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Novel approaches for the diagnosis of drug-resistance, treatment response, and infectiousness in patients with tuberculosis (the eDIToR study – Diagnosis Infectiousness and Treatment Response)
Thesis (PhD)--Stellenbosch University, 2020.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2020
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| _version_ | 1867614121385525248 |
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| access_status_str | Open Access |
| author | Venter, Rouxjeane |
| author2 | Theron, Grant |
| author_browse | Theron, Grant Venter, Rouxjeane |
| author_facet | Theron, Grant Venter, Rouxjeane |
| author_sort | Venter, Rouxjeane |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2020. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/108429 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:47:00.249Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2020 |
| publishDateRange | 2020 |
| publishDateSort | 2020 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/108429 Novel approaches for the diagnosis of drug-resistance, treatment response, and infectiousness in patients with tuberculosis (the eDIToR study – Diagnosis Infectiousness and Treatment Response) Venter, Rouxjeane Theron, Grant Warren, Robin M. Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics Tuberculosis Drug resistance -- Tuberculosis Infectious diseases Treatment monitoring Clinical research Multidrug resistance -- Diagnosis Thesis (PhD)--Stellenbosch University, 2020. ENGLISH ABSTRACT: Drug-resistance tuberculosis (DR-TB) is a major challenge facing TB control. Limiting personto-person transmission is key. This can be done by reducing time to drug susceptibility diagnosis and effective treatment initiation, which reduces infectiousness. Furthermore, DRTB patients have suboptimal outcomes even on effective treatment and we have few methods for monitoring treatment response. If patients are not responding to treatment, better methods are required to measure infectiousness so that transmission may be limited. First, to alleviate the under-diagnosis of drug-resistance stemming from additional sputa not submitted for drug susceptibility testing (DST) and infrastructural barriers, we showed that cartridge extract (CE) from used TB-positive Xpert MTB/RIF (Xpert) tests is directly usable for MTBDRsl (a second-line molecular DST). Furthermore, we showed that CE was useful for spoligotyping for molecular epidemiology. Second, we showed that this CE approach is feasible on Xpert MTB/RIF Ultra (Ultra), which is Xpert’s successor. We also evaluated the risk of rpoB amplicon escape during the extraction and the usefulness of material in other cartridge chambers for different molecular tests. In short, cross-contamination was possible but appears extremely unlikely. Only the diamond cartridge compartment contains useful material. Third, MTBDRsl itself has limitations. For example, it only measures susceptibility to two drug classes. We assessed the feasibility of ultra-deep sequencing (single molecule overlapping reads, SMOR) on CE. SMOR had more actionable results (useful for clinical decision making) on Xpert CE than Ultra CE, and detected micro-heteroresistance missed by conventional DST. Next, to evaluate the utility of new tools for treatment response, we leveraged a MDR-TB drug trial (NeXT, Clinicaltrials.gov #NCT02454205) to collect serial sputa. We assessed if sputa contained differentially culturable tubercle bacilli (DCTB) with a dormancy-associated. Doctoral 2020-02-21T11:34:04Z 2020-04-28T15:13:31Z 2020-02-21T11:34:04Z 2020-04-28T15:13:31Z 2020-03 Thesis http://hdl.handle.net/10019.1/108429 en_ZA Stellenbosch University 262 pages application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Tuberculosis Drug resistance -- Tuberculosis Infectious diseases Treatment monitoring Clinical research Multidrug resistance -- Diagnosis Venter, Rouxjeane Novel approaches for the diagnosis of drug-resistance, treatment response, and infectiousness in patients with tuberculosis (the eDIToR study – Diagnosis Infectiousness and Treatment Response) |
| title | Novel approaches for the diagnosis of drug-resistance, treatment response, and infectiousness in patients with tuberculosis (the eDIToR study – Diagnosis Infectiousness and Treatment Response) |
| title_full | Novel approaches for the diagnosis of drug-resistance, treatment response, and infectiousness in patients with tuberculosis (the eDIToR study – Diagnosis Infectiousness and Treatment Response) |
| title_fullStr | Novel approaches for the diagnosis of drug-resistance, treatment response, and infectiousness in patients with tuberculosis (the eDIToR study – Diagnosis Infectiousness and Treatment Response) |
| title_full_unstemmed | Novel approaches for the diagnosis of drug-resistance, treatment response, and infectiousness in patients with tuberculosis (the eDIToR study – Diagnosis Infectiousness and Treatment Response) |
| title_short | Novel approaches for the diagnosis of drug-resistance, treatment response, and infectiousness in patients with tuberculosis (the eDIToR study – Diagnosis Infectiousness and Treatment Response) |
| title_sort | novel approaches for the diagnosis of drug resistance treatment response and infectiousness in patients with tuberculosis the editor study diagnosis infectiousness and treatment response |
| topic | Tuberculosis Drug resistance -- Tuberculosis Infectious diseases Treatment monitoring Clinical research Multidrug resistance -- Diagnosis |
| url | http://hdl.handle.net/10019.1/108429 |
| work_keys_str_mv | AT venterrouxjeane novelapproachesforthediagnosisofdrugresistancetreatmentresponseandinfectiousnessinpatientswithtuberculosistheeditorstudydiagnosisinfectiousnessandtreatmentresponse |