Could a single dose of rifampicin stop leprosy transmission?

Decades after a cure for leprosy was found and the annual number of new cases plummeted, there are worrying signs the trend could be reversing.

The downward spiral which started three years after multidrug therapy was introduced in 1982 continued until 2005.

In the last decade the number of new case of leprosy has plateaued at about 200,000-250,000 per year. In Indonesia, Brazil, Madagascar and Sri Lanka the numbers rose in 2014 (World Health Organisation statistics).

Efforts to stem the tide resulted in a study in Bangladesh using rifampicin (part of leprosy treatment) to prevent transmission. The result has been promising and has led to wider trials across Africa, Asia and Latin America.

Could rifampicin be the key to eliminating leprosy by stopping transmission?

A single dose of rifampicin

Leprosy post-exposure prophylaxis (LPEP) involves giving close contacts of those with leprosy a single dose of rifampicin.

Health volunteers go from house to house in specific districts looking for patients recently diagnosed with the disease and screen their households for symptoms. If a case is confirmed they are referred  for treatment and the people with whom they have been in close contact are screened – family members, neighbours, fellow workers and in the case of children their classmates and teachers.

If they have no underlying illnesses they are given a single dose of rifampicin – a potent anti-bactericidal drug that is part of the multidrug therapy along with clofazimine and dapsone.

The fall in the number of new cases of leprosy was steep after multidrug therapy was introduced, dropping from 5.3 million to 3.1 million by 1991 and to 300,00 by 2005. It prompted the WHO to announce leprosy had been ‘eliminated as a public health problem’ - meaning fewer than 1 in 10,000 population is registered with an active case of the disease.

Little change in lasts 10 years

Dr Bart Vander Plaetse is Global Program Head, Health Impact, at Novartis Foundation, the philanthropic arm of the pharmaceutical giant Novartis, which has supplied multidrug therapy of free charge since 2000, distributing it through the WHO to national governments.

He said: “When the introduction of multidrug therapy led to a big fall in the number of new cases of leprosy, everyone thought it would keep dropping below targets and transmission would be reduced, leading to eventual elimination.

“But that has not been the case. In the last 10 years not much has changed. To the contrary, the approach of declaring leprosy eliminated as a public health problem led to some countries losing interest.

Study showed 60% success

Former British GP Dr Ruth Butlin is medical advisor for The Leprosy Mission England & Wales and is based at the leprosy hospital in Nilphamari,  Bangladesh.

She said: “The idea behind the trial of post-exposure prophylaxis was to see if leprosy could be prevented in people who have already been exposed to the risk of infection. We thought if people have ‘sub-clinical infection’ i.e they are not ill with leprosy but might progress to having the disease, they could be prevented from getting the disease with a single dose of the drug.

“People at highest risk of being sub-clinically infected are household contacts. They were already at risk because of their exposure to a known case (though, after taking multidrug therapy that first case will not infect anyone else) but many of them also had a common genetic heritage, meaning they were more susceptible to leprosy than an average person.”

In the pre LPEP study in Bangladesh 20,000 contacts of those diagnosed with leprosy were given rifampicin or a placebo in a double blind, randomised, controlled trial. When they were followed up for two years later the number of new cases among contacts who had the capsule was found to be almost 60% fewer than among those who had the placebo.

The study also found those who had had the childhood BCG (Bacillus Calmette-Guérin) vaccine to protect against Tuberculosis (TB) had 75% more protection when taking rifampicin.

Dr Vander Plaetse said: “Various other drugs have been evaluated, but the evidence from trials in Bangladesh suggest rifampicin has the potential to prevent leprosy in contacts.”

The current trials by the Novartis Foundation are being conducted with leprosy organisations including  the International Federation of Anti-Leprosy Associations and the governments of each country.

Contacts monitored for two years

Over the next two years the contacts who are given the single dose of rifampicin will be monitored to assess the programme’s feasibility.

Dr Vander Plaetse said:. “What we are aiming for is the long-term benefits – zero transmission. We are very confident the results of this program will contribute significantly to our fight to eliminate this disease, which still impacts the poorest of the poor around the world.”

Preliminary findings of the LPEP trials will be presented at the 19th International Leprosy Congress in Beijing in September.