{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:17:15Z","timestamp":1791566235698,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 22167-390884018"],"award-info":[{"award-number":["EXC 22167-390884018"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Kenya is a country with a high tuberculosis (TB) burden. However, knowledge on the genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains and their transmission dynamics is sparsely available. Hence, we used whole-genome sequencing (WGS) to depict the genetic diversity, molecular markers of drug resistance, and possible transmission clusters among MTBC strains in urban and slum settings of Nairobi. We analyzed 385 clinical MTBC isolates collected between 2010 and 2015 in combination with patients\u2019 demographics. We showed that the MTBC population mainly comprises strains of four lineages (L1\u2013L4). The two dominating lineages were L4 with 55.8% (n = 215) and L3 with 25.7% (n = 99) of all strains, respectively. Genome-based cluster analysis showed that 30.4% (117\/385) of the strains were clustered using a \u22645 single-nucleotide polymorphism (SNP) threshold as a surrogate marker for direct patient-to-patient MTBC transmission. Moreover, 5.2% (20\/385) of the strains were multidrug-resistant (MDR), and 50.0% (n = 10) were part of a genome-based cluster (i.e., direct MDR MTBC transmission). Notably, 30.0% (6\/20) of the MDR strains were resistant to all first-line drugs and are part of one molecular cluster. Moreover, TB patients in urban living setting had 3.8 times the odds of being infected with a drug-resistant strain as compared to patients from slums (p-value = 0.002). Our results show that L4 strains are the main causative agent of TB in Nairobi and MDR strain transmission is an emerging concern in urban settings. This emphasizes the need for more focused infection control measures and contact tracing of patients with MDR TB to break the transmission chains.<\/jats:p>","DOI":"10.3390\/genes13030475","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T12:35:37Z","timestamp":1646742937000},"page":"475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Molecular Epidemiology of Mycobacterium tuberculosis Complex Strains in Urban and Slum Settings of Nairobi, Kenya"],"prefix":"10.3390","volume":"13","author":[{"given":"Glennah","family":"Kerubo","sequence":"first","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel, 23845 Borstel, Germany"},{"name":"School of Medicine, Kenyatta University, Nairobi 43844-00100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perpetua","family":"Ndungu","sequence":"additional","affiliation":[{"name":"Jomo Kenyatta University of Agriculture and Technology, Nairobi 62000-00200, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5411-5765","authenticated-orcid":false,"given":"Yassir Adam","family":"Shuaib","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel, 23845 Borstel, Germany"},{"name":"College of Veterinary Medicine, Sudan University of Science and Technology, Khartoum North 13321, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0683-0585","authenticated-orcid":false,"given":"Evans","family":"Amukoye","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Disease Research, Kenya Medical Research Institute, Nairobi 54840-00200, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunturu","family":"Revathi","sequence":"additional","affiliation":[{"name":"Aga Khan University Hospital, Nairobi 30270-00100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Homolka","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel, 23845 Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3209-9503","authenticated-orcid":false,"given":"Samuel","family":"Kariuki","sequence":"additional","affiliation":[{"name":"Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi 54840-00200, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Merker","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel, 23845 Borstel, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 23845 Borstel, Germany"},{"name":"Evolution of the Resistome, Research Center Borstel, 23845 Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Niemann","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel, 23845 Borstel, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 23845 Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref_1","unstructured":"WHO (2021). Global Tuberculosis Report 2021, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a017798","DOI":"10.1101\/cshperspect.a017798","article-title":"Global epidemiology of tuberculosis","volume":"5","author":"Glaziou","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_3","first-page":"002","article-title":"The epidemiology of tuberculosis in Kenya, a high TB HIV burden country (2000-2013)","volume":"1","author":"Kipruto","year":"2015","journal-title":"Int. J. Public Health Epidemiol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1128\/CMR.00042-10","article-title":"HIV and tuberculosis: A deadly human syndemic","volume":"24","author":"Kwan","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1128\/AAC.01550-10","article-title":"Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis","volume":"55","author":"Campbell","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100603","DOI":"10.1016\/j.eclinm.2020.100603","article-title":"The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis","volume":"28","author":"Cilloni","year":"2020","journal-title":"EClinicalMedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"436","DOI":"10.5588\/ijtld.21.0148","article-title":"The impact of COVID-19 on TB: A review of the data","volume":"25","author":"McQuaid","year":"2021","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijmyco.2014.12.006","article-title":"Microscopy as a diagnostic tool in pulmonary tuberculosis","volume":"4","author":"Singhal","year":"2015","journal-title":"Int J. Mycobacteriol."},{"key":"ref_9","first-page":"8038137","article-title":"Smear Microscopy for Diagnosis of Pulmonary Tuberculosis in Eastern Sudan","volume":"2018","author":"Shuaib","year":"2018","journal-title":"Tuberc. Res. Treat."},{"key":"ref_10","doi-asserted-by":"crossref","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":"ref_11","doi-asserted-by":"crossref","unstructured":"Merker, M., Barbier, M., Cox, H., Rasigade, J.P., Feuerriegel, S., Kohl, T.A., Diel, R., Borrell, S., Gagneux, S., and Nikolayevskyy, V. (2018). Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia. Elife, 7.","DOI":"10.7554\/eLife.38200"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3201\/eid2603.191145","article-title":"Mycobacterium tuberculosis Complex Lineage 3 as Causative Agent of Pulmonary Tuberculosis, Eastern Sudan","volume":"26","author":"Shuaib","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s11904-013-0164-x","article-title":"Transmission of tuberculosis in resource-limited settings","volume":"10","author":"Kompala","year":"2013","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Enos, M., Sitienei, J., Ong\u2019ang\u2019o, J., Mungai, B., Kamene, M., Wambugu, J., Kipruto, H., Manduku, V., Mburu, J., and Nyaboke, D. (2018). Kenya tuberculosis prevalence survey 2016: Challenges and opportunities of ending TB in Kenya. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0209098"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wiens, K.E., Woyczynski, L.P., Ledesma, J.R., Ross, J.M., Zenteno-Cuevas, R., Goodridge, A., Ullah, I., Mathema, B., Djoba Siawaya, J.F., and Biehl, M.H. (2018). Global variation in bacterial strains that cause tuberculosis disease: A systematic review and meta-analysis. BMC Med., 16.","DOI":"10.1186\/s12916-018-1180-x"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/infdis\/jiu403","article-title":"Transmission of tuberculosis in a South African community with a high prevalence of HIV infection","volume":"211","author":"Middelkoop","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1099\/jmm.0.2008\/001339-0","article-title":"Novel hypertonic saline-sodium hydroxide (HS-SH) method for decontamination and concentration of sputum samples for Mycobacterium tuberculosis microscopy and culture","volume":"57","author":"Ganoza","year":"2008","journal-title":"J. Med. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3201\/eid2203.151673","article-title":"Tuberculosis Risk among Medical Trainees, Pune, India","volume":"22","author":"Basavaraj","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_19","unstructured":"GLI (2014). Mycobacteriology Laboratory Manual, WHO."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1128\/JCM.43.6.2996-2997.2005","article-title":"Extraction of Mycobacterium tuberculosis DNA: A question of containment","volume":"43","author":"Somerville","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Baym, M., Kryazhimskiy, S., Lieberman, T.D., Chung, H., Desai, M.M., and Kishony, R. (2015). Inexpensive multiplexed library preparation for megabase-sized genomes. PLoS ONE, 10.","DOI":"10.1101\/013771"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with Burrows-Wheeler transform","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","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":"ref_24","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1128\/JCM.00025-15","article-title":"PhyResSE: A Web Tool Delineating Mycobacterium tuberculosis Antibiotic Resistance and Lineage from Whole-Genome Sequencing Data","volume":"53","author":"Feuerriegel","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1093\/molbev\/msn083","article-title":"jModelTest: Phylogenetic model averaging","volume":"25","author":"Posada","year":"2008","journal-title":"Mol. Biol. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Price, M.N., Dehal, P.S., and Arkin, A.P. (2010). FastTree 2\u2014approximately maximum-likelihood trees for large alignments. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009490"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"W236","DOI":"10.1093\/nar\/gkw370","article-title":"Evolview v2: An online visualization and management tool for customized and annotated phylogenetic trees","volume":"44","author":"He","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S1473-3099(12)70277-3","article-title":"Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: A retrospective observational study","volume":"13","author":"Walker","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.ebiom.2018.10.013","article-title":"The relationship between transmission time and clustering methods in Mycobacterium tuberculosis epidemiology","volume":"37","author":"Meehan","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_30","unstructured":"MARCH (2009). DLTLD Guidelines on Management of Leprosy and Tuberculosis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4812","DOI":"10.1038\/ncomms5812","article-title":"A robust SNP barcode for typing Mycobacterium tuberculosis complex strains","volume":"5","author":"Coll","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/microbiolspec.TBTB2-0022-2016","article-title":"Impact of Genetic Diversity on the Biology of Mycobacterium tuberculosis Complex Strains","volume":"4","author":"Niemann","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"174732","DOI":"10.1155\/2015\/174732","article-title":"Genetic Diversity of Mycobacterium tuberculosis Complex Isolated from Tuberculosis Patients in Bahir Dar City and Its Surroundings, Northwest Ethiopia","volume":"2015","author":"Nuru","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.tube.2014.11.006","article-title":"Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania","volume":"95","author":"Mbugi","year":"2015","journal-title":"Tuberculosis"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Asiimwe, B.B., Ghebremichael, S., Kallenius, G., Koivula, T., and Joloba, M.L. (2008). Mycobacterium tuberculosis spoligotypes and drug susceptibility pattern of isolates from tuberculosis patients in peri-urban Kampala, Uganda. BMC Infect. Dis., 8.","DOI":"10.1186\/1471-2334-8-101"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ijid.2020.11.129","article-title":"Genetic diversity of the Mycobacterium tuberculosis complex s.strains from newly diagnosed tuberculosis patients in Northwest Ethiopia reveals a predominance of East-African-Indian and Euro-American lineages","volume":"103","author":"Ejo","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","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":"ref_38","doi-asserted-by":"crossref","unstructured":"Bazira, J., Asiimwe, B.B., Joloba, M.L., Bwanga, F., and Matee, M.I. (2011). Mycobacterium tuberculosis spoligotypes and drug susceptibility pattern of isolates from tuberculosis patients in South-Western Uganda. BMC Infect. Dis., 11.","DOI":"10.1186\/1471-2334-11-81"},{"key":"ref_39","first-page":"352","article-title":"Identification of MDR-TB BeijingW and other Mycobacterium tuberculosis genotypes in Nairobi, Kenya","volume":"8","author":"Githui","year":"2004","journal-title":"Int J. Tuberc. Lung Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1128\/JCM.03566-14","article-title":"Mycobacterium tuberculosis lineage 7 strains are associated with prolonged patient delay in seeking treatment for pulmonary tuberculosis in Amhara Region, Ethiopia","volume":"53","author":"Yimer","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3389\/fevo.2019.00112","article-title":"Multiple Introductions of Mycobacterium tuberculosis Lineage 2\u2013Beijing Into Africa Over Centuries","volume":"7","author":"Rutaihwa","year":"2019","journal-title":"Front. Ecol. Evol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mekonnen, A., Merker, M., Collins, J.M., Addise, D., Aseffa, A., Petros, B., Ameni, G., and Niemann, S. (2018). Molecular epidemiology and drug resistance patterns of Mycobacterium tuberculosis complex isolates from university students and the local community in Eastern Ethiopia. PLoS ONE, 13.","DOI":"10.1101\/322958"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cain, K.P., Marano, N., Kamene, M., Sitienei, J., Mukherjee, S., Galev, A., Burton, J., Nasibov, O., Kioko, J., and De Cock, K.M. (2015). The movement of multidrug-resistant tuberculosis across borders in East Africa needs a regional and global solution. PLoS Med., 12.","DOI":"10.1371\/journal.pmed.1001791"},{"key":"ref_44","first-page":"21","article-title":"Anti-tuberculosis drug resistance in Nairobi, Kenya","volume":"20","author":"Ogaro","year":"2012","journal-title":"African J. Health Sci."},{"key":"ref_45","first-page":"661","article-title":"First line anti-tuberculosis drug resistance among human immunodeficiency virus infected patients attending Maryland Comprehensive Care Centre, Mathare 4a, Nairobi, Kenya","volume":"15","author":"Obonyo","year":"2014","journal-title":"Int. J. Sci. Basic Appl. Res."},{"key":"ref_46","first-page":"1088","article-title":"Prevalence of multidrug resistant Mycobacterium tuberculosis and risk factors among youth attending MDR-TB unit in Mulago hospital","volume":"5","author":"Kateregga","year":"2018","journal-title":"J. Bacteriol. Mycol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.apjtm.2015.10.014","article-title":"Anti-TB drug resistance in Tanga, Tanzania: A cross sectional facility-base prevalence among pulmonary TB patients","volume":"8","author":"Hoza","year":"2015","journal-title":"Asian Pac. J. Trop. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/3\/475\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:34:03Z","timestamp":1760135643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/3\/475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":47,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["genes13030475"],"URL":"https:\/\/doi.org\/10.3390\/genes13030475","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]}}}