Beyond the fever: shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illness
Abstract Background Non-malarial febrile illnesses (NMFI) pose significant challenges in HIV-infected children, often leading to severe complications and increased morbidity. While traditional diagnostic approaches focus on specific pathogens, shotgun metagenomic sequencing offers a comprehensive to...
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2025-01-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-025-10517-1 |
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| author | Patricia Nabisubi Stephen Kanyerezi Grace Kebirungi Ivan Sserwadda Mike Nsubuga Grace Kisitu Patricia Ntege Nahirya Bonny Mulindwa George P. Akabwai Sylvia Nantongo Adeodata Kekitiinwa Edgar Kigozi Nsubuga Moses Luutu Fred Ashaba Katabazi Leymon Kalema Andrew Katabalwa Daudi Jjingo Gerald Mboowa |
| author_facet | Patricia Nabisubi Stephen Kanyerezi Grace Kebirungi Ivan Sserwadda Mike Nsubuga Grace Kisitu Patricia Ntege Nahirya Bonny Mulindwa George P. Akabwai Sylvia Nantongo Adeodata Kekitiinwa Edgar Kigozi Nsubuga Moses Luutu Fred Ashaba Katabazi Leymon Kalema Andrew Katabalwa Daudi Jjingo Gerald Mboowa |
| author_sort | Patricia Nabisubi |
| collection | DOAJ |
| description | Abstract Background Non-malarial febrile illnesses (NMFI) pose significant challenges in HIV-infected children, often leading to severe complications and increased morbidity. While traditional diagnostic approaches focus on specific pathogens, shotgun metagenomic sequencing offers a comprehensive tool to explore the microbial landscape underlying NMFI in this vulnerable population ensuring effective management. Methods In this study, we employed shotgun metagenomics to analyse stool samples from HIV-infected children at the Baylor Children’s Clinic Uganda presenting with non-malarial febrile illness. Samples were collected and subjected to DNA extraction at the Molecular and Genomics Laboratory, Makerere University followed by shotgun metagenomics sequencing at the Chan Zuckerberg Biohub San Francisco. Bioinformatics analysis was conducted to identify and characterise the microbial composition and potential pathogenic taxa associated with NMFI using the CZID pipeline. Results Our findings reveal a diverse array of microbial taxa in the stool samples of HIV-infected children with NMFI. Importantly, shotgun metagenomics revealed potentially pathogenic players including Trichomonas vaginalis, Candida albicans, Giardia, and Bacteroides in stool from this patient population. This sheds light on the complexities of microbial interactions that potentially underpin non-malarial febrile illness in this group. Taxonomic profiling identified recognised pathogens and comorbidities and revealed possible new correlations with NMFI, shedding light on the pathophysiology of fever in HIV-infected children. Conclusion Shotgun metagenomics is a valuable method for understanding the gut microbial landscape of NMFI in HIV-infected children, providing a comprehensive approach to pathogen identification and characterisation. By revealing potential pathogenic actors beyond the fever, this work demonstrates how metagenomic sequencing may improve our knowledge of infectious illnesses in vulnerable groups and inspire targeted therapies for better clinical care and outcomes. |
| format | Article |
| id | doaj-art-d65a3252f30443f6bcbc9a566ad48da7 |
| institution | Kabale University |
| issn | 1471-2334 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj-art-d65a3252f30443f6bcbc9a566ad48da72025-01-26T12:17:10ZengBMCBMC Infectious Diseases1471-23342025-01-0125111010.1186/s12879-025-10517-1Beyond the fever: shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illnessPatricia Nabisubi0Stephen Kanyerezi1Grace Kebirungi2Ivan Sserwadda3Mike Nsubuga4Grace Kisitu5Patricia Ntege Nahirya6Bonny Mulindwa7George P. Akabwai8Sylvia Nantongo9Adeodata Kekitiinwa10Edgar Kigozi11Nsubuga Moses Luutu12Fred Ashaba Katabazi13Leymon Kalema14Andrew Katabalwa15Daudi Jjingo16Gerald Mboowa17The African Centre of Excellence in Bioinformatics and Data-Intensive SciencesThe African Centre of Excellence in Bioinformatics and Data-Intensive SciencesThe African Centre of Excellence in Bioinformatics and Data-Intensive SciencesThe African Centre of Excellence in Bioinformatics and Data-Intensive SciencesThe African Centre of Excellence in Bioinformatics and Data-Intensive SciencesBaylor College of Medicine Children’s Foundation, Mulago HospitalBaylor College of Medicine Children’s Foundation, Mulago HospitalBaylor College of Medicine Children’s Foundation, Mulago HospitalBaylor College of Medicine Children’s Foundation, Mulago HospitalThe African Centre of Excellence in Bioinformatics and Data-Intensive SciencesBaylor College of Medicine Children’s Foundation, Mulago HospitalDepartment of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere UniversityDepartment of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere UniversityDepartment of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere UniversityDepartment of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere UniversityDepartment of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere UniversityThe African Centre of Excellence in Bioinformatics and Data-Intensive SciencesThe African Centre of Excellence in Bioinformatics and Data-Intensive SciencesAbstract Background Non-malarial febrile illnesses (NMFI) pose significant challenges in HIV-infected children, often leading to severe complications and increased morbidity. While traditional diagnostic approaches focus on specific pathogens, shotgun metagenomic sequencing offers a comprehensive tool to explore the microbial landscape underlying NMFI in this vulnerable population ensuring effective management. Methods In this study, we employed shotgun metagenomics to analyse stool samples from HIV-infected children at the Baylor Children’s Clinic Uganda presenting with non-malarial febrile illness. Samples were collected and subjected to DNA extraction at the Molecular and Genomics Laboratory, Makerere University followed by shotgun metagenomics sequencing at the Chan Zuckerberg Biohub San Francisco. Bioinformatics analysis was conducted to identify and characterise the microbial composition and potential pathogenic taxa associated with NMFI using the CZID pipeline. Results Our findings reveal a diverse array of microbial taxa in the stool samples of HIV-infected children with NMFI. Importantly, shotgun metagenomics revealed potentially pathogenic players including Trichomonas vaginalis, Candida albicans, Giardia, and Bacteroides in stool from this patient population. This sheds light on the complexities of microbial interactions that potentially underpin non-malarial febrile illness in this group. Taxonomic profiling identified recognised pathogens and comorbidities and revealed possible new correlations with NMFI, shedding light on the pathophysiology of fever in HIV-infected children. Conclusion Shotgun metagenomics is a valuable method for understanding the gut microbial landscape of NMFI in HIV-infected children, providing a comprehensive approach to pathogen identification and characterisation. By revealing potential pathogenic actors beyond the fever, this work demonstrates how metagenomic sequencing may improve our knowledge of infectious illnesses in vulnerable groups and inspire targeted therapies for better clinical care and outcomes.https://doi.org/10.1186/s12879-025-10517-1ChildrenHIV-InfectedNon-malarial febrile illnessShotgun metagenomic sequencingUganda |
| spellingShingle | Patricia Nabisubi Stephen Kanyerezi Grace Kebirungi Ivan Sserwadda Mike Nsubuga Grace Kisitu Patricia Ntege Nahirya Bonny Mulindwa George P. Akabwai Sylvia Nantongo Adeodata Kekitiinwa Edgar Kigozi Nsubuga Moses Luutu Fred Ashaba Katabazi Leymon Kalema Andrew Katabalwa Daudi Jjingo Gerald Mboowa Beyond the fever: shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illness BMC Infectious Diseases Children HIV-Infected Non-malarial febrile illness Shotgun metagenomic sequencing Uganda |
| title | Beyond the fever: shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illness |
| title_full | Beyond the fever: shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illness |
| title_fullStr | Beyond the fever: shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illness |
| title_full_unstemmed | Beyond the fever: shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illness |
| title_short | Beyond the fever: shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illness |
| title_sort | beyond the fever shotgun metagenomic sequencing of stool unveils pathogenic players in hiv infected children with non malarial febrile illness |
| topic | Children HIV-Infected Non-malarial febrile illness Shotgun metagenomic sequencing Uganda |
| url | https://doi.org/10.1186/s12879-025-10517-1 |
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