Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Clin Infect Dis. 2012 Sep;55(5):621-30. doi: 10.1093/cid/cis486. Epub 2012 May 18.
The aim of this study was to determine whether improvement of filarial lymphedema (LE) by doxycycline is restricted to patients with ongoing infection (positive for circulating filarial antigen [CFA]), or whether the majority of CFA-negative patients with LE would also show a reduction in LE severity.
One hundred sixty-two Ghanaian participants with LE stage 1-5 (Dreyer) were randomized blockwise into 2 groups (CFA positive or negative) and allocated to 3 treatment arms of 6 weeks: (1) amoxicillin (1000 mg/d), (2) doxycycline (200 mg/d), or (3) placebo matching doxycycline. All groups received standard hygiene morbidity management. The primary outcome was reduction of LE stages. Secondary outcomes included frequency of acute attacks and ultrasonographic assessment of skin thickness at the ankles. Parameters were assessed before treatment and after 3, 12, and 24 months.
Doxycycline-treated patients with LE stage 2-3 showed significant reductions in LE severity after 12 and 24 months, regardless of CFA status. Improvement was observed in 43.9% of doxycycline-treated patients, compared with only 3.2% and 5.6% in the amoxicillin and placebo arms, respectively. Skin thickness was correlated with LE stage improvement. Both doxycycline and amoxicillin were able to reduce acute dermatolymphangioadenitis attacks.
Doxycycline treatment improves mild to moderate LE independent of ongoing infection. This finding expands the benefits of doxycycline to the entire population of patients suffering from LE. Patients with LE stage 1-3 should benefit from a 6-week course of doxycycline every other year or yearly, which should be considered as an improved tool to manage morbidity in filarial LE. Clinical Trials Registration. ISRCTN 90861344.
本研究旨在确定多西环素改善丝虫性淋巴水肿(LE)是否仅限于正在感染(循环丝虫抗原 [CFA] 阳性)的患者,或者大多数 CFA 阴性的 LE 患者是否也会减轻 LE 严重程度。
162 名加纳 LE 1-5 期(Dreyer)患者按块随机分为 2 组(CFA 阳性或阴性),并分配到 3 个为期 6 周的治疗组:(1)阿莫西林(1000mg/d),(2)多西环素(200mg/d),或(3)与多西环素匹配的安慰剂。所有组均接受标准卫生发病管理。主要结局是 LE 分期减少。次要结局包括急性发作频率和踝关节皮肤厚度的超声评估。参数在治疗前和治疗后 3、12 和 24 个月进行评估。
LE 2-3 期的多西环素治疗患者无论 CFA 状态如何,在 12 和 24 个月后 LE 严重程度均显著降低。与阿莫西林和安慰剂组分别为 3.2%和 5.6%相比,多西环素治疗组中观察到改善的患者有 43.9%。皮肤厚度与 LE 分期改善相关。多西环素和阿莫西林均能减少急性皮肤淋巴管炎发作。
多西环素治疗可改善轻度至中度 LE,与持续感染无关。这一发现将多西环素的益处扩展到了所有患有 LE 的患者。LE 1-3 期的患者应受益于每 6 周一次的多西环素疗程,每年或每年一次,这应被视为改善丝虫性 LE 发病管理的工具。临床试验注册。ISRCTN 90861344。