- Author
-
K.C.S. Ng
- Title
- Utilization of molecular resistance test results as tools to support public health efforts for improved control of rifampicin-resistant tuberculosis
- Supervisors
-
F.G.J. Cobelens
J. Gonzales Martin - Co-supervisors
-
F.C.M. van Leth
B.C. de Jong - Award date
- 2 June 2020
- Number of pages
- 226
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Bridging diagnostic gaps may help reduce the global burden of rifampicin-resistant tuberculosis (RR-TB) transmission. Inaccurate diagnoses result in false RR-TB patients receiving toxic and less effective drugs, while false rifampicin-susceptible-TB patients continue to transmit RR-TB in the community which may lead to RR-TB outbreaks. Early detection of RR-TB outbreaks entails rapid and systematic analysis of RR data at the population level. The increasing use of Xpert MTB/RIF as a frontline diagnostic test for all presumptive TB patients provides an opportunity to utilize routinely produced RR-TB data for timely detection of RR-TB clusters. Currently, there is no system in place capable of performing this analysis.
The PhD thesis of Kamela Charmaine S. Ng entitled “Utilization of molecular resistance test results as tools to support public health efforts for improved control of RR-TB” has improved the understanding of routine diagnostic data and provided policy implications on addressing diagnostic challenges that affect interruption of RR-TB transmission.
Furthermore, this thesis developed an early warning tool which harnessed the full potential of routine Xpert data for improved RR-TB surveillance. This tool utilizes both projected site-specific numbers of RR-TB diagnoses and frequency of Xpert probe(s) which represents circulating RR-TB mutations in the setting. The National TB Control Program is then prompted to investigate further on Xpert site(s) with unusual RR-TB clusters, and tailor active case finding and initiate effective treatment to reduce the transmissibility of TB. This thesis demonstrates as a proof-of-concept, that routine Xpert data contain actionable information that could improve country surveillance of RR-TB. - Persistent Identifier
- https://hdl.handle.net/11245.1/99b13aa8-0ab8-4732-81d5-f19373ded9e3
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: Introduction
Chapter 2: Potential application of digitally linked tuberculosis diagnostics for real-time surveillance of drug-resistant tuberculosis transmission: Validation and analysis of test results
Chapter 3: Xpert Ultra can unambiguously identify specific rifampicin resistanceconferring mutations
Chapter 4: Variable ability of rapid tests to detect Mycobacterium tuberculosis rpoB mutations conferring phenotypically occult rifampicin resistance
Chapter 5: How well do routine molecular diagnostics detect rifampicin heteroresistance in Mycobacterium tuberculosis?
Chapter 6: Bridging the TB data gap: In silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data
Chapter 7: Identifying unusual clusters of rifampicin-resistant tuberculosis cases using statistical modelling of Xpert test results
Chapter 8: False rifampicin resistance in Xpert Ultra applied to lymph node aspirate: A case report
Chapter 9: Discussion, policy implications, recommendations, and future perspectives
List of abbreviations; Samenvatting; Summary; Acknowledgement; PhD portfolio; Publications; Curriculum vitae; About the author
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