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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Accepted version |
| Publication date: | 2024 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/215016 |
| Online Access: | https://hdl.handle.net/2445/215016 |
| Access Level: | Open access |
| Keyword: | Febre Dengue Malària Viatges Metagenòmica ADN Fever Malaria Travels Metagenomics DNA |
| _version_ | 1878730820443701248 |
|---|---|
| author | Camprubí Ferrer, Daniel |
| 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 |
| author_browse | Balerdi Sarasola, Leire Bottieau, Emmanuel Cadar, Daniel Camprubí Ferrer, Daniel Cobuccio, Ludovico G. Gandasegui Javier Genton, Blaise Horváth, Balázs Martínez Yoldi, Miguel Julián Muñoz, José Saloni Rodriguez, Meritxell Subirà, Carme Tomazatos, Alexandru Van Den Broucke, Steven Van Esbroeck, Marjan |
| 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 |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_2400a8de78eabac6b830bc77b9334eba |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/215016 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | Oxford University Press |
| publisherStr | Oxford University Press |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study 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 Febre Dengue Malària Viatges Metagenòmica ADN Fever Malaria Travels Metagenomics DNA 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. Oxford University Press https://hdl.handle.net/2445/215016 |
| 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 Malaria Travels Metagenomics DNA |
| status_str | acceptedVersion |
| title | 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_short | 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 |
| topic | Febre Dengue Malària Viatges Metagenòmica ADN Fever Malaria Travels Metagenomics DNA |
| topic_facet | Febre Dengue Malària Viatges Metagenòmica ADN Fever Malaria Travels Metagenomics DNA |
| url | https://hdl.handle.net/2445/215016 |