EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 1970-01-01
End Date 1970-01-01
Project Code TMA2016CDF1576
Status Active

Title

Evaluating the response to 4 and 6 month treatment of pulmonary tuberculosis by 18F-FDG PET/CT lung imaging.

Host Organisation

Institution Country
Stellenbosch University (SU) South Africa

Current Organisation

Stellenbosch University

Current Job Title

Principal Medical Officer

Awards

2017 HD Breede award for the best Tuberculosis related publication by post-graduate student in the Stellenbosch University Faculty of Medicine and Health Sciences.

Memberships

Role Committee/board Start Date End Date
Member MB,ChB Curriculum Renewal Committee 2017

Education

Institution Degree Year
Stellenbosch, South Africa MB.ChB 2006-12-16
Stellenbosch, South Africa PhD 2016-12-16

Areas Of Specialisation

Tuberculosis (TB)

Publications

Authors:
Young, Carly Ahlers, Petri Hiemstra, Andriette M Loxton, Andre G Gutschmidt, Andrea Malherbe, Stephanus T , oung et al. Translational Medicine Communications https://doi.org/10.1186/s41231-019-0039-2 (2019) 4:7
Date:
2019-06-05
Journal:
Translational Medicine Communications
Content:

Background: Tuberculosis (TB) remains a debilitating, deadly disease that warrants innovative research tools to fully understand the pathogenesis and host immune responses, particularly at the site of infection and disease. In this regard, bronchoscopies with bronchoalveolar lavage (BAL) serve as a valuable technique for site of disease sample retrieval for further clinical- and basic research. Here we investigate the feasibility of research bronchoscopies in a low/middle-income area, where TB remains rife, and assess the value of retrieved BAL cells (BALC) for downstream fluorescent-based cellular evaluations. Methods: Using quantitative and qualitative methods, we evaluate the outcomes, safety, tolerability, participant -perception and -experience, while also providing insight into participant recruitment and screening processes of our study. Using light microscopy differential counting for BALC analysis, we evaluate the cellular composition of BAL fluid (BALF) from TB patients, healthy community controls and patients with other lung diseases. We also use flow cytometry to describe the challenges associated with fluorescence-based phenotypic analysis of autofluorescent BALC. Results: Our findings suggest that research bronchoscopies are safe, acceptable procedures for research participants and are indeed a feasible technique for future study design. We also suggest that the majority of participants are receptive to the proposition of a second research bronchoscopy. This poses an important avenue for research entailing follow-up investigations of the same study participant. Furthermore, our results show that smoking is characterized by retrieval of BALC containing particulate matter, that interferes with fluorescence-based flow cytometry data analysis. Based on light microscopy differential cell counting, our findings suggest that there are differences in the cell yields and cellular composition of the BALF between TB patients, healthy community controls and patients with other lung diseases. We also report on subject characteristics and demographic factors, namely gender and age, that have the potential to affect cell yields and cellular data of BALF.

Conclusions: These findings will serve as a valuable reference for appropriate planning and design of studies involving clinical bronchoscopies for TB and lung disease research.
 

Identifiers:
Authors:
Malherbe, Stephanus T. Chen, Ray Y. Dupont, Patrick Kant, Ilse Kriel, Magdalena Loxton, André G. Smith, Bronwyn Beltran, Caroline G.G. van Zyl, Susan McAnda, Shirely Abrahams, Charmaine Maasdorp, Elizna Doruyter, Alex Via, Laura E. Barry, Clifton E. Alland, David Richards, Stephanie Griffith Ellman, Annare Peppard, Thomas Belisle, John Tromp, Gerard Ronacher, Katharina Warwick, James M. Winter, Jill Walzl, Gerhard , 10.1186/s13550-020-0591-9
Date:
2020-01-09
Journal:
EJNMMI Research
Content:

Background: There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes. Results: Quantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions. Conclusions: Quantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities.

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