Facilitating implementation of TB testing: The TB-CAPT (Close the gap, increase Access, Provide adequate Therapy)

The TB-CAPT (Close the gap, increase Access, provide adequate Therapy) project will provide evidence for impactful implementation of tuberculosis (TB) and TB/HIV co-infection diagnostic strategies including drug-susceptibility testing through a series of trials in Tanzania, Mozambique, and South Africa.

The TB-CAPT is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) and will run for 3.5 years, with the planned completion in 2023.

The Problem

It is estimated that each year more than 10 million people worldwide fall ill with tuberculosis (TB). However, currently, only around 7 million of them are identified – while the others are missed. Of the nearly 2 million deaths each year most are preventable with existing treatments, if diagnosed early, but diagnostic gaps in TB remain greater than for any other infectious disease.

There is an urgent need for TB tools and diagnostic technologies that can not only detect disease but can also identify strains that are resistant to the TB medications that are available. Containing the emergence of TB drug resistance is critical if we are to have a chance to beat the disease while the medicines that we have still work.

The introduction of automated real-time PCR-based technologies (i.e., GeneXpert®) improved TB case-detection and reduced diagnostic delay. Many studies conducted since then have contributed to both an understanding of the test’s limitations and the need for better tests to achieve the post-2015 TB targets of the World Health Organization (WHO). Even more importantly, the studies highlighted the need for optimized implementation strategies for novel tests and improved linkage to treatment.

Next-generation tests need to be placed at the point-of-care at microscopy centre level, fully integrated in the diagnostic and treatment network, connectivity enabled, more sensitive and able to perform expanded drug susceptibility testing (DST). Additionally, people living with HIV (PLHIV) are not well served by sputum-based diagnostics and non-traditional specimen-types (such as urine, oral swabs, and stool) and test technologies (such as the FujiLAM assay) have shown promise to improve diagnosis in this population.

Our Approach

TB-CAPT includes a series of clinical trials in Tanzania, Mozambique, and South Africa that will evaluate the impact of diagnostic interventions on outcomes, including the effects of expanding TB testing strategies to PLHIV. The trials have been designed to consider local epidemiology, as well as existing infrastructure, and will compare new strategies with current standards of care.

Specific objectives, aims, and activities to help achieve the overarching goal

1. To evaluate the most promising new technologies in settings of intended use.The GeneXpert Omni instrument with the Xpert MTB/RIF Ultra cartridge meet the high-priority target product profile (TPP) and thus have the potential to improve patient outcomes when replacing the current standard of care (sputum-smear testing or centralised testing). We have identified the following key TB diagnostic trials which are needed to inform policy development and country scale-up, and which we will implement in TB-CAPT:

• A pragmatic, randomized, controlled trial (—> our CORE trial) that assesses the impact of the implementation of Omni (with the Ultra assay) in settings of intended use.
• Enabling of culture-free diagnosis for drug-sensitive and drug-resistant TB through the implementation of the XDR cartridge (—> our XDR trial), and assess the impact
• Assess expanded testing strategies for the most vulnerable patients with HIV (—> our HIV trial) infection through testing unselected hospitalized PLHIV with Ultra on multiple available samples (sputum, urine, stool) and FujiLAM on urine.

2. Facilitate policy change and inform implementation strategies at global, national, and regional level: TB-CAPT will inform WHO recommendations on the implementation of the first diagnostic platform suitable to replace smear-microscopy at the most peripheral level of healthcare. Within our trial countries Mozambique, South Africa and Tanzania, we will work with national programmes, governments, and local implementers to generate data to support the development and execution of implementation plans. In addition, FIND and the African Society for Laboratory Medicine (ASLM) will assist in translating findings to aid scale-up also beyond trial countries. To achieve this, TB-CAPT will specifically:

• Join forces with other global trial sites to ensure global representativeness of the combined data
• Use transmission and socio-economic modelling to provide the health care system with predictions of impact and cost of implementation on population level.
• Ensure early and ongoing engagement with national TB programmes in early adopter countries, with ASLM and the WHO.

3. Strengthen in-country infrastructure and human capacity: TB-CAPT will work with renowned institutions in our trial countries (Mozambique, South Africa, and Tanzania), local researchers, and government infrastructure, to develop enhanced capacity for conducting clinical trials, implementation research and implementation plans for new diagnostics. Specifically, we will:

• Build capacity within our partner institutions for a series of implementation trials of novel diagnostic tests to follow the TB-CAPT project.
• Develop capacity to diagnose and treat DR-TB at level 1 settings

To learn more about this project visit the TB-CAPT consortium website.