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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, HbS\u03b20thalassemia, HbS\u03b2+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.<\/jats:p>","DOI":"10.1155\/2022\/3885979","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T06:50:13Z","timestamp":1665298213000},"page":"1-26","source":"Crossref","is-referenced-by-count":63,"title":["Sickle Cell Disease in Children and Adolescents: A Review of the Historical, Clinical, and Public Health Perspective of Sub-Saharan Africa and Beyond"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2318-2401","authenticated-orcid":true,"given":"Walufu Ivan","family":"Egesa","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Nile International Hospital, Jinja District, Uganda"},{"name":"Department of Pediatrics & Child Health, Faculty of Clinical Medicine & Dentistry, Kampala International University, Bushenyi District, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2982-1035","authenticated-orcid":true,"given":"Gloria","family":"Nakalema","sequence":"additional","affiliation":[{"name":"Department of Pediatrics & Child Health, Faculty of Clinical Medicine & Dentistry, Kampala International University, Bushenyi District, Uganda"},{"name":"Department of Pediatrics, Luweero Hospital, Luwero District, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2171-7097","authenticated-orcid":true,"given":"William M.","family":"Waibi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics & Child Health, Faculty of Clinical Medicine & Dentistry, Kampala International University, Bushenyi District, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-5593","authenticated-orcid":true,"given":"Munanura","family":"Turyasiima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics & Child Health, Faculty of Clinical Medicine & Dentistry, Kampala International University, Bushenyi District, Uganda"},{"name":"Standards Compliance Accreditation and Patient Protection (SCAPP) Department, Governance and Regulation Directorate, Ministry of Health, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4819-3545","authenticated-orcid":true,"given":"Emmanuel","family":"Amuje","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nile International Hospital, Jinja District, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0138-4304","authenticated-orcid":true,"given":"Gloria","family":"Kiconco","sequence":"additional","affiliation":[{"name":"Department of Pediatrics & Child Health, Faculty of Clinical Medicine & Dentistry, Kampala International University, Bushenyi District, Uganda"},{"name":"Department of Pediatrics, Fort Portal Regional Referral Hospital, Kabarole District, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1960-9970","authenticated-orcid":true,"given":"Simon","family":"Odoch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics & Child Health, Faculty of Clinical Medicine & Dentistry, Kampala International University, Bushenyi District, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2138-4632","authenticated-orcid":true,"given":"Patrick Kumbowi","family":"Kumbakulu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics & Child Health, Faculty of Clinical Medicine & Dentistry, Kampala International University, Bushenyi District, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9432-8565","authenticated-orcid":true,"given":"Said","family":"Abdirashid","sequence":"additional","affiliation":[{"name":"Department of Pediatrics & Child Health, Faculty of Clinical Medicine & Dentistry, Kampala International University, Bushenyi District, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-6013","authenticated-orcid":true,"given":"Daniel","family":"Asiimwe","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Clinical Medicine & Dentistry, Kampala International University, Bushenyi District, Uganda"},{"name":"Department of Surgery, Holy Family Virika hospital, Kabarole District, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1910.00050330050003"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1989.03420020120042"},{"key":"3","volume-title":"The diseases of tropical climates and their treatment","author":"J. 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