Role of histopathological, serological and molecular findings for the early diagnosis of treatment failure in leprosy
Background: Treatment failure (TF) in leprosy following multidrug therapy (MDT) presents a significant challenge. The current World Health Organization (WHO) fixed-duration MDT regimen, based on lesion count, might not be adequate. Leprosy lacks clear-cut objective cure criteria, and the predictive value of post-MDT histopathological findings remains uncertain. This study aims to identify predictive factors for TF among leprosy patients who have completed the WHO-recommended MDT.
Methods: An analysis was conducted on 80 individuals from a national leprosy reference center, comprising 40 TF cases (with a mean relapse at 13.0 months) and 40 controls (with a mean of 113.1 months without disease signs). Various epidemiological and clinical-laboratory parameters were assessed post-MDT.
Results: In skin samples, the presence of foamy granuloma (OR=7.36; 95%CI2.20-24.60; p=0.0012) and histological bacillary index (hBI)≥1+ (OR=1.55; 95%CI1. 22-1.99; p=0.0004) were significantly associated with TF, with odds ratios of 7.36 and 1.55, respectively. Individuals who experienced TF had a mean hBI of 3.02+ (SD±2.02), while the control group exhibited a mean hBI of 1.8+ (SD±1.88). An hBI≥3+showed a sensitivity of 73% and a specificity of 78% for TF detection (AUC: 0.75; p=0.0001). Other histopathological features like epithelioid granulomas, and skin changes did not show significant associations (p>0.05). Additionally, higher anti-phenolic glycolipid-I (anti-PGL-I) ELISA index (EI) levels were linked to a 1.4-fold increased likelihood for TF (OR=1.4; 95%CI1.13-1.74; p=0.0019). A mean EI of 4.48 (SD±2.80) was observed, with an EI≥3.95 showing a sensitivity of 79% and a specificity of 59% for TF detection (AUC: 0.74; p=0.0001). Moreover, the presence of Mycobacterium leprae (M. leprae) DNA in real-time polymerase chain reaction (qPCR) was associated with a 3.43-fold higher likelihood of TF. Multivariate regression analysis indicated that concurrent presentation of neural/perineural lymphocytic infiltrate, foamy granuloma, hBI≥1+, and EI≥1 markedly increased the likelihood of TF by up to 95.41%.