Tuberculosis

Aurum is a scientific leader in the field of TB, with a deep understanding of the science as well as the implementation approaches that lead to success.

Aurum has produced over 500 scientific articles in the last 20 years and has research experts ranging from epidemiologists, health economists and social scientists, to clinical trial specialists.

Aurum is involved in TB vaccine, HIV vaccine, TB drug and HIV drug trials. Several of these trials, such as the TB treatment shortening trials using Remox and Rifaquin provided landmark information for the management of tuberculosis. Likewise, the work on the AERAS GSK phase 2b study has provided new hope for a tuberculosis vaccine and Aurum led the SSI H1 and
Ad35 TB vaccine trials with SSI H1 and Ad35.
We have led landmark studies in the fields of TB case finding, TB preventive therapy and TB-HIV integration. These included those evaluating TB preventive therapy (Thibela INH study), done in three large-scale mining regions, and TB diagnosis (XTEND evaluation) that have had implications for global policy and practice. Other large cluster-randomized trials have evaluated TB/HIV integration interventions such as the use of presumptive TB treatment for ART patients (TB FastTrack), use of TB/HIV integration officers in clinics (MERGE) and introduction of INH and Point of care CD4 in households for contact tracing (Inhibit TB).
Image
Aurum also leads global research trials such as the WHIP3TB trial - a randomized trial evaluating the use of the 3HP regimen for PLHIV given annually - which is funded by the Challenge TB mechanism.
Image
Aurum leads the PHOENIx trial, one of the first trials to determine if a single drug can successfully prevent MDR-TB in adults and children. This trial is taking place in 27 sites in 12 countries.
Image

Host Directed Therapy Research

Aurum's TB host-directed therapy (TB-HDT) project is a study of drugs.
Image
Aurum co-leads and is the African coordinating partner for the TB-Sequel project, a pan-African project to understand the clinical, microbiologic, and host immune factors affecting or predicting the long-term sequelae and socio-economic impact of pulmonary tuberculosis and treatment outcome, taking place in Tanzania, The Gambia, Mozambique and South Africa.
Image
CUT-TB (Community and Universal Testing for TB among contacts) is a 4-year EDCTP funded cluster-randomised pragmatic that is being conduct in South Africa, Tanzania and Lesotho. The study  aims to measure effectiveness of universal testing compared to standard TB screening for detection of TB among household and community contacts.
Image
The Opt4TPT (Optimising the delivery cascade for tuberculosis preventive treatment among people living with HIV) study is a three-year programmatic assessment of TPT delivery across three countries, namely Ethiopia, South Africa and Zimbabwe, to generate critical knowledge to improve TPT uptake, implementation and outcomes
Image
DRTB-HDT The EU-funded DRTB-HDT (Stratified Host-Directed Therapy for Drug Resistant Tuberculosis) project will determine if two adjunctive host-directed therapies can prevent the poor outcomes of treatment in cases of RIF-R TB. Patients with RIF-R TB and other risk factors for poor outcome will participate in a randomised, controlled, three-armed multicentre trial.

Research Studies

Read the latest studies on TB

  • 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

    Timeline: 2014 – 2018
    Research Partners: London School of Hygiene and Tropical Medicine, The Aurum Institute , University of Washington
    Locations: Gold mines, Orkney, North West

  • 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).

    Timeline: 2015 - 2020
    Locations: Eastern Cape, KZN, Gauteng, WC

  • 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:

    Timeline: 2016 – 2021
    Research Partners: Case Western Reserve University, The Aurum Institute , University of Washington
    Locations: Gold mines, Orkney - North West Carletonville - Gauteng