Tuberculosis (TB) poses a significant challenge for global health. Developing countries most burdened by disease have insufficient laboratory resources and limited capacity to conduct clinical trials. This thesis aims to investigate microbiological methods currently employed in TB programmes to compare their value in diagnosing TB and monitoring treatment using data from smear-positive patients enrolled in the REMoxTB study. As TB culture remains out-of-reach in many settings, diagnosis continues to depend on sputum smear microscopy. Early morning samples are considered better than spot samples. However, the data presented show that spot samples have a higher positive yield and greater sensitivity for solid and liquid culture. This evidence does not support guidelines requiring early morning samples which inconvenience patients and complicates trial enrolment. The data also show a reducing correlation between smear microscopy and culture on solid and liquid media as treatment progresses. These findings question the use of smear microscopy as a proxy for culture during treatment which may prompt inappropriate treatment extensions or retreatments. Comparing solid and liquid culture, the analyses show that liquid culture is faster and more sensitive. The clinical significance of this increased sensitivity throughout treatment is uncertain, and some samples negative in liquid culture remain positive on solid culture. The relationship between solid and liquid culture changes during treatment suggesting they differentially support the metabolic requirements of changing mycobacterial populations. The value of measures of pre-treatment mycobacterial load are investigated and show they are poorly predictive of microbiological responses during treatment in either culture media. Better indicators of treatment response are required which reflect mycobacterial population dynamics. Increasing availability of TB culture would of great benefit. The data show that the incubation times for liquid cultures, particularly for diagnostic samples, may be significantly reduced without loss of sensitivity, which could increase laboratory capacity and remove barriers to implementation. Future work will investigate whether these findings are generalisable to smear-negative patients and assess their value in predicting long-term treatment outcomes.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:756026 |
| Date | January 2016 |
| Creators | Murphy, M. E. |
| Contributors | Gillespie, S. H. ; Lipman, M. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1485825/ |
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