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

Daniel Camprubí-Ferrer, Ludovico Cobuccio, Steven Van Den Broucke, Leire Balerdi-Sarasola, Blaise Genton, Emmanuel Bottieau, Jessica Navero-Castillejos, Miguel J Martinez, Corinne Jay, Anne Grange, Stéphanie Borland, Mike Vaughn, Natalia Rodriguez-Valero, Alex Almuedo-Riera, Valérie D'Acremont, Carme Subirà, Tessa Alba, Angeline Cruz, Marjan Van Esbroeck, Crystal SmithAshley Hillman, Brandon Hanberg, Rob Trauscht, Nerissa Spampanato, Jose Muñoz

Research output: Contribution to journalA1: Web of Science-articlepeer-review

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.

Original languageEnglish
Article numbertaad041
JournalJournal of Travel Medicine
Volume30
Issue number3
Number of pages8
ISSN1195-1982
DOIs
Publication statusPublished - 2023

Keywords

  • Adult
  • Chikungunya Fever/diagnosis
  • Dengue/diagnosis
  • Fever/etiology
  • Humans
  • Malaria/diagnosis
  • Multiplex Polymerase Chain Reaction
  • Prospective Studies
  • Rickettsia
  • Travel
  • Travel-Related Illness
  • Zika Virus
  • Zika Virus Infection

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