Clinical manifestations of sickle cell disease in Africa and its association with foetal haemoglobin parameters

Introduction

It is estimated that annually 515,000 babies are born with sickle cell disease (SCD) in Africa, mainly in the sub-Saharan Africa (SSA) region, with 50−90% dying before adulthood¹. Prevalence of SCD across African countries ranges between 1–3%; and contributes up to 7–16% of under-five mortality^{2, 3, 4–5}. Nigeria, Ghana and Tanzania are among the top ten countries globally, with more than 11,000 babies born with SCD annually in each country.

There is a substantial gap between high-income nations like the USA and Europe compared to those in Africa with respect to standards of care for SCD and cognate research. In order to bridge this gap, SickleInAfrica was established in 2017 to facilitate collaboration among African nations in order to establish regionally relevant healthcare standards for SCD patients^6,7. SickleInAfrica Phase II involves seven African countries including Ghana (Kwame Nkrumah University of Science and Technology), Nigeria (University of Abuja), Tanzania (Muhimbili University of Health and Allied Sciences (MUHAS), Mali (Centre de Recherche et Lutte contre la Drépanocytose), Uganda (Makerere University), Zimbabwe ((University of Zimbabwe) and Zambia (University Teaching Hospital in Zambia), the SPARCo Clinical Coordinating Centre based at MUHAS in Tanzania, and Data Coordinating Centre based at the University of Cape Town in South Africa. The SickleInAfrica network provides a unique platform to study SCD epidemiology and modifiers of the disease in an African context. The work reported in this manuscript utilised the SickleInAfrica phase I platform in all three countries, Ghana, Nigeria and Tanzania to study variations in SCD manifestation and disease modifiers.

The clinical intra- and inter-individual variation in individuals with SCD is due to both genetic and environmental factors⁸. Foetal haemoglobin (HbF), which is a product of gamma globin gene, is a major disease modifier^{9, 10–11}. To-date, several studies have shown that SCD patients with high HbF levels are protected from the severe expression of the disease^{12, 13, 14–15}. HbF modifies disease severity of SCD by directly inhibiting polymerisation of HbF S (HbS)¹⁰. The blood of normal adults contains HbF in small amounts, ranging from less than 0.03 up to 0.7% of the total HbF present in the whole hemolysate. These trace amounts are not uniformly distributed among erythrocytes,...