Single-dose rifampicin chemoprophylaxis protects those who need it least and is not a cost-effective intervention

We, as leprosy academics, have written the following letter to The Global Leprosy Programme and the Indian National Programme.Single-dose rifampicin (SDR) treatment being offered to household contacts of new leprosy patients is being practiced by the Indian National Leprosy Programme since November 2017 [1].We are concerned, because this is not an effective method for preventing multibacillary (MB) leprosy.It does not protect against the development of MB leprosy and does not protect immediate household contacts for a reasonable period of time.There are serious ethical problems related to identifying the contacts of patients with leprosy, it is not cost effective for household contacts, and there is a possibility of the widespread use of SDR promoting the development of rifampicin resistance genes in Mycobacterium leprae.It is claimed that SDR gives 57% protection against the development of leprosy in contacts [2].However, this is when all types of leprosy (paucibacillary [PB], MB, and single-lesion leprosy [SLL]) are combined.The main study testing the effectiveness of SDR in protecting against leprosy is the Chemoprophylaxis of Leprosy (COLEP) trial in Bangladesh [3].In this study, 21,711 contacts of newly diagnosed leprosy patients were randomized to receive SDR or a placebo.Household contacts who took SDR did not have significant protection against developing leprosy (odds ratio [OR] 0.46 [0.15-1.38],p = 0.1652); it only protected neighbours of neighbours (OR 0.24 [0.11-0.52])against the development of leprosy.SDR did not protect against the development of MB leprosy (0.52 [0.22-1.19],p = 0.1201); however, it did protect against the development of PB leprosy (0.38 [0.16-0.87],p = 0.0218) and single-lesion leprosy (0.42 [0.20-0.89]). Protection only lasted 2 years.These findings suggest that SDR treatment is only effective when patients have a low mycobacterial load, hence the protection only against the development of PB leprosy.In the nude mouse model, up to 20 doses of rifampicin 10 mg/ kg were required to significantly decrease mRNA M. leprae levels in experimental leprosy, which again suggests that multiple doses of rifampicin will be needed if this intervention is to be effective [4].One cannot assume that the index case is the source of infection to contacts in high endemic settings when there is a possibility of exposure to M. leprae from multiple resources.SDR is being promoted because it is an easier intervention and any intervention that required 2 doses of rifampicin would be very challenging to administer.However, previous studies on leprosy chemotherapy have found that killing M. leprae often requires multiple doses of an active agent over several months.