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.
Balagon
Marivic F
MF
Leonard Wood Memorial Center for Leprosy Research, Cebu, Philippines.
Cellona
Roland V
RV
Cruz
Eduardo dela
Ed
Burgos
Jasmin A
JA
Abalos
Rodolfo M
RM
Walsh
Gerald P
GP
Saunderson
Paul R
PR
Walsh
Douglas S
DS
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