Long-term relapse risk of multibacillary leprosy after completion of 2 years of multiple drug therapy (WHO-MDT) in Cebu, Philippines.
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.
Leonard Wood Memorial Center for Leprosy Research, Cebu, Philippines.
Marivic F
MF
Balagon
Roland V
RV
Cellona
Eduardo dela
Ed
Cruz
Jasmin A
JA
Burgos
Rodolfo M
RM
Abalos
Gerald P
GP
Walsh
Paul R
PR
Saunderson
Douglas S
DS
Walsh
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D006801:Humans; D007917:Leprostatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007918:Leprosy / Q000188:drug therapy*; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000187:drug effects; D010679:Philippines / Q000453:epidemiology; D012008:Recurrence; D013997:Time Factors; D055815:Young Adult
D007917:Leprostatic Agents