A beacon of hope: SDR-PEP as a new weapon in stopping leprosy transmission
In previous years, public campaigns around elimination of leprosy have focussed on identifying people with leprosy and treating them for the disease. Recent efforts, however, focus on prevention and include activities such as active case finding among close contacts of leprosy patients, such as family, neighbours, and friends, as they are at highest risk of becoming infected and developing the disease. These contacts can now be given an antibiotic that helps to prevent them from developing the disease. This preventive treatment is called post-exposure prophylaxis (PEP). The antibiotic that is proven to be effective as PEP for leprosy is a single dose of rifampicin (SDR). Rifampicin is a registered medicine that is already widely used in the management of mycobacterial infections, including in the treatment of leprosy and tuberculosis.
Robust evidence for the effectiveness of SDR as PEP (SDR-PEP) for leprosy has been generated through two large field-level studies. The first was a non-randomised controlled trial in Indonesia and the second a randomised double-blind placebo-controlled field trial in Bangladesh. In Indonesia the study took place on the islands of Pangkajene, South Sulawesi Province. This study showed positive results in reducing the risk of developing leprosy by around 60% among contacts who received two single doses of rifampicin. The study in a high endemic area in Bangladesh (COLEP study) confirmed these findings and provided more convincing evidence of the effectiveness of PEP, this time as a single dose of rifampicin.
PEP in WHO guidelines on leprosy
NLR and other leprosy-related NGOs have played a crucial role in global efforts to have the effectiveness of SDR-PEP for contacts of leprosy patients formally established and accepted by the WHO in 2018. To have this approach included in the WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy is a major breakthrough, as WHO Guidelines are evidence based and serve as an important reference for governments to follow. They also signify an important call for action.
Millions worldwide at risk of developing leprosy
NLR and ErasmusMC have carried out modelling research to predict the population at risk of leprosy, defined as the number of contacts to be treated with SDR-PEP in order to achieve a given reduction in the annual number of new cases of leprosy. The model predicts that, to achieve a 50% reduction in the global number of new cases of leprosy within 5 years, the number of people that needs to be treated with SDR-PEP is 20.4 million. When 40.1 million people are treated (this is a cumulative total – the maximum number per year would be 5 million contacts), then we can achieve a 90% reduction in new cases in 22 years.
NLR and its PEP experience
NLR has a substantial track record when it comes to research on, and implementation of SDR-PEP. We co-initiated and implemented a large five-year study across nine countries called the Leprosy Post-Exposure Prophylaxis Program (LPEP), which was funded by Novartis Foundation. It was implemented by NLR, together with other NGOs, health professionals, universities, and national leprosy programmes. The most important result of this project is that it was proven to be feasible to integrate contact screening and SDR-PEP administration into routine leprosy control programmes.
In addition, NLR is currently working on a large PEP clinical trial in Brazil, India and Indonesia, called Stop Transmission, funded by the Dutch Postcode Lottery. In this study, NLR and its partners investigate the effectiveness of a new enhanced preventive treatment regimen called PEP++ through which we hope to create evidence for an even more effective way of stopping transmission of leprosy. Young researchers from the three most infectious countries worldwide are being trained to contribute to this innovative study, thereby increasing local knowledge and capacity. The first results of this study will become available in 2022.
Finally, NLR is leading a large multi-actor implementation study, PEP4LEP, funded by the European Commission programme European and Developing Countries Clinical Trials Partnership (EDCTP) and the Leprosy Research Initiative (LRI). The aim of this study is to identify the most effective way of screening people at risk of developing leprosy and subsequently administer SDR-PEP in Ethiopia, Mozambique, and Tanzania. This will be done by comparing the effectiveness and feasibility of ‘skin camps’ versus a health centre based approach. The skin camps are organised events that improve health care access for the most marginalized by bringing trained health workers to leprosy patients’ communities, in order to provide skin screening and SDR-PEP administration. In the health centre based approach, household contacts of leprosy patients will be requested to visit a local health care facility for skin screening and SDR-PEP administration. The first results of this study will become available in 2023.
All these experiences combined have led NLR to gain the necessary expertise to assist governments in their preparations for large rollouts of SDR-PEP. This current proposal will concentrate on exactly this.
Criticism of PEP
As with any innovation in the medical field, the introduction of SDR-PEP has come with some criticism. One of the issues that is often raised is the likelihood of widespread distribution of rifampicin leading to resistance, especially in tuberculosis. An expert meeting was held in 2015 to address this issue, in which pharmacologists, leprologists, TB experts, and resistance experts took part. The conclusion of the experts was that the risk of inducing resistance is negligible.
Another argument against using SDR-PEP is that it is less effective with household contacts, especially when they are family members. It is true that a single dose of rifampicin is less effective in this group, but it still leads to a risk reduction of around 25%. The most likely reason for this group benefitting less from SDR-PEP, is that these contacts who are closest to the leprosy patient, have been exposed to the bacteria for a longer period of time and therefore have a higher bacterial load than more distant contacts, like neighbours. This is why we continue to look for alternative, more effective PEP (PEP++), but in the meantime we should use the means we have available to us now. As soon as proof becomes available of the enhanced regimen being more effective, SDR-PEP can easily be replaced as the infrastructure for the implementation has already been set up.
Thirdly, there is a concern in regards to increased stigmatisation of the patient since the implementation of SDR-PEP commonly requires disclosure of their disease status. This is a legitimate concern, though it has not proven to be a problem in the LPEP programme. Here, only less than 1% of leprosy patients refused to take part for fear of discrimination and other reasons. In addition, research in Bangladesh revealed that chemoprophylaxis for household contacts of leprosy patients is a socially acceptable addition to the current leprosy control programme. Study participants diagnosed with leprosy did not object to disclosure of the diagnosis to household members and nearby family. However, some participants were not willing to share information on their disease status with contacts like neighbors due to stigma of the disease. In that case, there are ways to work around the necessity of disclosure, like not providing names of patients or covering an entire district with SDR-PEP.
WHO’s response to the criticism is in line with that of NLR, which is why SDR-PEP is now part of the official WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy.