Structural Inequalities and Sickle Cell Disease

This year 2021 has witnessed the recent COVID-19 pandemic elucidating a large societal ill of structural and ethnic inequalities. The events encompassing the murder of George Floyd and resulting protests have also once again brought racism and inequality to the forefront of the political and social agendas.1  Consequently, the past year has seen great attention paid to racism and stark ethnic inequalities in medical health.2  Akin to poverty, racism is a marker of our global health and well-being as a collective. Society’s longstanding apathy to the issue has meant we have had to keep re-visiting the issue repetitively, almost synonymously like an exam one keeps failing and re-taking. Knowledge of racial inequality is not just simply re-hashing an uncomfortable history, but rather, drawing lessons from historical context with a view to collective action for change. For the sake of global well-being, these inequalities must be consistently addressed if we are to have any effective interventions at an individual and societal level.

Health inequalities associated with ethnicity and race have also led to deep mistrust of healthcare systems within some communities.3 These can only be understood against an examination of the consequences of colonialism,  past medical research abuses, and ongoing racism in our society.3,4 Individuals of African heritage have been used as unlawful subjects of unethical medical trials and testing such as many experimental operations without anaesthetic undertaken by Dr. James Marion Sims (otherwise known as the ‘father of modern gynaecology’), on Black slave women in the USA between 1845 and 1849.5 The Tuskegee Study of untreated syphilis, is another example, the ‘negro male’ subjects was enticed under the guise of free health checks, meals and treatment in 1932.3,4 They were not informed that they had syphilis and continued to be given placebo even after the discovery of the effective treatment of penicillin to allow the evolution of pathology to be researched.3,4

Even in today’s present day, it has become more apparent that racism can significantly affect health outcomes.2,6Ethnic inequalities are seen in many areas such as maternal health, genetic counselling, artificial intelligence and climate change where low to medium income countries face the greatest burden of impact.7–10 Consequently, whilst the world has made superior gains in life expectancy and health over the past century through medical science with antibiotics, insulin and vaccines; this has been superimposed by increase in both health and societal disparities.11 The health gap between the most affluent and least affluent in our society continues to widen with contributory factors embedded with complex social determinants of health, as well as healthcare systems and markets.11 In the UK currently, life expectancy has now plateaued and is no longer improving amongst the most deprived communities.11,12In addition, the COVID-19 pandemic in itself has also exacerbated economic inequalities in that those with highest rates of deprivation, have almost double risk of death from COVID-19.13 It is consequently no surprise the WHO Commission on Social Determinants of Health announced that ‘social injustice is killing people on a grand scale’.11,14Indeed, we are somewhat reminiscent of the echoes of physician Dr Rudolf Virchow statement in 1848 that ‘Medicine is a social science, and politics is nothing else but medicine on a large scale.15 Virchow explained that to understand the science of human beings, lays an obligation to highlight the problems and apply theoretical solutions.15 Virchow added that activity without understanding of these societal ills is unassertive and scientific knowledge without action is not genuine.15 In medical science, one can examine a phenomenon at the level of a molecule and fit that into the context of wider world, similarly in sociologic terms, we also require the ability for a more refined micro and macro understanding of ethnicity and race and how these complexities fit within the world at large.   

Sickle cell disease (SCD) is a global health condition and one of the most fastest growing genetic conditions worldwide.16 The pathophysiology of affected haemoglobin polymerisation in the deoxygenated state, leads to microvascular obstruction as well as the hallmark of debilitating vaso-occlusive pain crises.16 Associated tissue infarction, and a cascade of endothelial damage termed ‘vasculopathy’, lead to end organ damage such as stroke, kidney disease and avascular necrosis.16 SCD predominantly affects individuals from African, Mediterranean, Arabian, and Indian origins owing to natural selection of the gene mutation in malaria-endemic regions.17  Its peculiar clinical and epidemiological characteristics has meant that SCD too has long been at the intersection of politics, race and global health. It too therefore can be seen as a barometer for global health. In essence, how we view and treat SCD, may have some indication on human health and global equality. 

So what are some of the structural inequalities observed in SCD? 80% of SCD population disease burden resides in low-income countries in sub-Saharan Africa where fewer than 50% reach their 10th birthday.16 This is comparison to those with SCD born in high-income countries i.e. USA, UK & France, in which individuals with SCD are living longer and 95% survive to adulthood.16,18 In many of these low income countries, there is a myriad of disparity such as severe lack of comprehensive clinics, national SCD management, neonatal screening; inaccessibility and unaffordability of standard of care treatments such as antibiotics, analgesics, hydroxycarbamide and lack of blood safety for transfusions.16 This is not even taking into account more advanced or novel therapies such as bone marrow transplantation, L-Glutamine, Crizanlizumab, and Voxelotor.19

Furthermore, in many African countries, where SCD has been part of communities for millennia, there can be sophisticated traditional health beliefs such as abiku amongst the Yoruba tribes or ogbanje amongst the Igbo tribes which have been attributed to SCD and can lead to stigmatization on a sociological front.20 From a clinical practice front, these well-developed, local health beliefs, may encourage health seeking amongst local traditional herbalists in these regions as opposed to medical doctors.16

Cultural differences and racial inequalities also exist in developed countries with advanced health care systems which can be further aggravated by disparities in socio-economic and education status.16 Although, there are comprehensive sickle cell disease treatment centres with multidisciplinary teams available in high-income developed countries, nevertheless there is often a lack of specialist adult providers for SCD.16 Consequently, in areas where SCD prevalence is relatively low, patients can generally receive care in local hospitals without specialist expertise.16     

Although SCD had been recognized for decades as the ‘poster child’ for molecular medicine, progress from a genetics-front had been hampered due the underrepresentation of African data where there was an initial lack of inclusion of African data which caused the search for human genetic variation to suffer.21  It is now clear that genetic diversity originated in Africa and is the region with the most genetic diversity, as such, concerted efforts for greater inclusion of African data have recently taken off yielding important scientific insights.21 Similarly, regarding research funding disparity, it was published in a NEJM paper that cystic fibrosis, a monogenic disorder affecting predominantly White ethnicities, receives 7-11 times the research funding per patient in the US, compared to sickle cell disease, a monogenic disorder affecting predominantly individuals of Black heritage, despite sickle cell disease being 3 x more prevalent than cystic fibrosis in the same country.22 It is therefore no surprise, that there remains still no objective, quantifiable pain biomarkers which exist to evaluate and manage SCD vaso-occlusive crises.23 It is not just in medical research, but also politically and logistically, patients with SCD remain underserved, and having to pay for their NHS prescriptions, is an example of this.24  

Of course, we have the medical scientific landmark innovation of gene editing, and its application in the field of SCD, which has been welcomed by the medical community with optimism. However, with the price of 1 million dollars per patient,25 once again, access will be a huge issue. This cost would likely preclude use in the African continent where the disease burden is greatest. There have been recent strategies presently set up to try to meet these challenges through collaborations like that between Novartis and Gates Foundation.26

We have made huge medical scientific advances, such as landmarks with genome editing technology for SCD. Yet, on sociological terms, it seems our human species struggles to move with the same speed and vigour that seems to characterise the progress made by our biological advances. This dichotomy is set to get only wider, unless we remove historical shackles and begin to implement change in our approach to medical science adopting the need for inclusiveness of understanding and diversity both on biologic and sociologic terms. To dismantle racial inequalities, we must act together, to create strategies that will protect and enhance us all.6 Rather than slow down progress, medical science has the opportunity to lead the breaking down of inequalities because the very definition of science, if done right, is to provide ‘truth’ through knowledge and understanding of the natural and social world using systematic methodology based on evidence.27 Only through understanding and tackling these sociological disparities and its inter-relationship with health, are we then able to allow the true measure of medical scientific discovery and progress to flourish towards a honest hope of treatment and cure for SCD. 

Dr Norris Efe Igbineweka

Clinical Research PhD Fellow, Imperial College London/Oxford University

Haematology SpR/ST5, King’s College Hospital

References

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16.      Inusa, B. P. D., Jacob, E., Dogara, L. & Anie, K. A. Racial inequalities in access to care for young people living with pain due to sickle cell disease. The Lancet Child and Adolescent Health 5, 7–9 (2021).

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19.      Ali, M. A. et al. Efficacy and safety of recently approved drugs for sickle cell disease: a review of clinical trials. Experimental Hematology 92, 11-18.e1 (2020).

20.      Ameh, S. J., Tarfa, F. D. & Ebeshi, B. U. Traditional herbal management of sickle cell anemia: Lessons from Nigeria. Anemia 2012, (2012).

21.      Bentley, A. R., Callier, S. L. & Rotimi, C. N. Evaluating the promise of inclusion of African ancestry populations in genomics. npj Genomic Medicine 5, 1–9 (2020).

22.      Power-Hays, A. & McGann, P. T. When Actions Speak Louder Than Words — Racism and Sickle Cell Disease. N. Engl. J. Med. 383, 1902–1903 (2020).

23.      Pittman, D. D. et al. Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS) by patient-reported outcomes, actigraphy, and biomarkers. Blood 137, 2010–2020 (2021).

24.      Include Sickle Cell Anemia in the List of Illnesses Eligible for a MedEx Card – Petitions. Available at: https://petition.parliament.uk/petitions/333926. (Accessed: 9th July 2021)

25.      Sherkow, J. S. CRISPR, patents, and the public health. Yale J. Biol. Med. 90, 667–672 (2017).

26.      Novartis and the Bill & Melinda Gates Foundation collaborate to discover and develop an accessible in vivo gene therapy for sickle cell disease | Novartis. Available at: https://www.novartis.com/news/media-releases/novartis-and-bill-melinda-gates-foundation-collaborate-discover-and-develop-accessible-vivo-gene-therapy-sickle-cell-disease. (Accessed: 11th April 2021)

27.      Our definition of science – The Science Council ~ : The Science Council ~. Available at: https://sciencecouncil.org/about-science/our-definition-of-science/. (Accessed: 11th April 2021)

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