{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:39:20Z","timestamp":1787593160173,"version":"build-2736575974"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"The Ministry of Education Ghana, the German Academic Exchange Service","award":["Ghanaian-German Postgraduate Training Programme (57344816)"],"award-info":[{"award-number":["Ghanaian-German Postgraduate Training Programme (57344816)"]}]},{"name":"The German Center of Infection Research","award":["FKZ 8013802812"],"award-info":[{"award-number":["FKZ 8013802812"]}]},{"name":"Precision Medicine in Chronic Inflammation","award":["EXC 2167. Precision Medicine in Chronic InflammationN (PMI)"],"award-info":[{"award-number":["EXC 2167. Precision Medicine in Chronic InflammationN (PMI)"]}]},{"DOI":"10.13039\/100004423","name":"The World Health Organization","doi-asserted-by":"crossref","award":["WHO Agreement for performance of work,Purchase order 202945290"],"award-info":[{"award-number":["WHO Agreement for performance of work,Purchase order 202945290"]}],"id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Multidrug-resistant tuberculosis (MDR-TB) management has become a serious global health challenge. Understanding its epidemic determinants on the regional level is crucial for developing effective control measures. We used whole genome sequencing data of 238 of\n              <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n              complex (MTBC) strains to determine drug resistance profiles, phylogeny, and transmission dynamics of MDR\/rifampicin-resistant (RR) MTBC strains from Sierra Leone. Forty-two strains were classified as RR, 196 as MDR, 5 were resistant to bedaquiline (BDQ) and clofazimine (CFZ), but none was found to be resistant to fluoroquinolones. Sixty-one (26%) strains were resistant to all first-line drugs, three of which had additional resistance to BDQ\/CFZ. The strains were classified into six major MTBC lineages (L), with strains of L4 being the most prevalent, 62% (\n              <jats:italic>n<\/jats:italic>\n              = 147), followed by L6 (\n              <jats:italic>Mycobacterium africanum<\/jats:italic>\n              ) strains, (21%,\n              <jats:italic>n<\/jats:italic>\n              = 50). The overall clustering rate (using \u2264d12 single-nucleotide polymorphism threshold) was 44%, stratified into 31 clusters ranging from 2 to 16 strains. The largest cluster (\n              <jats:italic>n<\/jats:italic>\n              = 16) was formed by sublineage 2.2.1 Beijing Ancestral 3 strains, which developed MDR several times. Meanwhile, 10 of the L6 strains had a primary MDR transmission. We observed a high diversity of drug resistance mutations, including borderline resistance mutations to isoniazid and rifampicin, and mutations were not detected by commercial assays. In conclusion, one in five strains investigated was resistant to all first-line drugs, three of which had evidence of BDQ\/CFZ resistance. Implementation of interventions such as rapid diagnostics that prevent further resistance development and stop MDR-TB transmission chains in the country is urgently needed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>A substantial proportion of MDR-TB strains in Sierra Leone were resistant against all first line drugs; however this makes the all-oral-six-month BPaLM regimen or other 6-9 months all oral regimens still viable, mainly because there was no FQ resistance.Resistance to BDQ was detected, as well as RR, due to mutations outside of the hotspot region. While the prevalence of those resistances was low, it is still cause for concern and needs to be closely monitored.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.02405-23","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T14:01:41Z","timestamp":1706623301000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Molecular determinants of multidrug-resistant tuberculosis in Sierra Leone"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2997-9112","authenticated-orcid":true,"given":"Harriet N. A.","family":"Blankson","sequence":"first","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel Leibniz Lung Center, Borstel, Germany"},{"name":"German Center for Infection Research, Partner Site Hamburg-L\u00fcbeck-Borstel-Reims, Borstel, Germany"},{"name":"School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Korle-Bu, Accra, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashidatu Fouad","family":"Kamara","sequence":"additional","affiliation":[{"name":"National Leprosy and Tuberculosis Control Programme Sierra Leone, Freetown, Sierra Leone"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Barilar","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel Leibniz Lung Center, Borstel, Germany"},{"name":"German Center for Infection Research, Partner Site Hamburg-L\u00fcbeck-Borstel-Reims, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6nke","family":"Andres","sequence":"additional","affiliation":[{"name":"National and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel Leibniz Lung Center, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ousman S.","family":"Conteh","sequence":"additional","affiliation":[{"name":"National Leprosy and Tuberculosis Control Programme Sierra Leone, Freetown, Sierra Leone"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Dallenga","sequence":"additional","affiliation":[{"name":"German Center for Infection Research, Partner Site Hamburg-L\u00fcbeck-Borstel-Reims, Borstel, Germany"},{"name":"Cellular Microbiology, Research Center Borstel Leibniz Lung Center, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Foray","sequence":"additional","affiliation":[{"name":"National Leprosy and Tuberculosis Control Programme Sierra Leone, Freetown, Sierra Leone"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Maurer","sequence":"additional","affiliation":[{"name":"German Center for Infection Research, Partner Site Hamburg-L\u00fcbeck-Borstel-Reims, Borstel, Germany"},{"name":"National and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel Leibniz Lung Center, Borstel, Germany"},{"name":"Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-7270","authenticated-orcid":true,"given":"Katharina","family":"Kranzer","sequence":"additional","affiliation":[{"name":"Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5416-8253","authenticated-orcid":false,"given":"Christian","family":"Utpatel","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel Leibniz Lung Center, Borstel, Germany"},{"name":"German Center for Infection Research, Partner Site Hamburg-L\u00fcbeck-Borstel-Reims, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-0684","authenticated-orcid":true,"given":"Stefan","family":"Niemann","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Mycobacteriology, Research Center Borstel Leibniz Lung Center, Borstel, Germany"},{"name":"German Center for Infection Research, Partner Site Hamburg-L\u00fcbeck-Borstel-Reims, Borstel, Germany"},{"name":"National and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel Leibniz Lung Center, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_2_2","unstructured":"World Health Organization. 2022. Global tuberculosis report 2022. World Health Organization Geneva. Available from: https:\/\/apps.who.int\/iris\/handle\/10665\/363752. Retrieved 29 Nov 2022."},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-016-1725-6"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-64371-7_7"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02820"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.4102\/jsava.v87i1.1322"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161892"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2018.05.014"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077000"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018601"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-8-103"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010490"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5812"},{"key":"e_1_3_6_14_2","volume-title":"WHO Consolidated guidelines on tuberculosis. module 4, treatment: drug-susceptible tuberculosis treatment","year":"2022","unstructured":"2022. WHO Consolidated guidelines on tuberculosis. module 4, treatment: drug-susceptible tuberculosis treatment. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_6_15_2","unstructured":"World Health Organization. 2021. WHO announces updated definitions of extensively drug-resistant tuberculosis. WHO. Available from: https:\/\/www.who.int\/news\/item\/27-01-2021-who-announces-updated-definitions-of-extensively-drug-resistant-tuberculosis. Retrieved 31 Mar 2021."},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.0149-2021"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2701.203766"},{"key":"e_1_3_6_18_2","unstructured":"World Health Organization. 2022. Rapid communication: key changes to the treatement of drug-resistant tuberculosis. WHO"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00007-X"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01076-0"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00470-9"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00621-2021"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2103049"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00793-8"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1413930"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac070"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(22)00004-3"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.29.11.2578-2586.1991"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab359"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.38200"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128036"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.5895"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/31159"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_6_37_2","unstructured":"World Health Organization. 2021. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. World Health Organization Geneva. Available from: https:\/\/apps.who.int\/iris\/handle\/10665\/343656. Retrieved 13 Apr 2022."},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msu300"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4285"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mst024"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl529"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01599-17"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01586-22"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30496-1"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.10.4068-4074.2005"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jctube.2022.100319"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-018-3053-5"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.807095"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201909-1819LE"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02383-2019"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00543-6"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3704"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2012.02.004"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.09.012"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000325"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50078-3"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3195"},{"key":"e_1_3_6_58_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2603.190525"},{"key":"e_1_3_6_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32455-1"},{"key":"e_1_3_6_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-019-1487-2"},{"key":"e_1_3_6_61_2","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000477"},{"key":"e_1_3_6_62_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00726-5"},{"key":"e_1_3_6_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2016.05.014"},{"key":"e_1_3_6_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007297"},{"key":"e_1_3_6_65_2","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0377-2020"},{"key":"e_1_3_6_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01833-10"},{"key":"e_1_3_6_67_2","doi-asserted-by":"publisher","DOI":"10.2217\/pgs-2018-0166"},{"key":"e_1_3_6_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00353-10"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02405-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02405-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T14:04:56Z","timestamp":1709647496000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.02405-23"}},"subtitle":[],"editor":[{"given":"Silvia T.","family":"Cardona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,5]]},"references-count":67,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,5]]}},"alternative-id":["10.1128\/spectrum.02405-23"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.02405-23","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,5]]},"assertion":[{"value":"2023-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02405-23"}}