Using dried blood spot on HemoTypeSC™, a new frontier for newborn screening for sickle cell disease in Nigeria.

Background: HemoTypeSC is a rapid, point-of-care testing (POCT) device for sickle cell disease (SCD) that traditionally uses the capillary blood from heel stick collected at the point of testing, a procedure that makes mass screening cumbersome and less cost-effective. Using dried blood spots (DBS) on HemoTypeSC could mitigate this challenge. Therefore, this study aimed to determine the feasibility of eluting blood from DBS to read on HemoTypeSC. Methods: DBS and fresh samples from heel sticks were collected from 511 newborns at the immunization clinics of six Primary Health Centers in Abuja, Nigeria. The two samples from each newborn were analyzed using HemoType SC and then compared with the result of the isoelectric focusing (IEF) test. Results: Of the 511 newborns, 241 were males and 270 were females. Standard HemoTypeSC (using fresh samples collected from heel sticks) and HemoTypeSC using DBS identified 404 (79.0%) HbAA, 100 (19.6%) HbAS, 6 (1.2%) HbSS, and 1 (0.2%) HbAC phenotypes. The IEF tests identified 370 (72.4%) HbAA, 133 (26.0%) HbAS, 5 (1.0%) HbSS, and 3 (0.6%) HbAC phenotypes. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of HemoTypeSC using DBS, compared to standard HemoTypeSC POCT was 100%. IEF method showed for AA, AS, AC phenotypes; sensitivity; 84.7%, 67%,100% respectively, specificity; 67.6%, 86%, 99% respectively, PPV; 91.2%, 53%, 50% respectively, NPV; 52.7%, 91%, 100% respectively. For SS phenotype, IEF showed 100% specificity, sensitivity, PPV and NPV. Conclusion: HemoTypeSC test using dried blood spot is as accurate as the standard point-of-care HemoTypeSC test. The use of DBS on HemoTypeSC could ensure better efficiency and cost-effectiveness in mass newborn screening for SCD.

Determinants of hydroxyurea use among doctors, nurses and sickle cell disease patients in Nigeria.

BACKGROUND: Hydroxyurea (HU) is an evidence-based therapy that is currently the most effective drug for sickle cell disease (SCD). HU is widely used in high-income countries with consequent reduction of morbidity and mortality. In Nigeria, HU is prescribed by physicians while nurses are mainly involved in counseling the patients to ensure adherence. The extent of utilization and the determinant factors have not been sufficiently evaluated in Nigeria. OBJECTIVE: To assess the frequency of use of HU and factors affecting utilization among healthcare providers, patients, and caregivers for SCD. METHODS: A questionnaire was administered online and in- person to assess the frequency of HU use and the factors that promote and limit its use. The data were analyzed by descriptive statistics using IBM SPSS software version 23 and the result was presented in frequency tables and percentages. RESULT: A total of 137 physicians, 137 nurses, and 237 patients/caregivers responded to the survey. The rate of prescription of HU by doctors in the past 6 months was 64 (46.7%), 43 (31.4%) nurses provided counseling and 36 (15.6%) patients were on HU. Among doctors, adequate knowledge (91.3%), clinical benefits and safety (94.8%), and inclusion of HU in management guidelines (86.9%) were motivators for prescribing it while inadequate knowledge (60.9%) and unawareness of treatment guidelines (68.6%) constituted barriers. Among nurses, reduction of crisis (91.6%) and safety (64.8%) were the major motivators while barriers were high cost (79.1%) and intensive monitoring (63.1%) of HU treatment. Among the patients, the major motivator was the reduction of crises (80.3%) while poor knowledge (93.2%), high cost of the drug (92.2%) while monitoring (91.2%), non-availability (87.7%) and side effects (83.9%) were the major barriers for the utilization of HU. CONCLUSION: HU prescription and utilization are still poor among healthcare providers and patients. Inadequate knowledge, non-availability and high cost of HU as well as unawareness of treatment guidelines constitute major barriers to prescription and utilization.

Implementing newborn screening for sickle cell disease as part of immunisation programmes in Nigeria: a feasibility study.

BACKGROUND: Sickle cell disease is highly prevalent in sub-Saharan Africa, where it accounts for substantial morbidity and mortality. Newborn screening is paramount for early diagnosis and enrolment of affected children into a comprehensive care programme. Up to now, this strategy has been greatly impaired in resource-poor countries, because screening methods are technologically and financially intensive; affordable, reliable, and accurate methods are needed. We aimed to test the feasibility of implementing a sickle cell disease screening programme using innovative point-of-care test devices into existing immunisation programmes in primary health-care settings. METHODS: Building on a routine immunisation programme and using existing facilities and staff, we did a prospective feasibility study at five primary health-care centres within Gwagwalada Area Council, Abuja, Nigeria. We systematically screened for sickle cell disease consecutive newborn babies and infants younger than 9 months who presented to immunisation clinics at these five centres, using an ELISA-based point-of care test (HemoTypeSC). A subgroup of consecutive babies who presented to immunisation clinics at the primary health-care centres, whose mothers gave consent, were tested by the HemoTypeSC point-of-care test alongside a different immunoassay-based point-of-care test (SickleSCAN) and the gold standard test, high-performance liquid chromatography (HPLC). FINDINGS: Between July 14, 2017, and Sept 3, 2019, 3603 newborn babies and infants who presented for immunisation were screened for sickle cell disease at five primary health-care centres using the ELISA-based point-of-care test. We identified 51 (1%) children with sickle cell anaemia (HbSS), four (<1%) heterozygous for HbS and HbC (HbSC), 740 (21%) with sickle cell trait (HbAS), 34 (1%) heterozygous for HbA and HbC (HbAC), and 2774 (77%) with normal haemoglobin (HbAA). Of the 55 babies and infants with confirmed sickle cell disease, 41 (75%) were enrolled into a programme for free folic acid and penicillin, of whom 36 (88%) completed three visits over 9 months (median follow-up 226 days [IQR 198-357]). The head-to-head comparison between the two point-of-care tests and HPLC showed concordance between the three testing methods in screening 313 newborn babies, with a specificity of 100% with HemoTypeSC, 100% with SickleSCAN, and 100% by HPLC, and a sensitivity of 100% with HemoTypeSC, 100% with SickleSCAN, and 100% by HPLC. INTERPRETATION: Our pilot study shows that the integration of newborn screening into existing primary health-care immunisation programmes is feasible and can rapidly be implemented with limited resources. Point-of-care tests are reliable and accurate in newborn screening for sickle cell disease. This feasibility study bodes well for the care of patients with sickle cell disease in resource-poor countries. FUNDING: Doris Duke Charitable Foundation, Imperial College London Wellcome Trust Centre for Global Health Research, and Richard and Susan Kiphart Family Foundation.