Lymphatic pathology in asymptomatic and symptomatic children with <i>Wuchereria bancrofti</i> infection in children from Odisha, India and its reversal with DEC and albendazole treatment

Background Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally. Methods Children aged 5–18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years. Findings Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs. Interpretation A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration. Trial registration ClinicalTrials.gov No CTRI/2013/10/004121背景 一旦实现淋巴丝虫病（Lymphatic Filariasis, LF）的传播阻断，发病预防与管理便成为更为关键的工作。一项针对印度马来布鲁线虫（Brugia malayi）丝虫病的研究已证实存在具备潜在可逆性的亚临床淋巴病理改变。本研究针对全球淋巴丝虫病的主要致病原——班氏吴策线虫（Wuchereria bancrofti）感染人群展开研究。 方法 本研究对印度奥里萨邦5~18岁儿童开展班氏吴策线虫（Wuchereria bancrofti）感染与相关疾病的筛查。最终纳入102名班氏吴策线虫感染者，其中50名患有丝虫病性疾病，52名无相关症状。所有受试者均接受淋巴闪烁显像（lymphoscintigraphy）检查，随后被随机分配至接受督导下单次口服乙胺嗪（Diethylcarbamazine, DEC）与阿苯达唑（albendazole）治疗组，治疗方案分别为每年给药1次或每半年给药1次，并在后续两年内每6个月对其淋巴病理改变进行一次评估。 结果 基线淋巴闪烁显像（lymphoscintigraphy）结果显示，有症状患儿中有80%（40/50）、无症状患儿中有63.5%（33/52）存在下肢淋巴管异常。在随访6、12、18及24个月时，分别有70.8%、87.3%、98.6%及98.6%的受试者基线病理改变得到逐步改善，另有4.2%、22.5%、47.9%及64.8%的受试者病理改变完全恢复正常。上述改善效果与年龄（p=0.27）、症状状态（p=0.57）及给药频次（每年1次vs每半年1次，p=0.46）均无相关性。11例下肢淋巴水肿（lymphedema）患者中，有6例出现临床症状减轻。 解读 本研究结果表明，相当比例的年轻班氏吴策线虫（Wuchereria bancrofti）感染者存在淋巴病理改变，且通过每年1次的乙胺嗪（Diethylcarbamazine, DEC）与阿苯达唑（albendazole）治疗可实现病理逆转。该发现为早期淋巴水肿（lymphedema）的发病预防与治疗提供了依据，同时也可作为提升大规模药物治疗期间社区依从性的辅助手段。 试验注册 ClinicalTrials.gov 编号：CTRI/2013/10/004121