29 November 2017: The End TB Strategy introduced by the World Health Organization (WHO) and adopted by the World Health Assembly aims to reduce TB related deaths by 95% and new TB infections by 90% by 2035. Approximately one quarter to one third of the world’s population is currently infected with the M. tuberculosis bacteria and the risk of developing an active form of the disease among infected individuals is between 5 and 15 percent.
The ambitious targets of the End TB Strategy cannot be reached without addressing the diagnosis and treatment of latent TB infection (LTBI), an asymptomatic non-contagious form of the disease. A key component of the strategy to eliminate TB is the development of novel diagnostics that help predict whether or not LTBI will progress to active TB, or to detect incipient TB. Incipient TB is defined as LTBI that is very likely to develop into the active form of the disease within a short period of time. A diagnostic solution that could detect incipient TB would identify patients with LTBI that would benefit most from preventive therapy.
While current tests can detect whether someone has been exposed to TB, they are unable to predict whether an individual will progress to active TB in the future. It is unrealistic to treat all of the approximately 2 billion infected individuals, as the necessary resources are not available and most cases will never progress to an active form of the disease. A test that is able to detect incipient TB or accurately predict the development of the disease at various stages is therefore urgently needed.
A consensus meeting and subsequent published report for the “Development of a Target Product Profile (TPP) and framework for evaluation for a test for predicting progression from tuberculosis infection to active disease” recently took place, led by WHO and FIND. This document provides guidance to test manufacturers, researchers and research funders on the nature and significance of LTBI and the relevant implications for the development of new diagnostic technologies.
The report presents a TPP for a test of progression of LTBI that defines key specifications, such as intended use, pricing, performance and operational characteristics. It also provides a framework for the evaluation of tests that predict progression to active TB using standard study designs and evaluation protocols.
According to the report, the ideal test would be able identify incipient TB by detecting an immune response signature within the individual that indicates the progression of the disease. In support of these efforts, FIND will continue to collect suitable specimens, coordinate clinical trials, collaborate with researchers to model country-level data and estimate impact, and provide support tools for test development and implementation.
FIND’s work in this area is supported by the Australian government and UK aid from the UK government.