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dc.contributor.authorSsengooba, W.
dc.contributor.authorMeehan, Conor J.
dc.contributor.authorLukoye, D.
dc.contributor.authorKasule, G.W.
dc.contributor.authorMusisi, K.
dc.contributor.authorJoloba, M.L.
dc.contributor.authorCobelens, F.G.
dc.contributor.authorde Jong, B.C.
dc.date.accessioned2019-09-24T10:53:54Z
dc.date.accessioned2019-10-23T11:19:56Z
dc.date.available2019-09-24T10:53:54Z
dc.date.available2019-10-23T11:19:56Z
dc.date.issued2016-06
dc.identifier.citationSsengooba W, Meehan CJ, Lukoye D et al (2016) Whole genome sequencing to complement tuberculosis drug resistance surveys in Uganda. Infection, Genetics and Evolution. 40: 8-16.en_US
dc.identifier.urihttp://hdl.handle.net/10454/17316
dc.descriptionYesen_US
dc.description.abstractUnderstanding the circulating Mycobacterium tuberculosis resistance mutations is vital for better TB control strategies, especially to inform a new MDR-TB treatment programme. We complemented the phenotypic drug susceptibility testing (DST) based drug resistance surveys (DRSs) conducted in Uganda between 2008 and 2011 with Whole Genome Sequencing (WGS) of 90 Mycobacterium tuberculosis isolates phenotypically resistant to rifampicin and/or isoniazid to better understand the extent of drug resistance. A total of 31 (34.4 %) patients had MDR-TB, 5 (5.6 %) mono-rifampicin resistance and 54 (60.0 %) mono-isoniazid resistance by phenotypic DST. Pyrazinamide resistance mutations were identified in 32.3% of the MDR-TB patients. Resistance to injectable agents was detected in 4/90 (4.4%), and none to fluoroquinolones or novel drugs. Compensatory mutations in rpoC were identified in two patients. The sensitivity and specificity of drug resistance mutations compared to phenotypic DST were for rpoB 88.6% and 98.1%, katG 60.0% and 100%, fabG1 16.5% and 100%, katG and/or fabG1 71.8% and 100%, embCAB 63.0% and 82.5%, rrs 11.4% and 100%, rpsL 20.5% and 95.7% and rrs and/or rpsL 31.8% and 95.7%. Phylogenetic analysis showed dispersed MDR-TB isolate, with only one cluster of three Beijing family from South West Uganda. Among tuberculosis patients in Uganda, resistance beyond first-line drugs as well as compensatory mutations remain low, and MDR-TB isolates did not arise from a dominant clone. Our findings show the potential use of sequencing for complementing DRSs or surveillance in this setting, with good specificity compared to phenotypic DST. The reported high confidence mutations can be included in molecular assays, and population-based studies can track transmission of MDR-TB including the Beijing family strains in the South West of the country.en_US
dc.description.sponsorshipErasmus Mundus Joint Doctorate Program of the European Union through a training grant to WS and the European Research Council-INTERRUPTB starting grant (nr.311725) to BdJ.en_US
dc.language.isoenen_US
dc.rights© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.subjectWhole genome sequencingen_US
dc.subjectComplementen_US
dc.subjectTuberculosisen_US
dc.subjectDrug resistance surveysen_US
dc.titleWhole genome sequencing to complement tuberculosis drug resistance surveys in Ugandaen_US
dc.status.refereedYesen_US
dc.date.Accepted2016-02-15
dc.date.application2016-02-23
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.identifier.doihttps://doi.org/10.1016/j.meegid.2016.02.019
dc.date.updated2019-09-24T09:53:55Z
refterms.dateFOA2019-10-23T11:20:59Z


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