Sickle Cell Disease in Children and Adolescents: A Review of the Historical, Clinical, and Public Health Perspective of Sub-Saharan Africa and Beyond.

Sickle cell disease (SCD) is an umbrella term for a group of life-long debilitating autosomal recessive disorders that are caused by a single-point mutation (Glu→Val) that results in polymerization of hemoglobin (Hb) and reversible sickle-shape deformation of erythrocytes. This leads to increased hemolysis of erythrocytes and microvascular occlusion, ischemia-reperfusion injury, and tissue infarction, ultimately causing multisystem end-organ complications. Sickle cell anemia (HbSS) is the most common and most severe genotype of SCD, followed by HbSC, HbSß 0thalassemia, HbSß+thalassemia, and rare and benign genotypes. Clinical manifestations of SCD occur early in life, are variable, and are modified by several genetic and environmental factors. Nearly 500 children with SCD continue to die prematurely every day, due to delayed diagnosis and/or lack of access to comprehensive care in sub-Saharan Africa (SSA), a trend that needs to be urgently reversed. Despite proven efficacy in developed countries, newborn screening programs are not universal in SSA. This calls for a consolidated effort to make this possible, through the use of rapid, accurate, and cheap point-of-care test kits which require minimal training. For almost two decades, hydroxyurea (hydroxycarbamide), a century-old drug, was the only disease-modifying therapy approved by the U.S. Food and Drug Administration. Recently, the list expanded to L-glutamine, crizanlizumab, and voxelotor, with several promising novel therapies in the pipeline. Despite its several limitations, hematopoietic stem cell transplant (HSCT) remains the only curative intervention for SCD. Meanwhile, recent advances in gene therapy trials offer a glimpse of hope for the near future, although its use maybe limited to developed countries for several decades.

Germinal Matrix-Intraventricular Hemorrhage: A Tale of Preterm Infants.

Germinal matrix-intraventricular hemorrhage (GM-IVH) is a common intracranial complication in preterm infants, especially those born before 32 weeks of gestation and very-low-birth-weight infants. Hemorrhage originates in the fragile capillary network of the subependymal germinal matrix of the developing brain and may disrupt the ependymal lining and progress into the lateral cerebral ventricle. GM-IVH is associated with increased mortality and abnormal neurodevelopmental outcomes such as posthemorrhagic hydrocephalus, cerebral palsy, epilepsy, severe cognitive impairment, and visual and hearing impairment. Most affected neonates are asymptomatic, and thus, diagnosis is usually made using real-time transfontanellar ultrasound. The present review provides a synopsis of the pathogenesis, grading, incidence, risk factors, and diagnosis of GM-IVH in preterm neonates. We explore brief literature related to outcomes, management interventions, and pharmacological and nonpharmacological prevention strategies for GM-IVH and posthemorrhagic hydrocephalus.