(LML) Protection of cured LLp patients

Leprosy Mailing List – May 17,  2019

Ref.:  (LML)   Protection of cured LLp patients

From: Isabela Goulart, Uberlândia, Brazil 

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Dear Pieter,

This is a response to the recent post of Dr. Joel Ameida (May 12th) and to Dr. Paul Saunderson (May16th).

I have attended leprosy patients and their families for 35 years. In our National Leprosy Reference Center in Brazil, we report 230 cases/year: 56% of new cases, 15% of relapses and 24% of "therapeutic insufficiencies and failures" of MDT (1), the remaining cases being transferred from other municipalities or states.

During this period, we never stopped performing skin smear examinations (modified Ziehl-Neelsen) and lesion or nerve biopsy (Fite Faraco), even when WHO stopped recommending these tests.

From 2002, we added the anti-PGL-I IgM ELISA serology, qPCR DNA M. leprae and electroneuromyography, not only to aid in diagnosis but also the treatment monitoring. We have observed that 100% of LL patients have viable bacilli in skin biopsy in the 12th dose of MDT/MB and little more than 30% have viable bacilli in the 24th dose of MDT/MB. This percentage has risen silently.

In addition, several LL and BL patients who presented only fragmented or granular bacilli at discharge of 24th dose of MDT/MB,  one year or more in post-discharge monitoring, presented viable bacilli in the biopsy and/or a considerable increase in ELISA index (IE) and/or increased DNA loading in qPCR, with decrease of Ct (Cycle threshold: detection threshold - minimum number of cycles for amplification).

Thus, it is not difficult to prove the hypothesis that anergic individuals continue to disseminate bacillus in the post-discharge of scheme MDT / MB 12 doses of fixed duration, and even at high risk of being reinfected with M. leprae, becoming one of the links responsible for the transmission chain and maintenance of the endemic disease.

If bacilloscopy, serology and molecular tests were available in leprosy reference services, as recommended for the control of other infectious diseases that have resources, such as HIV / AIDS, we could easily prove the  therapeutic insufficiency of  scheme MDT/MB-12 doses  and  the therapeutic failure of scheme MDT/MB-24 doses, to cure LL and BL patients.

One must be ethical and have intellectual honesty to speak in healing anergic LL patients or those BL with discrete cellular immune response treated with 12 doses MDT/MB scheme. Of course, if we perform routine tests at discharge of 12 doses MDT/MB, we can prove that there are viable bacilli on the skin and intradermal skin smears, and those patients will not be able to clear that bacilli burden and will be abandoned to their own fate.

Mycobacterium leprae is a virulent bacillus because it damages the nerve and this is intolerable! We need to recover the knowledge of the microbiology of the bacillus, the pathophysiology of leprosy and the clinical expertise, so that we can really stand in front of questions of cure, therapeutic insufficiency, therapeutic failure and relapse. Unfortunately, the expertise in leprosy was lost with the simplification of the disease as a dermatological disease and without the necessary exams for diagnostics and to prove the cure. Most of the hegemonic knowledge produced in leprosy comes from researchers who stay at their desks without the slightest notion of what actually happens in the everyday practice, in monitoring patients in the long run.

Considering that leprosy is a bacterial chronic disease, we should evaluate the possibility a proposal to keep  LL/BL patients free of bacilli post-discharge, not as it was done in China with daily doses of dapsone or other monotherapy, but including in the post-discharge monitoring, a monthly dose supervised  of scheme ROM (Rifampicin+ Ofloxacin+ Minociclin) or scheme MCM (moxifloxacin + clarithromycin + minocycline) or scheme RMC (Rifampicin + moxifloxacin + clarithromycin)  for an indeterminate time, as it is done for HIV control, because it is a viral chronic disease.

In 2011, we have discussed about leprosy vaccine at the Federal University of Uberlândia / Minas Gerais, Brazil, with Dr. Steven G. Reed, Dr. Malcolm F. Duthie and Dr. Tom Gillis. Our concern at the time, which still remains today, is how to vaccinate against an intracellular bacillus of Schwann cells, without destroying this neural cells? What about infected contacts with subclinical disease? And the anergic ones?

When monitoring family contacts of leprosy, we found that the vast majority is weakly positive to Mitsuda test (4-7mm) and slightly more than 10% present negative Mitsuda test (0-3mm) (2). Therefore, our vast majority of the population would be genetically "borderline" and several are already infected, developing subclinical neural damage, as has been demonstrated by our research group (3).

It is necessary to face a new history for the leprosy of the XXI century and not to believe in that "historia de la carochinha" (children's fantasy), referring to the nineteenth century, that leprosy will end as a magic pass!

Nowadays, quite the contrary, with 10 million refugees worldwide, where the expertise of diagnosis and monitoring of the disease has been lost, where are we going to stop?

My best wishes for a real world without leprosy.

Isabela Goulart

References:

1-  Brasil/ Ministério da Saúde/ Secretaria de Vigilância em Saúde/ Departamento de Vigilância de Doenças Transmissíveis/ Coordenação Geral de Hanseníase e Doenças em Eliminação. NOTA INFORMATIVA Nº 51, 5 de outubro de 2015.

2- Araújo, Sérgio et al. Risk-benefit assessment of Bacillus Calmette-Guérin vaccination, anti-phenolic glycolipid I serology, and Mitsuda test response: 10-year follow-up of household contacts of leprosy patients. Rev. Soc. Bras. Med. Trop. [online]. 2015, vol.48, n.6, pp.739-745. ISSN 0037-8682.  

http://dx.doi.org/10.1590/0037-8682-0245-2015

3- Santos DFd, Mendonça MR, Antunes DE, Sabino EFP, Pereira RC, et al. (2018) Molecular, immunological and neurophysiological evaluations for early diagnosis of neural impairment in seropositive leprosy household contacts. PLOS Neglected Tropical Diseases 12(5): 0006494. 

https://doi.org/10.1371/journal.pntd.0006494

Dr. Isabela Maria Bernardes Goulart, MD, PhD

Associate Professor – School of Medicine
Universidade Federal de Uberlândia  - UFU
Coordinator and Head of the National Reference Center for Sanitary Dermatology and Leprosy - Clinics Hospital – UFU, Uberlândia - MG, Brazil
www.credesh.hc.ufu.br; credsh@hc.ufu.br; imbgoulart@gmail.com
Phone: +55 34 32391312; (34) 32391311

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

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

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