LAUSR

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, multicenter study to evaluate a prototype panel in whole blood samples of adult international travellers presenting with AUFI in three European travel Clinics/Hospitals (November2017-November2019). We evaluated 15 target analytes: Plasmodium spp., P.falciparum, P.knowlesi, P.malariae, P.ovale, P.vivax, chikungunya virus, dengue virus, Zika virus, Anaplasma phagocytophilum, Borrelia spp., Leptospira spp., Orientia tsutsugamushi, Rickettsia spp., Salmonella spp. Results were compared with composite reference standards(CRS) for each target infection, including direct methods (smear microscopy, rapid diagnostic test(RDT), reference NAAT, 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 to RDT, NAAT and CRS. Compared to 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, 2/2 and 2/55 Rickettsia spp., but 0/2 and 0/10 Zika, 0/1 and 0/11 A.phagocytophylum, 0/3 Borrelia spp. diagnosed by serology and 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.