Introduction: Half of all blood transfusions in Africa are administered to children. The World Health Organization attributes this burden primarily to malaria-related anemia and secondarily to iron deficiency anemia from malnutrition or intestinal parasites. Few studies have comprehensively assessed the transfusion burden in Africa from sickle cell anemia (SCA), which limits the implementation of strategies to prevent transfusions in this population.

Methods: Full Assessment of Clinical Transfusion Support (FACTS, NCT07094646) was a prospective, cross-sectional study conducted in Jinja, Uganda to characterize the etiologies of anemia in pediatric transfusion recipients, specifically to determine the proportion who have SCA and/or malaria. Jinja is an area of moderate, perennial malaria transmission on the shores of Lake Victoria in Eastern Uganda. All children receiving a red blood cell or whole blood transfusion at the pediatric ward of the Jinja Regional Referral Hospital during two distinct 30-day periods in the rainy and dry seasons were eligible. After written informed consent, clinical and laboratory data were recorded, and dried blood spots (DBS) were prepared from both recipients and donor units. DBS were analyzed by PCR for the sickle mutation and Plasmodium falciparum DNA.

Results: DBS from 250 children (40% female) who received 297 blood transfusions were collected; this represents 88% of the total number of children for whom a transfusion was requested during the study periods and includes 135 children (143 transfusions) in the rainy season and 115 children (154 transfusions) in the dry season. The average age of the transfusion recipients was 5.9 ± 4.1 (range 0.1-20.9) years), and the mean pre-transfusion hemoglobin was 5.3 ± 1.5 (range 2.3-10.1) g/dL. Primary transfusion indications per the treating clinicians were severe anemia due to malaria (n= 98, 39%); other febrile, non-malarial infections (n=91, 36%); anemia, not otherwise specified (n=29, 12%); sickle-related clinical events (n=24, 10%); neonatal jaundice (n=4, 2%); and malnutrition (n=3, 1%). Subsequent DBS analysis documented that the majority of transfusion recipients (n=138, 55%) had HbSS genotype, 29 (21%) of whom were not previously known to have SCA. Additionally, 102 (41%) transfusion recipients had HbAA genotype and only 10 (4%) had HbAS. Compared to children with HbAA, those with HbSS were older (7.2 ± 4.3 versus 4.4 ± 3.2 years, p<0.0001) and had a greater previous transfusion history (≥6 prior transfusions reported by 45% of children with HbSS versus 10% with HbAA, p<0.0001). Malaria parasitemia was detected in 166 (56%) DBS, in whom the majority (n=142, 86%) had Plasmodium falciparum and the remainder had other Plasmodium infections. During the rainy season, 93 (65%) DBS were positive for malaria compared with 73 (47%) during the dry season (p=0.002). Of the transfusions administered to children with detectable malaria, 86 (52%) were to children who also had HbSS, 75 (45%) to those with HbAA, and 5 (3%) to those with HbAS. Of the transfusions administered to children without detectable malaria, 82 (63%) were to children with HbSS, 43 (33%) to those with HbAA, and 6 (5%) were to those with HbAS.

Conclusion: FACTS reveals the high burden of SCA among pediatric transfusion recipients that rivals the recognized burden of malaria-related transfusions in both rainy and dry months in Jinja, Uganda. Although SCA affects only 1% of births in the region, children with the condition account for approximately 55% of all pediatric blood transfusions. While malaria remains a well-recognized driver of transfusion demand, the substantial and underrecognized impact of SCA with and without malaria warrants further attention. Specific interventions for the SCA population including early diagnosis, malaria prevention, and expanded access to disease-modifying treatment with hydroxyurea are necessary to decrease transfusion exposure and demand among this population. Many transfusion recipients in this study had both malaria and SCA. Broad recognition of these findings may provide leverage to increase access to SCA care in Africa for the benefit of individuals, communities, and health systems where both the burden of disease and the scarcity of blood are profound.

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2025
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