Molecular Detection of Invasive Fungal Infections

Information

  • Research Project
  • 8395132
  • ApplicationId
    8395132
  • Core Project Number
    R43AI102343
  • Full Project Number
    1R43AI102343-01
  • Serial Number
    102343
  • FOA Number
    PA-11-096
  • Sub Project Id
  • Project Start Date
    6/22/2012 - 12 years ago
  • Project End Date
    5/31/2014 - 10 years ago
  • Program Officer Name
    RITCHIE, ALEC
  • Budget Start Date
    6/22/2012 - 12 years ago
  • Budget End Date
    5/31/2013 - 11 years ago
  • Fiscal Year
    2012
  • Support Year
    01
  • Suffix
  • Award Notice Date
    6/21/2012 - 12 years ago
Organizations

Molecular Detection of Invasive Fungal Infections

DESCRIPTION (provided by applicant): The incidence of fungal infections and, in particular, Candida infections, the fourth most common nosocomial pathogen, has continued to increase over the past 20 years. This increase is due to the increasing numbers of patients subjected to severe immunosuppression as a result of transplant procedures, chemotherapy regimens, advances in medical and surgical therapies, and the increased use of invasive devices such as intravascular central lines. While the majority of invasive fungal disease (IFD) is caused by species of Candida and Aspergillus, other rare fungal pathogens have become more prevalent in recent decades and are associated with exceedingly high mortalities. Due to the slow turnaround time of current diagnostic methods, proper treatment of IFD is often delayed, contributing to the high mortality rates associated with this disease. Microbiologic culture, the current diagnostic standard, requires, on average, 48-72 hours for completion, and fails to detect roughly 50% of fungal species. As proper treatment of IFD calls for prompt and accurate diagnosis, an unmet need in the area of fungal diagnostics is a platform that can provide 1) early detection 2) sensitive results, 3) species level discrimination and 4) multiplex capability. Several molecular approaches have been developed to address this need but have failed to meet all these requirements. Our Reverse Line Blot (RLB) based assay uses PCR followed by hybridization with species specific probes, offering a solution to this unmet need by providing a sensitive and rapid (less than 8 hour) test for several fungal pathogens in a multiplex format. In this Phase I application we propose development of RLB based assays for the detection of 9 species of Candida, 5 species of Aspergillus, and several more rare species of IFD, including H. capsulatum, Fusarium spp, Zygomycetes, Cryptococcus spp, and Coccidioides spp. A major milestone of Phase I will be the development and validation of a multiplexed RLB-based, PCR assay for the detection of the majority of fungal pathogens implicated in IFD. We will validate our RLB assays in clinical blood and BAL samples obtained from several collaborators with expertise in mycology including Randall Hayden of St. Jude Medical Center, Peter Pappas of the University of Alabama, Luis Ostrosky of the University of Texas, David Snydman of Tufts University and Mary Brandt of the Centers for Disease Control. Our end product will be developed further in Phase II, where we will transition our open system to a closed system that performs the PCR and hybridization reactions in a dedicated instrument, designed and tested in collaboration with our engineering partner, Wi Engineering. This product offers a rapid, sensitive and multiplexed approach that meets the requirements of an ideal diagnostic platform for IFD. By significantly reducing time to detection, this innovative platform will lead to changes in the treatment of IFD, most notably, faster treatment with a targeted anti-fungal. PUBLIC HEALTH RELEVANCE: Project Narrative The incidence of fungal infections, many of which are associated with high mortality, has continued to increase over the past 20 years. Current diagnostic methods are limited by turnaround time and low sensitivity. We propose development of a rapid, molecular test that will significantly improve the detection and treatment of invasive fungal disease.

IC Name
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
  • Activity
    R43
  • Administering IC
    AI
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    299890
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    855
  • Ed Inst. Type
  • Funding ICs
    NIAID:299890\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    IMMUNETICS, INC.
  • Organization Department
  • Organization DUNS
    174347732
  • Organization City
    BOSTON
  • Organization State
    MA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    022102377
  • Organization District
    UNITED STATES