Hydroxyurea is associated with lower malaria incidence in children with sickle cell anemia in sub-Saharan Africa
| Autor: | Peter Olupot-Olupot, George Tomlinson, Thomas N. Williams, Léon Tshilolo, Brígida Santos, Luke R. Smart, Kathryn McElhinney, Thad A. Howard, Banu Aygun, Susan E. Stuber, Adam Lane, Teresa S. Latham, Russell E. Ware |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Blood. |
| ISSN: | 1528-0020 0196-6731 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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