TB & Aerobiology

March 2022 – February 2023

The DTHF remains actively engaged in epidemiological, behavioural and microbiological studies to increase the understanding of the community, socio-economic, social network and mycobacterial and host factors influencing Mtb transmission dynamics in affected communities. The overall aim of this work is to inform more effective social and biomedical interventions to break the cycle of TB transmission, including advancing efforts to upscale effective active case finding and potentially informing TB diagnostic development. Clinical trials include assessing biomedical interventions for the prevention of TB infection acquisition and reducing risk of TB disease, especially in the population of people living with HIV. Currently these studies are largely focused on TB vaccine trials, although other interventions such as Vitamin D supplementation have been performed.

The DTHC/DTHF TB Division work extends across the foundation’s sites, including TB vaccine studies at the Emavundleni and Groote Schuur sites, and clinical and epidemiology studies at Philippi Village, Masiphumelele and the Eastern Cape sites. This work is closely related to the TB Aerobiology Unit work in Masiphumelele.

TB TRANSMISSION studies

Spear-headed by the Aerobiology Unit in Masiphumelele, under the leadership of Prof Robin Wood, the DTHF/DTHC continues to contribute significantly to the understanding of the environmental, host and pathogen contributions to TB transmission.

Mathematical modelling and spatial data analysis were used to inform TB care and control strategies in high TB incidence settings with Professors McCreesh and White at the London School of Hygiene and Tropical medicine. Results from the social mixing data and patterns of contact in congregate and public transport settings have contributed to the discussions on improving estimates of social contact patterns in modelling transmission of airborne diseases such as TB.

In collaboration with colleagues at Gates MRI and Stanford University, protocols were established for environmental sampling approaches for detection and quantification of Mtb – showing it is possible to extract and quantify TB through air sampling in clinics and other spaces. With collaborators from the University of Bern work has been built on this, exploring novel approaches to estimate tuberculosis transmission at HIV care clinics. This study combined environmental Mtb sampling with CO2 measurements, clinical, and patient movement data to explore where and when TB transmission risk may be highest in clinics.

The aerobiology unit continues to optimise an aerosolized mycobacterial particulate sampling device and to characterize aerosolized respiratory particle produced by TB cases prior and post initiation of TB therapy. Prof Wood’s work has shown that in the course of 24 hours just breathing accounts for 90% of Mtb released – meaning that even those patients without a cough can contribute to TB transmission. These findings have important implications for how to approach active case finding for TB control.

TB PREVENTION studies

In 2022-2023 the DTHF was involved in 2 TB vaccine studies:

Gates MRI-TBV01-201: A Randomized, placebo-controlled phase llb study evaluating the safety, efficacy and immunogenicity of BCG revaccination in adolescents for the prevention of sustained Mtb infection. The Emavundleni site enrolled and vaccinated 362 adolescents into this study and has maintained a 94% retention rate since study start in 2019!
Gates MRI TBV02-202: A randomized, placebo-controlled phase 2 study evaluating the safety and immunogenicity of an investigational Mtb vaccine in virally suppressed, antiretroviral-treated participants with HIV. The Groote Schuur site enrolled 73 participants in this study. Data analysis has shown promising safety and immunogenicity data, which will be presented at the World Lung Health conference in Paris, 2023.

In 2022, the VidiKids study, a phase III double-blind randomised placebo-controlled trial of Vitamin D supplementation for the prevention of latent tuberculosis infection in Cape Town primary schoolchildren was completed, after enrolling 1682 participants and following them up for 5 years. Unfortunately, primary analysis showed no benefit of Vitamin D supplements for the prevention of latent TB infection, but data analysis of possible non-communicable disease benefits is still pending. Two papers have been published from this study in the past year, with a third currently under review.

Socio-behavioural and mental health factors influencing TB health CARE

The Eastern Cape site under Andrew Medina-Marino is leading the field in exploring socio-behavioral and mental health factors and TB, especially among male patients. The MISSED TB Outcomes Study is exploring multi-level and intersectional stigma and other social determinant effects on TB case detection, care, and treatment outcomes. Other studies have identified men’s preferences for a male-centered intervention to support men’s engagement and retention in TB care as well as measuring real-time influences of mental and tangible resources on men’s TB treatment lapses and adherence behaviours.

A hybrid effectiveness-implementation trial has been started in Cape Town and Eastern Cape sites, exploring the effectiveness and cost-effectiveness of implementing an evidence-based depression counselling intervention among TB patients. To date 8 staff members across the two sites have completed the training course, including practical assessment, for the counselling intervention.

In the field of TB case detection, an ongoing study is evaluating the predictive value of pooled individual oral swab specimens as a household-level triage test for TB during community-based household contact investigations, using GeneXpert Omni as point-of-care diagnostic platform.

In 2024, both Emavundleni and Groote Schuur sites will be participating in the Gates MRI TBV02-301 Phase 3 and the HVTN 605 Phase 2a studies, exploring two novel TB vaccines.

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