A Sample-to-Answer Point-of-Care Diagnostic for Recently Transfused Sickle Cell Anemia Patients in Low Resource Settings

Funding Agency:

NIH / National Heart, Lung, and Blood Institute


Rebecca Richards-Kortum (Rice), Gladstone Airewele(Baylor CoM), Venee Tubman (BaylorCoM), Nmazuo Ozuah (Baylor CoM)


Sickle cell disease (SCD) is an inherited hemoglobin disorder that is highly prevalent in low-and middle-income countries (LMICs), with over 75% of affected global births occurring in sub-Saharan Africa. Early diagnosis through pediatric screening, parental education, and preventive treatments are known to reduce deaths; however, lack of infrastructure and the high cost of diagnostic tools in low-resource settings severely limit early detection. As a result, many pediatric SCD patients present to a hospital with acute, severe anemia without a diagnosis and receive emergency blood transfusions. Existing point-of-care tests function by detecting and characterizing the hemoglobin proteins present in a sample. In cases of blood transfusion, these tests detect normal hemoglobin transfused from the blood donor as well as sickle hemoglobin, therefore misdiagnosing patients as sickle cell carriers. This limitation means existing point-of-care tests cannot be used for up to three months with patients who have received a blood transfusion, which causes significant delays in the time to diagnosis and prevents initiation of treatment. There is an urgent need for an inexpensive, easy-to-use test that targets the genetic basis of the disease and can rapidly deliver results so that accurate treatment can be initiated immediately at the point of care. To address this need, we will develop a rapid, inexpensive nucleic acid-based test to detect the common point mutations in the β globin gene that cause SCD: βS(Glu6Val)and βC(Glu6Lys). We propose a test that can differentiate the following clinically relevant genotypes: 1) SCD patients (βSβS: SS, βSβC: SC); 2) unaffected individuals(βAβA: AA); 3) SCD carriers (βAβS: AS, βAβC: AC); and 4) Hemoglobin C disease(βCβC: CC). Because blood transfusions contain globin proteins from the donor, a nucleic acid test is the only possibility to test infants and children who have recently undergone blood transfusions. An inexpensive point-of-care test that allows rapid detection of SCD in all patients would greatly improve care for children with SCD. We aim to: (1) Design and validate the first genetic point-of-care nucleic acid amplification test for sickle cell disease that can be used in recently transfused patients; (2) Implement the test on a low-cost, manufacturable, fully integrated sample-to-answer platform; and (3) Evaluate sensitivity, specificity, and usability of the test in two pilot clinical studies. Our team at Rice University, Baylor College of Medicine, and Kamuzu Central Hospital in Lilongwe, Malawi has the necessary expertise in bioengineering and clinical diagnostics to address the challenge of diagnosing SCD in resource-limited settings. Our proposed assay meets the optimal requirements for point-of-care testing in LMICs. Finally, it would eliminate the long delays currently associated with sample transport or transfusion from screen-positive patients to testing centers, and would enable immediate initiation of treatment for infants and children with a diagnosis of SCD.