, not the immunology.  Cell mediated immunity is the process that, if all goes well, controls the leprosy infection.  More cell mediated immunity (CMI) results in upgrading and increased control; less CMI results in downgrading and decreased control.

I think of a type 1 reaction as a hypersensitivity reaction between antigen and specifically sensitized lymphocytes.  Imagine the patient, or a nerve, to be a test tube containing antigen and lymphocytes.  Add more lymphocytes (as in upgrading) and the reaction, as measured by titrated thymidine incorporation, increases.  Add more antigen (as in downgrading) and the reaction increases.  Thus it is possible to have a type 1 reaction associated with upgrading and a type 1 reaction associated with downgrading.

Clinically, the reactions are indistinguishable.  The history, clinical examination and bacillary index indicate whether the underlying disease is upgrading or downgrading, and thus the prognosis.  If downgrading continues (the patient does not receive anti-leprosy treatment) the infection is uncontrolled and the concentration of antigen in the test tube continues to rise and will eventually suppress the reaction.

We might have a clearer understanding of reactions associated with shift along the borderline tuberculoid (BT) – borderline lepromatous (BL) spectrum if we were to replace the terms upgrading reactions and downgrading reactions with the terms type 1 reaction associated with upgrading, and type 1 reaction associated with downgrading.

With best wishes,

Anthony

There are no accepted criteria for the diagnosis of downgrading type 1 reaction


Leprosy Mailing List – April 23rd, 2012
Ref.:   There are no accepted criteria for the diagnosis of downgrading type 1 reaction.
FromC Shumin, Shandong, China



Dear Dr. Kar,
Thank you very much for your comments on the downgrading type 1 reaction [LML April 10th, 2012].  I agree with you.  So far there are no accepted criteria for the diagnosis of downgrading type 1 reaction.  If yes, what would be the meaning of the downgrading type 1 reaction in terms of the management of the patient?

Warm regards,

Dr. Chen Shumin
Head of Leprosy and STD Control Unit 
Shandong Provincial Institute of Dermatology

The DiaLep study


Leprosy Mailing List – April 12th, 2012

Ref.:    The DiaLep study
FromW de Bruin, Amsterdam, The Netherlands


Dear Salvatore,

I would be very grateful if you could post the following request via the leprosy mailing list (LML). 

Currently, the Netherlands Leprosy Relief is researching the possibility of combining care interventions for people affected by either leprosy or diabetes.  A study and a questionnaire have been developed for people with expertise in leprosy or in diabetes.  The name of the study is the DiaLep study.  We kindly ask the interested LML readers to contribute to our study by filling in the questionnaire.

It is available online at: https://www.surveymonkey.com/s/dialepstudy .  It will take approximately 15 minutes to complete the questionnaire.  We would appreciate if you could provide your input by 7 May 2012.  An offline version of the questionnaire is in attachment to this message; please only use it in case of a limited internet connection.

We encourage you to complete the questionnaire and to pass the link on to appropriate health-care workers, professionals and representatives of patient organisations active in the field of either leprosy or diabetes.  With as many responses as possible we aim to achieve a large sample and a broad perspective of the opinions on this topic worldwide.

The contact information of my colleague and mine are as follow:-
Email addresses are  w.d.bruin(at)leprastichting.nl and e.dijkkamp(at)leprastichting.nl
Office phone number is  +31 20 595 05 00.

Many thanks in advance for your collaboration and support.

Kind regards,

Willemijn de Bruin and Evelien Dijkkamp

Willemijn de Bruin
Leprastichting / Netherlands Leprosy Relief (NLR)
Postbus / P.O. Box 95005
1090 HA Amsterdam
The Netherlands
E-mail: W.d.Bruin(at)Leprastichting.NL

Downgrading type 1 reaction?


10 April 2012

Ref. Downgrading type 1 reaction?

From: H K Kar, New Delhi, India
Dear Dr Noto,
Thank you very much to Drs Barreto and Cabral for presenting their case (LML March 24th, 2012). A very good case of a child with untreated mid borderline (BB) leprosy presenting with downgrading (DG) type 1 reaction.
Many of us do not accept the existence of DG type of type 1 reaction. Many of the so called untreated borderline patients presenting with DG type 1 reaction are in true sense upgrading (UG) type 1 reaction. On taking detailed history we come to know that in the immediate past they took some antibiotics responsive to M. leprae for other infections which precipitated UG type 1 reaction. In true sense these reactions should be considered as Up-grading type 1 reaction, rather than DG type 1 reaction.
With 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