(LML) Manifest against the implementation of MDT-U

Leprosy Mailing List – July 6,  2018

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

From:  Diana Lockwood and Steve Walker, London, UK

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Dear colleagues,

 

We would like to join the conversation on U-MDT for leprosy patients started by Professor Salgado on behalf of the Brazilian Leprosy Society (LML June 12 2018).  Dr Narasimha Rao has also made some important points from an Indian perspective on (LML June 25 2018)

 

We think that these points about a possible U-MDT need to be considered. Moving to a newer shorter regimen means that toxicities need to be better monitored. It also offers opportunities for strengthening better case management of leprosy patients and their complications.

 

Paucilbacillary patients

 

1.    There is no evidence that the current PB regimen for patients is failing.  These patients make a good response to their 6-month 2 drug treatment.  It is therefore unethical to add on a third drug clofazimine. This has adverse effects, particularly skin discolouration. Brazilian PB patients treated with Clofazimine and dapsone had a higher incidence of haemolytic anaemia than patients treated with dapsone alone. This was probably due a drug interaction.(1) This will therefore reduce adherence to treatment in patients concerned about taking a medication that discloses their diagnosis to others and causes unacceptable changes to one's appearance.

 

Multibacillary patients

 

2.    Assessing the response of leprosy patients to multi-drug treatment has three components.

                     I.        clinical improvement of the skin lesions,

                    II.        fall in the BI of smear positive patients

                  III.        relapse rate. 

 

The clinical improvement of the skin lesions is often slow and we lack a robust, validated measure of improvement. It is important to separate out the clinical response from the bacteriological response. 

The clinical response to treatment in some patients is slow and even though they have been treated bacteriologically they still have active lesions.  The data from Penna et al. shows that the bacteriological response, as assessed by slit skin smears is falling at about 1 log unit per year. This continues to fall after six months treatment has been completed. The relapse rate in the Penna study was very low.(2)

 

3.    The large Indian trial was a significant contribution to showing that leprosy patients can be treated successfully with 6 months of a Rifampicin based regimen.(3)

 

4.    Further important data comes from the studies done in Bangladesh.  Here patients were treated with either 6 or 12 months of MDT. They were followed for 7 years and no relapses have been reported yet.(4) This suggests that a 6 month treatment may be adequate.

5.    If a shorter regimen is to be introduced then more attention needs to be given to the diagnosis of leprosy. Counting lesions will no longer be needed for classification. Health workers will need better training in recognizing leprosy.  Strengthening the capacity for slit skin smears to be done so that patients bacterial loads can be assessed is part of this.  

 

6.    More attention will need to be given to ensuring that patients are adherent if they are taking a shorter regimen.

 

7.    We need to use this opportunity to improve detection of nerve damage which has been overlooked in the current WHO pauci/multibacillary classification).

 

8.    The importance of reactions in the long term outcomes for leprosy patients is being forgotten in the discussions about UMDT.  In Pennas' study 85% of patients who had a BI greater than 4 had reactions.(2) It is vital that patients are adequately assessed and warned about the complications that will occur after a 6-month treatment period.  This applies to reactions and nerve damage. Saunderson (5) has mentioned this in his assessment of the risks and benefits of U-MDT.

 

It is vital that the national leprosy programmmes are able to detect and treat patients who develop complications post-treatment.

 

MDT toxicity

 

9.    Too little attention has been paid to the accumulating evidence that dapsone causes significant toxicity.  There are multiple case reports and a systematic review showing deaths associated with dapsone. (6),(7)  We therefore need a less toxic regimen urgently. The Rifampicin, Ofloxacin and minocycline based monthly regimen would be less toxic and needs to be assessed. (8)

 

 

We look further to more discussions on these important points.

 

Best wishes

Diana  Lockwood

Steve Walker

 

 

 

 

1.         Goncalves Hde S, Pontes MA, Buhrer-Sekula S, Cruz R, Almeida PC, Moraes ME, et al. Brazilian clinical trial of uniform multidrug therapy for leprosy patients: the correlation between clinical disease types and adverse effects. Mem Inst Oswaldo Cruz. 2012;107 Suppl 1:74-8.

2.         Penna GO, Buhrer-Sekula S, Kerr LRS, Stefani MMA, Rodrigues LC, de Araujo MG, et al. Uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): Results of an open label, randomized and controlled clinical trial, among multibacillary patients. PLoS Negl Trop Dis. 2017;11(7):e0005725.

3.         Manickam P, Mehendale SM, Nagaraju B, Katoch K, Jamesh A, Kutaiyan R, et al. International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes. Indian J Med Res. 2016;144(4):525-35.

4.         Butlin CR, Pahan D, Maug AKJ, Withington S, Nicholls P, Alam K, et al. Outcome of 6 months MBMDT in MB patients in Bangladesh- preliminary results. Leprosy Review. 2016;87(2):171-82.

5.         Saunderson PR. Uniform multidrug therapy for leprosy - time for a rethink? Indian J Med Res. 2016;144(4):499-501.

6.         Lorenz M, Wozel G, Schmitt J. Hypersensitivity reactions to dapsone: a systematic review. Acta Derm Venereol. 2012;92(2):194-9.

7.         Guragain S, Upadhayay N, Bhattarai BM. Adverse reactions in leprosy patients who underwent dapsone multidrug therapy: a retrospective study. Clin Pharmacol. 2017;9:73-8.

8.         Lockwood DN, Cunha Mda G. Developing new MDT regimens for MB patients; time to test ROM 12 month regimens globally. Lepr Rev. 2012;83(3):241-4.

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

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

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