Phase II year
2015
(last award dollars: 2017)
Phase II Amount
$1,222,445
Sickle cell disease (SCD) is the most common hemoglobinopathy associated with significant life-long morbidity and premature mortality. Over 200,000 children are born with SCD in sub-Saharan Africa annually - more than 50% of them die in early childhood. Most of these deaths could be prevented through simple and inexpensive prophylaxis if SCD was diagnosed soon after birth. Universal screening of newborns is impractical in low-income countries due to a large number of out-of-hospital births and the prohibitive cost of conventional testing methods. A simple, inexpensive, sensitive and specific point-of-care (POC) device is therefore urgently needed to enable testing infants and young children during their first visit to a local clinic. To address this unmet need, we recently developed an ultra-low-cost, paper-based test for SCD. Our test enables highly accurate diagnosis of SCD through simple visual interpretation of the pattern of the stain produced on chromatography paper by a droplet of blood mixed with hemoglobin (Hb) solubility buffer. By running the assay in a paper substrate and using the natural color of Hb for visual discrimination, we eliminated factors that interfere with conventional Hb solubility tests, while () gaining the capacity to accurately distinguish normal, sickle trait and SCD samples, (ii) reducing the required sample volume (<10 microL), (iii) lowering the per-test cost (<$0.03) and (iv) simplifying the interpretation of results. In a recent clinical study, we validated our test for adlts and children >12 months old. The test was able to detect the presence of sickling HbS with 100% sensitivity and specificity, demonstrating a positive predictive value of 100% and overall diagnostic accuracy of 100%, even for patients with severe anemia ([Hb]<8 g/dL). This Phase I project will focus on expanding the applicability of paper-based SCD test to infants (<12 months old), and developing a diagnostic kit for deploying the paper-based SCD test in the field. We will optimize the test to increase its sensitivity for HbS<20%, and investigate whether HbF>50% (present in younger infants) and common co-morbidities such as severe anemia, hyperlipidemia, elevated total protein and malaria have any effect on the diagnostic accuracy of the test. We will develop a sample preparation procedure utilizing low-cost, plastic components to enable a disposable kit, determine the range of operating conditions, and complete the studies required for regulatory approval of the test by the FDA. A successful diagnostic kit will have the number of components, number of operations, and cost per-test not to exceed those of existing solubility assays, and be able to detect the presence of HbS in samples from infants and young children with >80% sensitivity and positive predictive value and >90% overall diagnostic value. This project represents a crucial step toward the development of a low-cost, point-of-care diagnostic test for SCD that could have a potentially transformative impact on the health and well-being of tens of thousands of infants and young children worldwide.
Public Health Relevance Statement: Public Health Relevance: Most children born with sickle cell disease in sub-Saharan Africa die in early childhood from causes that could be easily prevented through simple and inexpensive prophylaxis if their disease was diagnosed soon after birth. Universal screening of newborns is impractical in low-income countries due to a large number of out-of- hospital births and the prohibitive cost of conventional testing methods. This highly-innovative project plans to develop and commercialize an ultra-low-cost, paper-based diagnostic test for sickle cell disease to enable screening infants and young children during their first visit to a local clinic. (End of Abstract)
NIH Spending Category: Clinical Research; Hematology; Pediatric; Prevention; Rare Diseases; Sickle Cell Disease
Project Terms: abstracting; accurate diagnosis; Address; adolescent patient; Adult; Affect; Africa South of the Sahara; Anemia; Angola; base; Biological Assay; Birth; Blood; Blood capillaries; Blood specimen; Buffers; capillary; Cessation of life; Child; Clinic; Clinical Research; Color; Comorbidity; cost; Country; Data; design; Detection; Development; Devices; Diagnosis; Diagnostic; diagnostic accuracy; Diagnostic tests; Discrimination (Psychology); Disease; Dose; early childhood; Ensure; Health; Hematology; Hemoglobin; hemoglobin AA; Hemoglobinopathies; Hospitals; Humidity; Hyperlipidemia; Infant; innovation; International; Laboratories; Life; Low income; Malaria; Measures; Methods; Morbidity - disease rate; Neonatal Screening; Notification; operation; Paper; Paper Chromatography; patient population; Patients; Pattern; Pediatric Hospitals; Performance; Personal Satisfaction; Phase; Plastics; point of care; point-of-care diagnostics; Predictive Value; Premature Mortality; Preparation; prevent; Procedures; programs; Property; Prophylactic treatment; Proteins; Reagent; Regression Analysis; Running; Sampling; screening; Sensitivity and Specificity; Sickle Cell Anemia; sickling; Site; Solubility; Solutions; Staining method; Stains; Temperature; Test Result; Testing; Texas; trait; Vial device; Visit; Visual; Work
