旅行者急性不明原因发热症的生物火®多重 PCR 检测板的临床评估：一项前瞻性多中心研究。

Clinical evaluation of BioFire® multiplex-PCR panel for acute undifferentiated febrile illnesses in travellers: a prospective multicentre study.

机构信息

ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.

Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.

出版信息

J Travel Med. 2023 May 18;30(3). doi: 10.1093/jtm/taad041.

DOI:10.1093/jtm/taad041

PMID:36988415

Abstract

BACKGROUND

Identifying the causes of Acute Undifferentiated Febrile Illness (AUFI) is key to improve the management of returning travellers with fever. We evaluated a BioFire®FilmArray® prototype panel of multiplex nucleic acid amplification tests (NAAT) targeting different relevant pathogens in travellers returning with fever.

METHODS

Prospective, multicentre study to evaluate a prototype panel in whole blood samples of adult international travellers presenting with AUFI in three European travel Clinics/Hospitals (November 2017-November 2019). We evaluated 15 target analytes: Plasmodium spp., Plasmodium falciparum, Plasmodium knowlesi, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, chikungunya virus, dengue virus, Zika virus, Anaplasma phagocytophilum, Borrelia spp., Leptospira spp., Orientia tsutsugamushi, Rickettsia spp. and Salmonella spp. Results were compared with composite reference standards (CRSs) for each target infection, including direct methods [smear microscopy, rapid diagnostic test (RDT), reference NAAT and blood cultures] and indirect methods (paired serology).

FINDINGS

Among 455 travellers with AUFI, 229 target infections were diagnosed; the prototype panel detected 143 (overall sensitivity and specificity of 62.5 and 99.8%, respectively). The panel identified all Plasmodium infections (n = 82). Sensitivity for dengue (n = 71) was 92.9, 80.8 and 68.5% compared with RDT, NAAT and CRS, respectively. Compared with direct methods and CRS, respectively, the prototype panel detected 4/4 and 4/6 chikungunya, 2/2 and 4/29 Leptospira spp., 1/1 and 1/6 O. tsutsugamushi and 2/2 and 2/55 Rickettsia spp., but 0/2 and 0/10 Zika, 0/1 and 0/11 A. phagocytophylum and 0/3 Borrelia spp. diagnosed by serology and only 1/7 Salmonella spp. diagnosed by blood cultures. 77/86 (89.5%) infections not detected by the panel were diagnosed by serology.

INTERPRETATION

The prototype panel allowed rapid and reliable diagnosis for malaria, dengue and chikungunya. Further improvements are needed to improve its sensitivity for Zika and important travel-related bacterial infections.

摘要

背景

明确急性未分化发热性疾病（AUFI）的病因是改善发热归国旅行者管理的关键。我们评估了一种生物火®FilmArray®多聚核苷酸扩增检测（NAAT）的原型试剂盒，该试剂盒针对发热的国际旅行者中不同相关病原体。

方法

前瞻性、多中心研究，评估了三种欧洲旅行诊所/医院（2017 年 11 月至 2019 年 11 月）中出现 AUFI 的成年国际旅行者的全血样本中的原型试剂盒。我们评估了 15 个靶标分析物：疟原虫属，恶性疟原虫，疟原虫 knowlesi，疟原虫疟原虫，疟原虫卵形，疟原虫 vivax，基孔肯雅病毒，登革热病毒，寨卡病毒，嗜吞噬细胞无形体，螺旋体属，钩端螺旋体属，恙虫病东方体，立克次体属和沙门氏菌属。结果与每个靶感染的复合参考标准（CRS）进行了比较，包括直接方法[涂片显微镜检查，快速诊断试验（RDT），参考 NAAT 和血液培养]和间接方法（配对血清学）。

发现

在 455 名 AUFI 旅行者中，诊断出 229 种目标感染；原型试剂盒检测到 143 种（总体敏感性和特异性分别为 62.5%和 99.8%）。该试剂盒鉴定了所有疟原虫感染（n=82）。与 RDT，NAAT 和 CRS 相比，登革热（n=71）的敏感性分别为 92.9、80.8 和 68.5%。与直接方法和 CRS 相比，原型试剂盒分别检测到 4/4 和 4/6 基孔肯雅病毒，2/2 和 4/29 螺旋体属，1/1 和 1/6 恙虫病东方体和 2/2 和 2/55 立克次体属，但 0/2 和 0/10 寨卡病毒，0/1 和 0/11 嗜吞噬细胞无形体和 0/3 螺旋体属通过血清学诊断，仅 1/7 沙门氏菌属通过血液培养诊断。未通过试剂盒检测到的 77/86（89.5%）种感染通过血清学诊断。