Highly Sensitive POC TB-LAM Rapid Diagnostic Test
  • Awarded Year
    2015
  • Awarded Amount
    $2,160,577
  • Disease
    Tuberculosis
  • Intervention
    Diagnostics
  • Development Stage
    Product Validation
  • Collaboration Partners
    Fujifilm Corporation , Foundation for Innovative New Diagnostics (FIND)

Introduction and Background of the Project

Introduction

A large proportion of people living with HIV die from undiagnosed TB, due to the absence of appropriate diagnosis and treatment. Implementation of systematic screening for TB among high-risk groups is expected to be a key intervention to reduce TB deaths by 75% by 2025. Achieving this ambitious goal will require novel, sensitive point-of-care tests for the detection of active TB in HIV-positives. Existing tests cannot detect TB among a substantial proportion of patients with HIV in decentralized settings due to the size and complexity of the required instrumentation and because a substantial proportion of patients with HIV-associated TB cannot produce sputum. Therefore a rapid, sensitive, biomarker-based, non-sputum-based point-of-care diagnostic that makes use of an easily accessible sample like blood or urine and is able to diagnose TB in HIV-infected individuals is considered to be one of the most urgently needed tests by expert stakeholder groups.

 

Project objective

Develop a highly sensitive, rapid point-of-care TB test to diagnose TB from urine in high-risk groups. Such a test will enable early treatment initiation, decrease mortality and cut transmission.

 

Project design

FIND and FUJIFILM’s project aims to: 1) Validate and select reagents to be used in the development of a LAM-based diagnostic test Lipoarabinomannan (LAM) is an antigen that has been explored extensively in blood, urine and sputum as a biomarker for active TB detection. It has the advantage of being very stable and detectable in a wide diagnostic time window. 2) Based on the selected reagents, develop a sensitive, point-of-care, rapid diagnostic test for the detection of TB infection in HIV infected patients, based on Fujifilm technology 3) Collect well-characterized patient samples from tuberculosis patients with and without HIV-coinfection, including endemic controls, and use the collected specimens to conduct an independent evaluation of the test under development.

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

TB is the most common cause of mortality in HIV patients. TB/HIV-coinfection often goes undiagnosed: first, many patients are unable to produce sputum (necessary for current diagnostics) and symptoms of TB in HIV patients vary greatly. Therefore, a test that uses either urine or blood (instead of sputum) which can be done at the point-of-care to screen HIV patients is urgently needed.

What sort of innovation are you bringing in your project?

Currently, no simple, rapid and affordable POC TB test with sufficient performance is available. In a priority-setting exercise involving different groups of global stakeholders (including national TB programmes), the non-sputum-based biomarker test was rated highest by all stakeholder groups. This project is a major step towards a test for the systematic screening of TB in the high-risk group of HIV-positives. The proposed test is expected to show increased sensitivity in HIV-positive patients, which would significantly decrease morbidity and mortality. If the developed test achieves sensitivity and specificity high enough to work as a general rapid biomarker-based POC test for TB (including HIV-negative adults and children), it would be a real game-changer for TB diagnosis. A modeling has demonstrated that a 16% decrease in TB incidence and a 39% decrease in mortality(1) if our project succeeds.

 

 (1) Sun, A. Y. et al. Modeling the impact of alternative strategies for rapid molecular diagnosis of tuberculosis in Southeast Asia. Am. J. Epidemiol. 178, 1740–1749 (2013).

Role and Responsibility of Each Partner

Fujifilm will be responsible for development, optimization and manufacturing of the assay prototype, as well as the provision of sufficient numbers of tests for the independent evaluation. FIND will be the overall coordinator of the project, responsible for establishing project goals and project management, monitoring and reporting on progress, collecting and providing reference materials, and engaging additional partners if needed. FIND will supply reagents and samples, set the product specifications, establish the reference assay and organize the independent evaluation with a WHO collaborating Centre for TB and Lung Diseases and conduct the statistical analysis of the obtained data.