Re: Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009–2015
Authors: B. Kumar
Journal: Clinical Microbiology and Infection (2018)

I read with great interest the article by Cambau et al. on their important work in detecting rifampicin resistance genes in samples from ‘relapsed’ leprosy patients [[1]Cambau E. Saunderson P. Matsuoka M. Cole S.T. Kai M. Suffys P. et al.Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009–2015.Clin Microbiol Infect. 2018; (Epub 2018/03/03. PubMed PMID: 29496597)https://doi.org/10.1016/j.cmi.2018.02.022Abstract Full Text Full Text PDF Scopus (89) Google Scholar]. A close look shows that there are flaws in the study about the definition of ‘relapse’ and recruitment of patients. This would mean that the findings have limited applicability. ‘Relapse’ can be understood only in the context of the definition of ‘cure’. The definition of ‘cure’ in leprosy is based on the completion of the prescribed treatment for a fixed duration. There are no clinically or bacteriologically defined criteria for cure. Inadequate and incomplete treatment in addition to a high initial bacteriological index (BI) and drug resistance are the causes for ‘reactivation’/‘relapse’. For operational purposes a leprosy patient who has undergone the prescribed therapy is declared ‘cured’, even when clinical subsidence of lesions, histopathological resolution and disappearance of the bacilli take months to years after multidrug therapy (MDT) has been stopped. Thus the term ‘relapse’ should be used with great caution. Because of the unsatisfactory definitions of ‘relapse’, varying incidences of ‘relapse’ have been reported. However, one criterion which can give us the most useful information is the ‘relapse interval’ or the incubation period of ‘relapse’. In the MDT era this was proposed to be 3 years for paucibacillary (PB) leprosy [[2]Ramu G. Clinical features and diagnosis of relapses in leprosy.Indian J Lepr. 1995; 67: 45-59PubMed Google Scholar] and up to 9 years (median) for multibacillary (MB) leprosy. Early ‘relapse’ (up to 3 years) is always ‘reactivation’ of the disease due to incomplete or inadequate treatment, which also indirectly implies misclassification. In 1988, the WHO defined the ‘relapse interval’ to be 2 years for PB and 5 years for MB [[3]World Health Organization Guide to leprosy control.2nd ed. World Health Organization, Geneva1988http://www.who.int/iris/handle/10665/37935Google Scholar]. In the present study the problematic definition of ‘relapse’ given by the WHO [[4]WHO Guidelines for global surveillance of drug resistance in leprosy. WHO, India2009Google Scholar] has been followed by the authors: (a) appearance of new lesion(s), or (b) more than a 2-unit increase in BI any time after the completion of MDT. For deciding time to ‘relapse’ after MDT, consider the ‘relapse interval’ the time for the bacilli to multiply and reach a level to produce symptoms of ‘relapse’. This interval cannot be a few weeks or months for the very slow-growing Mycobacterium leprae to multiply to a critical level, as after MDT the bacilli are scarce and in many cases undetectable on slit-skin smear. The second criterion—increase by 2 units or more of BI on slit-skin smear—it is most unlikely that ‘no’ bacilli or few bacilli at the end of treatment will become BI 2+, or that BI 1 + will increase to BI 3 + in a few weeks or months. The authors state that a deficiency in previous studies was “that they did not represent nationwide data and were more research oriented”. The same is true with the present study also: only three centres (because of the strict selection criteria) from a vast country like India were included, which are also research-oriented. If these designated ‘centres’ for study were getting referral of all the patients with suspected ‘relapse’ from peripheral clinics, then we are more unsure of the initial diagnosis, regularity of treatment, and lack of reliable reporting for slit-skin smears which are now not a part of the WHO recommended protocol. We would presume that the participating centres ensured or certified that all these patients had undergone full treatment regularly. How was this ascertained? Because of these issues relating to the lack of an acceptable definition of ‘relapse’, the data on the ‘relapsed’ patients has to be interpreted cautiously and may not indicate a serious problem with M. leprae resistance to rifampicin. I have no disclosures to declare. The study received no funding. Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009–15Clinical Microbiology and InfectionVol. 24Issue 12PreviewAntimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network. Full-Text PDF Open Access‘Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009–2015’ – Author's replyClinical Microbiology and InfectionVol. 25Issue 5PreviewWe thank our colleagues Diana Lockwood, Stephen Walker, and Bushan Kumar for their positive comments [1,2] about our paper published in Clinical Microbiology and Infection showing the results of antimicrobial resistance (AMR) testing in leprosy [3]. Full-Text PDF Open Archive