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评价在埃及上埃及地区一次由三氯苯达唑失败引起的人类片形吸虫病爆发中使用硝唑尼特治疗的效果。

Evaluation of nitazoxanide treatment following triclabendazole failure in an outbreak of human fascioliasis in Upper Egypt.

机构信息

Department of Tropical medicine and Gastroenterology, Faculty of Medicine, Assiut University, Egypt.

Department of Parasitology, Faculty of Medicine, Assiut University, Egypt.

出版信息

PLoS Negl Trop Dis. 2019 Sep 25;13(9):e0007779. doi: 10.1371/journal.pntd.0007779. eCollection 2019 Sep.

Abstract

BACKGROUND

Fascioliasis is a neglected zoonosis with major public health implications in humans. Although triclabendazole (TCBZ) is the drug of choice, there are records of TCBZ failure worldwide. TCBZ-resistant fascioliasis is treated with alternative approved drugs including nitazoxanide (NTZ), with varying levels of efficacy. Data on NTZ efficacy after TCBZ failure in Egypt is scarce. This study evaluated the efficacy of NTZ in cases of TCBZ failure during an outbreak of fascioliasis in Assiut governorate of Upper Egypt.

METHODOLOGY/PRINCIPAL FINDINGS: This prospective study included 67 patients from the outpatient clinic in Manfalout locality of Assiut governorate with clinical manifestations of acute fascioliasis. These included high eosinophilia (> 6% eosinophils in peripheral blood), positive anti-Fasciola antibodies, and hepatic focal lesions (HFL) or ascites on abdominal ultrasound or computed tomography. All patients initially received TCBZ at recommended doses. Patients were followed up after 1 month to assess response. According to the responses, patients were categorized as non-responders and responders. The non-responders received a trial of NTZ and were re-assessed for response based on clinical manifestations, eosinophil count, and abdominal ultrasound. Patients not responding to NTZ received additional doses of TCBZ. One month after initial TCBZ treatment, 37 patients responded well to TCBZ, while 30 patients failed to respond with persistence of fever, abdominal pain, high eosinophilia, and HFL. Most non-responders were male (56.7%); females predominated among TCBZ responders (62.2%). The mean age of the non-responders was relatively lower, at 20.57 ± 14.47 years (p = 0.004). Following NTZ therapy, HFL disappeared in 9/30 (30%) patients and eosinophil counts normalized in only 2 (6.7%) patients, indicating an overall efficacy of 36.6%. The remaining cases received additional doses of TCBZ with complete clinical, biochemical, and radiological resolution.

CONCLUSIONS/SIGNIFICANCE: Nitazoxanide was partially effective in TCBZ failure in acute human fascioliasis in Upper Egypt. Further studies with larger samples are highly encouraged and further research is urgently needed to find new therapeutic alternatives to TCBZ.

摘要

背景

片形吸虫病是一种被忽视的动物源性人畜共患病,对人类健康有重大影响。尽管三氯苯达唑(TCBZ)是首选药物,但在全球范围内都有 TCBZ 治疗失败的记录。用已批准的替代药物治疗 TCBZ 耐药的片形吸虫病,包括硝唑尼特(NTZ),但其疗效各不相同。关于埃及 TCBZ 治疗失败后 NTZ 疗效的数据很少。本研究评估了在埃及上埃及 Assiut 省片形吸虫病暴发期间,用 TCBZ 治疗失败的情况下,使用 NTZ 的疗效。

方法/主要发现:本前瞻性研究纳入了来自 Assiut 省 Manfalout 地区门诊的 67 名患者,这些患者有急性片形吸虫病的临床表现,包括外周血嗜酸性粒细胞计数高(>6%)、抗片形吸虫抗体阳性、肝局灶性病变(HFL)或腹水的腹部超声或计算机断层扫描。所有患者最初均按推荐剂量接受 TCBZ 治疗。治疗 1 个月后随访,评估疗效。根据疗效,患者分为无反应者和有反应者。无反应者接受硝唑尼特治疗,并根据临床表现、嗜酸性粒细胞计数和腹部超声评估反应。对硝唑尼特无反应的患者给予 TCBZ 加量治疗。初始 TCBZ 治疗 1 个月后,37 例患者对 TCBZ 反应良好,30 例患者无反应,表现为发热、腹痛、嗜酸性粒细胞计数高和 HFL 持续存在。大多数无反应者为男性(56.7%);TCBZ 反应者中女性居多(62.2%)。无反应者的平均年龄较低,为 20.57±14.47 岁(p=0.004)。硝唑尼特治疗后,30 例患者中有 9 例(30%)HFL 消失,2 例(6.7%)嗜酸性粒细胞计数正常,表明总有效率为 36.6%。其余病例接受了 TCBZ 加量治疗,临床、生化和影像学均完全缓解。

结论/意义:在埃及上埃及急性人类片形吸虫病中,硝唑尼特对 TCBZ 治疗失败有一定疗效。强烈鼓励开展更大样本量的进一步研究,迫切需要开展进一步的研究,以寻找 TCBZ 的新治疗替代方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9afe/6779272/1528ff76b1aa/pntd.0007779.g001.jpg

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