PEP++: an enhanced regimen for leprosy

An enhanced regimen as post-​exposure chemoprophylaxis for leprosy: PEP++ is the title of a recently published article on an expert meeting convened by NLR to advise on a combination of available drugs as post-​exposure prophylaxis (PEP) for leprosy.

A close contact of a person affected by leprosy takes preventative medication against leprosy

While single dose rifampicin as PEP gives a risk reduction of around 60% when given to contacts of leprosy patients, the PEP++ regimen seeks a risk reduction of 80 – 90%. Besides the bactericidal, sterilising and bacteriostatic activity of the possible drugs, the safety, acceptability, availability, feasibility, affordability and risk of drug resistance were considered. The expert meeting recommended a combination of moxifloxacin and rifampicin in three doses with an interval of one month between doses. The effectiveness of this ‘PEP++ regimen’ will be determined and compared to SDR-​PEP in the ‘PEP++ project’.

Preventing new cases

It is well known that contacts of (former) leprosy patients have a higher risk of developing leprosy as they are more likely to have been exposed to the bacteria. Providing post-​exposure prophylaxis (PEP) to these contacts will reduce their risk to develop the disease and will contribute to stopping the transmission of leprosy by preventing new cases. Several chemoprophylactic regimens have demonstrated to be effective in contacts, including single dose rifampicin (SDR), which reduces the risk by 60%. Preliminary results of the LPEP project also show that the level of acceptance of SDR-​PEP among contacts is very high and the integration of SDR-​PEP in routine leprosy control is feasible. A likely reason for its limited effectiveness to date is that a single dose is insufficient to prevent manifestations of the disease in those that have advanced subclinical infection. Therefore, a more potent antibiotic or regimen is needed as chemoprophylaxis to prevent new cases among the closest, mostly household, contacts.

Leprosy preventative medication pills

Innovative tools and best practices

The PEP++ project, designed by NLR, aims to stop the transmission of leprosy by using a package of innovative tools and best practices. Among them, an enhanced prophylactic regimen for contacts of leprosy patients. In November 2016, an expert meeting was held with epidemiologists, pharmacologists and public health scientists to come up with recommendations for such an enhanced regimen. They advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of intake, targeting a risk reduction of 80 – 90%. The drugs considered were rifampicin, rifapentine, clofazimine, dapsone, moxifloxacin, ofloxacin, minocycline and clarithromycin. Besides the effectiveness of the potential drugs, the feasibility, safety, acceptability, availability, affordability and risk of inducing drug resistance were taken into account. To minimise the risk of inducing drug resistance, it was decided to use a combination of at least two drugs and set up a surveillance system in the PEP++ project.

Enhanced regimen

Combinations that were considered but not recommended for several reasons were: one or two months of standard multi-​drug therapy (MDT) as prophylactic treatment and a combination with rifapentine. The expert meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at two– or four-​weekly intervals, although this was later set at four weeks to coincide with MDT practices. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).

PEP++ project