Methodological approach: A longitudinal (prospective cohort) study was conducted at South African gold mines to identify miners who have been working in the mines for at least 15 years but have no evidence of TB infection and are HIV negative. Miners were screened for eligibility and chest radiographs were reviewed to exclude current or prior TB. Quantiferon test (QFT) and tuberculin skin test were done to exclude latent TB infection and HIV test was offered. We enrolled HIV-negative miners and collected blood for QFT, plasma, peripheral blood mononuclear cells (PBMC) processing, whole blood assay and Paxgene tubes for transcriptomics. The plasma, PBMCs and Paxgene blood tubes were collected and analyzed to identify gene profiles and immune responses associated with TB protection. Miners who were QFT negative and those who were infected with latent TB (QFT and TST positive) at enrolment were followed up 12 months post enrolment and all enrolment procedures were repeated. Embedded within the longitudinal study was a case control study to identify gene expression and immunological profiles associated with being TB-uninfected using the stored blood specimens.

Key Findings: Still analysing and completing lab tests

Outputs/Outcomes: This work offers innovative approaches to understanding the mechanisms that underlie resistance and susceptibility to Mtb infection in HIV uninfected individuals which may point to novel approaches to TB vaccine and therapeutic strategies that incorporate host-directed therapies (HDT) to subvert immune evasion by Mtb.

Related resources: N/A

Methodological approach: A data quality methodology was applied, with a baseline data quality assessment (DQA) of DR-TB records conducted in 2017. Following the baseline, a data quality improvement process (QIP) was applied to the 2015 - 2017 records as the intervention methodology. In addition a quality assurance (QA) audit of the updated records was used to measure the intervention (data QIP). We use data completeness, Concordance and Validity as components to measure data quality.

Key Findings: Data quality improvement for approximately 6 500 records updated between 2015 - 2017. The data show 90% - 100% data completeness of primary data elements between the patient clinical folder (PCF) and EDRWeb; 100% agreement between PCF and EDRWeb with kappa (k) statistic = 1.0; Sensitivity and positive predictive values (PPV) 100% between 2015 - 17 records.

Outputs/Outcomes: This project has provided excellent quality data in support of full registration for Bedaquiline (BDQ) at the United States Food and Drug Agency (USFDA), European Medicines Agency (EMA) and South African Health Products Regulatory Authority (SAHPRA).

Related resources: Data quality abstraction and EDRWeb updating SOP, EDRWeb sampling SOP, Consolidated DQA report (2015-17), Baseline DQA report shared with funder for submission to FDA, EMA, SAHPRA Data Quality journal article submitted for publication to Public Health Action (PHA).

Methodological approach: A longitudinal (prospective cohort) study was conducted at South African gold mines to identify miners who have been working in the mines for at least 15 years but have no evidence of TB infection and were HIV positive. Miners were screened for eligibility and chest radiographs were reviewed to exclude current or prior TB, and medical records were also reviewed to confirm HIV status. Enrolment was offered to HIV-positive individuals with no prior or current TB and blood was collected for QFT, plasma, peripheral blood mononuclear cells (PBMC) processing, whole blood bactericidal assay (WBA) and transcriptomics. In addition to QFT for LTBI, tuberculin skin test (TST) was also done. Sputum was collected for culture testing to identify subclinical TB cases. To assess the stability of the resistant phenotype, miners who were QFT negative at enrolment were followed up six and 12 months post enrolment and further bloods were taken for plasma, PBMC processing, transcriptomics and WBA from those not started on TB treatment. Tests for LTBI (QFT and TST) was repeated at each follow up visit. Embedded within the longitudinal study was a case control study to identify gene expression and immunological profiles associated with being TB-uninfected

Key Findings: Still analysing and completing lab tests

Outputs/Outcomes: This work offers innovative approaches to understanding the mechanisms that underlie resistance and susceptibility to Mtb infection in HIV infected individuals which may point to novel approaches to TB vaccine and therapeutic strategies that incorporate host-directed therapies (HDT) to subvert immune evasion by Mtb.

Related resources: