Introduction and Background of the Project

Introduction

Tuberculosis causes more deaths worldwide than any other infectious disease and is the leading cause of death in people living with HIV (PLHIV). Most TB-related mortalities are preventable if diagnosed early. However, globally more than 3 million people who develop TB are missed every year. This is in large part due to limitations of available diagnostics tools and a lack of accurate, inexpensive, and rapid tests suitable for where people in high burden TB countries first present for care. Traditional diagnostic methods, such as culture or smear microscopy, are slow or have low sensitivity, and more modern techniques, such as sequencing or other WHO-recommended rapid molecular diagnostic tests such as cartridge-based nucleic acid amplification test systems, require specialized equipment and facilities, are costly, or are otherwise inaccessible to many populations at greatest risk of TB. Virtually all TB testing is sputum based, which is not always easy to collect, especially in PLHIV and children. People-centric, high-quality services are critical to reach the Sustainable Development Goals and End TB targets, but there are no sensitive point-of-care tests (POCT) to diagnose TB at lower health system levels. There remain insufficient true non-sputum POCTs for the detection of TB in PLHIV and HIV-negative adults and children. Currently, only one urine-based LAM assay is WHO recommended, solely for use among PLHIV, and performs well below desired targets for new diagnostics. Fujifilm (Tokyo, Japan) has developed a rapid diagnostic TB test that detects low concentrations of LAM-antigen in urine which has shown great promise as a true non-sputum POCT and aims to supplement it with a pre-test concentration device currently under development to further enhance its diagnostic performance.

Project objective

The primary objective of the project is to provide evidence on the performance of Fujifilm’s redesigned SILVAMP TB LAM II assay as well as a urine concentration device (UCD) which is expected to further increase sensitivity especially in HIV-negative individuals to obtain a WHO policy recommendation with strengthened evidence based on the operationalization, costing and feasibility studies to be conducted on this project.

Project design

We will prospectively evaluate the performance of the SILVAMP TB LAM Ⅱ assay as well as a urine concentration device across multiple sites in Cameroon, Nigeria and Vietnam. We will evaluate test performance among PLHIV and HIV-negative adults as well as children irrespective of HIV co-infection. Operationalization, costing and feasibility of the assay will also be addressed. 

How can your partnership (project) address global health challenges?

This project will evaluate the performance of one of the most advanced investigational non-sputum, point of care assays for TB, which will address several bottlenecks in the current landscape for TB diagnostics. A non-sputum-based test can improve the reach of a test for many people who have difficulty producing sputum including PLHIV, people who are severely ill, children and women. Secondly, as a rapid POCT, many more people can benefit from testing, increasing the reach of health systems closer to where people seek care and improving both the number of people who are able to receive a diagnosis as well as reducing diagnostic delay. Thirdly, by supplementing the test with a technology potentially capable of detecting TB in HIV-negative adults and children, the assay's market potential can be drastically expanded to achieve critical mass and more favorable conditions for need-based pricing.

What sort of innovation are you bringing in your project?

This project will evaluate a urine, lateral flow assay for TB diagnosis that is expected to have much higher sensitivity than current TB LAM test available. The assay is based on Fujifilm’s silver amplification immunochromatography which enables a 10 to 100-fold lower Level of Detection (LOD), compared to conventional lateral flow immunoassays. In addition, the UCD will bring an additional level of improved performance which will help with diagnosis in HIV-negative individuals.

Role and Responsibility of Each Partner

Center for Health Promotion and Research also known as the TB Reference Laboratory Bamenda in Cameroon, Zankli Research Centre, Bingham University in Nigeria, and Friends for International TB Relief (FIT) in Vietnam will implement the diagnostic evaluation in their respective countries. Fujifilm will be responsible for product development, design optimization, manufacturing, licensing, marketing, packaging, and shipping. Liverpool School of Tropical Medicine will provide technical support to project partners for study design, training, data management and analysis and act as the procurement agent for the LAM assays. Stop TB Partnership is the coordinator of the project responsible for establishing goals and overall management. Stop TB will provide technical support to Fujifilm and implementing partners, enable harmonization across sites, monitor and report on progress and final results to maximize the impact on policy development in coordination with WHO.

Others (including references if necessary)

1.   World Health Organization. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva, Switzerland; 2014
2.   Branigan D. 2023 Tuberculosis Diagnostics Pipeline Report. Treatment Action Group, New York, NY; 2023