The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
Timor-Leste Ministry of Health, Dili, Timor-Leste.
Lancet Glob Health. 2023 Jun;11(6):e924-e932. doi: 10.1016/S2214-109X(23)00134-1.
Integrated programmes that use combination mass drug administration (MDA) might improve control of multiple neglected tropical diseases simultaneously. We investigated the impact of Timor-Leste's national ivermectin, diethylcarbamazine citrate, and albendazole MDA, for lymphatic filariasis elimination and soil-transmitted helminth (STH) control, on scabies, impetigo, and STH infections.
We did a before-after study in six primary schools across three municipalities in Timor-Leste (urban [Dili], semi-urban [Ermera], and rural [Manufahi]) before (April 23 to May 11, 2019) and 18 months after (Nov 9 to Nov 27, 2020) MDA delivery between May 17 and June 1, 2019. Study participants included schoolchildren, as well as infants, children, and adolescents who were incidentally present at school on study days. All schoolchildren whose parents provided consent were eligible to participate in the study. Infants, children, and adolescents younger than 19 years who were not enrolled in the school but were incidentally present at schools on study days were also eligible to participate if their parents consented. Ivermectin, diethylcarbamazine citrate, and albendazole MDA was implemented nationally, with single doses of oral ivermectin (200 μg/kg), diethylcarbamazine citrate (6 mg/kg), and albendazole (400 mg) administered by the Ministry of Health. Scabies and impetigo were assessed by clinical skin examinations, and STHs using quantitative PCR. The primary (cluster-level) analysis adjusted for clustering while the secondary (individual-level) analysis adjusted for sex, age, and clustering. The primary outcomes of the study were prevalence ratios for scabies, impetigo, and STHs (Trichuris trichiura, Ascaris lumbricoides, Necator americanus, and moderate-to-heavy A lumbricoides infections) between baseline and 18 months from the cluster-level analysis.
At baseline, 1043 (87·7%) of 1190 children registered for the study underwent clinical assessment for scabies and impetigo. The mean age of those who completed skin examinations was 9·4 years (SD 2·4) and 514 (53·8%) of 956 were female (87 participants with missing sex data were excluded from this percentage calculation). Stool samples were received for 541 (45·5%) of 1190 children. The mean age of those for whom stool samples were received was 9·8 years (SD 2·2) and 300 (55·5%) were female. At baseline, 348 (33·4%) of 1043 participants had scabies, and 18 months after MDA, 133 (11·1%) of 1196 participants had scabies (prevalence ratio 0·38, 95% CI 0·18-0·88; p=0·020) in the cluster-level analysis. At baseline, 130 (12·5%) of 1043 participants had impetigo, compared with 27 (2·3%) of 1196 participants at follow-up (prevalence ratio 0·14, 95% CI 0·07-0·27; p<0·0001). There was a significant reduction in T trichiura prevalence from baseline (26 [4·8%] of 541 participants) to 18-month follow-up (four [0·6%] of 623 participants; prevalence ratio 0·16, 95% CI 0·04-0·66; p<0·0001). In the individual-level analysis, moderate-to-heavy A lumbricoides infections reduced from 54 (10·0%; 95% CI 0·7-19·6) of 541 participants to 28 (4·5%, 1·2-8·4) of 623 participants (relative reduction 53·6%; 95% CI 9·1-98·1; p=0·018).
Ivermectin, diethylcarbamazine citrate, and albendazole MDA was associated with substantial reductions in prevalence of scabies, impetigo, and T trichiura, and of moderate-to-heavy intensity A lumbricoides infections. Combination MDA could be used to support integrated control programmes to target multiple NTDs.
National Health and Medical Research Council of Australia and the Department of Foreign Affairs and Trade Indo-Pacific Centre for Health Security.
For the Tetum translation of the abstract see Supplementary Materials section.
采用联合群体药物治疗(MDA)的综合方案可能同时改善多种被忽视热带病的控制。我们研究了东帝汶全国伊维菌素、柠檬酸双羟萘酸噻嘧啶和阿苯达唑 MDA 用于淋巴丝虫病消除和土壤传播性蠕虫(STH)控制对疥疮、脓疱疮和 STH 感染的影响。
我们在东帝汶三个市(城市[帝力]、半城市[埃雷拉]和农村[马努法希])的六所小学进行了一项在 MDA 给药前(2019 年 4 月 23 日至 5 月 11 日)和给药后 18 个月(2020 年 11 月 9 日至 11 月 27 日)的前后研究。研究参与者包括在校学生,以及在研究日偶然在学校的婴儿、儿童和青少年。所有父母同意的在校学生都有资格参加研究。未在学校注册但在研究日偶然在学校的年龄在 19 岁以下的婴儿、儿童和青少年,如果父母同意,也有资格参加。伊维菌素、柠檬酸双羟萘酸噻嘧啶和阿苯达唑 MDA 由国家实施,给予单一剂量的口服伊维菌素(200μg/kg)、柠檬酸双羟萘酸噻嘧啶(6mg/kg)和阿苯达唑(400mg)。疥疮和脓疱疮通过临床皮肤检查进行评估,而 STH 使用定量 PCR 进行检测。主要(群集水平)分析在调整聚类的同时进行,次要(个体水平)分析在调整性别、年龄和聚类的同时进行。研究的主要结局是从聚类水平分析基线和 18 个月后疥疮、脓疱疮和 STH(鞭虫、蛔虫、美洲钩虫和中度至重度蛔虫感染)的患病率比值。
基线时,1190 名登记参加研究的儿童中有 1043 名(87.7%)接受了疥疮和脓疱疮的临床评估。完成皮肤检查的儿童平均年龄为 9.4 岁(SD 2.4),514 名(53.8%)为女性(87 名参与者的性别数据缺失,从这个百分比计算中排除)。收到了 541 名(45.5%)1190 名儿童的粪便样本。收到粪便样本的儿童平均年龄为 9.8 岁(SD 2.2),其中 300 名(55.5%)为女性。基线时,1043 名参与者中有 348 名(33.4%)患有疥疮,MDA 给药后 18 个月时,1196 名参与者中有 133 名(11.1%)患有疥疮(患病率比值 0.38,95%CI 0.18-0.88;p=0.020)。基线时,1043 名参与者中有 130 名(12.5%)患有脓疱疮,而在随访时,1196 名参与者中有 27 名(2.3%)患有脓疱疮(患病率比值 0.14,95%CI 0.07-0.27;p<0.0001)。从基线(541 名参与者中有 26 名[4.8%])到 18 个月随访(623 名参与者中有 4 名[0.6%]),鞭虫的患病率显著降低(患病率比值 0.16,95%CI 0.04-0.66;p<0.0001)。在个体水平分析中,中度至重度蛔虫感染从基线时的 54 名(10.0%;95%CI 0.7-19.6)减少到 18 个月随访时的 28 名(4.5%;1.2-8.4)(相对减少 53.6%;95%CI 9.1-98.1;p=0.018)。
伊维菌素、柠檬酸双羟萘酸噻嘧啶和阿苯达唑 MDA 联合治疗与疥疮、脓疱疮和鞭虫的患病率以及中度至重度蛔虫感染显著降低有关。联合 MDA 可用于支持综合控制方案,以针对多种 NTD。
澳大利亚国家卫生和医学研究委员会和外交和贸易部的印度太平洋卫生安全中心。