Early interventions to reduce sickle cell childhood mortality in Africa (Global Burden of Disease Impact)

Abstract Background Sickle cell disease (SCD) is a major contributor to under-five mortality in sub-Saharan Africa, where ~75% of the world's SCD births occur. An estimated 300,000 infants are born with SCD each year globally, nearly 80% of them in Africa. Due to lack of early diagnosis and basic care, 50–80% of African children with SCD die before their 5th birthday – making SCD responsible for about 6–7% of under-five deaths in some high-prevalence countries. In stark contrast, childhood SCD mortality in high-income countries has been virtually eliminated through newborn screening and prophylactic care. This study evaluates the impact of implementing early interventions (newborn screening and comprehensive prophylactic care) on survival outcomes in African children with SCD.Methods We conducted a retrospective analysis of survival outcomes in SCD infants across several African newborn screening pilot programs and used a population modeling approach for countries without programs. Data were collected from program reports in Ghana, Nigeria, Uganda, and Kenya, where infants diagnosed via newborn screening received a package of early interventions: penicillin prophylaxis, pneumococcal vaccination, parent education on fever/pain, and prompt clinic follow-up. We compared observed survival in screened/co-managed SCD cohorts to estimated survival in unscreened populations (using historical cohort and Global Burden of Disease data). Additionally, a decision-model projected the under-5 mortality reduction and lives saved if these interventions were scaled up to national levels.Results In the absence of interventions, under-5 mortality among children with SCD was estimated at 50–90% across sub-Saharan settings. In our modeled unscreened cohort (~2,000 infants), survival to age 5 was only ~30%. Introduction of newborn screening and comprehensive care was associated with a striking improvement in survival. Among 1,248 screen-identified SCD infants in pilot programs (pooled across sites), the under-5 mortality rate was reduced to approximately 10–15%. Several programs reported >85% survival to age 5, approaching the survival of the general infant population in those countries. In Uganda, for example, only 2 of 80 infants (2.5%) diagnosed through screening died by age 1 (with causes unrelated to SCD in both cases). Prospectively followed cohorts in Benin and Angola similarly demonstrated that early comprehensive interventions can reduce SCD infant mortality to levels comparable to children without SCD. Our model projected that scaling up newborn screening to cover 100% of newborns in high-burden countries and providing prophylactic care could avert roughly 70,000 under-5 deaths annually across sub-Saharan Africa. This corresponds to a 50% reduction in overall SCD-related child mortality region-wide, in line with prior estimates. Early intervention also led to reductions in morbidity. Documented rates of severe bacterial infections (e.g. pneumococcal sepsis) and overt stroke in the screened infants were far lower than historically seen in unscreened children, likely due to prophylactic antibiotics and immunizations. Families of screened children utilized healthcare proactively, and no deaths from splenic sequestration or acute chest syndrome were observed in the managed cohorts. The projected healthy life years gained from nationwide programs are substantial, and cost-effectiveness analyses indicate these interventions are highly cost-effective in most African countries (cost per DALY averted well below 1× GDP per capita in >75% of countries).Conclusion Implementing newborn screening and early comprehensive care for SCD in Africa can transform the disease from a tragic early killer into a manageable chronic condition. Our analysis across African contexts shows that simple, low-cost interventions in the first years of life – identification of affected infants, penicillin prophylaxis, immunizations, malaria prevention, parental education, and access to acute care – can reduce childhood SCD mortality. In pilot programs, survival of children with SCD to age 5 now exceeds. These findings underscore the urgent need for wider adoption of newborn SCD screening and prophylactic treatment programs in high-burden regions. Given the high burden of SCD in Africa and the proven effectiveness of early interventions, scaling up these programs could save tens of thousands of young lives each year and significantly improve childhood survival rates.