Poverty and severity of childhood sickle cell disease

Sickle cell disease (SCD) is a monogenetic disorder with multiple pathophysiological mechanisms. The primary event in SCD is the polymerisation of deoxygenated sickle haemoglobin (HbS), which leads to changes in the physical properties and shape of red blood cells. Overall, there is resultant haemolytic anaemia and vaso-occlusion. SCD is characterised by variable manifestations and downstream events. Several hypotheses have been proposed for these variations. These include the roles of genetic markers, intensity of haemolysis and environmental factors such as climate, air quality and socioeconomics. Very prominent among the genetic markers are the roles of alpha thalassaemia and fetal haemoglobin (HbF). Among patients with SCD, alpha thalassaemia has been associated with protection against leg ulcer, priapism stroke and abnormal transcranial Doppler (TCD) velocity, early hyposplenism, nephropathy, and gallstones. However, other studies have shown that co-inheritance of alpha thalassaemia with SCD increases the risk of painful episodes. Although SCD patients with alpha thalassaemia have a decreased admission rate, they have no survival advantage. Several studies have shown the direct protective effects among SCD patients of HbF for painful episodes, leg ulcer, splenic sequestration and function, and retinopathy. Genetic variations at three principal loci, BCL11A, HBS1LMYB and HBB, on chromosomes 2, 6 and 11 respectively, and the various b haplotypes, account for variable expression of HbF among different SCD populations through which the SCD phenotype is modified. Furthermore, several other non-globin genetic factors have variable effects on SCD complications among different populations. Despite the low proportion of intravascular haemolysis (approximately ≤30% of total haemolysis in SCD), several studies have associated intensity of haemolysis and its various consequences with some pathogenic processes and clinical phenotypes/complications in patients with SCD. As a result of haemolysis, several intracellular and membranous products of red blood cells are released which interact with other molecules to produce many downstream events. Despite the huge advancements provided by both genetic and haemolytic factors in understanding the various processes responsible for the observed clinical variability in SCD, a large knowledge gap still exists regarding the impact of other factors. The situation is more appalling for sub-Saharan Africa, where the bulk of SCD resides, as none of the SCD modifiers have been well studied. In this issue of the British Journal of Haematology, BelloManga et al. examined the roles of socioeconomic factors, using educational status of head of household and family income as surrogate markers for poverty as risk factors for severe anaemia (Hb <6 g/dl) among a cohort of 941 Nigerian children with SCD who were not on hydroxycarbamide. They found a 3 9% prevalence of severe anaemia. Also, they found that severe anaemia was significantly associated with lower educational status of the head of household, and greater number of children living per room, both of which are proxies for poverty and low socioeconomic status. Their results confirm some previous local studies from Nigeria, which found that children with SCD from low socioeconomic classes tended to have lower Hb concentrations and SCD complications related to severe anaemia. The authors‘ findings are important and have many implications for clinical practice and care of SCD patients in resourcepoor settings. Firstly, it represents an important addition to the body of knowledge on the roles of non-genetic factors in SCD especially among the Nigerian population. Secondly, it raises the hope of clinicians and other health workers in resourcelimited settings in using simple, non-invasive criteria related to poverty to triage children with SCD according to their risk for severe anaemia and other related SCD phenotypes/complications. This will allow for early interventions to prevent Correspondence: Oladele Simeon Olatunya, Department of Paediatrics, College of Medicine, Ekiti State University, Ado Ekiti, Ekiti State, Nigeria. E-mail: ladeletunya@yahoo.com commentary