Sickle cell disease in children: an update of the evidence in low- and middle-income settings

Abstract

Sickle cell disease (SCD), one of the most common monogenetic diseases in the world, is associated with multisystemic complications that begin in childhood. Most of the babies homozygous for the sickle haemoglobin gene are born in sub-Saharan Africa. Over the years, progress has been made with early diagnosis through newborn screening, penicillin prophylaxis, pneumococcal immunisation, transcranial Doppler (TCD) screening, hydroxyurea therapy and chronic blood transfusions with remarkably improved survival and quality of life of children with SCD. However, wide disparities in outcomes exist between high-income countries (HICs) where over 90% survive to adulthood, and low-income and middle-income countries (LMICs) where less than half achieve that milestone. Even in HICs, racial inequities pose barriers to accessing specialised care and receiving treatment for acute pain episodes. Better understanding of SCD pathophysiology is being exploited to develop new disease-modifying drugs and gene therapy approaches to further improve outcomes. Bone marrow transplantation is established as a curative treatment for SCD, but it is largely unavailable in LMICs. To bridge the disparity and inequity gaps, innovative approaches are needed in LMICs. Validated and more affordable, easy-to-use point-of-care tests offer opportunities to link early diagnosis with immunisation programmes and healthcare encounters. Widespread use of hydroxyurea therapy—a relatively affordable and effective disease-modifying drug—in LMICs would help improve survival and quality of life. Integration of SCD treatment into primary care linked to district level/provincial hospitals that are supported with evidence-based guidelines will help extend needed interventions to many more patients living in LMICs.

Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE II): Protocol for a single-arm open label trial

“…(6) TCD screening is not available to most people with SCA in Africa. (7) Our meta-analysis estimated that as many as 60,000 children in sub-Saharan Africa have SCA stroke, emphasizing the high burden in vulnerable children. (8) In addition, clinically unapparent stroke can only be detected by magnetic resonance imaging and arteriography (MRI-MRA).…”

“…More recently, some sub-Saharan studies of hydroxyurea have demonstrated improved TCD measurements and reduced stroke risk. (12, 14)…”

“…More recently, some sub-Saharan studies of hydroxyurea have demonstrated improved TCD measurements and reduced stroke risk. (12,14) BRAIN SAFE II is a single arm, open label 36-month trial of daily oral hydroxyurea therapy on the frequency and severity of SCVI, compared to baseline, in a cohort of children treated at the Mulago Hospital SCA clinic (MHSCC) in Kampala, Uganda. Our hypothesis is that hydroxyurea therapy will improve or stabilize SCVI, as measured by incident stroke, TCD velocity, neurocognitive testing, and -for a 30% sub-sample -stabilize MRI-MRA findings of cerebral infarcts and arterial stenoses.…”

Translation, transcultural adaptation, and validation of PedsQL 3.0 Sickle Cell Disease Module into Brazilian Portuguese

“…It is associated with several clinical complications in childhood and adolescence, such as anemia, pain, stroke, infections, delayed puberty, and progressive chronic organ damage. 1,2 SCD often requires chronic use of medications and frequent hospitalizations, leading to school absenteeism and poor academic performance, 3 emotional problems, and social limitations. 4,5 The evaluation of health-related quality of life (HRQoL) has been gradually incorporated into healthcare as a measure of assessing patients' perceptions and experiences of disease impact on their own lives.…”

“…Sickle cell disease (SCD) is an inherited, chronic, and debilitating illness, from both physical and psychosocial standpoints. It is associated with several clinical complications in childhood and adolescence, such as anemia, pain, stroke, infections, delayed puberty, and progressive chronic organ damage 1,2 . SCD often requires chronic use of medications and frequent hospitalizations, leading to school absenteeism and poor academic performance, 3 emotional problems, and social limitations 4,5 …”