Leprosy post-exposure prophylaxis risks not adequately assessed
Authors: Diana N J Lockwood, Barbara de Barros, Edessa Negera, Heitor Gonçalves, Roderick J Hay, Indira P Kahawita, Rajni Kant Singh, Bhushan Kumar, Saba M Lambert, Vivek Pai, Gerson O Penna, Geoff Prescott, Guilllermo Robert de Arquer, Sinesio Talhari, Aparna Srikantam, Stephen L Walker
Journal: The Lancet Global Health (2021)

We thank Jan Richardus and colleagues for their feasibility study of single-dose rifampicin for contacts of individuals diagnosed with leprosy.1Richardus JH Tiwari A Barth-Jaeggi T et al.Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme.Lancet Glob Health. 2021; 9: e81-e90Summary Full Text Full Text PDF PubMed Scopus (19) Google Scholar Single-dose rifampicin was incorporated into the WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy as a conditional recommendation based on moderate evidence.2WHOGuidelines for the diagnosis, treatment and prevention of Leprosy. World Health Organization, Regional Office for South-East Asia, New Delhi2018Google Scholar The roadmap for neglected tropical diseases 2021–30 targets leprosy for elimination (interruption of transmission) with single-dose rifampicin as a "core strategic intervention".3WHOEnding the neglected to attain the sustainable development goals: a roadmap for neglected tropical diseases 2021–2030. World Health Organization, Geneva, Switzerland2020Google Scholar We have raised our concerns about single-dose rifampicin previously.4Lockwood DNJ Krishnamurthy P Kumar B Penna G Single-dose rifampicin chemoprophylaxis protects those who need it least and is not a cost-effective intervention.PLoS Negl Trop Dis. 2018; 12e0006403Crossref PubMed Scopus (18) Google Scholar Richardus and colleagues acknowledge that single-dose rifampicin's 57% protective effect only lasts for 2 years, and contacts of those with multibacillary disease only have 24% protection.1Richardus JH Tiwari A Barth-Jaeggi T et al.Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme.Lancet Glob Health. 2021; 9: e81-e90Summary Full Text Full Text PDF PubMed Scopus (19) Google Scholar Individuals receiving single-dose rifampicin need to understand the temporary and limited effect against leprosy. The Article has insufficient detail to determine whether fully informed consent of the participants was obtained in all centres. Brazilians were reportedly told, "There is leprosy in your area, and that is why we offer people preventive treatment against leprosy" when being informed about the Leprosy post-exposure prophylaxis (LPEP) study, without indicating the temporary and partial effect of single-dose rifampicin.5Schoenmakers A Mieras L Budiawan T van Brakel WH the state of affairs in post-exposure leprosy prevention: a descriptive meta-analysis on immuno- and chemo-prophylaxis.Res Rep Trop Med. 2020; 11: 97-117Crossref PubMed Google Scholar The definition of contacts in this study differed from that in the COLEP cluster randomised controlled trial in Bangladesh.6Moet FJ Pahan D Oskam L Richardus JH Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial.BMJ. 2008; 336: 761-764Crossref PubMed Scopus (147) Google Scholar In Richardus and colleagues' study, contacts were given single-dose rifampicin up to 2 years after diagnosis of the index case; whereas, in the COLEP study, single-dose rifampicin was given to contacts of newly diagnosed index cases.6Moet FJ Pahan D Oskam L Richardus JH Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial.BMJ. 2008; 336: 761-764Crossref PubMed Scopus (147) Google Scholar The paediatric proportion of index leprosy cases was high in India (31·3%) and Nepal (28·7%), compared with reported national rates of 6·8% and 7·6%, respectively.7WHOGlobal leprosy (Hansen disease) update, 2019: time to step-up prevention initiatives.Wkly Epidemiol Rec. 2020; 95: 417-440Google Scholar The high proportion of cases in children resulted in a lower proportion of multibacillary cases (28·9%) in India than the national rate of 54·2%.7WHOGlobal leprosy (Hansen disease) update, 2019: time to step-up prevention initiatives.Wkly Epidemiol Rec. 2020; 95: 417-440Google Scholar These unusual leprosy cohorts and the variation in the selection of contacts mean that the results are not generalisable. The main outcome measure was the number of single-dose rifampicin given. No evaluation of the effect of this intervention on leprosy rates is planned. WHO advises that tuberculosis needs to be excluded in patients before administering single-dose rifampicin to reduce the risk of producing rifampicin-resistant M tuberculosis strains.2WHOGuidelines for the diagnosis, treatment and prevention of Leprosy. World Health Organization, Regional Office for South-East Asia, New Delhi2018Google Scholar Screening individuals for tuberculosis using clinical symptoms before administering single-dose rifampicin lacks sensitivity. Only one Indian participant (of 42 333 screened) was excluded on a suspicion of tuberculosis in a state with a reported incidence rate of 194 per 100 000 in 2019.8TBFactsTB statistics India.https://tbfacts.org/tb-statistics-india/Date accessed: November 24, 2020Google Scholar This low exclusion rate suggests that some leprosy control programmes cannot effectively screen for tuberculosis. The widespread use of single-dose rifampicin might promote the development of Mycobacterium leprae rifampicin resistance. The risk of M tuberculosis developing rifampicin resistance has not been assessed rigorously, it was deemed to be negligible by an expert group convened by the Novartis foundation and the LPEP group, without a systematic review. The authors extrapolate their interpretation of the risk of M tuberculosis resistance data to M leprae, but this is not described.9Mieras L Anthony R van Brakel W et al.Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy.Infect Dis Poverty. 2016; 5: 46Crossref PubMed Scopus (21) Google Scholar WHO have recommended multidrug therapy for patients with leprosy since 1982, to reduce the risk of rifampicin resistance.10WHOChemotherapy of leprosy for control programmes. Tech Rep Ser 675. World Health Organisation, Geneva1982Google Scholar The presence of M leprae rifampicin resistance genes has already been detected.11Cambau E Saunderson P Matsuoka M et al.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: 1305-1310Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar Dispensing millions of doses of single-dose rifampicin might jeopardise the effectiveness of the key antibacterial component of leprosy multidrug therapy. This policy recommendation undermines the global strategy to combat antimicrobial resistance. Richardus and colleagues' study shows that with active case finding, many people with leprosy are found and at rates greater than the reported national statistics.7WHOGlobal leprosy (Hansen disease) update, 2019: time to step-up prevention initiatives.Wkly Epidemiol Rec. 2020; 95: 417-440Google Scholar The Brazilian Ministry of Health, following wide consultation, has decided not to implement single-dose rifampicin because of lack of evidence for its efficacy.12Exclusão da rifampicina para quimioprofilaxia de contatos de pacientes com hanseníase. Ministério da Saúde, Brasilia2020http://conitec.gov.br/images/Relatorios/2020/Relatorio_Rifampicina_Quimioprofilaxia_Hansenase_525_2020_FINAL.pdfDate accessed: November 24, 2020Google Scholar Brazil has the second highest case numbers globally and was an LPEP study site. the diagnosis and management of people with leprosy should be prioritised rather than the short-lived, partial efficacy of single-dose rifampicin for contacts. WHO should review their recommendation to implement this intervention and the Global Leprosy Programme and other advocates of single-dose rifampicin should ensure robust mechanisms are in place to detect adverse effects of this policy. All authors declare no competing interests. Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programmePost-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. Full-Text PDF Open AccessLeprosy post-exposure prophylaxis risks not adequately assessed – Author's replyWe thank Diana Lockwood and colleagues for their concerns about leprosy post-exposure chemoprophylaxis with single-dose rifampicin (SDR-PEP) for contacts of people diagnosed with leprosy.1 Some of their concerns against SDR-PEP are based on misunderstandings of the outcome of the COLEP trial. Full-Text PDF Open Access