High disease burden, morbidity and mortality among children with sickle cell anaemia in Uganda

Purpose: Few studies have described in depth the burden of sickle cell anemia (SCA) related morbidity and mortality in children in Sub Saharan Africa, the continent with the highest burden of SCA. The goal of this study was to describe the morbidity and mortality in children with SCA Materials and methods: We enrolled 248 children aged 1-5 years with SCA who participated in the Zinc for Infection Prevention in Sickle cell anaemia (ZIPS) clinical trial and followed them for 1-year (Clinicaltrials.gov, NCT03528434) at Jinja Regional Referral Hospital, Uganda. Children were evaluated for all infections, SCA related complications and deaths during the study period by taking standard history and diagnostic work-up. All children received standard maintenance care for SCA, which included daily folic acid, penicillin prophylaxis, monthly sulphadoxine-pyrimethamine for malaria prophylaxis, and an insecticide treated mosquito net for malaria prevention. We initiated hydroxyurea to children meeting Uganda Ministry of Health SCA hydroxyurea treatment criteria at the time of the study, which included: \u3e 5 pain crises, stroke, and baseline Hb\u3c6g/dL, and history of or new acute chest syndrome (ACS). Infections were defined as severe or invasive if they met strict clinical and laboratory criteria Results:Between 2018 and 2019, 248 children with SCA were enrolled with a mean (SD) age of 2.8 (1.1) years. The mean (SD) baseline white cell count, hemoglobin level and fetal hemoglobin % were 19.2 (8.4) X109/L, 8.2 (1.3) g/dL and 13.7 (8.0) %, respectively. A total of 117 (47.2%) children were initiated on hydroxyurea at some point in the study. There were 1513 sick visits over 12 months, giving an incidence of 6.4 sick visits per year. Of these, 467 visits required hospital admission. A total of 121 children had more than 1 sick visit requiring hospitalisation. The mean (SD) hospital stay was 3.0 (1.8) days. The incidence of any severe or invasive and clinical infections was 276 and 516 infections per 100-person year respectively. Sepsis, malaria, gastroenteritis, and pharyngitis/tonsillitis were the most common forms of severe or invasive infections, while upper respiratory tract infections were the most common clinically defined infections. Vaso-occlusive crises (VOC) and severe anaemia requiring blood transfusion were the most common SCA related complications, with incidences of 160 and 135.7 events per 100 child years. Two children had a stroke over the 12 months study follow up. A total of 9 children died, and the likely cause of death was pneumonia/lower respiratory tract infection with accompanying respiratory failure in five children, sepsis with accompanying heart failure in one child, severe malaria in one child, and an unspecified cause in two children. The incidence of infections and SCA related complications reduced significantly in children initiated on hydroxyurea (5.2 vs. 2.0 infections per child per year and 12.0 vs.1 complication before and after hydroxyurea therapy, P Conclusion: There is high burden of SCA related morbidity and mortality in young children with SCA in Uganda. There is need to implement wider use of disease modifying therapies and research to understand risk factors for the high morbidity and mortality