高灵敏度诊断、PCR 和 UCP-LF CAA 揭示重复吡喹酮治疗曼氏血吸虫感染效果有限（RePST 试验）。
Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial).
机构信息
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
出版信息
PLoS Negl Trop Dis. 2022 Dec 22;16(12):e0011008. doi: 10.1371/journal.pntd.0011008. eCollection 2022 Dec.
BACKGROUND
Most studies assessing praziquantel (PZQ) efficacy have used relatively insensitive diagnostic methods, thereby overestimating cure rate (CR) and intensity reduction rate (IRR). To determine accurately PZQ efficacy, we employed more sensitive DNA and circulating antigen detection methods.
METHODOLOGY
A sub-analysis was performed based on a previously published trial conducted in children from Côte d'Ivoire with a confirmed Schistosoma mansoni infection, who were randomly assigned to a standard (single dose of PZQ) or intense treatment group (4 repeated doses of PZQ at 2-week intervals). CR and IRR were estimated based on PCR detecting DNA in a single stool sample and the up-converting particle lateral flow (UCP-LF) test detecting circulating anodic antigen (CAA) in a single urine sample, and compared with traditional Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA).
PRINCIPAL FINDINGS
Individuals positive by all diagnostic methods (i.e., KK, POC-CCA, PCR, and UCP-LF CAA) at baseline were included in the statistical analysis (n = 125). PCR showed a CR of 45% (95% confidence interval (CI) 32-59%) in the standard and 78% (95% CI 66-87%) in the intense treatment group, which is lower compared to the KK results (64%, 95% CI 52-75%) and 88%, 95% CI 78-93%). UCP-LF CAA showed a significantly lower CR in both groups, 16% (95% CI 11-24%) and 18% (95% CI 12-26%), even lower than observed by POC-CCA (31%, 95% CI 17-35% and 36%, 95% CI 26-47%). A substantial reduction in DNA and CAA-levels was observed after the first treatment, with no further decrease after additional treatment and no significant difference in IRR between treatment groups.
CONCLUSION/SIGNIFICANCE: The efficacy of (repeated) PZQ treatment was overestimated when using egg-based diagnostics (i.e. KK and PCR). Quantitative worm-based diagnostics (i.e. POC-CCA and UCP-LF CAA) revealed that active Schistosoma infections are still present despite multiple treatments. These results stress the need for using accurate diagnostic tools to monitor different PZQ treatment strategies, in particular when moving toward elimination of schistosomiasis.
CLINICAL TRIAL REGISTRATION
www.clinicaltrials.gov, NCT02868385.
背景
大多数评估吡喹酮（PZQ）疗效的研究都使用了相对不敏感的诊断方法，从而高估了治愈率（CR）和强度降低率（IRR）。为了准确确定 PZQ 的疗效，我们采用了更敏感的 DNA 和循环抗原检测方法。
方法
根据先前在科特迪瓦患有曼氏血吸虫感染的儿童中进行的一项试验进行了子分析，这些儿童被随机分配到标准（单次 PZQ 剂量）或强化治疗组（每 2 周重复 4 次 PZQ 剂量）。根据单个粪便样本中 PCR 检测 DNA 和单个尿液样本中上转换粒子侧向流动（UCP-LF）检测循环阳极抗原（CAA），估计 CR 和 IRR，并与传统的加藤氏（KK）和即时检测循环阴极抗原（POC-CCA）进行比较。
主要发现
基线时所有诊断方法（即 KK、POC-CCA、PCR 和 UCP-LF CAA）均为阳性的个体被纳入统计分析（n=125）。PCR 在标准治疗组的 CR 为 45%（95%CI 32-59%），在强化治疗组的 CR 为 78%（95%CI 66-87%），低于 KK 结果（64%，95%CI 52-75%）和 88%，95%CI 78-93%）。UCP-LF CAA 在两组中的 CR 均显著较低，分别为 16%（95%CI 11-24%）和 18%（95%CI 12-26%），甚至低于 POC-CCA（31%，95%CI 17-35%和 36%，95%CI 26-47%）。首次治疗后，DNA 和 CAA 水平明显降低，进一步治疗后无进一步降低，两组间 IRR 无显著差异。
结论/意义：当使用基于卵的诊断方法（即 KK 和 PCR）时，（重复）PZQ 治疗的疗效被高估了。定量基于蠕虫的诊断方法（即 POC-CCA 和 UCP-LF CAA）表明，尽管进行了多次治疗，但仍存在活动性血吸虫感染。这些结果强调需要使用准确的诊断工具来监测不同的 PZQ 治疗策略，特别是在朝着消除血吸虫病的方向发展时。
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