Hydroxyurea is an effective treatment for sickle cell anemia, but few studies have been conducted in sub-Saharan Africa, where the burden is greatest. Coexisting conditions such as malnutrition and malaria may affect the feasibility, safety, and benefits of hydroxyurea in low-resource settings. We enrolled children 1 to 10 years of age with sickle cell anemia in four sub-Saharan countries. Children received hydroxyurea at a dose of 15 to 20 mg per kilogram of body weight per day for 6 months, followed by dose escalation. The end points assessed feasibility (enrollment, retention, and adherence), safety (dose levels, toxic effects, and malaria), and benefits (laboratory variables, sickle cell–related events, transfusions, and survival). A total of 635 children were fully enrolled; 606 children completed screening and began receiving hydroxyurea at a mean (±SD) dose of 17.5±1.8 mg per kilogram per day. The retention rate was 94.2% at 3 years of treatment. Hydroxyurea therapy led to significant increases in both the hemoglobin and fetal hemoglobin levels. Dose-limiting toxic events regarding laboratory variables occurred in 5.1% of the participants, which was below the protocol-specified threshold for safety. During the treatment phase, 20.6 dose-limiting toxic effects per 100 patient-years occurred, as compared with 20.7 events per 100 patient-years before treatment. As compared with the pretreatment period, the rates of clinical adverse events decreased with hydroxyurea use, including rates of vaso-occlusive pain (98.3 vs. 44.6 events per 100 patient-years; incidence rate ratio, 0.45; 95% confidence interval [CI], 0.37 to 0.56), nonmalaria infection (142.5 vs. 90.0 events per 100 patient-years; incidence rate ratio, 0.62; 95% CI, 0.53 to 0.72), malaria (46.9 vs. 22.9 events per 100 patient-years; incidence rate ratio, 0.49; 95% CI, 0.37 to 0.66), transfusion (43.3 vs. 14.2 events per 100 patient-years; incidence rate ratio, 0.33; 95% CI, 0.23 to 0.47), and death (3.6 vs. 1.1 deaths per 100 patient-years; incidence rate ratio, 0.30; 95% CI, 0.10 to 0.88). Hydroxyurea treatment was feasible and safe in children with sickle cell anemia living in sub-Saharan Africa. Hydroxyurea use reduced the incidence of vaso-occlusive events, infections, malaria, transfusions, and death, which supports the need for wider access to treatment. (Funded by the National Heart, Lung, and Blood Institute and others; REACH ClinicalTrials.gov number, NCT01966731.)

Background: Despite the high prevalence of sickle cell disease in Africa, a neonatal screening programme is available in only a few countries in the sub-Saharan region. Aim: To describe our experience of a pioneer study on 31 304 newborns screened systematically in the Democratic Republic of the Congo. Methods: The prevalence of haemoglobinopathies was determined by a thin-layer isoelectric focusing method on dry filter-paper samples. Results: Of the 31 204 newborns screened by isoelectric focusing, 5276 (16.9%) displayed sickle cell trait and 428 (1.4%) were homozygous for haemoglobin S. No statistical differences were observed in the different ethno-linguistic groups, but some tribes displayed a higher prevalence of the βS gene, attributable to a higher prevalence of malaria, and a greater frequency of haemoglobin S homozygotes, in part attributable to an endogamic marriage system. Conclusion: The neonatal screening programme has now been introduced in the Democratic Republic of the Congo, but the main challenges are to track all the new cases for a confirmatory test and to initiate early management.

Rationale: Despite the high burden of respiratory disease, no spirometry reference values for African children are available. Objectives: Investigate whether the Global Lung Initiative (GLI-2012) reference values for spirometry are appropriate for children in sub-Saharan Africa and assess the impact of malnutrition on lung function. Methods: Anthropometry and spirometry were obtained in children aged 6 to 12 years from urban and semiurban schools in three African countries. Spirometry z-scores were derived using the GLI-2012 prediction equations for African Americans. Thinness (body mass index z-score < −2) was a surrogate for malnutrition. Spirometry outcomes were compared with those of African American children from the third National Health and Nutrition Survey. Measurements and Main Results: Spirometry data were analyzed from 1,082 schoolchildren (51% boys) aged 6.0 to 12.8 years in Angola (n = 306), Democratic Republic of the Congo (n = 377), and Madagascar (n = 399). GLI-2012 provided a good fit with mean (SD) z-scores of −0.11 (0.83) for FEV₁, −0.08 (0.86) for FVC, and −0.07 (0.83) for FEV₁/FVC. Because of low scatter, the fifth centile corresponded to −1.3 z-scores in boys and −1.5 z-scores in girls. Malnourished African children had a normal FEV₁/FVC ratio but significant reductions of ∼0.5 z-scores (∼5%) in FEV₁ and FVC compared with African American peers from the third National Health and Nutrition Survey. Children in Angola had the lowest, and those in Madagascar had the highest, zFEV₁ and zFVC. Conclusions: The results of this study support the use of GLI-2012 reference values for schoolchildren in sub-Saharan Africa. Malnutrition affects body growth, leading to a proportionately smaller FEV₁ and FVC without respiratory impairment, as shown by the normal FEV₁/FVC ratio.

Background: Sickle cell anemia (SCA) is an inherited hematological disorder that causes a large but neglected global health burden, particularly in Africa. Hydroxyurea represents the only available disease‐modifying therapy for SCA, and has proven safety and efficacy in high‐resource countries. In sub‐Saharan Africa, there is minimal use of hydroxyurea, due to lack of data, absence of evidence‐based guidelines, and inexperience among healthcare providers.Procedure: A partnership was established between investigators in North America and sub‐Saharan Africa, to develop a prospective multicenter research protocol designed to provide data on the safety, feasibility, and benefits of hydroxyurea for children with SCA.Results: The Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) trial is a prospective, phase I/II open‐label dose escalation study of hydroxyurea that will treat a total of 600 children age 1–10 years with SCA: 150 at each of four different clinical sites within sub‐Saharan Africa (Angola, Democratic Republic of Congo, Kenya, and Uganda). The primary study endpoint will be severe hematological toxicities that occur during the fixed‐dose treatment phase. REACH has an adaptive statistical design that allows for careful assessment of toxicities to accurately identify a safe hydroxyurea dose.Conclusions: REACH will provide data that address critical gaps in knowledge for the treatment of SCA in sub‐Saharan Africa. By developing local expertise with the use of hydroxyurea and helping to establish treatment guidelines, the REACH trial results will have the potential to transform care for children with SCA in Africa. Pediatr Blood Cancer

The world is currently facing a novel COVID-19 pandemic caused by SARS-CoV-2 that, as of July 12, 2020, has caused a reported 12,322,395 cases and 556,335 deaths. To date, only two treatments, remdesivir and dexamethasone, have demonstrated clinical efficacy through randomized controlled trials (RCTs) in seriously ill patients. The search for new or repurposed drugs for treatment of COVID-19 continues. We have witnessed anecdotal use of herbal medicines, including Artemisia spp. extracts, in low-income countries, and exaggerated claims of their efficacies that are not evidence based, with subsequent political controversy. These events highlight the urgent need for further research on herbal compounds to evaluate efficacy through RCTs, and, when efficacious compounds are identified, to establish the active ingredients, develop formulations and dosing, and define pharmacokinetics, toxicology, and safety to enable drug development. Derivatives from the herb Artemisia annua have been used as traditional medicine over centuries for the treatment of fevers, malaria, and respiratory tract infections. We review the bioactive compounds, pharmacological and immunological effects, and traditional uses for Artemisia spp. derivatives, and discuss the challenges and controversies surrounding current efforts and the scientific road map to advance them to prevent or treat COVID-19.