Sickle cell anemia in sub-Saharan Africa: advancing the clinical paradigm through partnerships and research

Abstract

Sickle cell anemia (SCA) carries orphan disease designation in the United States, with ∼2000 affected infants born annually and fewer than 100 000 persons living with this condition.1 Patients with SCA have numerous acute and chronic medical problems, which collectively contribute to life-threatening morbidity, early mortality, and annual domestic medical costs exceeding $1.1 billion.2-6 Worldwide, >300 000 infants are born with SCA each year,7 but <1% of sickle cell births occur in North America and the United Kingdom/Europe, where nearly all SCA research and health care dollars are spent. Millions of persons throughout the world are living with, and unfortunately dying from, this inherited blood disorder without the benefits of proper diagnosis and appropriate clinical care. Although the burden of SCA is truly global, with the highest incidence in Africa, India, the Caribbean, Central America, and South America, the focus of this editorial perspective is SCA within Africa. More than 75% of the global burden of SCA occurs in sub-Saharan Africa,8 where scarce health resources and inadequate awareness among health care providers and the general public contribute to shocking rates of early mortality. With few data from neonatal screening programs, and virtually no prospective natural history studies, true mortality rates are unknown, but an estimated 50% to 90% of infants born with SCA in sub-Saharan Africa die before their fifth birthday.9,10 Without early diagnosis, which allows early preventive treatments including pneumococcal vaccination, penicillin prophylaxis, and parental education, most infants will die of acute complications, most notably bacterial sepsis or severe anemia. Regrettably, death attributed to SCA is missing completely from recent global summaries,11 presumably because of a lack of accurate data, making SCA at best a neglected and, more accurately, an invisible killer of children.12,13 Over the past 40 years, beginning with the landmark US Cooperative Study of Sickle Cell Disease14-16 and Jamaican Cohort Study,17 substantial evidence has accumulated from well-designed prospective research trials. Together, these studies document the life-threatening severity of untreated SCA, but demonstrate unquestionable benefits of penicillin prophylaxis, pneumococcal vaccinations, transcranial Doppler (TCD) screening for primary stroke prevention, safe transfusions for acute and chronic complications, and hydroxyurea as a safe and potent disease-modifying therapy. Unfortunately, the status of SCA in Africa remains stagnant, with most affected persons lacking access to basic diagnostics and clinical care. As SCA finally begins to be addressed in Africa, we must ask whether proven evidence from well-resourced countries is directly transferable, or must additional studies be replicated and verified in the African setting? Are new National Heart, Lung, and Blood Institute (NHLBI) evidence-based guidelines for SCA18 feasible or even appropriate for limited-resource settings? How do we augment these guidelines to be clinically and economically feasible, while remaining effective across sub-Saharan Africa? Acknowledging the unjustifiable disparity in clinical care and outcomes between well-resourced and limited-resource settings for persons with SCA, some institutions that lead and fund sickle cell care and research have begun to take action. Both the NHLBI and American Society of Hematology (ASH) are committing financial and programmatic efforts to address the global burden of SCA in limited-resource settings, particularly in sub-Saharan Africa.19-21 We must think carefully about what is needed to improve outcomes, and how these needs can be met safely and effectively within the clinical and financial contexts of limited-resource settings. Although the HbS mutation is the same worldwide, the environment, infectious exposures, and general health care infrastructure faced by persons living with SCA in Africa are quite different from those in well-resourced settings. With our admittedly Western bias, we suggest that plans to shift our clinical care and treatment paradigms automatically to Africa are neither logical nor likely to succeed. Instead, we advocate for the formation of multidisciplinary partnerships and research collaborations with a shared vision and mutual benefits, with short-term goals of obtaining high-quality data while emphasizing local capacity building and health system strengthening, and long-term goals of helping to develop national (and global) strategies for SCA that are impactful and sustainable. Herein, we offer our subjective summary of opportunities by which sickle cell capacity and outcomes can be improved, based upon our own experiences with African partnerships and research collaborations. Each high burden country should carefully assess its own needs to develop national sickle cell strategies that are in line with their own resources, and offer a plan for sustainability.