The epidemiology of sickle cell disease in children recruited in infancy in Kilifi, Kenya: a prospective cohort study

Abstract

Background Sickle cell disease is the most common severe monogenic disorder in humans. In Africa, 50-90% of children born with sickle cell disease die before they reach their fifth birthday. In this study, we aimed to describe the comparative incidence of specific clinical outcomes among children aged between birth and 5 years with and without sickle cell disease, who were resident within the Kilifi area of Kenya. Methods This prospective cohort study was done on members of the Kilifi Genetic Birth Cohort Study (KGBCS) on the Indian Ocean coast of Kenya. Recruitment to the study was facilitated through the Kilifi Health and Demographic Surveillance System (KHDSS), which covers a resident population of 260 000 people, and was undertaken between Jan 1, 2006, and April 30, 2011. All children who were born within the KHDSS area and who were aged 3-12 months during the recruitment period were eligible for inclusion. Participants were tested for sickle cell disease and followed up for survival status and disease-specific admission to Kilifi County Hospital by passive surveillance until their fifth birthday. Children with sickle cell disease were offered confirmatory testing and care at a dedicated outpatient clinic. Findings 15 737 infants were recruited successfully to the KGBCS, and 128 (0•8%) of these infants had sickle cell disease, of whom 70 (54•7%) enrolled at the outpatient clinic within 12 months of recruitment. Mortality was higher in children with sickle cell disease (58 per 1000 person-years of observation, 95% CI 40-86) than in those without sickle cell disease (2•4 per 1000 person-years of observation, 2•0-2•8; adjusted incidence rate ratio [IRR] 23•1, 95% CI 15•1-35•3). Among children with sickle cell disease, mortality was lower in those who enrolled at the clinic (adjusted IRR 0•26, 95% CI 0•11-0•62) and in those with higher levels of haemoglobin F (HbF; adjusted IRR 0•40, 0•17-0•94). The incidence of admission to hospital was also higher in children with sickle cell disease than in children without sickle cell disease (210 per 1000 person-years of observation, 95% CI 174-253, vs 43 per 1000 person-years of observation, 42-45; adjusted IRR 4•80, 95% CI 3•84-6•15). The most common reason for admission to hospital among those with sickle cell disease was severe anaemia (incidence 48 per 1000 person-years of observation, 95% CI 32-71). Admission to hospital was lower in those with a recruitment HbF level above the median (IRR 0•43, 95% CI 0•24-0•78; p=0•005) and those who were homozygous for α-thalassaemia (0•07, 0•01-0•83; p=0•035). Interpretation Although morbidity and mortality were high in young children with sickle cell disease in this Kenyan cohort, both were reduced by early diagnosis and supportive care. The emphasis must now move towards early detection and prevention of long-term complications of sickle cell disease. Funding Wellcome Trust.

Association of sickle cell disease with nutritional status among under-five children and mediating role of hemoglobin level: secondary analysis of data from 2018 Nigeria Demographic and Health Survey

“…The mean Hb level of sickle children in our study (8.04 gm/dL, SD 1.65) was similar to that found in a multi-country (Mali, Senegal, Cameroon, Gabon, and the Ivory Coast) analysis [38], and in studies from Ghana [35] and Brazil [23]; but higher than that of Kenyan cohorts [36,39]. We captured a signi cant mediating role of Hb in SCD-nutritional status association.…”

“…This is appreciably lower than mean HAZ from children with SCD in Ilesa, Nigeria (− 0.52, SD 1.33) [18]; Enugu, Nigeria (− 0.50, SD 1.57) [34]; Ghana (− 0.86, SD 1.40) [35]; and Kenya (-1•10, SD 1•00) [36]. However, in the Kenyan SCD cohort (n = 128) with median age of 21.1 months, mean HAZ and WAZ did not signi cantly differ from those of non-sickle cell children [36]. No signi cant difference in mean HAZ was reported also in the study from Enugu, Nigeria [34] [37].…”

Anaemia among Kenyan children: a call for improved monitoring and intervention in school-aged children

“…A consequence of improved child survival of homozygotes (SS genotype) also means that these children will reach school age but remain in stable, anaemic states. 11 SAC should not be neglected as targets for interventions aimed at reducing the anaemia burden. They remain at risk and can be targeted with specific interventions aimed at reducing parasitic infections, as well as supportive iron supplementation and the practical combination of interventions within the school environment.…”

Poverty and severity of childhood sickle cell disease

“…8,11 Although SCD patients with alpha thalassaemia have a decreased admission rate, they have no survival advantage. 12 Several studies have shown the direct protective effects among SCD patients of HbF for painful episodes, leg ulcer, splenic sequestration and function, and retinopathy. 3,13,14 Genetic variations at three principal loci, BCL11A, HBS1L-MYB and HBB, on chromosomes 2, 6 and 11 respectively, and the various b s haplotypes, account for variable expression of HbF among different SCD populations through which the SCD phenotype is modified.…”

“…34 To further corroborate their findings, severe anaemia was the most common reason for admission among a cohort of Kenyan children with SCD who were followed longitudinally for five years. 12 Furthermore, severe anaemia was associated with increased rates of pain crisis, cognitive impairment, and infections among children with SCD in the USA. 35 Also, their findings indicate that, rather than relying solely on medical procedures, policies geared towards improvement in the socioeconomic status of people living in developing countries may mitigate some SCD complications.…”