03182nas a2200325 4500000000100000008004100001260004400042653003400086653004000120653001200160653001400172653002200186100002700208700001700235700001700252700001200269700001600281700002600297700001500323700001800338700001800356700001400374700001600388245012200404856008600526300000900612490000700621520221400628022001402842 2024 d bSpringer Science and Business Media LLC10aphenolic glycolipid-I (PGL-I)10aReal-Time Polymerase Chain Reaction10aLeprosy10aPathology10aTreatment Failure1 ade Carvalho Dornelas B1 ada Costa WVT1 ade Abreu JPF1 aDaud JS1 aCampos FDAR1 ade Oliveira Campos DR1 aAntunes DE1 ade Araújo LB1 ados Santos DF1 aSoares CT1 aGoulart IMB00aRole of histopathological, serological and molecular findings for the early diagnosis of treatment failure in leprosy uhttps://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-024-09937-2.pdf a1-130 v243 a

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%.

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