Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study

Background: Up to 45% of febrile returning travellers remain undiagnosed after a thorough diagnostic work-up, even at referral centres. Although metagenomic next-generation sequencing (mNGS) has emerged as a promising tool, evidence of its usefulness in imported fever is very limited. Methods: Trave...

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Autores: Camprubí Ferrer, Daniel, Tomazatos, Alexandru, Balerdi Sarasola, Leire, Cobuccio, Ludovico G., Van Den Broucke, Steven, Horváth, Balázs, Van Esbroeck, Marjan, Martínez Yoldi, Miguel Julián, Gandasegui Javier, Subirà, Carme, Saloni Rodriguez, Meritxell, Genton, Blaise, Bottieau, Emmanuel, Cadar, Daniel, Muñoz, José
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/215016
Acceso en línea:https://hdl.handle.net/2445/215016
Access Level:acceso abierto
Palabra clave:Febre
Dengue
Malària
Viatges
Metagenòmica
ADN
Fever
Malaria
Travels
Metagenomics
DNA
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spelling Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort studyCamprubí Ferrer, DanielTomazatos, AlexandruBalerdi Sarasola, LeireCobuccio, Ludovico G.Van Den Broucke, StevenHorváth, BalázsVan Esbroeck, MarjanMartínez Yoldi, Miguel JuliánGandasegui JavierSubirà, CarmeSaloni Rodriguez, MeritxellGenton, BlaiseBottieau, EmmanuelCadar, DanielMuñoz, JoséFebreDengueMalàriaViatgesMetagenòmicaADNFeverDengueMalariaTravelsMetagenomicsDNABackground: Up to 45% of febrile returning travellers remain undiagnosed after a thorough diagnostic work-up, even at referral centres. Although metagenomic next-generation sequencing (mNGS) has emerged as a promising tool, evidence of its usefulness in imported fever is very limited. Methods: Travellers returning with fever were prospectively recruited in three referral clinics from November 2017 to November 2019. Unbiased mNGS optimised for virus detection was performed on serum samples of participants with acute undifferentiated febrile illness (AUFI), and results were compared to those obtained by reference diagnostic methods (RDM). Results: Among 507 returned febrile travellers, 433(85.4%) presented with AUFI. Dengue virus (n = 86) and Plasmodium spp. (n = 83) were the most common causes of fever. 103/433(23.8%) AUFI remained undiagnosed at the end of the follow-up.Metagenomic next-generation sequencing unveiled potentially pathogenic microorganisms in 196/433(38.7%) AUFI. mNGS identifications were more common in patients with a shorter duration of fever (42.3% in ≤5 days vs 28.7% in >5 days, P = 0.005). Potential causes of fever were revealed in 25/103(24.2%) undiagnosed AUFI and 5/23(21.7%) travellers with severe undiagnosed AUFI. Missed severe aetiologies included eight bacterial identifications and one co-infection of B19 parvovirus and Aspergillus spp.Additional identifications indicating possible co-infections occurred in 29/316(9.2%) travellers with AUFI, and in 11/128(8.6%) travellers with severe AUFI, who had received a diagnosis through RDM. The most common co-infections detected in severe AUFI were caused by Gram-negative bacteria. Serum mNGS was unable to detect >50% of infectious diagnoses achieved by RDM and also yielded 607 non-pathogenic identifications. Discussion: mNGS of serum can be a valuable diagnostic tool for selected travellers with undiagnosed AUFI or severe disease in addition to reference diagnostic techniques, especially during the first days of symptoms. Nevertheless, mNGS results interpretation presents a great challenge. Further studies evaluating the performance of mNGS using different sample types and protocols tailored to non-viral agents are needed.Oxford University Press2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/215016Articles publicats en revistes (Fonaments Clínics)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1093/jtm/taae029Journal of Travel Medicine, 2024, vol. 31, num.3https://doi.org/10.1093/jtm/taae029(c) International Society of Travel Medicine, 2024info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2150162026-05-27T06:46:51Z
dc.title.none.fl_str_mv Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study
title Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study
spellingShingle Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study
Camprubí Ferrer, Daniel
Febre
Dengue
Malària
Viatges
Metagenòmica
ADN
Fever
Dengue
Malaria
Travels
Metagenomics
DNA
title_short Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study
title_full Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study
title_fullStr Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study
title_full_unstemmed Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study
title_sort Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study
dc.creator.none.fl_str_mv Camprubí Ferrer, Daniel
Tomazatos, Alexandru
Balerdi Sarasola, Leire
Cobuccio, Ludovico G.
Van Den Broucke, Steven
Horváth, Balázs
Van Esbroeck, Marjan
Martínez Yoldi, Miguel Julián
Gandasegui Javier
Subirà, Carme
Saloni Rodriguez, Meritxell
Genton, Blaise
Bottieau, Emmanuel
Cadar, Daniel
Muñoz, José
author Camprubí Ferrer, Daniel
author_facet Camprubí Ferrer, Daniel
Tomazatos, Alexandru
Balerdi Sarasola, Leire
Cobuccio, Ludovico G.
Van Den Broucke, Steven
Horváth, Balázs
Van Esbroeck, Marjan
Martínez Yoldi, Miguel Julián
Gandasegui Javier
Subirà, Carme
Saloni Rodriguez, Meritxell
Genton, Blaise
Bottieau, Emmanuel
Cadar, Daniel
Muñoz, José
author_role author
author2 Tomazatos, Alexandru
Balerdi Sarasola, Leire
Cobuccio, Ludovico G.
Van Den Broucke, Steven
Horváth, Balázs
Van Esbroeck, Marjan
Martínez Yoldi, Miguel Julián
Gandasegui Javier
Subirà, Carme
Saloni Rodriguez, Meritxell
Genton, Blaise
Bottieau, Emmanuel
Cadar, Daniel
Muñoz, José
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Febre
Dengue
Malària
Viatges
Metagenòmica
ADN
Fever
Dengue
Malaria
Travels
Metagenomics
DNA
topic Febre
Dengue
Malària
Viatges
Metagenòmica
ADN
Fever
Dengue
Malaria
Travels
Metagenomics
DNA
description Background: Up to 45% of febrile returning travellers remain undiagnosed after a thorough diagnostic work-up, even at referral centres. Although metagenomic next-generation sequencing (mNGS) has emerged as a promising tool, evidence of its usefulness in imported fever is very limited. Methods: Travellers returning with fever were prospectively recruited in three referral clinics from November 2017 to November 2019. Unbiased mNGS optimised for virus detection was performed on serum samples of participants with acute undifferentiated febrile illness (AUFI), and results were compared to those obtained by reference diagnostic methods (RDM). Results: Among 507 returned febrile travellers, 433(85.4%) presented with AUFI. Dengue virus (n = 86) and Plasmodium spp. (n = 83) were the most common causes of fever. 103/433(23.8%) AUFI remained undiagnosed at the end of the follow-up.Metagenomic next-generation sequencing unveiled potentially pathogenic microorganisms in 196/433(38.7%) AUFI. mNGS identifications were more common in patients with a shorter duration of fever (42.3% in ≤5 days vs 28.7% in >5 days, P = 0.005). Potential causes of fever were revealed in 25/103(24.2%) undiagnosed AUFI and 5/23(21.7%) travellers with severe undiagnosed AUFI. Missed severe aetiologies included eight bacterial identifications and one co-infection of B19 parvovirus and Aspergillus spp.Additional identifications indicating possible co-infections occurred in 29/316(9.2%) travellers with AUFI, and in 11/128(8.6%) travellers with severe AUFI, who had received a diagnosis through RDM. The most common co-infections detected in severe AUFI were caused by Gram-negative bacteria. Serum mNGS was unable to detect >50% of infectious diagnoses achieved by RDM and also yielded 607 non-pathogenic identifications. Discussion: mNGS of serum can be a valuable diagnostic tool for selected travellers with undiagnosed AUFI or severe disease in addition to reference diagnostic techniques, especially during the first days of symptoms. Nevertheless, mNGS results interpretation presents a great challenge. Further studies evaluating the performance of mNGS using different sample types and protocols tailored to non-viral agents are needed.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/215016
url https://hdl.handle.net/2445/215016
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1093/jtm/taae029
Journal of Travel Medicine, 2024, vol. 31, num.3
https://doi.org/10.1093/jtm/taae029
dc.rights.none.fl_str_mv (c) International Society of Travel Medicine, 2024
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) International Society of Travel Medicine, 2024
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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