Potential for a large-scale newborn screening strategy for sickle cell disease in Mali: A comparative diagnostic performance study of two rapid diagnostic tests (SickleScan® and HemotypeSC®) on cord blood.

Sickle cell disease (SCD) is a life-threatening disease requiring reliable early diagnosis. We assessed the acceptability and diagnostic performances of two rapid diagnostic tests (RDTs) to identify SCD (HbSS, HbSC, HbS/ß-thalassaemia) or SCD carrier (HbS/HbC) in a pilot SCD newborn screening (NBS) strategy in Mali. All consenting delivering women were offered SCD NBS using cord blood sampling on two RDTs (SickleScan® and HemotypeSC®) compared to the high-performance liquid chromatography (HPLC) gold standard to detect SCD states. From April 2021 to August 2021, 4333 delivering women were eligible of whom 96.1% were offered NBS: 1.6% refused, 13.8% delivered before consenting and 84.6% consented; 3648 newborns were diagnosed by HPLC; 1.64% had SCD (0.63% HbSS, 0.85% HbSC, 0.16 HbS/ß-plus-thalassaemia); 21.79% were SCD carrier. To detect accurately SCD, SickleScan® had a sensitivity of 81.67% (95% confidence interval [CI]: 71.88-91.46) and a negative predictive value (NPV) of 99.69% (95% CI: 99.51-99.87); HemotypeSC® had a sensitivity of 78.33% (95% CI: 67.91-88.76) and a NPV of 99.64% (95% CI: 99.44-99.83). To detect SCD carrier: SickleScan® sensitivity was 96.10% (95% CI: 94.75-97.45) and NPV, 98.90% (95% CI: 98.51-99.29); HemotypeSC® sensitivity was 95.22% (95% CI: 93.74-96.70) and NPV, 98.66% (95% CI: 98.24-99.03). Routine SCD NBS was acceptable. Compared with HPLC, both RDTs had reliable diagnostic performances to exclude SCD-free newborns and to identify SCD carriers to be further confirmed. This strategy could be implemented in large-scale NBS programmes.

Relationship between red blood cell polymorphisms and effectiveness of seasonal malaria chemoprevention in 2020 in Dangassa, Mali.

Treatment failure with amodiaquine was reported in Dangassa, where red blood cell (RBC) polymorphisms are found and seasonal malaria chemoprevention (SMC) is underway. Here, we aimed at assessing the influence of RBC polymorphisms on SMC effectiveness. This was a secondary analysis of data from a study conducted in Dangassa. Children aged 5 to 14 years enrolled in an open randomized study were assigned either to receive SMC (intervention arm) or not (control arm). SMC was implemented from July to November. For all children, hemoglobin type and blood group were determined at enrolment in July, and parasitemia and hemoglobin level were monthly monitored by finger-prick. Overall, 166 children were enrolled among which 82 (49.40%) in the control arm and 84 (50.60%) in the SMC arm. The prevalence of HbAS was 10.24% (17/166) with 12.20% in the control and 8.33% in the SMC arm. O group was the most common overall (45%) and in the SMC arm (54%), but the control arm had more B (39.02%) than O (36.59%). In the SMC arm, no case of Plasmodium infection and malaria disease was observed in the 7 HbAS children while in Non-HbAS children, peaks of infection and disease prevalence were respectively observed in October (24.66%) and November (7.14%). For the SMC arm, in group O and Non-group O, Plasmodium infection cases were observed from August to December. Plasmodium infection and malaria disease were more frequently observed in HbAS children in the control arm than in the SMC arm. Further studies are needed to assess factors associated with the asymptomatic carriage of parasites during SMC in Dangassa. NCT04149106.

Cell-derived microparticles and sickle cell disease chronic vasculopathy in sub-Saharan Africa: A multinational study.

Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the natural history of the disease on this continent remains largely unknown. Intravascular haemolysis results in activation of circulating blood cells and release of microparticles (MPs) that exert pro-inflammatory effects and contribute to vascular damage. We designed a case-control study nested in the CADRE cohort (Coeur-Artère-DRÉpanocytose, clinical trials.gov identifier NCTO3114137) and based on extreme phenotypes, to analyse blood cell-derived MPs in 232 adult SS patients at steady state in Bamako and Dakar. Thirty-six healthy adult controls matched by age and sex were recruited in Bamako. The MPs concentrations were higher in SS patients compared to AA controls with a predominance of erythrocyte- and reticulocyte-derived MPs. These erythroid-derived MPs were significantly lower in patients with retinopathy (P = 0·022). Reticulocyte-derived MPs were significantly negatively and positively associated with a history of priapism (P = 0·020) and leg ulcers (P = 0·041) respectively. We describe for the first time the comparative patterns of plasma MPs in healthy subjects and patients with SCD living in sub-Saharan Africa and exhibiting various complications. Because our present results show no clear pattern of correlation between erythroid MPs and the classical hyper-haemolytic complications, we hypothesise a weak relevance of the hyper-haemolysis versus hyper-viscous paradigm in Africa.