ArticleBlood2023
Hydroxyurea treatment is associated with lower malaria incidence in children with sickle cell anemia in sub-Saharan Africa.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01966731 (REALIZING EFFECTIVENESS ACROSS CONTINENTS WITH HYDROXYUREA), which is not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Realizing effectiveness across continents with hydroxyurea (reach): a phase i/ii pilot study of hydroxyurea for children with sickle cell anemia
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Weekly dihydroartemisinin-piperaquine versus monthly sulfadoxine-pyrimethamine for malaria chemoprevention in children with sickle cell anaemia in Uganda and Malawi (CHEMCHA): a randomised, double-blind, placebo-controlled trial.The Lancet. Infectious diseases · 2025Trial
- Hydroxyurea for Children and Adults with Hemoglobin SC Disease.NEJM evidence · 2025Trial
- Reducing transfusion utilization for children with sickle cell anemia in sub-Saharan Africa with hydroxyurea: Analysis from the phase I/II REACH trial.American journal of hematology · 2024Trial
- Persistent Splenomegaly Is Associated with Morbidity in Tanzanian Children with Sickle Cell Anemia: Secondary Analysis of the SPHERE Trial.Acta haematologica · 2026Article
- Haematological Profile of Patients with Sickle Cell Disease in the Acholi Sub-Region, Uganda.Journal of blood medicine · 2026Article
- Evaluating the long-term benefits of hydroxyurea in pediatric sickle cell anemia.Blood advances · 2025Article
- Preventive interventions and diagnostic testing compliance in the management of tropical infections among patients with sickle cell disease in Tanzania.Parasites, hosts and diseases · 2025Observational
- Modelling child anaemia and co-existing infections using log-linear models.Malaria journal · 2025Review
- Sickle cell anaemia therapy in 2025.British journal of haematology · 2025Review
- Newborn screening for sickle cell disease in Caluquembe, southwestern Angola, 2024-2025.PloS one · 2025Article
- Article
- Simultaneous adjunctive treatment of malaria and its coevolved genetic disorder sickle cell anemia.Blood advances · 2023Article
- Further evidence supporting the global use of hydroxyurea.Blood advances · 2023Article
- F-erythrocytes promote Plasmodium falciparum proliferation in sickle cell disease.American journal of hematology · 2023Article
- Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria.Frontiers in medicine · 2023Article
- Promoting access of hydroxyurea to sickle cell disease individuals: Time to make it an essential medicine.F1000Research · 2022Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 6 countries.
Funding
Abstract
Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) provides hydroxyurea at maximum tolerated dose (MTD) for children with sickle cell anemia (SCA) in sub-Saharan Africa. Beyond reducing SCA-related clinical events, documented treatment benefits include ∼50% reduction in malaria incidence. To identify associations and propose mechanisms by which hydroxyurea could be associated with lower malaria rates, infections were recorded across all clinical sites (Angola, Democratic Republic of Congo, Kenya, and Uganda). Hazard ratios (HR) with 95% confidence intervals (CIs) for baseline demographics, and time-varying laboratory and clinical parameters were estimated in a modified Cox gap-time model for repeated events. Over 3387 patient-years of hydroxyurea treatment, 717 clinical malaria episodes occurred in 336 of 606 study participants; over half were confirmed by blood smear and/or rapid diagnostic testing with 97.8% Plasmodium falciparum. In univariate analysis limited to 4 confirmed infections per child, malaria risk was significantly associated with absolute neutrophil count (ANC), splenomegaly, hemoglobin, and achieving MTD; age, malaria season, MTD dose, fetal hemoglobin, α-thalassemia, and glucose-6-phosphate dehydrogenase deficiency had no effect. In multivariable regression of confirmed infections, ANC was significant (HR, 1.37 per doubled value; 95% CI, 1.10-1.70; P = .0052), and ANC values <3.0 × 109/L were associated with lower malaria incidence. Compared with nonpalpable spleen, 1- to 4-cm splenomegaly also was associated with higher malaria risk (HR, 2.01; 95% CI, 1.41-2.85; P = .0001). Hydroxyurea at MTD is associated with lower malaria incidence in SCA through incompletely defined mechanisms, but treatment-associated mild myelosuppression with ANC <3.0 × 109/L is salutary. Splenomegaly is an unexplained risk factor for malaria infections among children with SCA in Africa.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.