Comparison of Sickle SCAN and Hemotype SC As Point-of-Care Newborn Screening Diagnostics for Sickle Cell Disease in Luanda, Angola

Background: Sickle cell disease (SCD) is among the most common, lethal and poorly recognized diseases globally. Over 300,000 children are born each year with SCA and most die by five years, primarily due to the lack of timely and accurate diagnosis. In high-resource countries, early identification of SCD through newborn screening (NBS) is routine and subsequent delivery of preventive measures and comprehensive care is highly effective in reducing morbidity and early mortality. In lower-resource settings, where the incidence of SCD is much higher, NBS is limited to only a few pilot programs. Despite the proven efficacy of NBS, large-scale implementation remains infeasible in many sub-Saharan countries due to inadequate financial, laboratory, and technical resources. In the pilot NBS program in Angola, only 56% of infants with SCD were able to be contacted to relay results due to delays in traditional laboratory diagnostic methods, lack of traditional mailing system or primary care providers, and inconsistent telephone numbers. The development and deployment of low-cost, rapid, user-friendly, and accurate diagnostic testing for SCD is imperative.

There are two promising point-of-care (POC) tests (Sickle SCAN and HemoTypeSC) that may allow for a simplified approach to newborn screening for SCD. There have been few real-world studies that compare these tests head to head, particularly in the setting of NBS, where accurate diagnosis amidst high levels of fetal hemoglobin is critical. We performed a study at maternity centers and immunization centers in Luanda, Angola to evaluate the real-world accuracy of these tests.

Methods: The study was a prospective evaluation of two rapid, POC tests (Sickle SCANÔ or HemoTypeSCÔ) ain Luanda, Angola, with laboratory confirmation using a dried blood spot (DBS) by isoelectric focusing (IEF), defined as the gold standard. To evaluate the real-world feasibility and accuracy, with the guidance of the Angolan Ministry of Health, we selected 10 sites, including both birth hospitals and vaccination sites, to screen infants < 6 months of age. Due to the complexity of performing more than one POC at once, we focused on one POC test at a time and planned to test 100 infants with each test at each site, for a total of 2,000 infants tested overall. The study was designed to mimic a real-world setting with all POC testing performed and interpreted by local healthcare staff (nurses, students, and laboratory technicians) with basic instructions as to the use of each test.

Results: Blood samples were collected from 2,000 infants from age 0 to 6 months of age, including 1,000 with Sickle SCAN and 1,000 with HemoTypeSC. 42 HemoTypeSC samples (4.2%) and 6 Sickle SCAN results (0.6%) were not included in the final analysis, as results were not interpreted in the recommended time frame (5 minutes for Sickle SCAN an 10 minutes for HemoTypeSC). Consistent with prior studies in Angola, the burden of sickle cell trait (AS, 21.9%) and sickle cell anemia (HbSS, 1.7%) was high. 63% of the tests were performed in maternity wards at the time/day of birth and 37% were performed in immunization centers through the first 6 months of life. The HemoTypeSCÔ took an average of 15 minutes to obtain a result, was repeated 68 times (6.8%) due to invalid results, and was read incorrectly 4 times (0.4%). The SickleScanÔ took an average of 7 minutes to run, was repeated 2 times (0.2%) due to invalid results, and read incorrectly 11 times (1.1%). All results were compared to the gold standard IEF and both tests correlated perfectly (100%) with the IEF results, excluding 12 samples that had inconclusive IEF results.

Conclusions: This study demonstrates the feasibility and accuracy of both HemoTypeSC and Sickle SCAN for diagnosing SCD in newborns in a limited-resource setting of Luanda, Angola. Given the complexities of testing in the newborn period at busy maternity hospitals, it appears that testing at immunization centers may be a more practical solution to early infant diagnosis programs for SCD. While both HemoTypeSC and Sickle SCAN were accurate, Sickle SCAN was preferred by local staff likely due to the shorter time to interpretation and reduced need for repeating the test. Further implementation studies are needed, including careful analysis of end-user cost, to determine the appropriate strategy for these POC tests in low-resource setting of sub-Saharan Africa.