TB TRIAGE+ - Community-based tuberculosis triage testing after symptom screening in hard-to-reach African populations: CAD4TB versus C-reactive protein

Background:
Tuberculosis (TB) is a poverty-related disease which particularly affects vulnerable and underserved populations. Community-based TB triage testing as an integral part of multi-disease health campaigns has the potential to offer an impactful diagnostic strategy for people living in rural and semi-rural areas of high TB/HIV burden countries.

Rationale:
The World Health Organization has developed target product profiles for community-based TB triage. CAD4TB, an extensively validated digital chest x-ray analysis platform using deep-learning technology, and point-of-care C-reactive protein blood test (POC-CRP) are two very promising diagnostic tools, which meet the targets for TB triage testing, and should thus be tested in large-scale randomised controlled clinical trials at community level.

Main objectives/approach:
The main objective of the proposed TB TRIAGE project is to assess the accuracy, impact and cost-effectiveness of CAD4TB and POC-CRP as triage tools for community-based TB screening. To test these tools, we will implement two trials in rural and semi-rural Lesotho and KwaZulu Natal, South Africa.

In the first trial -TB TRIAGE-ACCURACY- we will assess the diagnostic accuracy of POC-CRP and CAD4TB in 1400 presumptive TB patients and determine the optimal cut-offs for triage testing. In the second, community-based cluster-randomized trial -TB TRIAGE-RCT- we will assess the impact of CAD4TB and POC-CRP triage tests on TB notification rate, diagnostic/treatment delays and patient outcomes, and we will perform health economic and equity analyses based on the trial data. The triage tests will be used after symptom screening and prior to confirmatory on-site Xpert MTB/RIF testing. The control arm follows current standard of care with referral for confirmatory Xpert TB/RIF Ultra at the clinic in individuals presenting TB symptoms. The demonstration phase design with 35000 participants has been chosen to generate high-level evidence to inform policy.

Secondary Objectives:
Further objectives include the validation of a novel instrument-free point-of-care CD4 test, the development of an evidence-based clinical decision tool for TB in rural TB/HIV high-burden settings, the optimisation of CAD4TB, e.g. on characterisation of non-TB abnormalities, and a survey of non-communicable and communicable diseases in hard-to-reach communities. TB TRIAGE will build capacity for clinical trial conduct and scientific leadership in Southern Africa.

Relevance:
The development of an accurate, robust and cost-effective TB community-based triage algorithm will improve access to quality health care for hard-to-reach populations in Southern Africa and will ultimately contribute to end the epidemic of TB, as targeted by Sustainable Development Goal 3.

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