Yahathugoda Thishan Channa, De Silva Nirmitha Lalindi, Ruben Janaka, Gunawardena Sharmini, Weerasooriya Mirani Vasanthamala, Horton John, Budge Philip, Ottesen Eric, Sullivan Sarah Mary, Stephens Mariana, Shen John, Klarmann-Schulz Ute, Hoerauf Achim, Shott Joseph Patrick, Mackenzie Charles
Filariasis Research Training and Service Unit, Department of Parasitology, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka.
Department of Parasitology, Faculty of Medicine, University of Colombo, Sri Lanka.
Am J Trop Med Hyg. 2024 Jul 23;111(4_Suppl):52-65. doi: 10.4269/ajtmh.24-0050. Print 2024 Oct 1.
Morbidity management of filarial lymphedema remains a challenge even during the post-lymphatic filariasis elimination era in Sri Lanka despite provision of the predominantly hygiene-based WHO Essential Package of Care. Because prior studies have suggested that 6 weeks of doxycycline may reduce progression of limb lymphedema, we conducted a randomized, placebo-controlled, superiority study to evaluate this possibility in Sri Lanka. Patients aged 14 to 65 years with lymphedema in one or both legs received either 200 mg of doxycycline daily for 6 weeks or matching placebo. The primary efficacy endpoint was improvement or lack of progression in lymphedema stage at 24 months postenrollment. Secondary endpoints included change in lymphedema stage at 12 and 24 months, frequency of acute adenolymphangitis episodes, and perceived disability measured by the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). Training and supplies for limb hygiene were provided throughout the study. Two hundred participants (100 in each arm) with lymphedema of Dreyer stages 1 to 3 were enrolled. By the end of the 2-year study, 29% of the doxycycline patients and 34% of those on placebo showed improvement (i.e., a decrease in lymphedema stage), whereas 11% and 15% of the two groups showed worsening of the lymphedema. Adenolymphangitis rates were comparable in the two groups (43 doxycycline and 38 placebo recipients), although attacks lasted slightly longer in placebo patients (6.5 days versus 5.2 days). In both groups, perceived disability improved initially, with partial rebound in the second year. Only 34 adverse events affecting 24 patients (11%) occurred during the 6-week treatment period. Although doxycycline did not significantly impact lymphedema progression in this study, the results clearly indicate that clinical and personal benefits can be obtained from intensive hygiene management alone.
尽管斯里兰卡提供了以卫生为主的世界卫生组织基本护理包，但在淋巴丝虫病消除后的时代，丝虫性淋巴水肿的发病管理仍然是一项挑战。由于先前的研究表明，6周的强力霉素治疗可能会减少肢体淋巴水肿的进展，因此我们在斯里兰卡进行了一项随机、安慰剂对照的优效性研究，以评估这种可能性。年龄在14至65岁之间、单腿或双腿患有淋巴水肿的患者，接受为期6周的每日200毫克强力霉素治疗或匹配的安慰剂治疗。主要疗效终点是入组后24个月时淋巴水肿阶段的改善或无进展。次要终点包括12个月和24个月时淋巴水肿阶段的变化、急性腺淋巴管炎发作的频率，以及通过世界卫生组织残疾评估量表2.0（WHODAS 2.0）测量的感知残疾。在整个研究过程中，提供了肢体卫生方面的培训和用品。招募了200名患有德雷尔1至3期淋巴水肿的参与者（每组100名）。到2年研究结束时，29%的强力霉素治疗患者和34%的安慰剂治疗患者显示有改善（即淋巴水肿阶段降低），而两组分别有11%和15%的患者淋巴水肿恶化。两组的腺淋巴管炎发生率相当（强力霉素组43例，安慰剂组38例），尽管安慰剂组患者的发作持续时间略长（6.5天对5.2天）。在两组中，感知残疾最初都有所改善，在第二年出现部分反弹。在6周的治疗期内，仅发生了影响24名患者（11%）的34起不良事件。尽管在本研究中强力霉素对淋巴水肿进展没有显著影响，但结果清楚地表明，仅通过强化卫生管理就能获得临床和个人益处。
