Abstract Sickle cell disease (SCD) affects approximately 7.74 million people globally as of 2021, with nearly 80% residing in sub-Saharan Africa and South Asia. While 34,400 deaths were directly attributed to SCD through ICD-coded cause-specific data, the total estimated deaths from SCD, accounting for excess mortality, reach approximately 376,000—more than 10 times higher. Among children under five, SCD caused approximately 81,100 deaths in 2021, ranking as the 12th leading global cause of death in this age group. Despite this substantial mortality and disability burden, few studies have used DALY-based models to map the global and regional trends in SCD burden over time. This study aimed to quantify the age-specific and region-specific burden of SCD using disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) from 2000 to 2021, to project trends through 2030, and to examine implications for U.S. hematologists. We extracted SCD-specific DALY, YLD, and YLL estimates from the Global Burden of Disease (GBD) 2021 study, covering 204 countries and territories. Data were stratified by region (sub-Saharan Africa, South Asia, Middle East, North America), age (5, 5–14, ≥15 years), sex, and Sociodemographic Index (SDI). Temporal trends from 2000 to 2021 were analyzed. We also modeled forecasts of total DALYs to 2030 using UN population growth data and linear regression of prior trends. Between 2000 and 2021, global SCD prevalence increased by 41%, from approximately 5.46 million to 7.74 million individuals. Sub-Saharan Africa accounted for 75 to 80% of global DALYs and SCD-related deaths. In 2021 alone, under-5 mortality due to SCD in sub-Saharan Africa exceeded 80,000 deaths. The DALY rate per 100,000 population was more than 3 to 5 times higher in sub-Saharan Africa compared to South Asia, and over 20 times higher than in North America. To introduce a globally comparable benchmark of health system performance, we calculated DALYs per live birth with SCD. In 2021, Nigeria accounted for an estimated 2.1 million SCD-attributable DALYs and approximately 100,000 SCD births, yielding roughly 21 DALYs per birth. In contrast, the United States had an estimated 90,000 DALYs with approximately 2,000 SCD births, resulting in 45 DALYs per birth. The higher DALY-per-birth ratio in the U.S. reflects prolonged chronic morbidity among aging survivors, while Nigeria's lower ratio primarily reflects early mortality concentrated in childhood. This novel metric captures both the clinical and systemic dimensions of SCD burden and provides a standardized approach to compare health system effectiveness across regions. Despite modest improvements in care in some countries, population growth and stagnant early childhood intervention led to an overall increase in DALYs. Projections suggest that without accelerated implementation of newborn screening, hydroxyurea access, and standardized care pathways, DALYs in sub-Saharan Africa may rise by an additional 30% by 2030. In contrast, the United States maintains significantly lower SCD-related mortality and DALY rates due to early diagnosis and disease-modifying therapy. However, life expectancy remains low—approximately 42 years in males—and many patients face barriers to care, including those born outside the U.S. or diagnosed late. These findings underscore the severe and sustained burden of SCD in low- and middle-income regions. For U.S. hematologists, this has four key implications: (1) an increasing number of patients originate from high-burden countries and may present with underdiagnosed or atypical phenotypes; (2) regional burden data can guide research collaborations and capacity-building; (3) such data support advocacy for equitable access to therapies and curative interventions; and (4) genotype and phenotype diversity should inform inclusive gene therapy trial design. This study highlights the need for continued investment in global SCD surveillance, policy support, and partnership. A globally informed approach is essential for advancing clinical care, research, and health equity in hematology.
Younas et al. (Mon,) studied this question.