Results from the REACH clinical trial demonstrate that hydroxyurea treatment is associated with a lower incidence of malaria in children with sickle cell disease (SCD) in sub-Saharan Africa, according to a study published in Blood. 

The REACH clinical trial is a phase 1/2 prospective multicenter study of the use of hydroxyurea at a maximum tolerated dose for children with SCD living in sub-Saharan Africa. Children from 4 clinical sites received hydroxyurea at a fixed dose of 15 to 20 mg/kg per day for 6 months, followed by dose escalation to the maximum tolerated dose. Six hundred six children fully participated in the study. 

“The primary results of REACH documented both the safety and feasibility of hydroxyurea treatment in this patient population, as well as expected benefits for both laboratory and clinical complications of SCD,” the authors wrote. 

Nevertheless, around 50% of the participants of the study contracted malaria, which was an intriguing and unexpected observation. The investigators performed a longitudinal analysis of all malaria events reported in the REACH study to identify any links between hydroxyurea treatment and reduced malaria infection rates. 

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To carry out their study, the research team conducted scheduled visits every month during the first year of treatment, which was reduced to once every 2 months and finally once every 3 months. During each visit, the research team inquired about their medical history and performed a physical examination; the spleen was also palpated. 

During history-taking, the research team asked about signs and symptoms of malaria, including infectious treatment at other healthcare facilities. Any attachment to malaria was deemed “clinical malaria infection” and patients were treated accordingly. Aside from watchful waiting for the signs and symptoms of the disease, malaria rapid diagnostic tests could be performed at REACH clinical sites. 

The authors of the study reported 717 malaria infections in the REACH cohort between September 2014 and January 2022 over 3387 patient-years of hydroxyurea treatment.  

“In summary, hydroxyurea at maximum tolerated dose for children with SCD is associated with a significantly lower incidence of malaria infections; this association is greater at higher hydroxyurea doses and is sustained over time,” the authors wrote. “Since malaria is documented to cause frequent and severe anemia in children with SCD, understanding the clinically significant association between hydroxyurea and lower malaria incidence represents an important research goal while expanding hydroxyurea treatment across Africa.” 

Reference

Olupot-Olupot P, Tomlinson G, Williams TN, et al. Hydroxyurea treatment is associated with lower malaria incidence in children with sickle cell anemia in sub-Saharan Africa. Blood. Published online November 16, 2022. doi:https://doi.org/10.1182/blood.2022017051