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Research Article

Adding Virome Capture Metagenomic Sequencing to Conventional Laboratory Testing Increases Unknown Fever Etiology Determination in Bamako, Mali

Amadou Koné University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;
Global Alliance for Preventing Pandemics, Columbia University, New York, New York;

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Fousseyni Kané University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;
Global Alliance for Preventing Pandemics, Columbia University, New York, New York;

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Aaron Neal Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

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Issa Konate University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Bintou Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Djeneba K. Dabitao University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Bassirou Diarra University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Ibrahim Sanogo University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Yeya Dit Sadio Sarro University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Tenin A. Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Dramane Diallo University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;
Global Alliance for Preventing Pandemics, Columbia University, New York, New York;

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Seydou Samake University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Ilo Dicko University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Mountaga Diallo University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Ayouba Diarra University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Mamadou D. Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Daouda Keita University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Nadié Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Isaac Koloma University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Mamadou Perou University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Hawa Boukary Diarra University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Boubacar Elmadane Cisse University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Antieme Combo Georges Togo University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Gagni Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Fah Gaoussou Traoré University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Moumine Sanogo University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Mahamadou Diakité University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Jamila Aboulhab Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

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Esther Akpa Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

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Karine Fouth-Tchos Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

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Kathryn Shaw-Saliba Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

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John Collins Global Alliance for Preventing Pandemics, Columbia University, New York, New York;
Center for Infection and Immunity, Columbia University, New York, New York

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Xiang-Jun Lu Global Alliance for Preventing Pandemics, Columbia University, New York, New York;
Center for Infection and Immunity, Columbia University, New York, New York

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Mishra Nischay Global Alliance for Preventing Pandemics, Columbia University, New York, New York;
Center for Infection and Immunity, Columbia University, New York, New York

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J. Kenneth Wickiser Global Alliance for Preventing Pandemics, Columbia University, New York, New York;
Center for Infection and Immunity, Columbia University, New York, New York

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Thomas Briese Global Alliance for Preventing Pandemics, Columbia University, New York, New York;
Center for Infection and Immunity, Columbia University, New York, New York

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W. Ian Lipkin Global Alliance for Preventing Pandemics, Columbia University, New York, New York;
Center for Infection and Immunity, Columbia University, New York, New York

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Ray Y. Chen Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

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Seydou Doumbia University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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Sounkalo Dao University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

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DOI:
https://doi.org/10.4269/ajtmh.24-0449
Volume/Issue:
Volume 112: Issue 3
Page(s):
626–635
Restricted access
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ABSTRACT.

Unexplained fever poses significant diagnostic challenges in resource-limited settings like Bamako, Mali, where overlapping endemic diseases include malaria, HIV/AIDS, yellow fever, typhoid, and others. This study aimed to elucidate the infectious etiologies of acute febrile illnesses in this context. Acute febrile patients of any age were enrolled after informed consent or assent. Baseline clinical and demographic data were collected, and samples were analyzed by using rapid diagnostic tests, reverse transcriptase polymerase chain reaction, ELISA, and virus-targeted metagenomic sequencing (virome capture sequencing platform for vertebrate viruses [VirCapSeq-VERT]). Among 108 enrolled subjects, most were male (51.9%) and under 15 years old (56.5%). Measles virus was identified in 39.8% of cases, primarily among children. Other findings included Plasmodium spp. (12%), Salmonella spp. (13%), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; 8.7%). The virome capture sequencing platform for vertebrate viruses was used for 101 subjects, corroborating many routine test results and identifying additional cases of measles virus (1), SARS-CoV-2 (5), and numerous other agents. Notably, nearly all subjects showed evidence of herpesviruses (90%) and anelloviruses (98%). Hemorrhagic fever viruses were not observed. With the inclusion of VirCapSeq-VERT, identifiable pathogens were found in 79.6% of cases, leaving 20.4% without a clear etiology. The identification of more than one concurrent pathogen was common (41.5%). Integrating metagenomic sequencing with routine laboratory diagnostic testing enhances the detection of pathogens in acute febrile illnesses, highlighting its potential value in identifying infectious etiologies in resource-limited settings.

    • Supplemental Materials (PDF 628.11 KB)

Author Notes

Financial support: This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under Contract No. 75N91019D00024, Task Order No. 75N91020F00004 and 75N91024F00012. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. This work was also supported by the Skoll Foundation and the Moore Charitable Foundation.

Disclosure: This study obtained approval from the ethics committee of the Faculty of Medicine, Pharmacy, and Odontostomatology of the University of Sciences, Techniques, and Technologies of Bamako under number 2018/05/CE/FMPOS on January 10, 2018. Adult subjects enrolled in the study provided informed consent. Children aged 12 and younger provided assent in addition to consent from their parent or legal guardian.

Current contact information: Amadou Koné, Fousseyni Kané, Issa Konate, Bintou Coulibaly, Djeneba K. Dabitao, Bassirou Diarra, Ibrahim Sanogo, Yeya Dit Sadio Sarro, Tenin Aminatou Coulibaly, Dramane Diallo, Seydou Samake, Ilo Dicko, Mountaga Diallo, Ayouba Diarra, Mamadou D. Coulibaly, Daouda Keita, Nadié Coulibaly, Isaac Koloma, Mamadou Perou, Hawa Boukary Diarra, Boubacar Elmadane Cissé, Antieme Combo Georges Togo, Gagni Coulibaly, Fah Gaoussou Traoré, Moumine Sanogo, Mahamadou Diakité, Seydou Doumbia, and Sounkalo Dao, University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali, E-mails: amadoukone@icermali.org, fouskane@icermali.org, issakonate@icermali.org, bintoucoulibaly@icermali.org, ddabitao@icermali.org, bdiarra@icermali.org, isanogo@icermali.org, sadio@icermali.org, tenina.coulibaly@icermali.org, dramanediallo@icermali.org, seydousamake@icermali.org, ilo@icermali.org, mountaga.diallo@icermali.org, ayouba.diarra@icermali.org, mdcoulibaly@icermali.org, daouda.keita@icermali.org, nadie@icermali.org, isaacdenisk@icermali.org, mamadouperou@icermali.org, hawa.drame@icermali.org, boubacar-e.cisse@icermali.org, togoacg@icermali.org, gagni@icermali.org, fahgaoussou.traore@icermali.org, smoumine@icermali.org, mdiakite@icermali.org, sdoumbi@icermali.org, and sounkalomdao@yahoo.fr. Aaron Neal, Jamila Aboulhab, Esther Akpa, Karine Fouth-Tchos, Kathryn Shaw-Saliba, and Ray Y. Chen, Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, E-mails: aaron.neal@nih.gov, jamila.aboulhab@nih.gov, esther.akpa@nih.gov, karine.fouthtchos@nih.gov, katy.saliba@nih.gov, and ray.chen@nih.gov. John Collins, Xiang-Jun Lu, Mishra Nischay, J. Kenneth Wickiser, Thomas Briese, and W. Ian Lipkin, Global Alliance for Preventing Pandemics and Center for Infection and Immunity, Columbia University, New York, NY, E-mails: jc5966@cumc.columbia.edu, xl2134@columbia.edu, nm2641@cumc.columbia.edu, jkw2161@cumc.columbia.edu, tb2047@cumc.columbia.edu, and wil2001@cumc.columbia.edu.

Address correspondence to Fousseyni Kané, University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali. E-mail: fouskane@icermali.org
Copyright:
© American Society of Tropical Medicine and Hygiene 2025
Received:
06 Jul 2024
|
Accepted:
13 Sep 2024
|
Published Online:
24 Dec 2024
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
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