A Rapid Blood Test to Differentiate Latent Tuberculosis from Active Disease
Abstract
Background: Tuberculosis (TB) is a contagious infection caused by the bacteria Mycobacterium tuberculosis that typically infects the lungs. It is spread from person to person through the air when someone coughs, sneezes, or spits, which propel TB bacteria into the air and another individual inhales these germs. Only 10% of those who are infected with the bacteria fall ill with active TB; approximately 90% remain latently infected their whole life and suffer no consequences. Almost 2 billion individuals are infected with Mycobacterium tuberculosis, and the human cost of TB is enormous – at least 1.4 million deaths annually are due to TB, and it is the world s leading cause of death from infectious disease. TB is both curable and preventable – appropriate antibiotics are effective when an individual is properly diagnosed and medications are taken. Unfortunately, existing TB diagnostics require specialized equipment and training to administer, are costly, and the sample required is sputum (coughed-up mucus also known as phlegm), which can be challenging to obtain from many patients. Modern science has progressed to the state where we can read how our immune system attempts to fight off diseases with a simple blood test. We have extended this concept by discovering a TB signature in blood that tracts the human body’s production of proteins critical to its defense (gene expression). We have tested this TB signature with blood from a limited number of individuals (Brazil, South Africa, and Sweden) and have found it to have excellent performance. Proposal Overview: The University of California at San Diego, Stanford University, the University of Arkansas, the Institute of Phthisiopneumology (Republic of Moldova), and our commercial partner Cepheid Corporation (Sunnyvale, California) will work together in this proposal to translate our promising preclinical findings into a commercialized product for the detection of TB. This proposal will fund the creation of a preclinical prototype disposable, single-use cartridge to be used in Cepheid’s on-demand molecular diagnostic GeneXpert or Omni Systems. Cepheid Corp. has a proven track record of rolling out cartridges for its system and currently has 26 commercialized assays, 20 of which have US Food and Drug Administration approval including tests for hospital acquired infections (e.g., norovirus, Clostridium difficile, MRSA [methicillin-resistant Staphylococcus aureus]), infectious diseases (e.g., influenza, meningitis, Streptococcus, TB), and sexual health (e.g., chlamydia and gonorrhea). Our goal is to translate our preclinical findings into a finger-stick blood test that meets or exceeds the WHO’s Target Product Profiles for a rapid biomarker-based non-sputum-based triage test for dealing with patients suspected of having TB. Our triage test would be part of the diagnostic process that would rapidly assess patients and quickly identify subjects who do not have TB but identify those subjects who require the use of a very specific test to confirm the diagnosis of TB. To achieve our goal, we will first analyze our large databases that we have assembled with data from all over the world on blood-based investigations of the body’s defensive response to TB. Our goal would be to find two to five additional gene expression targets that would increase the performance of our previously discovered three-gene TB signature. We next will test this TB signature on blood collected from patients suffering from TB or who have been exposed to TB and translate our TB signature into a prototype cartridge. Finally, we will test the performance of our new TB signature and prototype cartridge with blood from individuals in the Republic of Moldova whom a physician suspects of having TB and has ordered a diagnostic test. Impact of Research: TB is a curable disease when properly diagnosed and treated with appropriate antibiotics, yet the WHO estimates that >40% of the 10.7 million in
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810253
Entities
People
- Antonino Catanzaro
Organizations
- United States Army
- University of California, San Diego