Mulders-Manders C, Simon A, Bleeker-Rovers C, 2015. Fever of unknown origin. Clin Med (Lond) 15: 280–284.
Safronetz D et al., 2016. Vectorborne infections, Mali. Emerg Infect Dis 22: 340–342.
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.
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.
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.
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.
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.
Diarra B et al., 2016. Laboratory response to 2014 Ebola virus outbreak in Mali. J Infect Dis 214: S164–S168.
Koné A et al., 2023. Dynamics of SARS-CoV-2 variants characterized during different COVID-19 waves in Mali. IJID Reg 6: 24–28.
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.
Harris PA et al., REDCap Consortium, 2019. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform 95: 103208.
Chen S, Zhou Y, Chen Y, Gu J, 2018. Fastp: An ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34: i884–i890.
Wood DE, Lu J, Langmead B, 2019. Improved metagenomic analysis with Kraken 2. Genome Biol 20: 257.
Bankevich A et al., 2012. SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 19: 455–477.
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.
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.
RStudio Team. The R Project for Statistical Computing. Available at: https://www.r-project.org/. Accessed May 23, 2024.
Levine ZC et al., 2024. Investigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing. Nat Commun 15: 747.
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.
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.
De Vlaminck I et al., 2013. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell 155: 1178–1187.
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.
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.
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.
Minta AA et al., 2023. Progress toward measles elimination – Worldwide, 2000–2022. MMWR Morb Mortal Wkly Rep 72: 1262–1268.
Wölfel R et al., 2020. Virological assessment of hospitalized patients with COVID-2019. Nature 581: 465–469.
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.
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.
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.
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.
World Health Organization, 2024. WHO COVID-19 Dashboard. Available at: https://data.who.int/dashboards/covid19/cases?n=c. Accessed April 11, 2024.
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.
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.
Gire SK et al., 2014. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 345: 1369–1372.
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 | |
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Abstract Views | 2748 | 2748 | 1376 |
Full Text Views | 120 | 120 | 33 |
PDF Downloads | 123 | 123 | 38 |
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.
Financial support: This project has been funded in whole or in part with federal funds from the
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.
Mulders-Manders C, Simon A, Bleeker-Rovers C, 2015. Fever of unknown origin. Clin Med (Lond) 15: 280–284.
Safronetz D et al., 2016. Vectorborne infections, Mali. Emerg Infect Dis 22: 340–342.
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.
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.
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.
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.
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.
Diarra B et al., 2016. Laboratory response to 2014 Ebola virus outbreak in Mali. J Infect Dis 214: S164–S168.
Koné A et al., 2023. Dynamics of SARS-CoV-2 variants characterized during different COVID-19 waves in Mali. IJID Reg 6: 24–28.
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.
Harris PA et al., REDCap Consortium, 2019. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform 95: 103208.
Chen S, Zhou Y, Chen Y, Gu J, 2018. Fastp: An ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34: i884–i890.
Wood DE, Lu J, Langmead B, 2019. Improved metagenomic analysis with Kraken 2. Genome Biol 20: 257.
Bankevich A et al., 2012. SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 19: 455–477.
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.
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.
RStudio Team. The R Project for Statistical Computing. Available at: https://www.r-project.org/. Accessed May 23, 2024.
Levine ZC et al., 2024. Investigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing. Nat Commun 15: 747.
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.
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.
De Vlaminck I et al., 2013. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell 155: 1178–1187.
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.
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.
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.
Minta AA et al., 2023. Progress toward measles elimination – Worldwide, 2000–2022. MMWR Morb Mortal Wkly Rep 72: 1262–1268.
Wölfel R et al., 2020. Virological assessment of hospitalized patients with COVID-2019. Nature 581: 465–469.
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.
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.
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.
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.
World Health Organization, 2024. WHO COVID-19 Dashboard. Available at: https://data.who.int/dashboards/covid19/cases?n=c. Accessed April 11, 2024.
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.
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.
Gire SK et al., 2014. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 345: 1369–1372.
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 | 2748 | 2748 | 1376 |
Full Text Views | 120 | 120 | 33 |
PDF Downloads | 123 | 123 | 38 |