Research Project
6736678
DESCRIPTION (provided by applicant): Entamoeba histolytica, the cause of amoebiasis, is a Category B pathogen considered in the top three biodefense parasites because it is difficult to diagnose. The disease caused by this protozoan pathogen occurs due to intestinal and extra-intestinal infections, both of which are major problems in developing countries. For these reasons, there is an urgent need for new and improved diagnostics for this organism and its disease. In Phase I we will continue and expand our developmental work on stool dipstick antigen detection tests for intestinal amebiasis, including critical clinical evaluations in Bangladesh, Vietnam, and Turkey. Clinical investigators will utilize PCR technology to evaluate test performance. We will transfer the technology to a manufacturer of rapid membrane tests and establish test performance of dipsticks manufactured under GMP. Data for 510(k) submissions to the Food and Drug Administration will be collected from in-house performance studies and on-site clinical evaluations. As a logical extension of this work, the dipsticks will be evaluated for the detection of circulating antigen in persons with amebic liver abscess. We will extend efforts on an ELISA for use by military and reference labs for the detection of lectin in fixed specimens. The ELISA will be manufactured under GMP at TechLab and evaluated on-site at reference laboratories in the U.S. The data for a 510(k) submission will be collected and submitted to the FDA. In addition to the ELISA, efforts will continue on a stool antigen detection dipstick that works with fixed specimens for use in the U.S. and other industrialized countries. For extra-intestinal amebiasis, the highest sensitivity diagnostic approach utilizes detection of both serum antigen and antibody. Therefore, we will develop a new serodiagnostic test for extra-intestinal amebiasis utilizing lecA (a recombinant peptide of the lectin) as the capture antigen. In Phase II, clinical evaluations will be extended to include on-site studies in other countries. In addition, we will expand efforts to develop tests for E. histolytica cysts as well as develop a panel test for E. histolytica/Cryptosporidium/Giardia. This project will lead to a battery of tests that have broad application in the diagnosis of amebiasis, making these tests suitable for biodefense purposes and for improving global healthcare.
