Clofazimine and dapsone compliance in leprosy

Abstract

SummaryThe regularity with which multi bacillary patients, who were being treated with the WHO Study Group regimen in a THELEP-sponsored field trial in South India, ingested their prescribed daily clofazimine and dapsone was studied. The ingestion of clofazimine was monitored using a specially prepared fo rmulation containing minute amounts of isoniazid as an innocuous marker. Overall drug acceptability and compliance was excellent. Approximately 75% of the prescribed daily clofazimine and dapsone doses were being ingested and it was concluded that only 5% of the patients would have benefited if their treatment had been supplemented by acedapsone injections.There was however a marked correlation between the self-administration of the 2 drugs with the consequence that the patients at greatest risk of developing rifampicin resistance because of poor dapsone compliance were the very ones most unlikely to take their daily clofazimine treatment. The results obtained emphasize the importance of employing regimens containing high degrees of supervised drug administration, especially in areas where drug compliance is known to be poor.It is recommended that all multibacillary patients should be treated with a combination of rifampicin plus dapsone plus clofazimine.1 The efficiency of two such regimens is currently being evaluated in a THELEP-sponsored field trial at the Schieffelin Leprosy Research and Training Centre in Karigiri, in the North Arcot District of Tamil Nadu in South India. 2 In regimen A, supervised 600 mg doses of rifampicin and of clofazimine were given on each of 2 consecutive days once every 4 weeks. The patients were also given 100 mg tablets of dapsone for daily self administration supplemented with intramuscular injections of 225 mg diacetyldapsone (acedap sone) once every 8 weeks which release on average 3 mg dapsone daily. Regimen B was identical to that recommended by the WHO Study Group for the routine treatment of multibacillary patients, I consisting of monthly supervised doses of600 mg rifampicin and 300 mg clofazimine supplemented by daily doses of 50 mg clofazimine and 100 mg dapsone for self-administration. Treatment was to be continued for at least 2 years and until the patients became smear-negative.

Leprosy therapy, past and present: Can we hope to eliminate it?

“…[28] With MDT, the adherence was only 70–80%. [29] However, to accelerate leprosy elimination process, recently the WHO leprosy programme and its TAG have changed dramatically their position on supervised therapy. They concluded that after the first dose of MDT “supervision of the subsequent monthly component of the MDT regimens is no longer essential.“[30] Further, on the basis of this conclusion they recommended large-scale implementation of accompanied multidrug therapy (AMDT), which refers to a policy that patients are provided the entire supply of MDT drugs at the time of diagnosis, when choosing someone close to them to accompany them with their treatment.…”

Bactericidal Activity of a Single-Dose Combination of Ofloxacin plus Minocycline, with or without Rifampin, against Mycobacterium leprae in Mice and in Lepromatous Patients

“…The major objective of combining RMP with DDS and CLO is to ensure the elimination of spontaneously occurring RMP-resistant mutants before stopping chemotherapy (14). However, even in the best leprosy control program, it is difficult to persuade patients to adhere to the self-administered daily therapy (3), suggesting that RMP resistance may still develop if the DDS-CLO component is not taken regularly. RMP resistance might be reduced if a fully supervised, monthly administered MDT regimen can be developed, i.e., if all of the components are given under supervision once monthly.…”

Advances and hurdles on the way toward a leprosy vaccine

“…For example, patients often neglect their treatments, because clofazimine causes stigmatizing skin discoloration or they become weary of the length of treatment. 13,14 The largest reported study is a 6-y follow up of 47,276 patients conducted in China, which revealed an overall relapse rate of 0.73/1,000 person-years [with the risk of PB patient relapse (1.04/1,000 person-years) significantly greater than that for MB patients (0.61/1,000 personyears)]. 15,16 A 10-y prospective study in the Philippines observed an overall relapse rate equivalent to 2.8/1,000 person-years.…”