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Competing Interests: We declare no competing interests. PM, ISF, and MJ contributed equally.

This proposed scientific statement is focused on providing new insights regarding challenges and opportunities for cardiovascular health (CVH) promotion in Africa. The statement includes an overview of the current state of CVH in Africa, with a particular interest in the cardiometabolic risk factors and their evaluation through metrics. The statement also explains the main principles of primordial prevention, its relevance in reducing noncommunicable disease and the different strategies that have been effective worldwide. Also, the statement addresses challenges for implementing primordial prevention strategies in Africa, such as socioeconomic, cultural, lifestyle, and environmental factors, and highlights the importance of adapting strategies to the context. Finally, the statement recommends fundamental approaches for promoting CVH with the help of various partnerships and the involvement of communities., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Sickle cell disease (SCD) is a prevalent inherited blood disorder. Globally, approximately 515 000 babies are born with SCD annually, with 75% of these births occurring in Africa. Integrating newborn screening (NBS) for SCD into primary healthcare structures, such as immunisation programmes, holds significant promise, with dried blood spots (DBS)-point-of-care technologies (POCT) like HaemoTypeSC offering cost-effective screening solutions. However, scaling up DBS-POCT for NBS of SCD in Africa remains challenging., Objective: This study aims to explore individual, organisational and external factors that may influence the reliability, feasibility, acceptability, adoption and sustainability of using DBS-POCT with HaemoTypeSC for NBS of SCD at primary healthcare centres in African countries., Method: This qualitative study will be conducted in seven African countries that are part of the SickleInAfrica consortium sites. The study design is informed by the Consolidated Framework for Implementation Research (CFIR) and the Implementation Outcome Model. Participants will be mothers whose babies have been diagnosed with SCD, healthcare professionals and policy-makers. In-depth interviews and focus group discussions will be used for data collection. Data analysis will be through thematic analysis., Ethics and Dissemination: Research ethics approvals have been obtained from the seven countries. Written informed consent will be obtained from all participants. The study results will be disseminated in peer-reviewed scientific journals, scientific conferences, reports to national ministries of public health and webinars., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: IO receives a research grant from Novartis, is on a data safety monitoring board for Pfizer, and receives honoraria from Novo Nordisk and Vertex. LT receives consulting fees from Novo Nordisk and honoraria from Pfizer and Novo Nordisk. BI is an employee of Novo Nordisk; receives consulting fees from Novartis, Pfizer, and Vertex; and receives honoraria from Pfizer. All other authors declare no competing interests.

Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests.

Glomerular hyperfiltration and albuminuria are frequent kidney abnormalities in children with sickle cell anaemia (SCA). However, little is known about their persistence in African SCA children. This prospective study included 600 steady-state SCA children aged 2-18 years from the Democratic Republic of Congo. Participants were genotyped for apolipoprotein L1 (APOL1) risk variants (RVs) and haem oxygenase-1 (HMOX1) GT-dinucleotide repeats. Kidney abnormalities were defined as albuminuria, hyperfiltration or decreased estimated creatinine-based glomerular filtration rate (eGFRcr). At baseline, 247/600 (41.2%) participants presented with kidney abnormalities: 82/592 (13.8%) with albuminuria, 184/587 (31.3%) with hyperfiltration and 15/587 (2.6%) with decreased eGFRcr. After a median follow-up of 5 months, repeated testing was performed in 180/247 (72.9%) available participants. Persistent hyperfiltration and persistent albuminuria (PA) were present in 29.2% (38/130) and 39.7% (23/58) respectively. eGFR normalized in all participants with a baseline decreased eGFRcr. Haemoglobinuria (p = 0.017) and male gender (p = 0.047) were significantly associated with PA and persistent hyperfiltration respectively. APOL1 RVs (G1G1/G2G2/G1G2) were borderline associated with PA (p = 0.075), while HMOX1 long repeat was not associated with any persistent kidney abnormality. This study reveals that a single screening can overestimate the rate of kidney abnormalities in children with SCA and could lead to overtreatment., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to increased red blood cell (RBC) turnover, SCA is specifically characterized by susceptibility to infections. In this study, histological lesions in the spleens of pediatric patients with SCA were analyzed, in close correlation with past clinical history and comparatively to HS, healthy and transfused β-thalassemia patients (TDT). An evaluation of red pulp elementary lesions (red pulp fibrosis, iron deposition, number of Gandy-Gamna, and RBC trapping) combined into a severity score was established, as well as B-cell follicles analysis. Quantification on digitalized slides of iron deposition, RBC trapping, and red pulp fibrosis was additionally performed. Spleens from 22 children with SCA, eight with HS, eight with TDT, and three healthy controls (HC) were analyzed. Median age at splenectomy was not different between SCA and HS patients, 6.05 years (range: 4.5-16.0) versus 4.75 (range: 2.2-9.5). Marked heterogeneity was found in SCA spleens in contrast to other conditions. Contrary to previous reports, B-cell follicles were generally preserved in SCA. While RBC trapping was significantly increased in both SCA and HS (compared to TDT and HC), quantitative fibrosis and overall red pulp severity score were significantly increased in SCA spleens compared to other conditions. Moreover, there was an inverse correlation between quantitative fibrosis and number of B-cell follicles, linking these two compartments as well as spleen fibrosis to infectious susceptibility in SCA, potentially through impaired red pulp macrophage scavenging and B-cell subpopulations defects., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

The degree of anaemia in sickle cell disease (SCD) is a well-known contributor to morbidity and mortality. We aimed to explore the factors affecting haemoglobin (Hb) level in African SCD patients, considering haemolysis biomarkers (LDH and bilirubin level, and reticulocyte count), leucocyte and platelet counts and socio-demographic characteristics (gender, age group, country of residence and BMI). The research was part of the CADRE multinational cohort and involved 3699 SCD patients living in Mali, Senegal, Ivory Coast, Democratic Republic of Congo, Gabon and Cameroon: 2936 SS/Sβ0, 587 SC and 176 Sβ + patients with median Hb level of 8, 11.3 and 11.2 g/dL respectively (p < 0.001). In multivariate analysis conducted in 1394 SS/Sβ0 patients, living in Cameroon, female gender, lower BMI, higher haemolysis markers (especially LDH) and higher leucocyte and platelet counts were independently associated with lower Hb level (all p < 0.05). In 497 SC and 156 Sβ + patients, female gender (p < 0.001), lower BMI (p < 0.05) and higher platelet counts (p < 0.001) were independently associated with lower Hb level. Anaemia in African SCD patients is not only associated with haemolysis but also with the country of residence, lower BMI and leucocyte or platelet counts which might reflect inflammation related to infectious burden in the region., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years., Methods: In this open-label, non-randomised, phase 1/2 trial, participants were recruited from four clinical sites in Kilifi, Kenya; Mbale, Uganda; Luanda, Angola; and Kinshasa, Democratic Republic of Congo. Eligible children were 1-10 years old with documented haemoglobin SS or haemoglobin Sβ zero thalassaemia, weighing at least 10 kg. Participants received fixed-dose hydroxyurea of 17.5 (±2.5) mg/kg per day for 6 months (fixed-dose phase), followed by 6 months of dose escalation (2·5-5·0 mg/kg increments every 8 weeks) as tolerated, up to 20-35 mg/kg per day (maximum tolerated dose; MTD), defined as mild myelosuppression. After the MTD was reached, hydroxyurea dosing was optimised for each participant on the basis of changes in bodyweight and laboratory values over time (MTD with optimisation phase). After completion of the first 12 months, children with an acceptable toxicity profile and favourable responses were given the opportunity to continue hydroxyurea until the age of 18 years. The safety and feasibility results after 3 years has been reported previously. Here, haematological responses, clinical events, and toxicity rates were compared across the dosing phases (fixed-dose hydroxyurea vs MTD with optimisation phase) as protocol-specified outcomes. REACH is registered on ClinicalTrials.gov (NCT01966731) and is ongoing., Findings: We enrolled 635 children between July 4, 2014, and Nov 11, 2016. 606 children were given hydroxyurea and 522 (86%; 266 [51%] boys and 256 [49%] girls) received treatment for a median of 93 months (IQR 84-97) with 4340 patient-years of treatment. The current (Oct 5, 2023) mean dose is 28·2 (SD 5·2) mg/kg per day with an increased mean haemoglobin concentration (7·3 [SD 1·1] g/dL at baseline to 8·5 [1·5] g/dL) and mean fetal haemoglobin level (10·9% [SD 6·8] to 23·3% [9·5]) and decreased absolute neutrophil count (6·8 [3·0] × 10 9 cells per L to 3·6 [2·2] × 10 9 cells per L). Incidence rate ratios (IRR) comparing MTD with fixed-dose hydroxyurea indicate decreased vaso-occlusive episodes (0·60; 95% CI 0·52-0·70; p<0·0001), acute chest syndrome events (0·21; 0·13-0·33; p<0·0001), recurrent stroke events (0·27; 0·07-1·06; p=0·061), malaria infections (0·58; 0·46-0·72; p<0·0001), non-malarial infections (0·52; 0·46-0·58; p<0·0001), serious adverse events (0·42; 0·27-0·67; p<0·0001), and death (0·70; 0·25-1·97; p=0·50). Dose-limiting toxicity rates were similar between the fixed-dose (24·1 per 100 patient-years) and MTD phases (23·2 per 100 patient-years; 0·97; 0·70-1·35; p=0·86). Grade 3 and 4 adverse events were infrequent (18·5 per 100 patient-years) and included malaria infection, non-malarial infections, vaso-occlusive pain, and acute chest syndrome. Serious adverse events were uncommon (3·6 per 100 patient-years) and included malaria infections, parvovirus-associated anaemia, sepsis, and stroke, with no treatment-related deaths., Interpretation: Hydroxyurea dose escalation to MTD with dose optimisation significantly improved clinical responses and treatment outcomes, without increasing toxicities in children with sickle cell anaemia in sub-Saharan Africa., Funding: US National Heart, Lung, and Blood Institute and Cincinnati Children's Research Foundation., Competing Interests: Declaration of interests REW receives hydroxyurea donations from Bristol Myers Squibb and Addmedica; research donations from Hemex Health; and serves as Medical Advisor to Nova Laboratories. BA served on the Medical Advisory Board for Global Blood Therapeutics, Pfizer, Agios, and Bluebird Bio and receives research support from Pfizer and Bluebird Bio. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: To assess the safety and efficacy of partial splenic embolization (PSE) to reduce the need of transfusions and improve hematologic parameters in patients with hypersplenism and sickle cell disease (SCD)., Material and Methods: This prospective study includes 35 homozygous hemoglobin S patients with SCD and hypersplenism who underwent PSE from 2015 until 2021 in Kinshasa. Patients were evaluated, before and after PSE (1, 3 and 6 months), using clinical, laboratory and ultrasonographic methods. PSE was performed with the administration of gelatin sponge particles embolizing 60-70% of the splenic parenchyma., Results: The mean age was 10 (± 4) years and (21/35, 60%) were male. After PSE Leucocytes decreased at 3 months (16 692.94 vs 13 582.86, p = 0.02) and at six months Erythrocytes increased 2 004 000 vs. 2 804 142 (p < 0.001), Platelets increased (168 147 vs. 308 445, p < 0.001) and Hemoglobin increased (5.05 g/dL vs. 6.31 g/dL, p < 0.001) There was a significant dicrease in the need of transfusions from 6 (2-20) before PSE to 0.06 (0-1) after PSE (p < 0.001). The most frequent complication was splenic rupture (4/35, 11.4%), seen only and in all patients with hypoechogenic nodules at baseline., Conclusion: PSE is a safe procedure in patients with SCD and hypersplenism, that do not have hypoechogenic nodules in the spleen. PSE improves the hematological parameters and reduces the frequency of blood transfusions., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion utilization in children with SCA before and during hydroxyurea treatment. REACH (Realizing Effectiveness Across Continents with Hydroxyurea, NCT01966731) is a longitudinal Phase I/II trial of hydroxyurea in children with SCA from Angola, Democratic Republic of Congo, Kenya, and Uganda. After enrollment, children had a two-month pre-treatment screening period followed by 6 months of fixed-dose hydroxyurea (15-20 mg/kg/day), 18 months of dose escalation, and then stable dosing at maximum tolerated dose (MTD). Characteristics associated with transfusions were analyzed with univariate and multivariable models. Transfusion incidence rate ratios (IRR) across treatment periods were calculated. Among 635 enrolled children with 4124 person-years of observation, 258 participants (40.4%) received 545 transfusions. The transfusion rate per 100 person-years was 43.2 before hydroxyurea, 21.7 on fixed-dose, 14.5 during dose escalation, and 10.8 on MTD. During MTD, transfusion incidence was reduced by 75% compared to pre-treatment (IRR 0.25, 95% confidence interval [CI] 0.18-0.35, p < .0001), and by 50% compared to fixed dose (IRR 0.50, 95% CI 0.39-0.63, p < .0001). Hydroxyurea at MTD decreases transfusion utilization in African children with SCA. If widely implemented, universal testing and hydroxyurea treatment at MTD could potentially prevent 21% of all pediatric transfusions administered in sub-Saharan Africa. Increasing hydroxyurea access for SCA should decrease the transfusion burden and increase the overall blood supply., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Competing Interests: Declaration of interests MRA has received grants or contracts with Novartis, Pfizer, Global Blood Therapeutics, and Forma Therapeutics; and participated in Data Safety Monitoring Boards or Advisory Boards for Vertex, GBT, Forma, Novartis, and Aggios. BA has participated in Data Safety Monitoring Boards or Advisory Boards for Agios, Aruvant, bluebird bio, CRISPR, Accordant (CVS), Emmaus, Forma Therapeutics, Fulcrum, Global Blood Therapeutics, Hemanext, Novartis, NovoNordisk, and Vertex. RF has received grants from the European Horizon 2020 and Horizon Europe schemes and a contract with Global Blood Therapeutics; received consulting fees from Novartis and Global Blood Therapeutics; received honoraria for a Physicians’ Education Resource and from Global Blood Therapeutics; participated in Data Safety Monitoring Boards or Advisory Boards for Vertex, Addmedica and Novonordisk; and a leadership or fiduciary role as a member of the Steering Committee and Coordinator of the Red Cell Disorder Working Group of the Italian Association of Pediatric Hematology Oncology. NC has received a research grant for Novartis Precision Medicine. MdM has received honoraria for presentations by Addmedica and Novartis and support from Addmedica for attending a conference; and participated in a Data Safety Monitoring Board or Advisory Board for Addmedica, Vertex, and Novartis. JE has received grants from the European Horizon 2020 scheme and participated in the Data Safety Monitoring Board or Advisory Board of the Fondation Pierre Fabre. EE has received consulting fees from bluebird bio. ALG has an honorary advisory role on the Australian Sickle Cell Advisory Board. IMI has received a grant from the American Society of Hematology; consulting fees from Agios Pharmaceuticals; and honoraria from the American Society of Hematology. LCJ received royalties for a book chapter. AAK has received support from the Health resources and Services Administration. MLP has received consulting fees from the American College of Medical Genetics and Genomics; and participated in a Data Safety Monitoring Board or Advisory Board for the American College of Medical Genetics and Genomics and the American Academy of Pediatrics. ON has received travel support from the American Society of Hematology to attend a conference. DCR has received consulting fees from Vertex, Forma, Agios, and Vifor; received honoraria from Vertex; and participated in a Data Safety Monitoring Board or Advisory Board for TauRx and Mitsubishi. AS has received a scholar award from the American Society of Hematology, an advancing cures research award from the Doris Duke Charitable Foundation, and a Working group award from the Center for ELSI Resources and Analysis; consulting fees from Spotlight Therapeutics, Medexus, Vertex, Editas Medicine, and Sangamo Therapeutics; has received honoraria from Vindico Medical Education; and has a leadership or fiduciary role in the American Society for Transplantation and Cellular Therapy Content Committee, the Scientific Executive Committee, Sickle Cell Transplant Advocacy & Research Alliance, and the Pediatric Transplantation and Cellular Therapy Consortium Supportive Care Committee; and has financial interests with CRISPR Therapeutics, Vertex Pharmaceuticals, Novartis Pharmaceuticals, Magenta Therapeutics, and Beam Therapeutics. AAT has received consulting fees from GlaxoSmithKline and Global Blood Therapeutics; and honoraria from Novartis. REW has received consulting fees from Nova Laboratories; participated in a Data Safety Monitoring Board for Novartis and Editas; and received donations and support for clinical trials from Bristol Myers Squib, Addmedica, and Hemex Health. DJW has received a grant or contract from the US National Institutes for Health; received payment for expert testimony from Fredslough Law Firm; participated in a Data Safety Monitoring Board or Advisory board for Northwestern University; and is the founder and chairman of eNursing.

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., (© 2023 by The American Society of Hematology.)

Objective: To investigate the availability of and access to opioid analgesics at hospital level in the Democratic Republic of Congo., Methods: Exploratory mixed-method study combining a descriptive survey of the availability of opioid analgesics at hospital pharmacies with a qualitative survey that explored the experiences and perceptions of healthcare workers, managers, patients and caregivers, by means of a short questionnaire and of semi-structured interviews. The study was conducted in a convenience sample of 12 hospitals, located in five different provinces, in 2021., Results: The quality and completeness of stock data for opioid analgesics were generally poor. Stock-outs were frequent. Only five hospital pharmacies had records on prescriptions of opioids in 2020. In-patients and caregivers indicated they generally must purchase opioids out-of-pocket, sometimes far from the place of residence. Doctors and nurses confirmed that prescribed opioids are often unavailable at the hospital pharmacy. Furthermore, they suggested an important need of training in pain management with opioids, and of effective regulation to ensure opioid availability. Pharmacists and managers recognised important weaknesses in the processes of needs quantification, stock management, planning and supply., Conclusions: Our exploratory study suggests the need of a complex set of coordinated actions to be undertaken by all relevant actors in DRC to correct the poor practices in opioids' management and to improve opioids' availability, affordability and adequate use. This will require a change of mindset to overcome the neglect of the health needs of persons with acute and chronic pain., (© 2022 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)