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TB is arguably the biggest killer of mankind, with over a billion people succumbing to this disease over many centuries, and in 2023 more people died of TB than COVID-19. Detection of this ancient disease remains a challenge, and shockingly in 2023 over 3 million of the 11 million newly ill patients with TB remained undiagnosed, the majority living in peri-urban informal settlements of large Asian and African cities. Keertan’s main research interests include the diagnosis, determinants, and outcomes of respiratory infections, in particular, drug sensitive and drug resistant TB. His work has focussed on the evaluation of new tools to improve the diagnosis of TB, and the application of these tools to maximise patient benefit.  This work has shaped guidelines and global policy including that of the World Health Organisation (WHO). 

Work published in PLoS Medicine defined a new diagnostic standard for TB meningitis globally and has shaped the WHO Guidelines on how TB-meningitis is diagnosed. Other work highlighted the notion that global case finding strategies require a reconfiguration, from one of passive (patient-reported) to active case finding, which is critical to interrupt transmission and facilitate control (now a priority given reduced TB detection due to COVID-19). Keertan’s distinctive evidenced-based approach, in contradistinction to traditional accuracy-based evaluation methodology, has leveraged randomised controlled trial design to evaluate the impact of new TB diagnostic tools on patient important outcomes. A randomised trial reported in The Lancet (2014) highlighted the futility of a passive case finding strategy and has catalysed the point-of-care placement of newer DNA-based in TB hotspots such as prisons, mines, and high burden clinics.  This spawned the development of a novel active case finding model (Lancet Infectious Diseases, 2017) that was recently refined and validated (Nature Medicine, 2023).  These were the first randomised controlled trials using DNA-based diagnostics, showing that active case-finding is feasible and more effective than traditional tools (leading to shortened time-to-treatment and early identification of undiagnosed infectious TB cases). Further work published in The Lancet (2016) underpinned WHO policy for the roll-out and scale-up of the urine TB LAM test globally. 

Keertan has published a series of seminal papers regarding the epidemiology, transmission, and management of drug-resistant TB.  A paper published in The Lancet (2010) suggested a clinical working definition for treatment failure and informed management decisions by national TB programmes in resource limited settings.  The work accelerated access to newer drugs and diagnostics for drug-resistant TB globally.  A subsequent paper (Annals of Internal Medicine, 2010), shaped policy guidelines emphasising the need for intensified screening and infection control for healthcare workers in high burden settings. It remains the first and only comprehensive (yet worrying) landscaping report of drug-resistant TB in health care workers. Further work (Lancet, 2013) highlighted, for the first time, the widespread discharge of patients with incurable TB back into the community and the onward transmission of disease (Lancet Infect Dis, 2017); this accelerated the introduction of newer drugs into treatment programmes. Further work (Nature Medicine, 2020) showed that patients with drug-resistant TB produced infectious aerosols to the same extent as those with drug-sensitive TB, debunking the myth that patients with drug-resistant TB were less infectious due to fitness cost. Most recently, his work demonstrating the proof-of-concept feasibility of an all oral 6-month regimen for MDR-TB (AJRCCM, 2022), informed WHO guidance on radically shortened treatment regimens for drug-resistant TB.

The immunopathogenesis of TB and why some people get TB and others don’t is poorly understood. Keertan’s work establishing the feasibility and safety of a first-in-human lung challenge model for Mycobacterium tuberculosis complex (Am J Respir Crit Care Med; 2020) provides the foundation for better understanding of TB immunopathogenesis. This will accelerate the development of a much-needed vaccine for the disease, and has implications for the development of new diagnostics and treatment interventions. Work is ongoing.

Keertan holds 6 patents related to new TB diagnostic, therapeutic or infection control technologies, one of which is currently being developed as a user-friendly test for tuberculosis. He serves in an editorial advisory capacity of several journals including Lancet Respiratory Medicine (highest ranked in Respiratory Medicine & TB), American Journal of Respiratory and Critical Medicine (second highest ranked in Respiratory Medicine and TB), and the British Medical Journal (ranked 4th amongst general medical journals), amongst others. He has been the recipient of several prestigious international awards including the International Union Against Tuberculosis and Lung Disease Scientific Award, SA MRC Platinum Life Time Achievement Award, and the European Union-funded EDCTP Scientific Leadership Award. He is the founder and co-director of the charity, Free of TB, which seeks to promote the well-being of patients with TB.