Evidence of leprosy post exposure prophylaxis in highly endemic regions

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which affects skin and peripheral nerves and results in deformities and disability. In 1982, WHO introduced the effective regimen for treatment, a combination of dapsone, rifampin, and clofazimine (multidrug therapy). Henceforth, thousands of patients with leprosy have been treated, and a rapid decline reached in the global prevalence of leprosy.1Smith CS Aerts A Saunderson P Kawuma J Kita E Virmond M Multidrug therapy for leprosy: a game changer on the path to elimination.Lancet Infect Dis. 2017; 17: e293-e297Summary Full Text Full Text PDF PubMed Scopus (72) Google Scholar So far, an effective leprosy-specific vaccine is still absent. Although active and regular treatment had once successfully reduced the incidence of leprosy,1Smith CS Aerts A Saunderson P Kawuma J Kita E Virmond M Multidrug therapy for leprosy: a game changer on the path to elimination.Lancet Infect Dis. 2017; 17: e293-e297Summary Full Text Full Text PDF PubMed Scopus (72) Google Scholar this approach alone cannot guarantee the continuous success of leprosy control. The decline in leprosy cases slowed down since 2000, and incidence and prevalence have persistently remained at a steady plateau.2Lockwood DNJ Suneetha S Leprosy: too complex a disease for a simple elimination paradigm.Bull World Health Organ. 2005; 83: 230-235PubMed Google Scholar This status indicates that there should have been more focus on research on preventive tools and other newer approaches to accelerate reduction of the incidence of leprosy. As the most highly bactericidal component of multidrug therapy, rifampin have raised lots of enthusiasm and interest to study the effects of post-exposure prophylaxis (PEP) on leprosy in the past 20 years worldwide.3Ferreira SMB Yonekura T Ignotti E de Oliveira LB Takahashi J Soares CB Effectiveness of rifampicin chemoprophylaxis in preventing leprosy in patient contacts: a systematic review of quantitative and qualitative evidence.JBI Database Syst Rev Implement Rep. 2017; 15: 2555-2584Crossref PubMed Scopus (0) Google Scholar Among these studies, the COLEP trial conducted in Bangladesh is worth noticing.4Moet FJ Pahan D Oskam L Richardus JH COLEP Study GroupEffectiveness 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 (181) Google Scholar This randomised controlled trial found that single-dose rifampicin (SDR) could provide an overall protective effect of 57% for contacts of patient with leprosy in the first 2 years after intervention, although no additional protection beyond 2 years. Based on this evidence, in 2018, WHO decided to recommend SDR-PEP for all contacts of patients with leprosy.5WHOLeprosy/Hansen disease: contact tracing and post-exposure prophylaxis.https://www.who.int/publications-detail-redirect/9789290228073Date accessed: November 28, 2022Google Scholar In the Lancet Global Health, Epco Hasker and colleagues6Hasker E Assoumani Y Randrianantoandro A et al.Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.Lancet Glob Health. 2024; 12: e1017-e1026Summary Full Text Full Text PDF Google Scholar did a cluster randomised trial, which is the largest to date, to compare the effectiveness of three different modalities of provision of PEP, with a comparator arm, in which no PEP was provided, in Comoros and Madagascar. About 100 000 participants, including household contacts and neighbors of leprosy index patients, enrolled and received at least one follow-up; a single double-dose rifampicin (SDDR) was chosen as the PEP regimen. Although SDDR-PEP showed no protective effect for all intervention arms based on intention to treat and per-protocol analysis at population level, there was a 20–42% unadjusted reduction of incidence in arm 3 and arm 4. After adjusting for imbalance in baseline prevalence, a 44% protective effect was shown in arm 3. In addition, a 45% protective effect was observed at individual level. These outcomes are generally consistent with previous studies, and verify the protective effect of PEP to the extent, although the specific protective rates were lower than studies in other settings.4Moet FJ Pahan D Oskam L Richardus JH COLEP Study GroupEffectiveness 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 (181) Google Scholar, 5WHOLeprosy/Hansen disease: contact tracing and post-exposure prophylaxis.https://www.who.int/publications-detail-redirect/9789290228073Date accessed: November 28, 2022Google Scholar, 7Wang L Wang H Yan L et al.Single-dose rifapentine in household contacts of patients with leprosy.N Engl J Med. 2023; 388: 1843-1852Crossref Scopus (8) Google Scholar, 8Bakker MI Hatta M Kwenang A et al.Prevention of leprosy using rifampicin as chemoprophylaxis.Am J Trop Med Hyg. 2005; 72: 443-448Crossref PubMed Scopus (65) Google Scholar Different from the most other clinical studies, this trial was carried out in an environment with the average incidence rate of 10·9 per 10 000, thus it not only filled the research gap, but also provided high quality evidence to conduct PEP intervention in other, similar, highly leprosy endemic regions. Another novelty of this trial was that the physical distances were taken into account in the evaluation of the risk of leprosy for different subpopulation. Household contacts and neighbours living within 75 m of an index patient were found to be key populations, with two to four times higher risk compared with those living at a distance of 100 m or beyond.9Ortuno-Gutierrez N Baco A Braet S et al.Clustering of leprosy beyond the household level in a highly endemic setting on the Comoros, an observational study.BMC Infect Dis. 2019; 19: 501Crossref PubMed Scopus (18) Google Scholar This finding further indicates that the spatial association is clearly an important risk factor, just as described elsewhere.4Moet FJ Pahan D Oskam L Richardus JH COLEP Study GroupEffectiveness 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 (181) Google Scholar Although there is no leprosy-specific vaccine, immunoprophylaxis with BCG vaccine was proved to be effective in previous studies.10Tawfik GM Biala M Yousef YM et al.Efficacy of chemoprophylaxis and immunoprophylaxis in leprosy prevention: a systematic review and network meta-analysis of randomized controlled trials.Clin Microbiol Infect. 2021; 27: 1754-1761Summary Full Text Full Text PDF Scopus (0) Google Scholar In this trial by Hasker and colleagues, BCG vaccine was also associated with a 38% reduction in leprosy risk. In addition, protection provided by BCG vaccine is thought to be longer lasting than chemoprophylaxis,10Tawfik GM Biala M Yousef YM et al.Efficacy of chemoprophylaxis and immunoprophylaxis in leprosy prevention: a systematic review and network meta-analysis of randomized controlled trials.Clin Microbiol Infect. 2021; 27: 1754-1761Summary Full Text Full Text PDF Scopus (0) Google Scholar which protects only until subsequent exposure. Therefore, chemoprophylaxis and immunoprophylaxis, both alone and combined, could be the main effective intervention methods for preventing the disease among contacts of patients with leprosy in endemic areas. It is worth noting the value of comprehensive strategies around PEP, such as regular follow-up and active case-finding especially for key populations. It is also essential to continuously investigate and optimise the PEP regimen in the aspects of component selection, dosage adjustment, administration frequency, combination with immunoprophylaxis, and so on. Some novel successful regimens, such as single dose of rifapentine also could potentially apply in leprosy high endemic areas.7Wang L Wang H Yan L et al.Single-dose rifapentine in household contacts of patients with leprosy.N Engl J Med. 2023; 388: 1843-1852Crossref Scopus (8) Google Scholar In conclusion, the Article by Hasker and colleagues shows the protective effect of SDDR-PEP in high endemicity settings, even if the protective effect was lower than anticipated. As to leprosy prevention, much remains to be done, and better PEP regimen and immunoprophylaxis intervention might ensure a promising future. I declare no competing interests. Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trialSDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission. Full-Text PDF Open Access