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Suppression of host gene expression is associated with latent TB infection : a possible diagnostic biomarker
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dc.contributor.author | Nakiboneka, Ritah | |
dc.contributor.author | Margaritella, Nicolò | |
dc.contributor.author | Nyirenda, Tonney | |
dc.contributor.author | Chaima, David | |
dc.contributor.author | Walbaum, Natasha | |
dc.contributor.author | Musisi, Emmanuel | |
dc.contributor.author | Tionge, Sikwese | |
dc.contributor.author | Msosa, Takondwa | |
dc.contributor.author | Nliwasa, Marriott | |
dc.contributor.author | Msefula, Chisomo L | |
dc.contributor.author | Sloan, Derek | |
dc.contributor.author | Sabiiti, Wilber | |
dc.date.accessioned | 2024-07-15T09:30:15Z | |
dc.date.available | 2024-07-15T09:30:15Z | |
dc.date.issued | 2024-07-07 | |
dc.identifier | 305347058 | |
dc.identifier | 5c7bce95-3e20-4e17-91d5-ec235dcc6902 | |
dc.identifier | 38972907 | |
dc.identifier | 85197715661 | |
dc.identifier.citation | Nakiboneka , R , Margaritella , N , Nyirenda , T , Chaima , D , Walbaum , N , Musisi , E , Tionge , S , Msosa , T , Nliwasa , M , Msefula , C L , Sloan , D & Sabiiti , W 2024 , ' Suppression of host gene expression is associated with latent TB infection : a possible diagnostic biomarker ' , Scientific Reports , vol. 14 , 15621 . https://doi.org/10.1038/s41598-024-66486-z | en |
dc.identifier.issn | 2045-2322 | |
dc.identifier.other | PubMedCentral: PMC11228037 | |
dc.identifier.other | ORCID: /0000-0002-7888-5449/work/163571231 | |
dc.identifier.other | ORCID: /0000-0002-4742-2791/work/163571301 | |
dc.identifier.uri | https://hdl.handle.net/10023/30163 | |
dc.description | Funding:This work was Supported by the Wellcome Trust Institutional Strategic Support fund of the University of St Andrews, grant code 204821/Z/16/Z. Additional funding was obtained from Helse Nord Tuberculosis Initiative (HNTI), Pathology Department, Kamuzu University of Health Sciences and the Africa Centre for Public Health and Herbal Medicines (ACEPHEM), Kamuzu University of Health Sciences. | en |
dc.description.abstract | The World Health Organization End TB strategy aims for a 90% reduction of tuberculosis (TB) incidence by 2035. Systematic testing and treatment of latent TB infection (LTBI) among contacts of active TB patients is recommended as one of the ways to curtail TB incidence. However, there is a shortage of tools to accurately diagnose LTBI. We assessed the appropriateness of whole blood host transcriptomic markers (TM) to diagnose LTBI among household contacts of bacteriologically confirmed index cases compared to HIV negative healthy controls (HC). QuantiFERON-TB Gold Plus Interferon gamma release assay (IGRA) and reverse-transcriptase quantitative PCR were used to determine LTBI and quantify TM expression respectively. Association between TM expression and LTBI was evaluated by logistic regression modelling. A total of 100 participants, 49 TB exposed (TBEx) household contacts and 51 HC, were enrolled. Twenty-five (51%) TBEx individuals tested positive by IGRA, and were denoted as LTBI individuals, and 37 (72.5%) HC were IGRA-negative. Expression of 11 evaluated TM was significantly suppressed among LTBI compared to HC. Out of the 11 TM, ZNF296 and KLF2 expression were strongly associated with LTBI and successfully differentiated LTBI from HC. Paradoxically, 21 (49%) TBEx participants who tested IGRA negative exhibited the same pattern of suppressed TM expression as IGRA positive (LTBI-confirmed individuals). Results suggest that suppression of gene expression underlies LTBI and may be a more sensitive diagnostic biomarker than standard-of-care IGRA. | |
dc.format.extent | 11 | |
dc.format.extent | 1854559 | |
dc.language.iso | eng | |
dc.relation.ispartof | Scientific Reports | en |
dc.subject | Humans | en |
dc.subject | Latent tuberculosis/diagnosis | en |
dc.subject | Male | en |
dc.subject | Female | en |
dc.subject | Adult | en |
dc.subject | Biomarkers/blood | en |
dc.subject | Middle aged | en |
dc.subject | Interferon-gamma release tests/methods | en |
dc.subject | Young adult | en |
dc.subject | Transcriptome | en |
dc.subject | Case-control studies | en |
dc.subject | Adolescent | en |
dc.subject | RA0421 Public health. Hygiene. Preventive Medicine | en |
dc.subject | E-DAS | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | RA0421 | en |
dc.title | Suppression of host gene expression is associated with latent TB infection : a possible diagnostic biomarker | en |
dc.type | Journal article | en |
dc.contributor.sponsor | The Wellcome Trust | en |
dc.contributor.sponsor | The Wellcome Trust | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Infection and Global Health Division | en |
dc.contributor.institution | University of St Andrews. Statistics | en |
dc.identifier.doi | 10.1038/s41598-024-66486-z | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | 204821/Z/16/Z | en |
dc.identifier.grantnumber | N/A | en |
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