Description:
OBJECTIVE: Demonstrate a prototype diagnostic test for gastroenteritis caused by Norovirus infection. The technology shall be able to detect infection at the onset of symptoms, be able to test unprocessed samples, incorporate all necessary controls, be compatible with use in an austere environment (small, lightweight, and insensitive to environmental extremes), and provide users with automated results interpretation. DESCRIPTION: Infectious diseases can have a significant impact on the operational readiness of military forces. The military has a requirement for innovative technologies to diagnose patients at or near the point of care or point of need to improve clinical outcome and conserve resources. Due to the operational environment, patients seen at the military equivalent of an outpatient clinic (doctrinally termed Role of Care 1 or 2) must be quickly treated and returned to duty or evacuated to a more capable medical unit (Role of Care 3). Therefore, diagnosis on the day of symptom onset is essential. In military settings, the point of need is frequently an austere environment without, for example, access to typical laboratory infrastructure, reliable electric power, refrigeration or controlled room-temperature storage, or specially trained laboratory personnel. Therefore, the proposed solution should be small, lightweight, and insensitive to environmental extremes such as dust, high humidity, and storage temperatures of up to 45degreesC. If electric power is required, it should be provided by rechargeable or disposable commercially available batteries. The use of lithium-ion batteries is discouraged due to restrictions on their shipment by air. The proposed solution should test unprocessed clinical samples and provide easily interpretable results. A single test should be complete (sample to answer) within 60 minutes, and the proposed solution should be able to test 20 patient samples in four hours. The device should be designed to minimize the risk of contamination and resulting false positive or false negative results. The proposed technology and approach should be consistent with obtaining U.S. Food and Drug Administration (FDA) clearance as a Clinical Laboratory Improvement Act (CLIA)-waived diagnostic device allowing use outside a CLIA-regulated laboratory (e.g., a doctor"s office), or, in the military, use by non-laboratory personnel (e.g., medic or independent duty corpsman) when prescribed by a physician. The Army is not planning to field current and future US military polymerase chain reaction diagnostic devices (the Joint Biological Agent Identification and Diagnostic System and the Next Generation Diagnostic Systems Increment 1) at Army Role of Care 1 or 2, so development of assays for these systems is not consistent with the objective of this Topic. This effort is also intended to demonstrate the ability to develop rapidly diagnostic tests for novel diseases. If an analyzer component is proposed, it should be designed so that the system can be easily upgraded by the user to incorporate additional tests. Proposed solutions that utilize synthetic or molecular biology approaches and simplified manufacturing requirements are desired. Noroviruses are the most common cause of epidemic gastroenteritis. Most human cases of Norovirus gastroenteritis are caused by viruses in genogroups II and I. Norovirus genogroup IV may also cause human illness. The clinical symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Norovirus infection is readily communicable between individuals sharing close quarters such as military camps and bases, cruise ships, and naval vessels. Transmission is most frequently through the consumption of contaminated food and person-to-person contact. Asymptomatic viral shedding for two or more weeks may complicate outbreak control. There is only one FDA-cleared diagnostic device for Norovirus (FDA, http://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm), and it is not cleared for the diagnosis of individual patients but only as an aid in investigating the cause of acute gastroenteritis outbreaks. Further, the technology used (Enzyme Immunoassay) is not compatible with use in the military equivalent of an outpatient clinic. The U.S. Department of Defense is seeking innovative materiel solutions to provide a deployable, rapid, easy to use capability to diagnose Norovirus infection. Development of an FDA-cleared diagnostic device is not contemplated within the scope of Phases I or II of this effort. PHASE I: Specific Aim 1: If an analyzer device is required by the technical approach proposed by the Offeror, demonstrate a breadboard prototype of such a device in conjunction with the reagents developed as part of Specific Aim 2. Specific Aim 2: Demonstrate the development of reagents (compatible with the prototype device under Specific Aim 1) capable of detecting Norovirus genogroup II viruses (or appropriate simulant) in clinically relevant sample matrix. Deliver a report describing the design of the reagents and initial assay performance data, if available. PHASE II: Specific Aim 3: Based on the Phase I prototype device and development feasibility report, produce a pre-production prototype demonstrating potential military utility. Deliver the pre-production prototype for DoD laboratory evaluation. Deliver a report describing the design and operation of the pre-production prototype device. Specific Aim 4: Further develop the Norovirus genogroup II analyte-specific reagents to include the ability to detect genogroup I (minimum) and genogroup IV (objective). Deliver a report documenting the performance of the reagents. Deliver sufficient quantities of reagents to allow the DoD to perform 50 tests during a DoD in-house laboratory evaluation. PHASE III: By the end of Phase III, the Contractor will obtain FDA 510(k) clearance or Pre-Market Approval from the FDA to market the device and reagents as a diagnostic device for Norovirus infection. Ideally, the device will receive a CLIA waiver. Such a device will fulfill a documented capability gap (Initial Capability Document for Infectious Disease Countermeasures, CARDS Number 14057, February 2007), and supports the Military Infectious Disease Research Program, U.S. Army Medical Research and Materiel Command, and the Pharmaceutical Systems Project Management Office, U.S. Army Medical Materiel Development Activity (USAMMDA). USAMMDA is the advanced developer of medical materiel for the U.S. Army and manages contracts for product development from after the proof-of-concept phase through initial fielding to operational units. Further, the device may have commercial market applicability to the health care and cruise ship industries and possibly also the airline, hospitality, and food service industries, and non-governmental and intergovernmental organizations (NGOs and IGOs) implementing public health, humanitarian assistance, and disaster relief projects in the developing world.
