EPiTB

The challenge

Tuberculosis is generally thought of as a respiratory disease, but Mycobacterium tuberculosis can also infect other body compartments, including membranes around the heart (pericardial TB), lungs (pleural TB), or abdominal cavity (peritoneal TB). It can also lodge in the brain, causing TB meningitis. This so-called extra-pulmonary TB accounts for around 15% of cases, but more than a third of cases occur in areas with a high burden of HIV.

Traditional diagnostic tools are not necessarily effective at detecting some or all categories of extra-pulmonary TB. Researchers in South Africa have recently shown that the detection of interferon-gamma in tissue samples is a more accurate way to detect extra-pulmonary TB infections. The test differs from conventional interferon-gamma testing (the IGRA test), requiring no stimulation of blood cells. 

This new test, known as IRISA-TB, has been developed by a local biotech company into a diagnostic product, which has been approved by the South African national medicines regulatory authority and endorsed by the Global Fund.

Although small-scale trials have demonstrated good diagnostic performance for extra-pulmonary TB, a large-scale trial would provide strong evidence to national decision-makers on its performance in programmatic settings and its potential impact.

The project

The EpiTB project is conducting a large-scale trial of IRISA-TB at centres in South Africa, Zambia and Zimbabwe. It is recruiting more than 2,000 patients with different types of suspected extra-pulmonary TB (pericardial, pleural or peritoneal, or TB meningitis).

Because of the likely use of empiric TB treatment, a randomised controlled trial of IRISA-TB is not feasible. Instead, the study will examine how the phased release of test data, from IRISA-TB and other diagnostic tools, affects clinical decision-making on treatment. This will provide real-world evidence on how IRISA-TB is actually used and its clinical impact. 

Although a point-of-care version of the test would be of less clinical utility than in other diagnostic contexts, a prototype lateral flow assay has been developed. The project will explore whether new detection technology used in other diagnostics can improve the performance of this test and ultimately provide an additional diagnostic option.

Impact

The EPiTB project will provide further data on an innovative diagnostic that has been developed and manufactured in sub-Saharan Africa and could have a significant impact on patient care. It will:

• Provide data on diagnostic performance from a large-scale trial in a programmatic trial, delivering evidence highly relevant to policymakers.
• Show more clearly how clinical practice could be changed using IRISA-TB and provide insight into its likely cost-effectiveness.
• Help to grow an innovative biotech company based in sub-Saharan Africa.

Implementation of IRISA-TB could potentially reduce empirical use of TB antibiotics in people suspected of having extra-pulmonary TB, ensuring that treatment is directed at those in need and initiated quicker – a key advance given that many patients begin treatment after significant delays or are never treated appropriately.