Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
PLoS Negl Trop Dis. 2022 Feb 9;16(2):e0010096. doi: 10.1371/journal.pntd.0010096. eCollection 2022 Feb.
Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG.
All consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy.
Of the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007).
IDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG.
Registration number NCT02899936; https://clinicaltrials.gov/ct2/show/NCT02899936.
巴布亚新几内亚（PNG）由于班克罗夫特氏丝虫（Wuchereria bancrofti）导致的淋巴丝虫病负担沉重，估计有 420 万人面临感染风险。在小型临床试验中，伊维菌素、乙胺嗪和阿苯达唑（IDA）联合单次给药在持续清除微丝蚴方面的疗效明显优于乙胺嗪和阿苯达唑（DA）。在 PNG 中度流行且未经治疗的地区，进行了一项社区为基础的、基于群组的、随机对照试验，比较了 DA 与 IDA 治疗 LF 的安全性和疗效。
所有同意并符合条件的 PNG Madang 省 Bogia 区 24 个村庄的居民都参与了这项研究，他们接受了班克罗夫特氏丝虫抗原血症和微丝蚴（Mf）筛查，并根据居住的村庄随机接受 IDA（N = 2382）或 DA（N = 2181）治疗。通过主动随访 2 天和被动随访 5 天评估不良事件（AE）。抗原阳性的参与者在 MDA 一年后再次接受检测，以评估治疗效果。
在 4563 名参与者中，96%的参与者在治疗后 2 天内接受了 AE 评估。接受 DA（18%）或 IDA（20%）治疗后的 AE 总体发生率相似。对于那些有 AE 的人，87%是轻度（1 级），13%是中度（2 级），没有 3 级、4 级或严重 AE（SAE）。在 Mf 阳性的参与者中，接受 IDA 治疗的 AE 发生率高于 Mf 阴性参与者（39%比 20%，p<0.001），接受 IDA 治疗的 Mf 阳性参与者（39%）高于接受 DA 治疗的参与者（24%，p = 0.023）。治疗一年后，基线时抗原阳性的 64%（645/1013）的参与者再次接受筛查，其中 74%（475/645）的参与者仍然抗原阳性。IDA 组感染个体中 96%（52/54）清除了 Mf，而 DA 组中 84%（56/67）清除了 Mf（相对风险（RR）1.15；95%置信区间，1.02 至 1.30；p = 0.019）。接受 DA 治疗的参与者未能清除 Mf 的可能性高 4 倍（RR 4.67（95%置信区间：1.05 至 20.67；p = 0.043）。在 DA 组中，未能清除 Mf 的显著预测因素是基线 Mf 密度（RR 1.54；95%置信区间，1.09 至 2.88；p = 0.007）。
IDA 耐受性良好，清除 Mf 的效果优于 DA。广泛使用这种方案可以加速 PNG 消除 LF。
注册号 NCT02899936；https://clinicaltrials.gov/ct2/show/NCT02899936。
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