Efficacy and safety of praziquantel and dihydroartemisinin piperaquine combination for treatment and control of intestinal schistosomiasis: A randomized, non-inferiority clinical trial.
Efficacy and safety of praziquantel and dihydroartemisinin piperaquine combination for treatment and control of intestinal schistosomiasis: A randomized, non-inferiority clinical trial.
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DOI：
10.1371/journal.pntd.0008619
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发表时间：
2020-09
影响因子：
3.8
通讯作者：
Aklillu E
中科院分区：
文献类型：
--
作者：
Mnkugwe RH;Minzi O;Kinung'hi S;Kamuhabwa A;Aklillu E
尽管据报告在降低发病率方面取得了成功，但仅用吡喹酮不足以控制和消除血吸虫病，部分原因是其对幼蠕虫的疗效差。青蒿素衍生物对蠕虫有效，但对蠕虫不太有效。比较吡喹酮与双氢青蒿素-哌喹联合用药与吡喹酮单药治疗肠道血吸虫病的疗效和安全性。在这项随机、开放标签、非劣效性试验中，639例曼氏血吸虫感染儿童入组并随机接受吡喹酮单药治疗或吡喹酮加双氢青蒿素-哌喹联合治疗。在基线、治疗后3周和8周连续采集两份粪便样本，并使用厚涂片Kato Katz方法进行分析。通过治疗后3周和8周的治愈率和减蛋率评估疗效。不良事件在服药后4小时内进行评估。主要结局是治疗后8周的治愈率。次要结果是治疗后8周的卵子减少率和治疗相关不良事件。治疗后3周，治愈率为88.3%（263/298，95% CI = 84.1%- 91.4%）和81.2%（277/341，95% CI = 76.7%- 85.0%），分别为联合治疗组和吡喹酮单药组（p < 0.01，比值比（OR）= 1.74，OR的95%CI = 1.11至2.69）。8周时，单用吡喹酮组治愈率明显下降，为63.9%（218/341，95% CI = 58.7%- 68.8%）与81.9%相比（244/298，95%CI = 77.1%- 85.8%）（p < 0.0001，OR = 2.55，OR的95%CI = 1.75 - 3.69）。联合治疗组治疗后8周的卵子减少率为93.6%（95% CI = 90.8%- 96.4%），显著高于吡喹酮单药治疗组的87.9%（95% CI = 84.4%- 91.4%）（p = 0.01）。在单变量和多变量回归分析中，接受的治疗类型是治疗后第8周治愈的重要预测因素。总体而言，30.8%（95% CI = 27.2%- 34.4%）的研究参与者发生了轻度和一过性治疗相关不良事件，治疗后腹痛（27.1%）是观察到的最常见不良事件。两个治疗组之间不良事件的总体发生率无显著差异。吡喹酮和双氢青蒿素哌喹联合治疗肠道血吸虫病是安全的，并且比吡喹酮单独治疗更有效。需要进一步的研究来探索联合治疗是否可以被认为是大规模药物管理的一种选择，以控制并最终消除血吸虫病。血吸虫病是一种被忽视的热带疾病，由一种名为血吸虫的寄生虫引起。该病主要表现为血尿（尿血吸虫病）和血性腹泻（肠血吸虫病）。血吸虫病在感染早期通常无症状，但如果不治疗，可能会导致毁灭性的长期并发症，包括儿童生长和认知发育不良、门脉高压和癌症。几年来，撒哈拉以南非洲的儿童一直在接受有针对性的大规模吡喹酮治疗，以控制和消除血吸虫病。尽管据报告在降低发病率方面取得了成功，但单剂量吡喹酮治疗显然不足以在流行国家消除血吸虫病。这部分是由于其对寄生虫的未成熟/幼年期的活性差。先前的研究报道青蒿素衍生物对蠕虫有效。在这项研究中，我们探讨了吡喹酮和双氢青蒿素-哌喹的联合治疗是否会通过靶向杀死寄生虫的两个发育阶段（成熟和蠕虫）来提高疗效。在一项随机临床试验中，我们比较了吡喹酮和双氢青蒿素-哌喹联合治疗与标准吡喹酮单独治疗坦桑尼亚西北部农村流行性肠道血吸虫病的疗效和安全性。结论吡喹酮联合双氢青蒿素哌喹治疗肠道血吸虫病安全有效。
Despite the reported success in reducing morbidity, praziquantel alone is insufficient for the control and elimination of schistosomiasis, partly due to its poor efficacy against the juvenile worms. Artemisinin derivatives are effective against juvenile worms but are less effective against adult worms. We compared the safety and efficacy of praziquantel and Dihydroartemisinin-piperaquine combination against the standard praziquantel alone for treatment of intestinal schistosomiasis. In this randomized, open-label, non-inferiority trial, 639 Schistosoma mansoni infected children were enrolled and randomized to receive either praziquantel alone or praziquantel plus Dihydroartemisinin-piperaquine combination. Two stool samples were collected on consecutive days at baseline, 3 and 8 weeks post-treatment and analyzed using thick smear Kato Katz method. Efficacy was assessed by cure and egg reduction rates at 3 and 8 weeks post-treatment. Adverse events were assessed within four hours of drugs intake. The primary outcome was cure rates at 8 weeks of post-treatment. Secondary outcomes were egg reduction rates at 8 weeks of post-treatment and treatment-associated adverse events. At 3 weeks of post-treatment, cure rates were 88.3% (263/298, 95% CI = 84.1%– 91.4%) and 81.2% (277/341, 95% CI = 76.7%– 85.0%) for the combination therapy and praziquantel alone, respectively (p < 0.01, odds ratio (OR) = 1.74, 95% CI of OR = 1.11 to 2.69). At 8 weeks, there was a significant drop in the cure rates in praziquantel alone group to 63.9% (218/341, 95% CI = 58.7%– 68.8%) compared to 81.9% (244/298, 95% CI = 77.1%– 85.8%) in the combination therapy group (p < 0.0001, OR = 2.55, 95%CI of OR = 1.75 to 3.69). Egg reduction rates at 8 weeks post-treatment were significantly higher in the combination therapy group 93.6% (95% CI = 90.8%– 96.4%) compared to 87.9% (95% CI = 84.4%– 91.4%) in the praziquantel only group (p = 0.01). On both Univariate and Multivariate regression analysis, type of treatment received was a significant predictor of cure at week 8 post-treatment. Overall, 30.8% (95% CI = 27.2%– 34.4%) of the study participants experienced mild and transient treatment-associated adverse events, post-treatment abdominal pain (27.1%) being the most common adverse event observed. There was no significant difference in the overall occurrence of adverse events between the two treatment groups. Praziquantel and Dihydroartemisinin piperaquine combination therapy is safe, and more efficacious compared to praziquantel alone for the treatment of intestinal schistosomiasis. Further studies are needed to explore if the combination therapy can be considered as an option for mass drug administration to control and eventually eliminate schistosomiasis. Schistosomiasis is a Neglected Tropical Disease, which is caused by a parasite called Schistosoma. The disease is mainly manifested by bloody urine (urinary schistosomiasis) and bloody diarrhea (intestinal schistosomiasis). Schistosomiasis is usually asymptomatic during early infection but, if not treated, may cause devastating long-term complications, including poor growth and cognitive development in children, portal hypertension, and cancers. For several years, children in Sub Saharan Africa have been receiving targeted mass praziquantel treatments for the control and elimination of schistosomiasis. Despite the reported success in reducing morbidity, single dose praziquantel alone treatment is apparently insufficient for elimination of schistosomiasis in endemic countries. This is partly due to its poor activity against the immature/juvenile stage of the parasite. Previous studies reported that artemisinin derivatives are effective against juvenile worms. In this study, we explored if combination therapy of praziquantel and Dihydroartemisinin-piperaquine would increase the efficacy by targeting to kill both developmental stages (matured and juvenile worms) of the parasite. In a randomized clinical trial, we compared the efficacy and safety of combination therapy of praziquantel and Dihydroartemisinin-piperaquine against the standard praziquantel alone for the treatment of intestinal schistosomiasis in a rural endemic setting in North-Western Tanzania. Our findings indicate that praziquantel and Dihydroartemisinin piperaquine combination therapy is safe and more effective than praziquantel alone for the treatment of intestinal schistosomiasis.
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影响因子：
3.8
作者：
Hotez PJ;Alvarado M;Basáñez MG;Bolliger I;Bourne R;Boussinesq M;Brooker SJ;Brown AS;Buckle G;Budke CM;Carabin H;Coffeng LE;Fèvre EM;Fürst T;Halasa YA;Jasrasaria R;Johns NE;Keiser J;King CH;Lozano R;Murdoch ME;O'Hanlon S;Pion SD;Pullan RL;Ramaiah KD;Roberts T;Shepard DS;Smith JL;Stolk WA;Undurraga EA;Utzinger J;Wang M;Murray CJ;Naghavi M
通讯作者：
Naghavi M
影响因子：
3.8
作者：
Coulibaly, Jean T.;N'Gbesso, Yve K.;Utzinger, Juerg
通讯作者：
Utzinger, Juerg
影响因子：
3.8
作者：
Andrade G;Bertsch DJ;Gazzinelli A;King CH
通讯作者：
King CH
DOI：
10.1016/j.trstmh.2008.08.002
发表时间：
2009-01-01
影响因子：
2.2
作者：
Inyang-Etoh, P. C.;Ejezie, G. C.;Inyang-Etoh, E. C.
通讯作者：
Inyang-Etoh, E. C.
影响因子：
1.9
作者：
Abay, Solomon M.;Tilahun, Mulugeta;Habtewold, Abiy
通讯作者：
Habtewold, Abiy