Long-Term Relapse Risk of Multibacillary Leprosy after Completion of 2 Years of Multiple Drug Therapy (WHO-MDT) in Cebu, Philippines

• Published in: The American journal of tropical medicine and hygiene Vol. 81; no. 5; pp. 895 - 899
• Main Authors: Balagon, Marivic F, Cellona, Roland V, Cruz, Eduardo dela, Burgos, Jasmin A, Abalos, Rodolfo M, Walsh, Gerald P, Saunderson, Paul R, Walsh, Douglas S
• Format: Journal Article
• Language: English
• Published: Deerfield, IL ASTMH 01.11.2009; American Society of Tropical Medecine and Hygiene
• Subjects: Adolescent; Adult; Aged; Bacterial diseases; Biological and medical sciences; Child; Drug Resistance, Bacterial; Drug Therapy, Combination; Human bacterial diseases; Humans; Infectious diseases; Leprostatic Agents - administration & dosage; Leprostatic Agents - therapeutic use; Leprosy; Leprosy - drug therapy; Medical sciences; Middle Aged; Mycobacterium leprae; Mycobacterium leprae - drug effects; Philippines - epidemiology; Recurrence; Time Factors; Tropical bacterial diseases; Young Adult; Asia; Philippines; Infection; Skin disease; Relapse; Multiple; Treatment; Risk factor; Bacteriosis; Multibacillary leprosy; Tropical medicine; Mycobacterial infection; Long term; WHO
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.2009.09-0189

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) ≥ 2+ (≥ 100×) 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 ≥ 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.