{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:36:05Z","timestamp":1753893365211,"version":"3.41.2"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Tuberc."],"abstract":"<jats:p>Zoonotic and reverse zoonotic tuberculosis pose a risk to human and animal health, especially when individuals are in close contact. Whole genome sequencing (WGS) has led to significant advancements in our comprehension of bacterial disease dynamics, particularly regarding the transmission of pathogens at the population and individual levels. <jats:italic>Mycobacterium tuberculosis<\/jats:italic> was cultured from respiratory samples, including ante-mortem trunk wash, bronchoalveolar lavage, and post-mortem lung tissue samples of one African elephant (<jats:italic>Loxodonta africana<\/jats:italic>) euthanized in a South African zoo. The elephant presented with chronic weight loss and lethargy. Animal-side serological testing (Chembio DPP<jats:sup>\u00ae<\/jats:sup> VetTB for Elephants) conducted on elephant serum yielded a positive result before euthanasia. At post-mortem examination, signs of chronic pneumonia and extensive macroscopic lesions compatible with tuberculosis were observed, confirming the presence of the disease. Genomic DNA was extracted from liquid MGIT culture and an improved culture medium (TiKa) and subjected to WGS analysis. Using a bioinformatic approach, the study identified a mixed infection involving two distinct strains of <jats:italic>M. tuberculosis<\/jats:italic>. The predominant strain was classified as lineage 1 and a second strain was identified as lineage 4. Both lineages have been found in a significant proportion of human tuberculosis cases in South Africa. No mutations associated with drug resistance were detected. The report highlights the susceptibility of elephants to human pathogens, particularly in high-burden settings. Biosafety challenges associated with handling and diagnosing tuberculosis in human-managed elephants are reported. We emphasize the importance of implementing effective preventive measures to ensure the safety of both humans and animals in zoo environments. Finally, the importance of multiple sampling and analysis of within-host mycobacterial populations for investigations of transmission is demonstrated.<\/jats:p>","DOI":"10.3389\/ftubr.2024.1484394","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T07:21:37Z","timestamp":1737357697000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Implications of serological, genomic, and epidemiological insights into Mycobacterium tuberculosis mixed infection in a human-managed African elephant (Loxodonta africana)"],"prefix":"10.3389","volume":"2","author":[{"given":"Giovanni","family":"Ghielmetti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya J.","family":"Kerr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Loubser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennie","family":"Hewlett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anzaan","family":"Dippenaar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre G.","family":"Loxton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin M.","family":"Warren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wynand J.","family":"Goosen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele A.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"volume-title":"Bovine Tuberculosis","year":"2018","key":"B1"},{"key":"B2","doi-asserted-by":"publisher","first-page":"6099","DOI":"10.1038\/s41467-021-26248-1","article-title":"Population structure, biogeography and transmissibility of Mycobacterium tuberculosis","volume":"12","author":"Freschi","year":"2021","journal-title":"Nat Commun"},{"key":"B3","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.ijid.2016.02.981","article-title":"Cross-species transmission of Mycobacterium tuberculosis in mahouts and captive elephants: implications to health policy","volume":"45","author":"Abraham","year":"2016","journal-title":"Int J Infect Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"7343","DOI":"10.1038\/s41598-024-57318-1","article-title":"Genomic insights into anthropozoonotic tuberculosis in captive sun bears (Helarctos malayanus) and an Asiatic black bear (Ursus thibetanus) in Cambodia","volume":"14","author":"Officer","year":"2024","journal-title":"Sci Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1186\/s12917-019-2185-1","article-title":"Reverse zoonotic tuberculosis transmission from an emerging Uganda I strain between pastoralists and cattle in South-Eastern Nigeria","volume":"15","author":"Adesokan","year":"2019","journal-title":"BMC Vet Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.tvjl.2010.05.005","article-title":"Mycobacterium tuberculosis infection in grazing cattle in central Ethiopia","volume":"188","author":"Ameni","year":"2011","journal-title":"Vet J."},{"key":"B7","first-page":"283","article-title":"Mycobacterium tuberculosis infection as a zoonotic disease: transmission between humans and elephants","volume-title":"Emerg Infect Dis.","author":"Michalak","year":"1998"},{"key":"B8","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1638\/2017-0200.1","article-title":"Outbreak of Mycobacterium tuberculosis in a herd of captive Asian elephants (Elephas maximus): antemortem diagnosis, treatment, and lessons learned","volume":"49","author":"Miller","year":"2018","journal-title":"J Zoo Wildl Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3389\/fvets.2019.00018","article-title":"Fatal tuberculosis in a free-ranging African elephant and One Health implications of human pathogens in wildlife","volume":"6","author":"Miller","year":"2019","journal-title":"Front Vet Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"000477","DOI":"10.1099\/mgen.0.000477","article-title":"Phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history","volume":"7","author":"Coscolla","year":"2021","journal-title":"Microb Genom."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2917","DOI":"10.1038\/s41467-020-16626-6","article-title":"A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region","volume":"11","author":"Ngabonziza","year":"2020","journal-title":"Nat Commun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/ng.3195","article-title":"Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage","volume":"47","author":"Merker","year":"2015","journal-title":"Nat Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1038\/ng.3704","article-title":"Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages","volume":"48","author":"Stucki","year":"2016","journal-title":"Nat Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"832054","DOI":"10.3389\/fmicb.2022.832054","article-title":"Sub-lineage specific phenolic glycolipid patterns in the Mycobacterium tuberculosis complex lineage 1","volume":"13","author":"Gisch","year":"2022","journal-title":"Front Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"60","DOI":"10.12688\/f1000research.28318.1","article-title":"Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean Rim","volume":"10","author":"Menardo","year":"2021","journal-title":"F1000Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3241","DOI":"10.1111\/mec.15120","article-title":"Lineage specific histories of Mycobacterium tuberculosis dispersal in Africa and Eurasia","volume":"28","author":"O'Neill","year":"2019","journal-title":"Mol Ecol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"600692","DOI":"10.3389\/fgene.2020.600692","article-title":"Methods for detecting mycobacterial mixed strain infections-a systematic review","volume":"11","author":"Byrne","year":"2020","journal-title":"Front Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"17100","DOI":"10.1038\/s41598-023-44341-x","article-title":"Mixed infections in genotypic drug-resistant Mycobacterium tuberculosis","volume":"13","author":"Wang","year":"2023","journal-title":"Sci Rep"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00062-18","article-title":"Deciphering within-host microevolution of Mycobacterium tuberculosis through whole-genome sequencing: the phenotypic impact and way forward","author":"Ley","year":"2019","journal-title":"Microbiol Mol Biol Rev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12864-020-6486-3","article-title":"QuantTB - a method to classify mixed Mycobacterium tuberculosis infections within whole genome sequencing data","volume":"21","author":"Anyansi","year":"2020","journal-title":"BMC Genomics."},{"key":"B21","doi-asserted-by":"publisher","first-page":"000607","DOI":"10.1099\/mgen.0.000607","article-title":"SplitStrains, a tool to identify and separate mixed Mycobacterium tuberculosis infections from WGS data","volume":"7","author":"Gabbassov","year":"2021","journal-title":"Microb Genom."},{"key":"B22","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1186\/s12864-018-4988-z","article-title":"Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data","volume":"19","author":"Sobkowiak","year":"2018","journal-title":"BMC Genomics."},{"key":"B23","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1128\/CVI.00038-09","article-title":"Highly accurate antibody assays for early and rapid detection of tuberculosis in African and Asian elephants","volume":"16","author":"Greenwald","year":"2009","journal-title":"Clin Vaccine Immunol."},{"key":"B24","first-page":"1","article-title":"AVMA guidelines for the euthanasia of animals: 2020 Edition","volume":"42","author":"Leary","year":"2020","journal-title":"J Am Vet Med A"},{"key":"B25","doi-asserted-by":"publisher","first-page":"14482","DOI":"10.1038\/s41598-020-71568-9","article-title":"The Xpert MTB\/RIF Ultra assay detects Mycobacterium tuberculosis complex DNA in white rhinoceros (Ceratotherium simum) and African elephants (Loxodonta africana)","volume":"10","author":"Goosen","year":"2020","journal-title":"Sci Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"104980","DOI":"10.1016\/j.prevetmed.2020.104980","article-title":"Utility of xpert(R) MTB\/RIF ultra assay in the rapid diagnosis of bovine tuberculosis in wildlife and livestock animals from South Africa","volume":"177","author":"Hlokwe","year":"2020","journal-title":"Prev Vet Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1177\/10406387211044192","article-title":"Improved detection of Mycobacterium tuberculosis and M. bovis in African wildlife samples using cationic peptide decontamination and mycobacterial culture supplementation","volume":"34","author":"Goosen","year":"2022","journal-title":"J Vet Diagn Invest."},{"key":"B28","first-page":"818","article-title":"Differentiation of Mycobacterium tuberculosis complex by PCR amplification of genomic regions of difference","volume":"10","author":"Warren","year":"2006","journal-title":"Int J Tuberc Lung Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1128\/jcm.29.11.2578-2586.1991","article-title":"Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence-dependent DNA polymorphism as a tool in the epidemiology of tuberculosis","volume":"29","author":"van Soolingen","year":"1991","journal-title":"J Clin Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"674307","DOI":"10.3389\/fvets.2021.674307","article-title":"Whole genome sequencing links Mycobacterium bovis from cattle, cheese and humans in Baja California, Mexico","volume":"8","author":"Ortiz","year":"2021","journal-title":"Front Vet Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e5895","DOI":"10.7717\/peerj.5895","article-title":"MTBseq: a comprehensive pipeline for whole genome sequence analysis of Mycobacterium tuberculosis complex isolates","volume":"6","author":"Kohl","year":"2018","journal-title":"PeerJ."},{"key":"B32","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13073-019-0650-x","article-title":"Integrating informatics tools and portable sequencing technology for rapid detection of resistance to anti-tuberculous drugs","volume":"11","author":"Phelan","year":"2019","journal-title":"Genome Med."},{"journal-title":"Grading Scales for Bright Field (Ziehl-Neelsen) and Fluorescence Microscopy, Priorities for Tuberculosis Bacteriology Services in Low-Income Countries","year":"2007","author":"Reider","key":"B33"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.3389\/fmicb.2019.01922","article-title":"Comprehensive characterization of the attenuated double auxotroph Mycobacterium tuberculosis \u0394leuD \u0394 panCD as an alternative to H37Rv","volume":"10","author":"Mouton","year":"2019","journal-title":"Front Microbiol."},{"key":"B35","article-title":"Loxodonta africana (amended version of 2021 assessment)","volume-title":"The IUCN Red List of Threatened Species 2022: e.T181008073A223031019","author":"Gobush","year":"2022"},{"volume-title":"Elephas maximus. The IUCN Red List of Threatened Species 2020: e.T7140A45818198","year":"2020","author":"Williams","key":"B36"},{"key":"B37","article-title":"African elephant status report - an update from the African elephant database","volume-title":"Occasional Paper of the IUCN Species Survival Commission No 60","author":"Thouless","year":"2016"},{"key":"B38","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1017\/S1367943003003421","article-title":"Fragmentation of Asia's remaining wildlands: implications for Asian elephant conservation","volume":"6","author":"Leimgruber","year":"2003","journal-title":"Anim Conserv."},{"key":"B39","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1126\/science.abm5609","article-title":"Protect elephants from tuberculosis","volume":"374","author":"Shah","year":"2021","journal-title":"Science."},{"key":"B40","doi-asserted-by":"publisher","first-page":"504","DOI":"10.3201\/eid2303.161741","article-title":"Mycobacterium tuberculosis in wild Asian Elephants, Southern India","volume":"23","author":"Zachariah","year":"2017","journal-title":"Emerg Infect Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"555","DOI":"10.3201\/eid2303.161439","article-title":"Mycobacterium tuberculosis infection in free-roaming wild Asian elephant","volume":"23","author":"Chandranaik","year":"2017","journal-title":"Emerg Infect Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"990","DOI":"10.3201\/eid2703.204729","article-title":"Mycobacterium bovis infection in free-ranging African elephants","volume":"27","author":"Miller","year":"2021","journal-title":"Emerg Infect Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"3936","DOI":"10.1128\/IAI.66.8.3936-3940.1998","article-title":"Heterogeneous antibody responses in tuberculosis","volume":"66","author":"Lyashchenko","year":"1998","journal-title":"Infect Immun."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.3201\/eid2505.181898","article-title":"Mixed Mycobacterium tuberculosis lineage infection in 2 Elephants, Nepal","volume":"25","author":"Paudel","year":"2019","journal-title":"Emerg Infect Dis."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e0200632","DOI":"10.1371\/journal.pone.0200632","article-title":"Geospatial distribution of Mycobacterium tuberculosis genotypes in Africa","volume":"13","author":"Chihota","year":"2018","journal-title":"PLoS ONE."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e0154571","DOI":"10.1371\/journal.pone.0154571","article-title":"Mapping of Mycobacterium tuberculosis complex genetic diversity profiles in Tanzania and other African countries","volume":"11","author":"Mbugi","year":"2016","journal-title":"PLoS ONE."},{"key":"B47","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s12866-021-02232-z","article-title":"Distribution and clonality of drug-resistant tuberculosis in South Africa","volume":"21","author":"Said","year":"2021","journal-title":"BMC Microbiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"667","DOI":"10.3390\/microorganisms8050667","article-title":"Mycobacterium bovis: from genotyping to genome sequencing","volume":"8","author":"Guimaraes","year":"2020","journal-title":"Microorganisms."},{"key":"B49","doi-asserted-by":"publisher","first-page":"14647","DOI":"10.1038\/s41598-017-15278-9","article-title":"Tuberculosis in Swiss captive Asian elephants: microevolution of Mycobacterium tuberculosis characterized by multilocus variable-number tandem-repeat analysis and whole-genome sequencing","volume":"7","author":"Ghielmetti","year":"2017","journal-title":"Sci Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.15585\/mmwr.mm6452a2","article-title":"Diagnosis of tuberculosis in three zoo elephants and a human contact - Oregon, 2013","volume":"64","author":"Zlot","year":"2016","journal-title":"MMWR Morb Mortal Wkly Rep."}],"container-title":["Frontiers in Tuberculosis"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftubr.2024.1484394\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T07:21:45Z","timestamp":1737357705000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftubr.2024.1484394\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":50,"alternative-id":["10.3389\/ftubr.2024.1484394"],"URL":"https:\/\/doi.org\/10.3389\/ftubr.2024.1484394","relation":{},"ISSN":["2813-7868"],"issn-type":[{"type":"electronic","value":"2813-7868"}],"subject":[],"published":{"date-parts":[[2025,1,20]]},"article-number":"1484394"}}