02017nas a2200409   4500000000100000008004100001260001300042653001500055653001000070653000900080653001000089653003100099653003000130653001100160653002300171653001200194653001600206653002500222653001600247653001500263653001700278653001600295100001400311700001500325700001600340700001300356700001300369700001300382700001700395700001300412245013800425856005600563300001000619490000700629520095700636022001401593       2009                            d  c2009 Nov10aAdolescent10aAdult10aAged10aChild10aDrug Resistance, Bacterial10aDrug Therapy, Combination10aHumans10aLeprostatic Agents10aleprosy10aMiddle Aged10aMycobacterium leprae10aPhilippines10aRecurrence10aTime Factors10aYoung Adult1 aBalagon M1 aCellona RV1 aDela Cruz E1 aBurgos J1 aAbalos R1 aWalsh GP1 aSaunderson P1 aWalsh DS00aLong-term relapse risk of multibacillary leprosy after completion of 2 years of multiple drug therapy (WHO-MDT) in Cebu, Philippines.  uhttp://www.ajtmh.org/content/81/5/895.full.pdf+html  a895-90 v813 a<p>From 1987 to 1994, we enrolled 500 subjects completing 2-year WHO multiple drug therapy (MDT) for multibacillary leprosy in a prospective relapse study. Relapse was defined as new skin lesions and an increase in the bacterial index (BI) > or = 2+ (> or = 100x) at any single slit-skin smear site. At the study end in 2006, follow-up was 6,401 subject-years, a mean of 12.8 years/subject. We observed 23 relapses, 6-16 years after MDT (mean, 10.5 years; 95% confidence interval [CI], 9.2-11.8), peaking in Years 11-12 (> 1%/year). The cumulative risk was 6.6% (95% CI, 5.0-8.2%). In a subset of 181 subjects with pre-MDT average BI > or = 4+, 11 relapses occurred (cumulative risk, 10.1%). In mouse footpad assays, Mycobacterium leprae from relapsed subjects were rifampin and clofazimine sensitive. Taken together, the data suggest relapses are related to activation of dormant organisms (persisters) not killed by MDT rather than new infection.</p>  a1476-1645