XACT-19 - Evaluating the impact of computer-assisted x-ray diagnosis and other triage tools to optimise Xpert orientated community-based active case finding for TB and COVID-19

Abstract: A startling statistic is that over 40% of TB cases in endemic countries are "missing" (~3 million cases globally remain undiagnosed or unreported)! Most of these undiagnosed cases, which continue to transmit disease, are concentrated in the peri-urban 'slums' and 'shanty towns' of large African cities. Without addressing the 'missing cases' the TB epidemic will never be controlled. Unfortunately, the same communities have now been ravaged by the COVID-19 pandemic and outbreaks are likely to occur for some time to come. A strategy is therefore required to seamlessly detect TB and, when warranted, COVID-19 in the same communities. Over the last 5 years we have optimised a model for Xpert-orientated community-based active case finding for TB (XACT; Appendix, additional information, Figure 3). In XACT 1 we showed that community-based screening with molecular diagnostic tools (Gene Xpert) is highly effective in detecting the missing cases (Calligaro & Dheda, Lancet Infect Dis, 2017). In XACT II (recruitment complete and submitted for publication) we confirmed the feasibility and validated the use of scalable XACT model using battery-operated, point-of care (POC) Xpert-Edge for community-based ACF using a low-cost panel van (XACT II; NIH-funded; n= 5500 participants). XACT III is currently recruiting and is a demonstration project of this scalable model in multiple African countries and will also clarify how Xpert should be best located (POC compared Xpert performed in a centralized laboratory; Wellcome Trust and UKMRC-funded & EDCTP co-funded). Funding of ~€5.5 million is now being requested for a study that seeks to determine the utility of computer-assisted x-ray diagnosis (TB-CAD), as a triage tool, to further optimise the XACT model (XACT-19). Thus, we will screen community-based participants and perform an RCT to determine the impact of a CAD + Xpert versus Xpert-only strategy for ACF in symptomatic or HIV-infected participants. In addition, we will determine the utility of TB-CAD and Xpert in asymptomatic HIV-uninfected persons. In the same cohorts we will investigate the utility of COVID-CAD and Xpert COVID cartridges for community-based detection of COVID-19. We will also opportunistically evaluate the utility of nascent community-based urine-orientated triage tests for TB and COVID-19 (these will involve an African-based SME). Co-funding of ~€ 1.6 million has been leveraged. In summary, this proposal (XACT-19) will likely define a new standard of care for TB (and COVID-19 ACF) and revolutionize TB detection, moving it out of clinics and into the community.