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‘Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009–2015’ – Author's reply

2019; Elsevier BV; Volume: 25; Issue: 5 Linguagem: Inglês

10.1016/j.cmi.2019.01.004

1469-0691

Emmanuelle Cambau, Paul Saunderson, Laura Gillini,

Bacterial Identification and Susceptibility Testing

We thank our colleagues Diana Lockwood, Stephen Walker, and Bushan Kumar for their positive comments [1Lockwood D. Walker S. Re: Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009–15.Clin Microbiol Infect. 2019; 25: 643Abstract Full Text Full Text PDF Scopus (1) Google Scholar, 2Kumar B. Re: 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. 2019; 25: 644-645Abstract Full Text Full Text PDF Scopus (1) Google Scholar] about our paper published in Clinical Microbiology and Infection showing the results of antimicrobial resistance (AMR) testing in leprosy [[3]Cambau E. Saunderson P. Matsuoka M. Cole S.T. Kai M. Suffys P. et al.WHO surveillance network of antimicrobial resistance in leprosy. Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009–15.Clin Microbiol Infect. 2018; 24: 1305-1310Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar]. Before this survey, detection of resistance in leprosy was not done in any country as a routine surveillance, although antileprosy drug resistance was known and described using both microbiological and molecular methods. Although the network of colleagues who participated in this survey and wrote the paper was guided by the WHO Global Leprosy Programme (GLP) team and several international experts in leprosy, the study itself took place using the resources of national programmes, together with NGO support. This may explain why some data are missing, since this was not conducted as part of a funded clinical research study. The definition of 'relapse' is difficult in leprosy since the evolution of the infection and the disease can run over several decades. Moreover, leprosy reactions can mimic relapse, potentially causing confusion if the patient is not consulting a medical doctor with leprosy expertise. For our study, the definition of relapse was that given in the WHO GLP recommendations, i.e. 'the re-occurrence of the disease (appearance of definite new skin lesions and/or an increase in the bacteriological index (BI) of two or more units at any single site compared to BI taken from the same site) after the completion of a full course of treatment with WHO recommended MDT. Care should be taken to exclude patients suffering from leprosy reactions.' [4Jamet P. Ji B. Relapses in multibacillary leprosy patients after stopping treatment with rifampin-containing combined regimens. Marchoux Chemotherapy Study Group.Int J Lepr Other Mycobact Dis. 1992; 60: 525-535PubMed Google Scholar, 5Ji B. Jamet P. Sow S. Perani E.G. Traore I. Grosset J.H. High relapse rate among lepromatous leprosy patients treated with rifampin plus ofloxacin daily for 4 weeks.Antimicrob Agents Chemother. 1997; 41: 1953-1956Crossref PubMed Google Scholar]. This was written in the guide in accordance with the discussion within the network, at the beginning [[6]WHO Guidelines for global surveillance of drug resistance in leprosy. WHO, India2009Google Scholar]. We agree with our colleagues that reaching a consensus for the definition of relapse is difficult. This is the reason why the definitions were modified for the future AMR surveillance starting from 2016 and it now involves all patients undergoing retreatment [7WHO Global leprosy Strategy 2016–2020 "Accelerating towards a leprosy-free world". Regional Office for South-East Asia, Delhi, India2016Google Scholar, 8WHO A guide for surveillance of antimicrobial resistance in leprosy: 2017 update. World Health Organization, Delhi2017Google Scholar]. Molecular detection of resistance is the method of choice for leprosy since the bacteria do not grow in vitro, and phenotypic susceptibility can be assessed only in the mouse footpad assay, done today in fewer than ten laboratories in the world. In the AMR surveillance, we took into account only the mutations demonstrated to be related to resistance in the mouse footpad assay [8WHO A guide for surveillance of antimicrobial resistance in leprosy: 2017 update. World Health Organization, Delhi2017Google Scholar, 9Cambau E. Williams D. Anti-leprosy drugs: modes of action and mechanisms of resistance in Mycobacterium leprae.in: Gillis T. Scollard D. International textbook on leprosy. 2019Google Scholar]. They have been previously described in patients with clinical relapse in most of the cases. The recruitment was done on a voluntary basis at sentinel sites where colleagues could examine the patient, ask for consent, sample a skin specimen (slit skin smear or biopsy), send it to a laboratory where the molecular detection can be done, i.e. PCR and sequencing, and interpretation for mutation screening. Such places in countries endemic for leprosy are not numerous. We agree that the selection criteria were in some cases biased since more subjects were recruited at tertiary referral centres than from primary care facilities. This is the reason why in the 2016–2020 strategy and in the updated guide for antimicrobial resistance surveillance, the WHO recommends to carefully define the sentinel sites and calculate the ratio of new cases and retreated cases with regard to the total number of cases over the country and in collaboration with the Leprosy Programme Manager. In summary, while this study had a number of limitations, we feel that it has been a helpful first step towards a more comprehensive programme of monitoring drug resistance in leprosy. Logistics, materials, and meetings benefit from annual grants from Ministries of Health from all countries and from non-governmental agencies supporting leprosy, including Fondation Raoul Follereau, American Leprosy Missions, National Hansen's Disease Programs, Sasakawa Memorial Health Foundation, Damien Foundation, and Lepra. Specific grants were also used to support the study: Swiss National Science Foundation grant IZRJZ3_164174. Dr Cambau reports annual grants from Fondation Raoul Follereau, and MALTA grant from Ordre de Malte France for the development of the molecular test GenoType LepraeDR together with Hain Lifescience, Nehren, Germany. The authors declare that they have no conflicts of interest. 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 AccessRe: Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009–2015Clinical Microbiology and InfectionVol. 25Issue 5PreviewI 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]. 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. Full-Text PDF Open ArchiveRe: 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. 25Issue 5PreviewCambau et al. are to be congratulated on their important work on detecting rifampicin resistance genes in samples from patients with leprosy [1]. Setting up this network to look at the level of rifampicin resistance in Mycobacterium leprae is an important step. This work has been widely discussed and there were fears that this could indicate rising levels of rifampicin resistance in M. leprae in leprosy patients. However, a close inspection of the study shows that there are major design problems, which means that the findings have limited applicability. Full-Text PDF Open Archive