Sunday, July 15, 2018

(LML) Single-dose rifampicin chemoprophylaxis

Leprosy Mailing List – July 15,  2018

Ref.:  (LML) Single-dose rifampicin chemoprophylaxis 

From:  Joel Almeida, London and Mumbai


 

Dear Pieter,

 

 

A recently reported study gave single dose rifampicin (SDR) to most people on a small island. That is a good way to test and demonstrate the potential of chemoprophylaxis. 

 

What were the results?

The number of new cases among the 1071 who had received SDR was 6 and the number of cases among the 410 who had not received SDR was 4. The odds ratio is 0.57 (95% CI: 0.16–2.03).

 

In short, there was no statistically significant difference between the SDR group and the non-SDR group. 

 

Unfortunately, the report fails to state this clearly. In such matters, however, facts are quite important.

 

Do these results mean that chemoprophylaxis is completely useless? Of course not. It means merely that claims of its efficacy are insufficiently substantiated by fact in this study.

 

It is far better to keep attempting elimination on a small island and discover the limitations than to rely on exaggerated claims.

 

 

Joel Almeida

 

 

Reference

 

Anuj Tiwari, Steaven Dandel, Rita Djupuri, Liesbeth Mieras and Jan Hendrik Richardus. Population-wide administration of single dose rifampicin for leprosy prevention in isolated communities: a three-year follow-up feasibility study in Indonesia. BMC Infectious Diseases 2018.18:324

https://doi.org/10.1186/s12879-018-3233-3


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

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

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


Saturday, July 14, 2018

(LML) The misuse of “leprosy” in political exchanges

Leprosy Mailing List – July 14,  2018

Ref.:   (LML) The misuse of "leprosy" in political exchanges

From:  Editor LML, Maastricht, the Netherlands


 

Dear colleagues,

 

 

We received the following message:

 

 

France's Macron and Italy's deputy PM urged to stop misuse of "leprosy" in political exchanges

 

GENEVA (3 July 2018) – Political leaders in France and Italy must immediately stop using "leprosy" as a metaphor in debates on nationalism, says a UN human rights expert.

 

"Remarks reportedly made by the French President, Emmanuel Macron, and the Italian Deputy Prime Minister, Luigi Di Maio, in which leprosy was used as a metaphor for a rise in nationalism, are appalling," said Alice Cruz, the Special Rapporteur on the elimination of discrimination against persons affected by leprosy and their family members.

 

Mr. Macron was reported as saying of nationalists: "You can see them rise a bit like leprosy all across Europe, in countries where we thought that it would be impossible to see them again, in neighbouring countries."

 

Mr. Macron's comments were allegedly followed by a statement by Mr. Di Maio saying: "The real leprosy is the European hypocrisy of someone who pushes back migrants at [the French-Italian border at] Ventimiglia, and then moralises about how to manage them."

 

The UN expert stressed: "The use of such expressions and references to leprosy in political debate only promotes misunderstanding of leprosy and discrimination against people affected by it.

 

"Leprosy has become much more than a disease. It has become a metaphor for everything that is socially considered 'shameful' and disrupting and should be kept apart," Ms Cruz noted.

 

"National leaders should choose their words appropriately and responsibly, and they should avoid attacking one of the most marginalised groups," Ms Cruz added.

 

"Remarks made by national leaders undoubtedly have widespread implications and could strengthen the wrongly held view that leprosy has been eliminated across the world - ignoring the fact that hundreds of thousands of individuals are affected each year and millions others live with the disease and related stigma and discrimination.

 

"The view that leprosy no longer exists could lead to a loss of already scarce financial support for scientific research, public health initiatives and other targeted programmes, including those aimed at combating discrimination and stigma against those affected.

 

"We should all lift the veil of stigma and stereotypes that render invisible the actual human beings affected by leprosy, acknowledge the impact the disease has on them and their family members, and commit ourselves to the protection and promotion of their rights," Ms. Cruz emphasized.

 

The Special Rapporteur reminded France and Italy of their obligations and commitments under the Principles and Guidelines for the Elimination of Discrimination against Persons affected by Leprosy and their Family members. The document makes clear that the use of discriminatory language including the derogatory use of the term "leper" or its equivalent in any language and dialect, is prohibited.

 

"States that have voluntarily approved the Principles and Guidelines should promote them and help in the elimination of discrimination and stigma against people affected by leprosy and their family members," Ms Cruz stressed.

 

ENDS

 

Ms Alice Cruz (Portugal) was appointed in November 2017 as the first UN Special Rapporteur on the elimination of discrimination of persons affected by leprosy and their family members. She is an External Professor at the Law School of University Andina Simón Bolívar in Ecuador. Ms Cruz has conducted fieldwork in Portugal, Brazil, South Africa, Bolivia and Ecuador, and has researched and written on the subject of eliminating leprosy and the stigma attached to it. Her doctoral work in sociology focuses on the biosocial dimensions of leprosy and identifies the different barriers to access to early diagnosis and to high quality care by those affected, as well as their social, economic, family and personal life conditions.

 

The Special Rapporteurs are part of what is known as the Special Procedures of the Human Rights Council. Special Procedures, the largest body of independent experts in the UN Human Rights system, is the general name of the Council's independent fact-finding and monitoring mechanisms that address either specific country situations or thematic issues in all parts of the world. Special Procedures experts work on a voluntary basis; they are not UN staff and do not receive a salary for their work. They are independent from any government or organization and serve in their individual capacity.

 

For more information and media requests, please contact Naveed Ahmed (+41 22 928 9477 / Nahmed@ohchr.org)

 

For media inquiries related to other UN independent experts please contact:
Jeremy Laurence, UN Human Rights – Media Unit (+41 22 917 9383 / jlaurence@ohchr.org)



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

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

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


Friday, July 13, 2018

(LML) Manifest against the implementation of U-MDT

Leprosy Mailing List – July 13,  2018

Ref.:  (LML) Manifest against the implementation of U-MDT 

From:  Narasimba Rao, Hyderabad, India


 

Dear Pieter,

 

 

We are having an absorbing discussion on the proposed implementation of U-MDT of 6 months duration for all leprosy patients in Brazil. 

 

Today (13 July 2108), in the  'annual meeting of state leprosy officers' being held in Goa, India, Dr Ervin Cooreman, team leader global leprosy programme,  in his talk titled 'brief review new WHO guidelines', spoke briefly on the new proposed guidelines for leprosy. 

 

The important new strategy he mentioned was:

to retain the same 3 drug combination of rifampicin, dapsone and clofazimine for leprosy therapy, however all the 3 drugs to  be used to all leprosy patients; for 6-month duration for PB-MDT and for 12-month duration for MB-MDT. 

 

This is definitely very good news to global leprosy programme as the new therapy guidelines do not shorten the duration of therapy for MB cases to 6 months (as was envisaged in the U-MDT proposal).

 

It is only a uniform drug regimen, but of different durations for PB and MB leprosy. 

It includes the drug clofazimine into the drug regimen of PB leprosy 

 

In response to the question whether this means that U-MDT of 6 months is completely discarded, Dr Cooremen replied that he can only say that it is not being considered for now. 

 

I just thought I shall share this Information with fellow LML readers at this juncture. 

 

Please find as attachment the jpg of the synopsis provided to all the delegates regarding the same. 

 

With best regards, 

 

P Narasimha Rao

--

 

P. Narasimha Rao, MD, D.D, PhD

President- Elect, National IADVL 2018

 

dermarao@gmail.com

 

Phone- 040-23514566

Mobile-09849044898


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

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

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

 


(LML) Improving the quality of leprosy treatment

Leprosy Mailing List – July 13,  2018

Ref.:    (LML) Improving the quality of leprosy treatment

From:  Joel Almeida, London and Mumbai


 

Dear Pieter,

 

 

Several important points are being made in recent discussions by esteemed colleagues: Leprosy spreads, and Leprosy disfigures.

 

If we take care of those two problems, we will protect people adequately.

 

Slit skin smears

 

In recent decades we have discouraged and discontinued slit skin smears. Even though we know that an inadequately treated person with polar lepromatous leprosy can spread up to one million times the number of M. leprae as a person with TT leprosy. This error is highly favourable to M. leprae and highly unfavourable to human beings. It would be good to correct this error. How?

 

First by reminding ourselves that one inadequately treated polar LL patient is equivalent, epidemiologically, to one million TT patients. 

 

It is not the patient's fault. It is our fault for discontinuing slit skin smears as a routine. Consequently, inadequate anti-microbial treatment for polar LL leprosy has become widespread. In effect, these patients remain susceptible to relapse or re-infection but are left without anti-microbial protection. Such a situation would probably not be tolerated in any other disease. Every human being deserves an adequate quality of care. The human rights of people with leprosy do not begin only after they suffer disfigurement. 

 

It would be good to resume slit skin smears that were a routine part of leprosy control programs. It is important for the individual and for society. We need to scale up training and supplies to achieve this.

 

 

Nerve monitoring

 

Leprosy disfigures, largely by damaging nerves. MDT or any other anti-microbial treatment helps, but it does not suffice to protect against nerve damage. Despite exaggerated claims to the contrary.  

 

A randomized controlled trial (van Brakel at al 2003) compared prednisolone, given for 4 months, with placebo. During these 4 months, the placebo group had a 158% higher risk of deterioration in sensory scores between the start and end of treatment (confidence interval 19% to 460%).

 

Regular monitoring of nerve function during and after anti-microbial treatment is necessary to reduce the risk of disfigurement. Especially since as much as 85% of new nerve damage in South Asians with leprosy occurs without any signs of inflammation ("silent neuritis").

 

 

We have an opportunity to restore science to leprosy treatment, so that people at risk of leprosy are treated no less humanely and competently than other human beings. 

 

Once we improve the quality of treatment for leprosy we can hope to

a) reduce the spread of leprosy;

b) reduce the risk of disfigurement among those infected with M. Leprae.

 

We tried propaganda, for many years. It harmed leprosy work, harmed patients and drove young talent away from leprosy. It may be time for new faces and new thinking to take us forward. 

 

 

Joel Almeida

 

 

Reference:

 

Van Brakel WHAnderson AMWithington SGCroft RPNicholls PGRichardus JH, et al. The prognostic importance of detecting mild sensory impairment in leprosy: a randomized control


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

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

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

 

 


(LML) Improving the quality of leprosy treatment

Leprosy Mailing List – July 13,  2018

Ref.:    (LML) Improving the quality of leprosy treatment

From:  Joel Almeida, London and Mumbai


 

Dear Pieter,

 

 

Several important points are being made in recent discussions by esteemed colleagues: Leprosy spreads, and Leprosy disfigures.

 

If we take care of those two problems, we will protect people adequately.

 

Slit skin smears

 

In recent decades we have discouraged and discontinued slit skin smears. Even though we know that an inadequately treated person with polar lepromatous leprosy can spread up to one million times the number of M. leprae as a person with TT leprosy. This error is highly favourable to M. leprae and highly unfavourable to human beings. It would be good to correct this error. How?

 

First by reminding ourselves that one inadequately treated polar LL patient is equivalent, epidemiologically, to one million TT patients. 

 

It is not the patient's fault. It is our fault for discontinuing slit skin smears as a routine. Consequently, inadequate anti-microbial treatment for polar LL leprosy has become widespread. In effect, these patients remain susceptible to relapse or re-infection but are left without anti-microbial protection. Such a situation would probably not be tolerated in any other disease. Every human being deserves an adequate quality of care. The human rights of people with leprosy do not begin only after they suffer disfigurement. 

 

It would be good to resume slit skin smears that were a routine part of leprosy control programs. It is important for the individual and for society. We need to scale up training and supplies to achieve this.

 

 

Nerve monitoring

 

Leprosy disfigures, largely by damaging nerves. MDT or any other anti-microbial treatment helps, but it does not suffice to protect against nerve damage. Despite exaggerated claims to the contrary.  

 

A randomized controlled trial (van Brakel at al 2003) compared prednisolone, given for 4 months, with placebo. During these 4 months, the placebo group had a 158% higher risk of deterioration in sensory scores between the start and end of treatment (confidence interval 19% to 460%).

 

Regular monitoring of nerve function during and after anti-microbial treatment is necessary to reduce the risk of disfigurement. Especially since as much as 85% of new nerve damage in South Asians with leprosy occurs without any signs of inflammation ("silent neuritis").

 

 

We have an opportunity to restore science to leprosy treatment, so that people at risk of leprosy are treated no less humanely and competently than other human beings. 

 

Once we improve the quality of treatment for leprosy we can hope to

a) reduce the spread of leprosy;

b) reduce the risk of disfigurement among those infected with M. Leprae.

 

We tried propaganda, for many years. It harmed leprosy work, harmed patients and drove young talent away from leprosy. It may be time for new faces and new thinking to take us forward. 

 

 

Joel Almeida

 

 

Reference:

 

Van Brakel WHAnderson AMWithington SGCroft RPNicholls PGRichardus JH, et al. The prognostic importance of detecting mild sensory impairment in leprosy: a randomized control


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

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

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

 

 


Thursday, July 12, 2018

(LML) Manifest against the implementation of U-MDT

Leprosy Mailing List – July 12,  2018

 

Ref.:    (LML) Manifest against the implementation of U-MDT

From:  Claudio Salgado, Marituba, Pará, Brazil and Colleagues from Brazil and USA


 

Dear LML colleagues,

 

We also believe the discussion about adopting U-MDT treatment regimens for leprosy clearly needs debate from all stakeholders, but it is really important for the welfare of our patients that we always keep the main focus on new and better treatment options for them. In general, leprosy patients are poor, and have no access to other possible drugs, so they rely on public health systems, most of the time with no other options. In our view, MDT is a classical case of the real-life situation here, patients can only take the medication available to them. Thus, it is really important to understand that although we are aware of the millions of people treated and cured by MDT over the years, the greater need is for new, better and less toxic drugs, not shorter regimens with the same old drugs that have known side effects or toxicities.

Considering the important topics raised by Drs. Lockwood and Walker (LML, July 6, 2018), we would like to make comments that we believe are crucial for the future of leprosy treatment and, of course, leprosy research. Therefore, we will make comments point by point.

We sincerely do not understand the idea that "moving to a newer shorter regimen means that toxicities need to be better monitored" and that "it also offers opportunities for strengthening better case management of leprosy patients and their complications". We have been treating leprosy patients with MDT for decades. We have treated millions of MB patients for 1 to 2 years or even more, and people – patients and doctors – have been dealing with that for a long time. What is the point of better monitoring toxicities with a possible shortening of MDT? More to the point, how can U-MDT implementation bring opportunities for better case management and fewer complications? It is really difficult for us to understand how U-MDT use will show improvement in these areas based on the facts as we know them.

Concerning the absence of evidence that the PB regimen is failing, it is hard to say. There are only a few good studies of cohorts of PB patients followed over the years. Besides having a few PB patients relapsing as PB again, there are many patients classified and treated as PB, that we later had to reclassify to MB when they appear years later with disease activity likely due to misdiagnosis. Since they were released by cure, administratively, after 6 doses, when they enter in the system again, they are not classified as relapses, they are classified as a diagnostic error, even by doctors that have never seen the patient before. This is one of the sources of our beliefs about PB/MB misclassifications. Are we correct? But we do not believe this should be a primary concern about this U-MDT discussion. The main problem is with the MB patients, especially those who are AFB positive on slit skin smear.

It is true that clinical improvement of skin lesions, fall in the BI, and relapse rate were the only three components to evaluate the response of leprosy patients to antibiotics 30 or 40 years ago, but this should not be the case anymore. We cannot accept this in 2018. In the last 3 or 4 decades there have been huge advances in understanding the immunology and use of treatment strategies to achieve better outcomes for patients, and new data have been produced about leprosy patients with different techniques. Electroneuromyography and ultrasound, serology using different markers, and molecular biology to detect M. leprae DNA by real time PCR are among the techniques that are becoming more routinely used, including the old but not outdated Shepard technique that can tell us if a given strain has drug resistance to any drug in the standard MDT regimen. Why not use all those tools with our leprosy patients? Science and medicine must be used to improve the outcomes for our patients and to improve our knowledge concerning their management. Nerve evaluation, forgotten in many trials, including those of U-MDT, cannot be outside of the boundaries used to evaluate leprosy patients.

Concerning the decrease in the BI over time in the Penna work, as cited by Lockwood and Walker, this is true. However, we must remember a few things about this odd bacterium: 1. M. leprae has a very slow rate of multiplication, 12-14 days, the longest of any bacterium; 2. Studies with a single dose of rifampicin chemoprophylaxis showed that it could delay the diagnosis of leprosy by two years in the treated group. Therefore, just showing that there is a decrease in the BI after 6 U-MDT doses within 4.7 years of follow up is not a long enough time to say that the patients are cured of disease. Based on the very slow growth of M. leprae this assumption is false, one would need a much greater time of follow-up. If it is true that one capsule of rifampicin given to a contact who is not AFB positive may delay the diagnosis of leprosy for two years, widespread undertreatment of an entire class of leprosy patients with U-MDT could result in serious problems many years later. These problems will likely only appear in 5, 10, or >15 years from now. Brazilian patients and leprosy patients from any other country do not deserve to be treated in such a haphazard or irresponsible manner.

The other trials comparing shorter treatment regimens have similar deficiencies. They did not evaluate the number or percentage of patients that were really cured and did not evaluate nerve damage. Bangladesh is a case apart. A seven-year trial that doesn't have one relapse raises real doubts, particularly since they used the same MDT regimen. We have experienced relapses in patients even after completing 24 doses of MDT. We have many more relapses with 12 doses. And even in Penna's study, there were 7 times the number of relapses with the six doses of U-MDT than the standard MDT regimen, and some of these occurred in under 5 years, reflecting the likelihood of undertreatment, a real cause for concern that seems to have been overlooked.

When Lockwood and Walker say that "If a shorter regimen is to be introduced then more attention needs to be given to the diagnosis of leprosy", once again we do not understand. We have been saying that there is already a lack of proper diagnosis in leprosy now. Absence of diagnosis is to be partially blamed for the low number of cases of leprosy that we see today in the world. Patients who were released from the leprosariums into the surrounding community mostly remained there, establishing towns around the former colonies populated by their descendants, having much higher rates of leprosy than other nearby towns. For people who are not aware of the disease, leprosy is over, nobody really thinks that it still exists anymore. In addition, expertise is lost, there are fewer dedicated leprosy dermatologists remaining. So, there is no connection at all between a short U-MDT implementation and diagnosis. These are different things altogether.

"Counting lesions will no longer be needed, but health workers will need better training in recognizing leprosy"? Health workers certainly need to be trained now, and in order to be well trained, it should be by experienced leprologists, while they still exist. We do not need a shortened regimen of old drugs to do this. Training must be included in the front line of the fight against leprosy, now. Patients need more attention now, with or without a shortened treatment and yes, we need to detect nerve damage, as said above. It is true.

After so many years of research, why do we still know so little about leprosy reactions? There is still discussion about why some people have reactions while others do not. Reactions could be a result of bacilli multiplication? If not, we need to better understand the disease interfaces on pathology and immunology. If yes, then we have a problem, a big one. How about different strains giving different results? Do we know that? Do we know if our patients have only one strain or two or more strains, with possible drug resistance? Do we know if a strain has a higher capacity of developing reactions or if a strain is more resistant to antibiotics? We do not know. These are all basic questions for any disease that we want to control.

Unfortunately, we still need to work hard to show the world that leprosy is a big problem, particularly in Brazil, and that leprosy patients need better management and new drugs that are more effective and less toxic, some of which are already available. We need to show that patients are often forgotten by inflexible or uncaring systems, and that they are living with sequelae, lost among other poor people with equal or worse health problems struggling in our communities. A shorter, less effective, regimen of MDT definitely will not bring this to our patients. Not at all.

 

Thanks for the opportunity of sharing our thoughts with this unique community.

 

Claudio Salgado, presidente Brazilian Leprosy Society (SBH), Professor at Pará Federal University

Marco Andrey Frade, vice-president SBH, Professor at University of São Paulo

Isabela Goulart, scientific diretor SBH, Professor at Uberlândia Federal University

Laila de Laguiche, South Brazil representative and international public relations SBH

John Spencer, Professor at Colorado State University


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

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

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