Article Category:
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;

Search for other papers by Amadou Koné in
Current site
Google Scholar
PubMed Close
,
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;

Search for other papers by Fousseyni Kané in
Current site
Google Scholar
PubMed Close
,
Aaron Neal Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

Search for other papers by Aaron Neal in
Current site
Google Scholar
PubMed Close
,
Issa Konate University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Issa Konate in
Current site
Google Scholar
PubMed Close
,
Bintou Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Bintou Coulibaly in
Current site
Google Scholar
PubMed Close
,
Djeneba K. Dabitao University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Djeneba K. Dabitao in
Current site
Google Scholar
PubMed Close
,
Bassirou Diarra University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Bassirou Diarra in
Current site
Google Scholar
PubMed Close
,
Ibrahim Sanogo University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Ibrahim Sanogo in
Current site
Google Scholar
PubMed Close
,
Yeya Dit Sadio Sarro University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Yeya Dit Sadio Sarro in
Current site
Google Scholar
PubMed Close
,
Tenin A. Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Tenin A. Coulibaly in
Current site
Google Scholar
PubMed Close
,
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;

Search for other papers by Dramane Diallo in
Current site
Google Scholar
PubMed Close
,
Seydou Samake University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Seydou Samake in
Current site
Google Scholar
PubMed Close
,
Ilo Dicko University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Ilo Dicko in
Current site
Google Scholar
PubMed Close
,
Mountaga Diallo University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Mountaga Diallo in
Current site
Google Scholar
PubMed Close
,
Ayouba Diarra University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Ayouba Diarra in
Current site
Google Scholar
PubMed Close
,
Mamadou D. Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Mamadou D. Coulibaly in
Current site
Google Scholar
PubMed Close
,
Daouda Keita University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Daouda Keita in
Current site
Google Scholar
PubMed Close
,
Nadié Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Nadié Coulibaly in
Current site
Google Scholar
PubMed Close
,
Isaac Koloma University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Isaac Koloma in
Current site
Google Scholar
PubMed Close
,
Mamadou Perou University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Mamadou Perou in
Current site
Google Scholar
PubMed Close
,
Hawa Boukary Diarra University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Hawa Boukary Diarra in
Current site
Google Scholar
PubMed Close
,
Boubacar Elmadane Cisse University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Boubacar Elmadane Cisse in
Current site
Google Scholar
PubMed Close
,
Antieme Combo Georges Togo University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Antieme Combo Georges Togo in
Current site
Google Scholar
PubMed Close
,
Gagni Coulibaly University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Gagni Coulibaly in
Current site
Google Scholar
PubMed Close
,
Fah Gaoussou Traoré University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Fah Gaoussou Traoré in
Current site
Google Scholar
PubMed Close
,
Moumine Sanogo University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Moumine Sanogo in
Current site
Google Scholar
PubMed Close
,
Mahamadou Diakité University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Mahamadou Diakité in
Current site
Google Scholar
PubMed Close
,
Jamila Aboulhab Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

Search for other papers by Jamila Aboulhab in
Current site
Google Scholar
PubMed Close
,
Esther Akpa Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

Search for other papers by Esther Akpa in
Current site
Google Scholar
PubMed Close
,
Karine Fouth-Tchos Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

Search for other papers by Karine Fouth-Tchos in
Current site
Google Scholar
PubMed Close
,
Kathryn Shaw-Saliba Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

Search for other papers by Kathryn Shaw-Saliba in
Current site
Google Scholar
PubMed Close
,
John Collins Global Alliance for Preventing Pandemics, Columbia University, New York, New York;
Center for Infection and Immunity, Columbia University, New York, New York

Search for other papers by John Collins in
Current site
Google Scholar
PubMed Close
,
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

Search for other papers by Xiang-Jun Lu in
Current site
Google Scholar
PubMed Close
,
Mishra Nischay Global Alliance for Preventing Pandemics, Columbia University, New York, New York;
Center for Infection and Immunity, Columbia University, New York, New York

Search for other papers by Mishra Nischay in
Current site
Google Scholar
PubMed Close
,
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

Search for other papers by J. Kenneth Wickiser in
Current site
Google Scholar
PubMed Close
,
Thomas Briese Global Alliance for Preventing Pandemics, Columbia University, New York, New York;
Center for Infection and Immunity, Columbia University, New York, New York

Search for other papers by Thomas Briese in
Current site
Google Scholar
PubMed Close
,
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

Search for other papers by W. Ian Lipkin in
Current site
Google Scholar
PubMed Close
,
Ray Y. Chen Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

Search for other papers by Ray Y. Chen in
Current site
Google Scholar
PubMed Close
,
Seydou Doumbia University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Seydou Doumbia in
Current site
Google Scholar
PubMed Close
, and
Sounkalo Dao University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali;

Search for other papers by Sounkalo Dao in
Current site
Google Scholar
PubMed Close
DOI:
https://doi.org/10.4269/ajtmh.24-0449
Volume/Issue:
Volume 112: Issue 3
Page(s):
626–635
Restricted access
Get Permissions

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
  • 1.

    Mulders-Manders C, Simon A, Bleeker-Rovers C, 2015. Fever of unknown origin. Clin Med (Lond) 15: 280–284.

  • 2.

    Safronetz D et al., 2016. Vectorborne infections, Mali. Emerg Infect Dis 22: 340–342.

  • 3.

    Ghansah A et al., Plasmodium Diversity Network Africa, 2019. Targeted next generation sequencing for malaria research in Africa: Current status and outlook. Malar J 18: 324.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Inzaule SC, Tessema SK, Kebede Y, Ogwell Ouma AE, Nkengasong JN, 2021. Genomic-informed pathogen surveillance in Africa: Opportunities and challenges. Lancet Infect Dis 21: e281–e289.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Omotoso OE, Teibo JO, Atiba FA, Oladimeji T, Adebesin AO, Babalghith AO, 2022. Bridging the genomic data gap in Africa: Implications for global disease burdens. Global Health 18: 103.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Briese T, Kapoor A, Mishra N, Jain K, Kumar A, Jabado OJ, Ian LW, 2015. Virome capture sequencing enables sensitive viral diagnosis and comprehensive virome analysis. mBio 6: e01491–e01415.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Kapoor V, Briese T, Ranjan A, Donovan WM, Mansukhani MM, Chowdhary R, Lipkin WI, 2024. Validation of the VirCapSeq-VERT system for differential diagnosis, detection, and surveillance of viral infections. J Clin Microbiol 62: e0061223.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Diarra B et al., 2016. Laboratory response to 2014 Ebola virus outbreak in Mali. J Infect Dis 214: S164–S168.

  • 9.

    Koné A et al., 2023. Dynamics of SARS-CoV-2 variants characterized during different COVID-19 waves in Mali. IJID Reg 6: 24–28.

  • 10.

    Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG, 2009. Research electronic data capture (REDCap) – A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42: 377–381.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Harris PA et al., REDCap Consortium, 2019. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform 95: 103208.

  • 12.

    Chen S, Zhou Y, Chen Y, Gu J, 2018. Fastp: An ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34: i884–i890.

  • 13.

    Wood DE, Lu J, Langmead B, 2019. Improved metagenomic analysis with Kraken 2. Genome Biol 20: 257.

  • 14.

    Bankevich A et al., 2012. SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 19: 455–477.

  • 15.

    Goodacre N, Aljanahi A, Nandakumar S, Mikailov M, Khan AS, 2018. A reference viral database (RVDB) to enhance bioinformatics analysis of high-throughput sequencing for novel virus detection. mSphere 3: e00069-18.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    López-Labrador FX et al.; ESCV Network on Next-Generation Sequencing, 2021. Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure. J Clin Virol 134: 104691.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    RStudio Team. The R Project for Statistical Computing. Available at: https://www.r-project.org/. Accessed May 23, 2024.

  • 18.

    Levine ZC et al., 2024. Investigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing. Nat Commun 15: 747.

  • 19.

    Nooh F, Chernet A, Reither K, Okuma J, Brattig NW, Utzinger J, Probst-Hensch N, Paris DH, Dreyfus A, 2023. Prevalence of fever of unidentified aetiology in East African adolescents and adults: A systematic review and meta-analysis. Infect Dis Poverty 12: 55.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Gutierrez R et al., 2024. Aetiology of non-malaria acute febrile illness fever in children in rural Guinea-Bissau: A prospective cross-sectional investigation. Front Epidemiol 4: 1309149.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    De Vlaminck I et al., 2013. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell 155: 1178–1187.

  • 22.

    Nampota-Nkomba N et al., 2024. An upsurge of measles cases in mali – A consequence of pandemic-associated disruption in routine immunization. Open Forum Infect Dis 11: ofae154.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Medicins Sans Frontieres, 2020. Measles in Mali: Prevention is Better Than Cure in Timbuktu. Available at: https://www.doctorswithoutborders.ca/measles-in-mali-prevention-is-better-than-cure-in-timbuktu/. Accessed April 11, 2024.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Imperato PJ, Sow O, Fofana B, 1972. The epidemiology of smallpox in the Republic of Mali. Trans R Soc Trop Med Hyg 66: 176–182.

  • 25.

    Minta AA et al., 2023. Progress toward measles elimination – Worldwide, 2000–2022. MMWR Morb Mortal Wkly Rep 72: 1262–1268.

  • 26.

    Wölfel R et al., 2020. Virological assessment of hospitalized patients with COVID-2019. Nature 581: 465–469.

  • 27.

    Kaboré B et al., 2021. Aetiology of acute febrile illness in children in a high malaria transmission area in West Africa. Clin Microbiol Infect 27: 590–596.

  • 28.

    D’Acremont V, Kilowoko M, Kyungu E, Philipina S, Sangu W, Kahama-Maro J, Lengeler C, Cherpillod P, Kaiser L, Genton B, 2014. Beyond malaria – Causes of fever in outpatient Tanzanian children. N Engl J Med 370: 809–817.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Baba M, Logue CH, Oderinde B, Abdulmaleek H, Williams J, Lewis J, Laws TR, Hewson R, Marcello A, D’ Agaro P, 2013. Evidence of arbovirus co-infection in suspected febrile malaria and typhoid patients in Nigeria. J Infect Dev Ctries 7: 51–59.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Pokharel S, White LJ, Aguas R, Celhay O, Pellé KG, Dittrich S, 2020. Algorithm in the diagnosis of febrile illness using pathogen-specific rapid diagnostic tests. Clin Infect Dis 70: 2262–2269.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    World Health Organization, 2024. WHO COVID-19 Dashboard. Available at: https://data.who.int/dashboards/covid19/cases?n=c. Accessed April 11, 2024.

  • 32.

    Spengler JR, Ervin ED, Towner JS, Rollin PE, Nichol ST, 2016. Perspectives on West Africa Ebola virus disease outbreak, 2013–2016. Emerg Infect Dis 22: 956–963.

  • 33.

    Coltart CEM, Lindsey B, Ghinai I, Johnson AM, Heymann DL, 2017. The Ebola outbreak, 2013–2016: Old lessons for new epidemics. Philos Trans R Soc Lond B Biol Sci 372: 20160297.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Gire SK et al., 2014. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 345: 1369–1372.

  • 35.

    Vetter P et al., 2016. The 2014–2015 Ebola outbreak in West Africa: Hands on. Antimicrob Resist Infect Control 5: 17.

Past two years Past Year Past 30 Days
Abstract Views 2835 2835 1447
Full Text Views 121 121 34
PDF Downloads 125 125 40
 

 

 

 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save