Leprosy Mailing List – May 11, 2021
Ref.: (LML) Leprosy Cure
From: David Scollard, Baton Rouge, USA
Dear Pieter,
Dra. Laquiche's thoughtful question has pointed out a long-standing difficulty in establishing when HD is cured. As Henk Eggers has pointed out, also, 'cure' often means different things to a patient vs a physician.
If we consider this to mean 'cure of the infection', the problem has always been that we cannot culture M. leprae in the laboratory, so it has been very difficult to determine if an antimicrobial regimen has killed them. For decades the only rigorous method to determine that M. leprae had been killed by treatment was to obtain bacilli from a patient's skin biopsy and inoculate them into mouse footpads (mfp) to see if they would grow. This is a very slow, difficult and expensive test, requiring a very specialized laboratory and a year or more to obtain a result. It is not feasible to do this routinely. However, studies using this method generated data showing the duration of treatment needed to kill M. leprae in clinical practice. This, together with supporting data from mouse footpad studies, provided the laboratory basis for the WHO recommendations for MDT. (Reviewed in Lahiri and Adams, 2016).
Long term follow-up studies of relapse have provided additional evidence regarding the overall efficacy of MDT regimens. Sometimes these studies have used mfp assays and sometimes conclusions were based on clinical criteria alone. But relapse in HD occurs several years after completion of treatment, and such follow up studies are also slow and expensive.
Recently, a molecular viability assay (MVA) has been developed (Davis et al, 2013; Lahiri & Adams, 2016). This assay basically measures the amount of RNA produced by a specified number of leprosy bacilli obtained from a skin biopsy, expressed as a ratio of RNA/ DNA. Preliminary studies using this method to study biopsies from patients are in progress (Linda Adams, personal communication).
It is likely that the MVA will enable us, for the first time, to assess viability / death of M. leprae in a specimen directly from a patient, in a relatively short time, and at a relatively low cost. It is the closest we have ever had to a rapid 'culture and sensitivity' method for this pathogen. Hopefully this method will be more widely used in the near future and will provide the kind of direct evidence that modern physicians expect to have to establish that, after a particular treatment regimen, infection with M. leprae has truly been 'cured'.
David Scollard
References
Lahiri R, Adams LB. 18 September 2016, posting date. Cultivation and viability determination of Mycobacterium leprae, Chapter 5.3. In Scollard DM, Gillis TP (ed), International Textbook of Leprosy. www.internationaltextbookofleprosy.org.
Davis GL, Ray NA, Lahiri R, Gillis TP, Krahenbuhl JL, Williams DL, Adams LB. 2013. Molecular assays for determining Mycobacterium leprae viability in tissues of experimentally infected mice. PLoS Negl Trop Dis 7:e2404.
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