EPiTB: Addressing an unmet need: same day diagnosis of extra-pulmonary TB in a high burden setting.

Better diagnostic approaches are required to improve TB control in Africa, which is suboptimal. One neglected aspect of TB diagnosis is that of extrapulmonary TB (EPTB), which comprises ~15% of the TB caseload.

However, in HIV-endemic settings over one third of cases are due to EPTB (the most common manifestation being pleural TB).

Frontline same day sputum-based diagnostic tools such as GeneXpert perform poorly when using fluid derived from EPTB-specific compartments (e.g. pleural fluid). Indeed, GeneXpert sensitivity in pleural TB is ~35%.

ADA, the current standard of care used in clinical practice has poor specificity, especially in pericardial TB and TB-meningitis (see preliminary data).

By contrast, unstimulated interferon-gamma (not T-cell-based IGRAs that require overnight stimulation) is an excellent biomarker for the diagnosis of EPTB (confirmed in 2 meta-analyses).

A South African university start-up has now developed a low-cost same-day EPTB diagnostic test (IRISA-TB), which has been evaluated and published in several small clinical trials (see main proposal) and is locked-in for scale-up dissemination in 2022. The test is CE marked, SAHPRA approved, and endorsed by the Global Fund.

This proposal encompasses a large prospective multicentric study (n= 2170 patients) of IRISA-TB in various forms of EPTB (pleural, pericardial, and peritoneal TB, and TB meningitis).

The proposed study (EPiTB) has excellent fidelity with the EDCTP call because it will enable “the registration of a new health technology through pragmatic effectiveness studies”, “enable uptake of results into clinical practice” and facilitate WHO endorsement. Thus, EPiTB will drive the facilitation and uptake of an important new TB diagnostic test in Africa.

Importantly, an African-invented and designed test will be promoted. Indeed, innovation and the development of an African knowledge-based economy is a key priority of the EDCTP.