Post-Exposure Prophylaxis (PEP) has become big news in the leprosy world over recent years. A post-exposure prophylactic is a medicine that prevents people from developing a disease after they have been exposed.
In practice for leprosy, PEP means that we identify people who are close contacts of someone who has recently been diagnosed with leprosy and we give them a single dose of an antibiotic called Rifampicin. This single dose reduces the likelihood that they will go on to develop leprosy by as much as 60 percent. In people who are already vaccinated against TB, the risk is reduced by as much as 80 percent.
PEP is not the tool that will single-handedly end leprosy transmission, but it has unlocked a world of opportunity.
So what has gotten us to this point? For decades, scientists have been working hard to get us here and even now they are working to improve and perfect PEP to make it more effective.
We talk to Professor Jan Hendrik Richardus, who has been there for much of that journey, to find out how we reached this point.
“The idea of a post-exposure prophylaxis is not unique to leprosy and is used in a lot of other illnesses (for example, HIV). In the leprosy world, PEP was already been considered as early as the 1970s. At that time, they were using Dapsone and variations of Dapsone as the prophylactic.
“They could see that this was having an impact, but it was far from a perfect scenario. Patients had to take Dapsone for years before they could be sure that leprosy had been prevented.
“Not long after this, MDT was developed and rolled out and people thought this would be the ‘silver bullet’ that would end leprosy transmission once and for all. Because many scientists held onto this belief, PEP was de-prioritised. We were very happy to see that MDT was curing patients, but ultimately there was an acknowledgement that it was not interrupting transmission. That is when PEP was revisited.”
“Of the three medications that make up MDT, Rifampicin is the most potent by some distance. Dapsone and Clofazimine slow down the growth of the bacteria, but they don’t kill the bacteria; it is Rifampicin that kills bacteria. Even one dose of Rifampicin can kill up to 99 percent of leprosy bacteria in the body.
“Because scientists could see the potency of Rifampicin from the very beginnings of MDT, Rifampicin became the obvious drug to start using for PEP.
MDT Distribution in Mozambique (Photo credit: Ricardo Franco)
“In the 1990s this was trialled in a few places in the Pacific, but the studies had not been designed in the most rigorous way and so the results were inconclusive.
“Next, the Royal Tropical Institute in Amsterdam began working with Indonesian partners in a PEP trial. The study was quite an elegant one and was trialled on five small Indonesian islands with high levels of leprosy.
“On two of the islands, everyone received a single dose of Rifampicin. On another two islands, only the close contacts of leprosy cases were given a single dose of Rifampicin. On the final island, no one was given Rifampicin as PEP. The researchers saw that PEP was quite effective on the island where everyone received a single dose of Rifampicin but less effective on the island where only close contacts received a dose.
“These were interesting results, but these were very small islands and so you could argue that everyone was a close contact of a new leprosy case. The idea of giving a single dose of Rifampicin to everyone in a country is also both highly impractical and would increase the risk of drug resistance.
“This was the point when it was decided that we needed a properly designed, thorough, Randomised Controlled Trial (RCT) with high numbers of participants.”
“The COLEP study took place at TLM’s Nilphamari centre with funding from American Leprosy Missions. This was an easy choice of location. There were high numbers of cases and a well-trained network of field staff who could implement a project like this. We also didn’t face significant problems in accessing the communities involved; they weren’t too far away or difficult to reach.
“The study began in 2002 and by the end there were over 20,000 contacts involved in the trial. Because this was a Randomised Controlled Trial, the methodology was as solid as it could be and the results were as statistically significant as we could hope for.
“The COLEP study showed that after two years there was a 60 percent drop in the number of leprosy diagnoses among individuals who received a single dose of Rifampicin. This increased to 80 percent for individuals who had received the BCG vaccine for Tuberculosis as a child.
“It became a watershed moment in the movement towards establishing a post-exposure prophylaxis for leprosy. The COLEP study showed that PEP was cheap, feasible, and an effective way to prevent leprosy.
“The results from COLEP were published in 2008 and by 2018, PEP was adopted into the WHO’s guidelines for leprosy control. That might seem like a big gap, but it is quite common that new approaches take around a decade before they are adopted into official guidelines.”
“PEP is the most effective preventative for leprosy that we have right now. That is not to say that it is perfect. There are two problems that we need to consider.
“The first problem is that PEP is not effective for all individuals. People who have been exposed to high levels of leprosy bacteria do not respond as well as we’d like to receiving a single dose of Rifampicin. Because they already have a high bacterial load, the single dose simply isn’t sufficient.
“What these individuals need is something that is halfway between a single dose of Rifampicin and receiving a full course of Multi Drug Therapy.
“That is what the PEP++ project is hoping to determine. In Indonesia, India, Nepal, Bangladesh, and Brazil, a trial is underway to see if there is another antibiotic that people could take after they’ve been exposed to leprosy. Or perhaps they need to take more than one dose. Or perhaps they need a combination of Rifampicin and something else. These trials are aiming to help us find the right combination of medication to prevent leprosy.
“In the future we can use improved diagnostic tests to identify who has a high bacterial load so that we can give them the enhanced PEP regime and everyone else can receive a single dose of Rifampicin.
“The second problem with PEP at the moment is the complications around implementation. How do we get preventative antibiotics into the hands of everyone who has been exposed to leprosy? No NGO has the capacity to make that happen. It will certainly require us to work in partnership with national health systems.
A participant in the LPEP study in Nepal
“The LPEP project looked closely at this issue of implementation in Indonesia, India, Nepal, Myanmar, Sri Lanka, Tanzania, and Brazil. They wanted to create rigorous, best-practice systems for implementing PEP. This means identifying new cases, conducting surveys to identify their close contacts, and getting PEP to those close contacts. This requires precise thinking and a degree of health systems strengthening. The LPEP project got us a long way towards getting this right.”
“No. But no single thing will ever be the key to that.
“PEP is an enormous step forward, but it has to work in tandem with a number of different things. We have to have effective programmes for active case finding and contact tracing. These two interventions on their own are vital to interrupting transmission. PEP, when used in combination with these things, is going to even further interrupt transmission.
“New diagnostic tools, vaccines, and PEP will all be crucial interventions that scientists will make in the coming years, but they will have very limited success if we don’t make the move from passive case detection to active case finding.
“My team are currently mapping the extent to which these interventions can impact transmission rates in contexts around the world. It’s hard work, but it’s giving us significant reason to be hopeful.”
Front cover photo credit: Sabrina Dangol
Read Professor Jan Hendrik's paper, 'Protecting people against leprosy: Chemoprophylaxis and immunoprophylaxis' >
