A recent study indicates that the death toll attributed to sickle cell disease could be as much as 11 times higher than what mortality records alone suggest, with scientists saying numbers are actually increasing, particularly in sub-Saharan Africa.
Not only is the hereditary illness, which affects 8m people worldwide, often underdiagnosed, but it also heightens the risk of complications like infections, strokes, cardiac issues, kidney dysfunction and complications during pregnancy.
The researchers said the findings imply that a healthcare provider treating a patient with sickle cell disease who dies from a stroke might be unaware, for instance, that that person had the condition, or may not recognise that sickle cell disease can cause a stroke.
When other sources of data on prevalence and birth incidence were combined with mortality data in epidemiological modelling, in 2021, the “total mortality burden” of sickle cell disease was 373 000 deaths, compared with 34 600 sickle-cell-only deaths, or “cause-specific deaths”.
The increase was especially pronounced in South Asia and sub-Saharan Africa, where the fatality figures were 67 times higher and nine times higher, respectively, said the scientists.
The study analysed global health data from 2000 to 2021 and was published in The Lancet Haematology journal. The research is part of the Global Burden of Disease 2021 study co-ordinated by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington’s School of Medicine.
“Our research reveals the stark reality that sickle cell disease is far deadlier than its textbook description,” said senior author Dr Nicholas Kassebaum, Adjunct Associate Professor at IHME. “The number of babies born with sickle cell disease is rising, which means a very difficult early childhood. Patients are more susceptible to infections and other severe conditions, so early detection is key for treatment.”
In 2021, half a million babies were born with sickle cell disease, and more than three-quarters of those were in sub-Saharan Africa. Under the analysis of total mortality burden (including secondary conditions), sickle cell disease was the 12th leading cause of death globally for children under five.
However, total sickle cell disease mortality burden was among the top three causes of death in Portugal, Jamaica, Libya, Oman and San Marino.
“Improved data collection is critical to tracking progress on sickle cell disease. To overcome the limitation, instead of using mortality data alone to estimate total sickle cell disease deaths, we used a mathematical algorithm that also takes input data from birth incidence, survival over time, and prevalence, and ensures these measures are internally consistent,” said Azalea Thomson, first author and IHME researcher on the Neonatal and Child Health Team.
“By using all available data, we were able to strengthen our understanding of the true burden of the disease and better contextualise it alongside other leading causes of death.
For example, in 2021, in children under five in sub-Saharan Africa, total sickle cell disease deaths exceeded those from malnutrition, measles, or syphilis.”
The research also underscores the need for policymakers and public health advocates to address the largely under-recognised burden of sickle cell disease.
Universal newborn screening, case monitoring through public registries, and early intervention treatment can alleviate suffering for some 8m people living with the disease.
Study details
Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021
Sickle Cell Disease Collaborators
Published in The Lancet on 15 June 2023
Summary
Background
Previous global analyses, with known under-diagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021.
Methods
We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures – borrowing strength from predictive covariates and across age, time, and geography – and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs).
Findings
Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1–16·5), to 515 000 (425 000–614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3–44·9), from 5·46 million (4·62–6·45) in 2000 to 7·74 million (6·51–9·2) in 2021. We estimated 34 400 (25 000–45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000–467 000). In children under five, there were 81 100 (58 800–108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021.
Interpretation
Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease.
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