Leprosy post-exposure prophylaxis: innovation and precision public health
Authors: Milton Ozório Moraes, Nádia Cristina Düppre
Journal: The Lancet Global Health (2020)

Eradicating leprosy as a public health issue has been hindered by difficulties. Since the 1980s, an effective multidrug therapy (MDT) has been available, curing more than six million people. When treatment is correctly delivered, the rates of relapse, including those due to resistance, are low. So why has the rate of new cases been stagnant at more than 200 000 patients worldwide every year for the past 10 years? Firstly, leprosy is a disease of neglected populations affecting the poorest people. Populations affected tend to have lower levels of education and live in areas in which we typically find primary care units with poorer infrastructure,1Nery JS Ramond A Pescarini JM et al.Socioeconomic determinants of leprosy new case detection in the 100 Million Brazilian Cohort: a population-based linkage study.Lancet Glob Health. 2019; 7: e1226-36Summary Full Text Full Text PDF PubMed Scopus (34) Google Scholar attended by patients who are often neglected by health systems. Adding to that, leprosy is a chronic disease with a long incubation period in which patients have a myriad of clinical forms that are difficult to diagnose. No clear markers can discriminate infection from active disease. Finally, delayed diagnosis is very common, thereby maintaining the transmission cycle, which generally occurs before patient treatment. Large-scale novel public policies are needed to assist leprosy control and reduce the number of new cases. The population at risk is concentrated to households, neighbours, or social contacts of patients who have clinical forms of leprosy with higher bacterial load.2Moet 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 (136) Google Scholar Control, therefore, must be focused on two pillars—contact tracing and dermatoneurological evaluation of contacts for early detection of new cases. The epidemiological features of patients who are newly diagnosed by contact surveillance show that these individuals have lower levels of disability and immunological reactions, as well as lower bacterial loads.3Hacker MA Duppre NC Nery JAC Sales AM Sarno EN Characteristics of leprosy diagnosed through the surveillance of contacts: a comparison with index cases in Rio de Janeiro, 1987–2010.Mem Inst Oswaldo Cruz. 2012; 107: 49-54Crossref PubMed Scopus (10) Google Scholar Once a contact is identified as a new case, they can be treated adequately, but the management and follow-up of healthy contacts is more difficult.4Manta FSN Barbieri RR Moreira SJM et al.Quantitative PCR for leprosy diagnosis and monitoring in household contacts: a follow-up study, 2011–2018.Sci Rep. 2019; 916675Crossref PubMed Scopus (7) Google Scholar Cohort studies and, in the past 10 years, randomised controlled trials have suggested prophylaxis for the healthy population who are at risk. Observational studies have indicated that BCG given at birth or revaccination as a booster for healthy household contacts of people with leprosy confers up to 56% protection.5Düppre NC Camacho LA da Cunha SS et al.Effectiveness of BCG vaccination among leprosy contacts: a cohort study.Trans R Soc Trop Med Hyg. 2008; 102: 631-638Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 6Merle CS Cunha SS Rodrigues LC BCG vaccination and leprosy protection: review of current evidence and status of BCG in leprosy control.Expert Rev Vaccines. 2010; 9: 209-222Crossref PubMed Scopus (96) Google Scholar Among different protocols for chemoprophylaxis, single-dose rifampicin (SDR) has also been shown to be effective. A seminal randomised controlled trial (COLEP),2Moet 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 (136) Google Scholar provided evidence that SDR has an overall efficacy of 57% in reducing the risk of leprosy during the first 2 years of follow-up after administration. Furthermore, the combination of SDR with BCG at birth increases the protective effect to 80%, although blood-related contacts show lower protective rates.2Moet 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 (136) Google Scholar SDR can decrease the incidence of leprosy, thus WHO guidelines from 2018 recommended SDR as prophylaxis for contacts.7Global Leprosy Strategy WHO2016–2020. Accelerating towards a leprosy-free world. World Health Organization, Geneva2016https://apps.who.int/iris/handle/10665/208824Date accessed: November 6, 2020Google Scholar An extension of the strategy has also been evaluating multidose and multidrug leprosy post-exposure prophylaxis (LPEP) initiatives.8Mieras LF Taal AT van Brakel WH et al.An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP+.BMC Infect Dis. 2018; 18: 506Crossref PubMed Scopus (18) Google Scholar, 9Ortuno-Gutierrez N Younoussa A Randrianantoandro A et al.Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): a cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts.BMC Infect Dis. 2019; 191033Crossref PubMed Scopus (7) Google Scholar In The Lancet Global Health, the biggest multinational strategy implemented thus far is presented by Jan Hendrik Richardus and colleagues,10Richardus 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: e81-90Summary Full Text Full Text PDF PubMed Scopus (12) Google Scholar describing the long endeavour to assess the feasibility of an LPEP programme using SDR; the results are encouraging. Chemoprophylaxis is safe, affordable, and well accepted. LPEP enrolled 9170 index patients and listed 179 769 contacts. 174 782 (97·2%) were successfully traced and screened. SDR was subsequently administered to 151 928 (86·9%) screened contacts. The data suggest that LPEP could empower health systems, overcoming potential contact screening failures. LPEP can facilitate and promote the training of field workers. Then, health professionals can either detect leprosy early and treat the patient with MDT, or give SDR to healthy contacts. However, there are challenges ahead. Differences in the detection of new cases during the screening of contacts are expected in different countries. In Brazil, for example, a higher number of patients with leprosy have been observed among contacts at intake. Precision public health strategies need to be defined by country or region according to the local epidemiological situation, such as endemicity, multibacillary to paucibacillary ratio, and household size, while respecting cultural, political, and social conditions of different countries. The specifics of the national leprosy programmes must also be considered, such as whether chemoprophylaxis is combined with BCG vaccination, since SDR, by definition, provides only temporary protection. Bacterial load reduction with use of antimicrobial agents could last longer if a subsequent immunological booster with BCG is used in combination. With the challenges of controlling leprosy in mind, a multidisciplinary approach combining translational and operational research is essential. At present, the priorities include the need to create precise methods to detect individuals who are at risk (subclinical infection) and correctly diagnose new cases, especially at the early stages of the disease; provide continuous professional health training; use mapping and geographical information systems tools to expand epidemiological assessment of highly endemic areas; and generate communication campaigns to bring awareness towards the disease and reduce stigma. Nevertheless, LPEP provides hope and indicates that we are moving forward. Innovative and feasible public policies, such as SDR, along with the priorities listed above could be, at least in part, a step towards leprosy control, providing patients and their families with a better future. We 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 Access