de Carvalho Dornelas Bruno, da Costa Willian Vargas Tenório, de Abreu João Pablo Ferraz, Daud Juliana Salomão, Campos Felipe Dos Anjos Rodrigues, de Oliveira Campos Deiriene Rodrigues, Antunes Douglas Eulálio, de Araújo Lúcio Borges, Dos Santos Diogo Fernandes, Soares Cleverson Teixeira, Goulart Isabela Maria Bernardes
Pathology Unit, Hospital of Clinics, Federal University of Uberlândia, Brazilian Company for Hospital Services (HC-UFU/EBSERH), Uberlândia, MG, Brazil.
Post-Graduation Program in Health Science, School of Medicine, Federal University of Uberlândia, Uberlândia, MG, Brazil.
BMC Infect Dis. 2024 Oct 1;24(1):1085. doi: 10.1186/s12879-024-09937-2.
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.
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.
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%.
Persistence of nerve-selective lymphocytic infiltrate, foamy granulomas, and bacilli in skin biopsies, and elevated EI post-MDT, may serve as predictive factors for identifying individuals at higher probability of TF.
多药联合疗法（MDT）治疗麻风病后的治疗失败（TF）是一个重大挑战。目前世界卫生组织（WHO）基于皮损数量的固定疗程MDT方案可能并不充分。麻风病缺乏明确的客观治愈标准，MDT后组织病理学检查结果的预测价值仍不确定。本研究旨在确定已完成WHO推荐的MDT的麻风病患者中TF的预测因素。
对一家国家麻风病参考中心的80名个体进行分析，其中包括40例TF病例（平均复发时间为13.0个月）和40名对照（平均113.1个月无疾病体征）。MDT后评估了各种流行病学和临床实验室参数。
在皮肤样本中，泡沫状肉芽肿的存在（OR = 7.36；95%CI 2.20 - 24.60；p = 0.0012）和组织学细菌指数（hBI）≥1+（OR = 1.55；95%CI 1.22 - 1.99；p = 0.0004）与TF显著相关，比值比分别为7.36和1.55。发生TF的个体平均hBI为3.02+（标准差±2.02），而对照组平均hBI为1.8+（标准差±1.88）。hBI≥3+对TF检测的敏感性为73%，特异性为78%（曲线下面积：0.75；p = 0.0001）。其他组织病理学特征如上皮样肉芽肿和皮肤改变未显示出显著相关性（p > 0.05）。此外，较高的抗酚糖脂-I（anti-PGL-I）酶联免疫吸附测定（ELISA）指数（EI）水平与TF可能性增加1.4倍相关（OR = 1.4；95%CI 1.13 - 1.74；p = 0.0019）。观察到平均EI为4.48（标准差±2.80），EI≥3.95对TF检测的敏感性为79%，特异性为59%（曲线下面积：0.74；p = 0.0001）。此外，实时聚合酶链反应（qPCR）中麻风分枝杆菌（M. leprae）DNA的存在与TF可能性高3.43倍相关。多变量回归分析表明，神经/神经周围淋巴细胞浸润、泡沫状肉芽肿、hBI≥1+和EI≥1同时出现使TF可能性显著增加高达95.41%。
皮肤活检中神经选择性淋巴细胞浸润、泡沫状肉芽肿和杆菌的持续存在，以及MDT后EI升高，可能作为识别TF可能性较高个体的预测因素。
