Thesis Title: Development and validation of liquid chromatography-tandem mass spectrometry assays for rifampicin, levofloxacin, bedaquiline and its metabolite, M2, in cerebrospinal fluid, and the analysis of clinical samples.

Chanel Steele's journey in academia began with her pursuit of Bachelor’s and Honours degrees at North-West University and University of Cape Town, respectively. Her thirst for knowledge and passion for science led her to join the Division of Clinical Pharmacology at UCT in August 2015. Before joining UCT, Chanel worked as an analyst in a Food Testing and Pesticides laboratory for approximately 2.5 years, where she meticulously tested for all nutritional information, and later delved into testing vitamins in various edible products and pesticide analysis in fruit.

Chanel’s MSC (Med) thesis focuses on the development and validation of liquid chromatography-tandem mass spectrometry assays for rifampicin, levofloxacin, bedaquiline and its metabolite, M2, in cerebrospinal fluid, and the analysis of clinical samples. Tuberculosis meningitis (TBM) is a devastating illness that can cause permanent brain damage or death. Many patients with TBM are infected with multi-drug resistant (MDR) strains of the TB bacteria, making it hard to treat. For a drug to be effective against the bacteria, it must travel to the site of infection – which, in this case, is the brain. The drug must move into the cerebrospinal fluid (CSF) and travel through the blood-brain barrier (BBB), transferring the drug to the brain. As part of her MSc. Med degree, she developed a bioanalytical method to test the concentration of the anti-TB drug bedaquiline (used in treating pulmonary MDR-TB) in CSF samples. It has been speculated that bedaquiline is not helpful in the treatment of TBM because it cannot cross the BBB. In her MSc study, in collaboration with the TASK team (ACTG A5343 clinical trial), it was shown that bedaquiline crosses the BBB freely into CSF. Furthermore, she developed a bioanalytical method to test anti-TB drugs rifampicin and levofloxacin concentrations in CSF samples taken from children to assess the effect of increased rifampicin doses with and without levofloxacin (TBM Kids Trial). The results from the clinical samples provided to these clinical teams may be used to adjust the TB treatment guidelines regarding the use of bedaquiline in TBM and optimised rifampicin dosing for children with TBM.

Chanel’s journey is a testament to the transformative power of dedication, innovation, and collaboration in advancing healthcare solutions. Balancing academia, motherhood, and leadership roles, she serves as an inspiration to aspiring researchers in the Health Science community. Her advice to them is simple yet profound: surround yourself with a supportive team in the workplace and at home, embrace challenges as opportunities for growth, and persevere in the pursuit of knowledge. In doing so, the rewards will be immeasurable.