Tuberculosis (TB) is one of the top ten causes of death worldwide with approximately 10 million cases globally and 1.2 million deaths. Sub-Saharan Africa carries the highest burden of TB. South Africa has one of the highest HIV and TB rates worldwide with an HIV prevalence rate in adults of 19% and a TB case notification rate of 615/100,000 in 2019. Over many years, focus has been paid to pulmonary TB and extrapulmonary TB (EPTB) has received only little attention even though it accounts for almost a quatre of all TB cases. The diagnosis of EPTB remains challenging simply because sample collection requires invasive procedures in the absence of a blood-based diagnostic test. Spinal TB (spondylitis or spondylodiscitis caused by Mycobacterium tuberculosis) - often known as Pott's disease - accounts for up to 10% of EPTB and affects young children, people with HIV-coinfection and elderly, and often leads to lifelong debilitating disease due to devastating deformation of the spine and compression of neural structures. Little is known with regards to the extent of disease and isolated TB spine as well as a disseminated form of TB spine have been described. The latter presents with a spinal manifestation plus disseminations to other organs such as the lungs, pleura, lymph nodes, the GIT or urinary tract or even the brain.
In the Spinal TB X cohort, the investigators aim to describe the clinical phenotype of spinal TB using whole body PET/CT and identify a specific gene expression profile for the different stages of dissemination and compare findings to previously described signatures for latent and active pulmonary TB. A blood-based test for spinal TB would lead to earlier diagnosis and treatment in all settings globally and improve treatment outcome of this devastating disease.
Participant has completed the written informed consent process prior to undergoing any clinical evaluations and willing to undergo HIV testing
TB spine based on clinical and radiological criteria
Age 18 or older with a body weight of at least 40 kg body weight
Able and willing to return to follow-up
Pregnancy or active desire to become pregnant within the next 6 months.
Uncontrolled diabetes (HbA1c ≥ 6.5% / random glucose concentration ≥11.1 mmol/l, fasting plasma glucose ≥ 7.0 mmol/l)
Alcohol and substance abuse which might interfere with medication adherence during the trial
Positive SARS-CoV-2 PCR in the past 4 weeks
Participants with clinically and MR-suspected spinal TB will be recruited from the Department of Orthopaedics, Groote Schuur Hospital, Cape Town, South Africa. According to the current caseload, the investigators will be able to include 50-100 participants per year, aiming for 100 participants in total. In result, the investigators are aiming for 300 PET/CTs (100 initial, 100 at 6 months, 100 at 12 months) and 300 peripheral blood samples for gene expression analysis.
Cohort
Prospective
Not listed
Clinical phenotype of spinal TB
To describe the clinical phenotype of spinal TB using whole body PET/CT a semiquantitative approach will be used. Regions of interest (ROIs) will be identified with increased FDG uptake against background and total lesion glycolysis (TLG) of each ROI will be measured using MIM software
mRNA gene expression profiles of spinal TB
mRNA gene expression profiles of isolated spinal TB versus disseminated spinal TB described in outcome 1 will be measured and stratified by HIV status.
MRI vs. PET/CT at the site of disease (spine level)
To identify the distributive patterns of suspected spinal TB using two imaging modalities: MRI and PET/CT. MRI is measure T1, T2 and diffusion weighted images. Regions of interest (ROIs) in the spine will be identified with increased FDG uptake against background and total lesion glycolysis (TLG) of each ROI will be measured using MIM software
Whole Genome Sequencing of Mtb. isolates
To analyse the genomes of Mtb. extracted from different sites of the body (if available) and to identify differences in their genome regarding SNPs and drug sensibility.
PET/CT changes over 12 months
Regions of interest (ROIs) in the spine will be identified with increased FDG uptake against background and total lesion glycolysis (TLG) of each ROI will be measured using MIM software at different timepoints: treatment initiation, 6 months, and 12 months
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University of Cape Town
Lead sponsor
University of Zurich
Collaborator
