The primary goal of this proposed research is to develop a rapid point-of-care (POC) test that can be used to identify neonatal sepsis in high-risk infants in a simple, user-friendly and portable device suitable for use in the NICU setting. Since sepsis presents a very serious threat to neonates, there is an urgent need to obtain confirmation as soon as possible. Currently, there are no reliable, POC markers for this life threatening disease. Blood culture results are considered the gold standard for bacterial sepsis, but confirmatory results may not be available until at least 48 hours. In this proposal, we will attemp to develop a quantitative rapid test based on Inter-alpha Inhibitor Proteins (IAIP) that has been recently demonstrated as a valuable biomarker with high sensitivity and specificity (89.5% and 99%, respectively) and a high positive and negative predictive value (85% and 98% respectively) for neonatal sepsis. We hypothesize that endogenous IAIP, as part of the innate immune response, protect against the damaging effects of proteases released during acute systemic inflammation following severe infections, burn, trauma and injury. As a consequence, these proteins are rapidly consumed and excreted in the urine, leading to a rapid decrease in plasma levels. Furthermore, the IAIP level seems to inversely correlate with disease severity and progression, thus, a rapid IAIP test with result that can be obtained within 10- 15 min would be useful as a diagnostic and/or theranostic marker in neonatal sepsis. The proposed specific aims of the study are: 1) Validation and comparison studies of the predictive value of IAIP alone and with other biomarkers in detecting infants with sepsis and systemic inflammation and 2) Prototype development of a quantitative lateral flow immunoassay (LFIA) for IAIP that can be used to diagnose neonatal sepsis and NEC. As a replacement therapy with plasma derived IAIP has been demonstrated to be effective in experimental models of sepsis and clinical trials in adult septic patients are currently underway, our long-term objective is to study the efficacy of concomitant IAIP treatment in critically ill infants due to suspected sepsis or NEC with low levels of IAIP as revealed by the rapid test. By combining the predictive test and therapeutic replacement of plasma derived IAIP, this novel approach may offer a rational, targeted solution for reducing the morbidity and mortality associated with neonatal sepsis and NEC in infants. Furthermore, an IAIP-based rapid test will provide an objective means for reducing antibiotic overuse in infants with suspected but unproven systemic infection. The potential impact of the proposed research is immense when one considers the serious unmet medical need for infants who suffer from the devastating effects of neonatal sepsis and NEC.

Public Health Relevance

The goal of this proposed research is to develop a rapid test that can be used to detect life-threatening conditions such as whole body infection (sepsis and necrotizing enterocolitis) in infants using a simple, user-friendly and portable device suitable fo a bedside testing in the neonatal intensive care unit. The test is based on the level of blood proteins called Inter-alpha Inhibitors that are consumed during the disease. The faster the patient is diagnosed and treated, the better the prognosis and a chance of fewer complications. The potential impact of the proposed research is immense as it will reduce the devastating effects of these diseases.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1-SBIB-V (90))
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Raju, Tonse N
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Prothera Biologics, LLC
East Providence
United States
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