欧洲发热儿童分子病原体检测与临床疾病之间的关系：一项多中心前瞻性观察研究。
Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study.
作者信息
Shah Priyen, Voice Marie, Calvo-Bado Leonides, Rivero-Calle Irene, Morris Sophie, Nijman Ruud, Broderick Claire, De Tisham, Eleftheriou Irini, Galassini Rachel, Khanijau Aakash, Kolberg Laura, Kolnik Mojca, Rudzate Aleksandra, Sagmeister Manfred G, Schweintzger Nina A, Secka Fatou, Thakker Clare, van der Velden Fabian, Vermont Clementien, Vincek Katarina, Agyeman Philipp K A, Cunnington Aubrey J, De Groot Ronald, Emonts Marieke, Fidler Katy, Kuijpers Taco W, Mommert-Tripon Marine, Brengel-Pesce Karen, Mallet Francois, Moll Henriette, Paulus Stéphane, Pokorn Marko, Pollard Andrew, Schlapbach Luregn J, Shen Ching-Fen, Tsolia Maria, Usuf Effua, van der Flier Michiel, von Both Ulrich, Yeung Shunmay, Zavadska Dace, Zenz Werner, Wright Victoria, Carrol Enitan D, Kaforou Myrsini, Martinon-Torres Federico, Fink Colin, Levin Michael, Herberg Jethro
机构信息
Section of Paediatric Infectious Disease, Department of Infectious Diseases, and Centre for Paediatrics and Child Health, Imperial College, London, UK.
Micropathology Ltd, University of Warwick, Coventry, UK.
出版信息
Lancet Reg Health Eur. 2023 Jul 26;32:100682. doi: 10.1016/j.lanepe.2023.100682. eCollection 2023 Sep.
BACKGROUND
The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.
METHODS
Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.
FINDINGS
Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for (OR: 3.37, 95% CI: 1.92-5.99), (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.
INTERPRETATION
Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.
FUNDING
EU Horizon 2020 grant 668303.
背景
PERFORM研究旨在通过比较分子病原体检测与当前临床实践来了解儿童发热性疾病的病因。
方法
2016年至2020年期间，在9个欧洲国家的医院招募了发热儿童和对照儿童。根据对当地临床和微生物学数据的回顾性审查，为每个儿童指定一个标准化诊断类别。随后，对19种呼吸道病原体和27种血液病原体进行了集中分子检测（CMT）。
结果
在4611名发热儿童中，643名（14%）被归类为确诊细菌感染（DB），491名（11%）为确诊病毒感染（DV），3477名（75%）病因不明。招募了1061名无感染的对照儿童。CMT在DB病例中检测出血液细菌的频率高于DV病例，包括肺炎链球菌（OR：3.37，95%CI：1.92 - 5.99）、金黄色葡萄球菌（OR：3.89，95%CI：2.07 - 7.59）、A组链球菌（OR 2.73，95%CI 1.13 - 6.09）和B组链球菌（OR 2.7，95%CI 1.02 - 6.71）。发热儿童中的呼吸道病毒比对照儿童更常见，但只有甲型流感（OR 0.24，95%CI 0.11 - 0.46）、乙型流感（OR 0.12，95%CI 0.02 - 0.37）和呼吸道合胞病毒（OR 0.16，95%CI：0.06 - ）在DB病例中比DV病例中更少见。在16种血液病毒中，肠道病毒（OR 0.43，95%CI 0.23 - 0.72）和EB病毒（OR 0.）在DB病例中比DV病例中检测到的频率更低。联合当地诊断和CMT分别在360名（56%）和161名（25%）DB病例中检测出血液病毒和呼吸道病毒，病毒检测对排除细菌感染的效果不佳，预测值分别为0.64和0.68。
解读
当分子检测补充传统方法时，大多数发热儿童不能明确界定为细菌或病毒感染。在大多数细菌感染患者中检测到病毒，个体病原体检测在确定治疗方面的临床价值较低。需要新的方法来帮助确定哪些发热儿童需要使用抗生素。
资金来源
欧盟地平线2020资助项目668303。
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