Systematic, Point-of-Care Newborn Screening and Treatment for Sickle Cell Disease in Rural Mali, West Africa: Results from an Ongoing Implementation Project

Introduction: Sickle cell disease (SCD) is highly prevalent across sub-Saharan Africa and is a significant source of under-5 mortality. Accurate characterization of the disease prevalence is difficult to determine due to the absence of systematic newborn screening in most African countries. Mali is a land-locked West African country with a high burden of sickle cell disease. Despite the critical need for early diagnosis of SCD to improve survival, wide scale diagnostic efforts utilizing IEF or HPLC in sub-Saharan Africa have been limited by a paucity of laboratory equipment and trained personnel, unreliable supply chain for consumables, and overall expense. Point-of-Care (POC) testing for SCD is advancing rapidly and has the potential to reduce these barriers. This analysis will review the results of an ongoing POC newborn screening program for SCD at a single rural hospital in Mali and will evaluate the acceptance rates and basic outcomes of resource-adapted treatment.

Methods: Between March 2019 and March 2023, all newborns at Koutiala Women's and Children's Hospital in Koutiala, Mali were offered screening for SCD with the HemoTypeSC ™ POC test kit (Silver Lake Research, California, USA). After verbal consent, heel-stick samples were procured within the first 24 hours of life. The samples were processed according to the package insert. The results were available within 10 minutes and were provided to the caregiver prior to discharge. Newborns who were found to have sickle cell disease were referred to the SCD treatment program where they were offered ongoing access to basic treatment measures such as antibiotic prophylaxis, malaria prevention, and hydroxycarbamide therapy. Parents of infants with HbSS who had not been seen in the clinic for follow-up within at least 6 months were contacted by phone at the time of this analysis to provide an update on their clinical status. Families of infants with HbS trait or HbC trait received appropriate genetic counseling. Statistical analysis was performed using a paired t-test.

Results: 11,938 infants were born over the study period and 11,818 (99%) received POC screening. Screening results revealed Hb S trait; n=1,119 (9.47%), Hb C trait; n=1,285 (10.87%), Hemoglobin SS; n=81 (0.69%), Hemoglobin SC; n=100 (0.85%), and homozygous C; n=20 (0.54%). In all, 181 infants (1.54%) were found to have sickle cell disease and were offered follow-up care in the SCD treatment program at Koutiala Hospital. In addition, 2,404 infants (20.34%) were found to be carriers of either HbC trait or HbS trait. The mean age of those children diagnosed with HbSS and HbSC at the time of this analysis was 22.20mo (3-42mo) and 21.46mo (4-37mo), respectively. 89% (n=72) of the infants with HbSS received ongoing disease management. Penicillin prophylaxis was accepted in 82% (n=59) of the children in this cohort. Additionally, 44% (n=32) were started on hydroxycarbamide at a low, fixed dose (20ml/kg/day) based on disease severity parameters. Mean MCV for those children receiving hydroxycarbamide was 89.06fL (+/- 9.5fL) and for the non-hydroxycarbamide group was 79.83fL (+/- 14.3fL) (p= 0.025). While the most common reason for clinical follow-up was routine treatment, patients were also seen for fever, malaria treatment, and bone pain episodes. Based on clinical records and phone follow-up, there were two confirmed deaths (2.5%) in the HbSS cohort. One infant died of non-SCD complications on the first day of life and the other died at 6 months of age without returning to the clinic for follow-up treatment.

Conclusions: This program is the first to examine the impact of systematic POC infant screening and treatment for SCD in rural Mali, West Africa. The low cost and rapidity of POC testing resulted in a high rate of newborns screened and positively impacted the success of clinical follow-up. POC testing results were comparable when reviewed alongside historical IEF-based screening at Koutiala Hospital (Table 1). The higher percentage of infants screened by POC when compared to IEF may have been slightly affected by an increase in the general awareness of SCD amongst the regional population. There was a high acceptance rate of ongoing clinical care (89%) and low death rate (2.5%) within the HbSS cohort which may be attributable to early access to diagnosis and treatment. Results from a larger patient size and longer treatment duration will provide more insight into the benefits of POC screening in this setting.