Biomimicry to democratise access to infectious disease diagnostics  through the  DSI-NRF Centre of Excellence for Biomedical TB Research (CBTBR) in advancing impact 

Tuberculosis (TB) has claimed more human lives than any other bacterial disease, influenced by inefficient diagnosis. For TB-infected individuals, an accurate, timeous diagnosis is the first step to accessing appropriate care. The CBTBR’s cross-disciplinary research programme has yielded a series of exceptional scientific breakthroughs on the biology of the TB bacillus, that spans characterisation of the bacterial cell wall to translating how this affects TB diagnosis. The CBTBR made use of this research  for direct patient benefit by developing methods allowing for greater recovery of TB bacteria in patient specimens. The CoE applied these findings to enhance the diagnosis of TB in people living with HIV or extra-pulmonary TB. Based on fundamental research in TB diagnostics, the CBTBR was able to translate research into products that enabled mass rollout of TB testing in South Africa and globally.

The CBTBR supported the National Department of Health in their rollout of new TB diagnostics. A critical component of diagnostic testing is ensuring that tests are operating optimally, requiring a sample of the disease-causing agent for instrument validation in diagnostic labs. The lack of such control products locally limited widespread rollout. The CBTBR addressed this problem in two ways: First by developing a series of products comprised of inactivated TB bacteria. Second through developing a second-generation series of biomimetic products wherein only the specific TB DNA targets were present in non-infectious bacteria, thus mimicking TB bacteria during validation of diagnostic tests. This novel technology has been expanded to other pathogens, including drug resistant TB, SARS-CoV-2 (COVID-19) and the human immunodeficiency virus (HIV). These innovative technologies allowed patients affected by these diseases to get a diagnosis and access to care.

The CBTBR’s products enabled diagnostic labs to run quality assurance programmes, which then facilitated TB testing to be brought online nationwide and globally. For maximum  impact from these products, the University of the Witwatersrand (Wits) spun out a company, SmartSpot Quality (Pty) Ltd, to market diagnostic controls globally. CBTBR intellectual property was licensed to SmartSpot and CBTBR continues to produce the verification material. In terms of societal impact, CBTBR products have enabled hundreds of thousands of patients to access diagnostic tests for drug sensitive TB in 46 countries, where over forty thousand quality assurance specimens have been used to date to verify thousands of instruments, as well as for drug resistant TB in 22 countries, with almost 1400 quality assurance specimens tested. Moreover, the team secured endorsement from the World Health Organization and the United States (US) Centres for Disease Control for CBTBR products, which has allowed for broader use and impact.

Following this, in 2020, the South African national testing system struggled with mass Covid-19 testing, partly due to the lack of appropriate control material to validate diagnostic tests. To address this, the CBTBR developed the world’s first series of biologically safe SARS-CoV-2 biomimetic control products, which allowed for rapid and immediate rollout of Covid-19 mass testing in South Africa and globally in 30 other countries (with 6475 quality assurance specimens tested), primarily in the global South. The collective effort enabled access to life-saving diagnostics for millions of people.

Overall, these products have helped to improve levels of confidence in testing programmes and have limited the number of false negative results, which affects the spreading of diseases in communities. As an example, drug resistant TB is primarily acquired by transmission. Accurate diagnosis allows for isolation of patients whilst ensuring that, where possible, individual patients can receive treatment speedily. The platform created at Wits has strengthened the national and global health response for management for many diseases.

In terms of policy impact, South Africa is the first country globally to incorporate new TB diagnostic tests into the National Guidelines and CBTBR products have facilitated effective implementation of this national strategy. Recently, South Africa announced a new policy for inclusion of a short antibiotic programmes for treatment of drug resistant TB. The availability of CBTBR’s diagnostic verification controls have supported rapid diagnosis and implementation of these new treatments for those suffering with drug resistant TB. Furthermore, in ensuring a sustainable project, SmartSpot Quality has generated net profits since its establishment and Wits University benefits from commercial returns through its shareholding in the company, as well as royalties paid for specific product ranges.

Global impact of CBTBR innovations and products. The maps show the global distribution (to date) for drug sensitive TB, drug resistant TB and Covid-19 diagnostic control products. These products were used in national diagnostic testing systems either for External Quality Assurance of diagnostics or for Verification of whether diagnostic tests are operating correctly and being used optimally.