Transcranial doppler velocity in iron-deficient Nigerian children with sickle cell anemia.

Oral iron supplementation in iron deficient children with sickle cell anemia and normal transcranial Doppler ultrasound (TCD) velocities does not reduce arterial flow in the middle cerebral artery.

Establishing Sickle Cell Disease Stroke Prevention Teams in Africa is Feasible: Program Evaluation Using the RE-AIM Framework.

We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to evaluate a Stroke Prevention Team's readiness to prevent strokes in children with sickle cell anemia living in northern Nigeria. The NIH sponsored Stroke Prevention Trial in Nigeria included a goal of a sustainable stroke prevention program. The program's 1-year reach for transcranial Doppler screening was 14.7% (4710/32,000) of which 6.0% (281/4710) had abnormal velocities (≥200 cm/s). All participants with abnormal transcranial Doppler velocities were started on hydroxyurea (effectiveness). The leaders of all 5 hospitals agreed to adopt the program. After 1 year, program-implementation and maintenance rates were 100%, demonstrating the program's feasibility and short-term sustainability.

Strengthening research capacity through an intensive training program for biomedical investigators from low- and middle-income countries: the Vanderbilt Institute for Research Development and Ethics (VIRDE).

BACKGROUND: Capacity strengthening initiatives aimed at increasing research knowledge and skills of investigators in low- and middle-income countries (LMICs) have been implemented over the last several decades. With increased capacity, local investigators will have greater leadership in defining research priorities and impact policy change to help improve health outcomes. Evaluations of models of capacity strengthening programs are often limited to short-term impact. Noting the limitations of traditional output-based evaluations, we utilized a broader framework to evaluate the long-term impact of the Vanderbilt Institute in Research Development and Ethics (VIRDE), a decade-old intensive grant development practicum specifically tailored for investigators from LMICs. METHODS: To assess the impact of VIRDE on the research careers of alumni over the past 10 years, we surveyed alumni on research engagement, grant productivity, career trajectory, and knowledge gained in grant writing. Descriptive statistics, including means and total counts, and paired sample t-tests were used to analyze the data. RESULTS: Forty-six of 58 alumni completed the survey. All respondents returned to their home countries and are currently engaged in research. Post-VIRDE grant writing knowledge ratings were significantly greater than pre-VIRDE. The number of respondents submitting grants post-VIRDE was 2.6 times higher than before the program. Eighty-three percent of respondents submitted a total of 147 grants post-VIRDE, of which 45.6% were awarded. Respondents acknowledged VIRDE's positive impact on career growth and leadership, with 88% advancing in career stage. CONCLUSIONS: Gains in grant writing knowledge and grant productivity suggest that VIRDE scholars built skills and confidence in grant writing during the program. A substantial proportion of respondents have advanced in their careers and continue to work in academia in their country of origin. Results show a sustained impact on the research careers of VIRDE alumni. The broader framework for research capacity strengthening resulted in an expansive assessment of the VIRDE program and alumni, illuminating successful program elements and implications that can inform similar capacity strengthening programs.

Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial.

Strokes in children with sickle cell anemia (SCA) are associated with significant morbidity and premature death. Primary stroke prevention in children with SCA involves screening for abnormal transcranial Doppler (TCD) velocity coupled with regular blood transfusion therapy for children with abnormal velocities, for at least one year. However, in Africa, where the majority of children with SCA live, regular blood transfusions are not feasible due to inadequate supply of safe blood, cost, and the reluctance of caregivers to accept transfusion therapy for their children. We describe the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria Trial [StrokePreventioninNigeria (SPRING) trial, NCT02560935], a three-center double-blinded randomized controlled Phase III clinical trial to 1) determine the efficacy of moderate fixed-dose (20 mg/kg/day) versus low fixed-dose (10 mg/kg/day) hydroxyurea therapy for primary stroke prevention; 2) determine the efficacy of moderate fixed-dose hydroxyurea for decreasing the incidence of all cause-hospitalization (pain, acute chest syndrome, infection, other) compared to low fixed-dose hydroxyurea. We will test the primary hypothesis that there will be a 66% relative risk reduction of strokes in children with SCA and abnormal TCD measurements, randomly allocated, for a minimum of three years to receive moderate fixed-dose versus low fixed-dose hydroxyurea (total n = 220). The results of this trial will advance the care of children with SCA in sub-Saharan Africa, while improving research capacity for future studies to prevent strokes in children with SCA.

Low educational level of head of household, as a proxy for poverty, is associated with severe anaemia among children with sickle cell disease living in a low-resource setting: evidence from the SPRING trial.

Severe anaemia, defined as haemoglobin level < 6·0 g/dl, is an independent risk factor for death in individuals with sickle cell disease living in resource-limited settings. We conducted a cross-sectional study of 941 children with sickle cell anaemia, who had been defined as phenotype HbSS or HbSß0 thalassaemia, aged five to 12 years, and were screened for enrollment into a large primary stroke prevention trial in Nigeria (SPRING; NCT02560935). The main aim of the study was to determine the prevalence and risk factors for severe anaemia. We found severe anaemia to be present in 3·9% (37 of 941) of the SPRING study participants. Severe anaemia was significantly associated with the lower educational level of the head of the household (P = 0·003), as a proxy for poverty, and a greater number of children per room in the household (P = 0·004). Body mass index was not associated with severe anaemia. The etiology of severe anaemia in children living with sickle cell anaemia in Nigeria is likely to be multifactorial with an interplay between an individual's disease severity and other socio-economic factors related to poverty.

Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial).

The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (≥200 cm/s) received moderate fixed-dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements <200 cm/s was followed prospectively. Approximately 88% (330 of 375) of families agreed to be screened, while 87% (29 of 33) of those with abnormal TCD measurements, enrolled in the trial. No participant elected to withdraw from the trial. The average mean corpuscular volume increased from 85.7 fl at baseline to 95.5 fl at 24 months (not all of the children who crossed over had a 24 month visit), demonstrating adherence to hydroxyurea. The comparison group consisted of initially 210 children, of which four developed abnormal TCD measurements, and were started on hydroxyurea. None of the monthly research visits were missed (n = total 603 visits). Two and 10 deaths occurred in the treatment and comparison groups, with mortality rates of 2.69 and 1.81 per 100 patient-years, respectively (P = .67). Our results provide strong evidence, for high family recruitment, retention, and adherence rates, to undertake the first randomized controlled trial with hydroxyurea therapy for primary stroke prevention in children with SCA living in Africa.

Barriers and facilitators to a task-shifted stroke prevention program for children with sickle cell anemia in a community hospital: a qualitative study.

BACKGROUND: Children with sickle cell anemia (SCA) are at high risk for stroke. Protocols for stroke prevention including blood transfusions, screening for abnormal non-imaging transcranial Doppler (TCD) measurements, and hydroxyurea therapy are difficult to implement in low-resource environments like Nigeria. This study aimed to examine the contextual factors around TCD screening in a community hospital in Nigeria using qualitative interviews and focus groups. METHODS: We conducted a descriptive qualitative study in a community hospital in Kaduna, Nigeria, using focus groups and interviews. Interview guides and analysis were informed by the Consolidated Framework for Implementation Research (CFIR) framework and the Theory of Planned Behavior. Transcripts were coded and analyzed using an iterative deductive (CFIR)/Inductive (transcribed quotes) qualitative methodology. RESULTS: We conducted two focus groups and five interviews with health care workers (nurses and doctors) and hospital administrators, respectively. Themes identified key elements of the inner setting (clinic characteristics, resource availability, implementation climate, and tension for change), characteristics of individuals (normative, control, and behavioral beliefs), and the implementation process (engage, implement, and adopt), as well as factors that were influenced by external context, caregiver needs, team function, and intervention characteristics. Task shifting, which is already being used, was viewed by providers and administrators as a necessary strategy to implement TCD screening in a clinic environment that is overstressed and under-resourced, a community stressed by poverty, and a nation with an underperforming health system. CONCLUSION: Task shifting provides a viable option to improve health care by making more efficient use of already available human resources while rapidly expanding the human resource pool and building capacity for TCD screening of children with SCD that is more sustainable. TRIAL REGISTRATION: NCT05434000.

Single-cell RNA seq analysis of erythroid cells reveals a specific sub-population of stress erythroid progenitors.

BACKGROUND: : Erythroid cells play important roles in hemostasis and disease. However, there is still significant knowledge gap regarding stress erythropoiesis. METHODS: : Two single-cell RNAseq datasets of erythroid cells on GEO with accession numbers GSE149938 and GSE184916 were obtained. The datasets from two sources, bone marrow and peripheral blood were analyzed using Seurat v4.1.1, and other tools in R. QC metrics were performed, data were normalized and scaled. Principal components that capture the variation of the data were determined. In clustering the cells, KNN graph was constructed and Louvain algorithm was applied to optimize the standard modularity function. Clusters were defined via differential expression of features. RESULTS: We identified 9 different cell types, with a particular cluster representing the stress erythroids. The clusters showed differentially expressed genes as observed from the gene signature plot. The stress erythroid cluster differentially expressed some genes including ALAS2, HEMGN, and GUK1. CONCLUSION: The erythroid population was found to be heterogeneous, with a distinct sub-cell type constituting the stress erythroids; this may have important implications for our knowledge of steady-state and stress erythropoiesis, and the markers found in this cluster may prove useful for future research into the dynamics of stress erythroid progenitor cell differentiation.

Barriers and Facilitators to a Task-Shifted Stroke Prevention Program for Children with Sickle Cell Anemia in a Community Hospital: A Qualitative Study.

Background: Children with sickle cell anemia (SCA) are at high risk for stroke. Protocols for stroke prevention including blood transfusions, screening for abnormal non-imaging transcranial Doppler (TCD) measurements, and hydroxyurea therapy are difficult to implement in low-resource environments like Nigeria. This study aimed to examine the contextual factors around TCD screening in a community hospital in Nigeria using qualitative interviews and focus groups. Methods: We conducted focus groups with health care providers and interviews with administrative leadership of the community hospital. Interview guides and analysis were informed by the Consolidated Framework for Implementation Research (CFIR) framework. Transcripts were coded and analyzed using an iterative deductive (CFIR)/Inductive (transcribed quotes) qualitative methodology. Results: We conducted two focus groups and five interviews with health care workers (nurses and doctors) and hospital administrators, respectively. Themes identified key elements of the inner setting (clinic characteristics, resource availability, implementation climate, and tension for change), characteristics of individuals (normative, control, and behavioral beliefs), and the implementation process (engage, implement, and adopt), as well as factors that were influenced by external context, caregiver needs, team function, and intervention characteristics. Task shifting, which is already being used, was viewed by providers and administrators as a necessary strategy to implement TCD screening in a clinic environment that is overstressed and under-resourced, a community stressed by poverty, and a nation with an underperforming health system. Conclusion: Task shifting provides a viable option to improve health care by making more efficient use of already available human resources while rapidly expanding the human resource pool and building capacity that is more sustainable. Trial registration: NCT05434000.

Strategies to increase access to basic sickle cell disease care in low- and middle-income countries.

INTRODUCTION: Sickle cell disease (SCD) is the most common hemoglobinopathy in the world. Over 90% of those born with SCD live in low- and middle-income countries (LMICs), yet individuals in these settings have much poorer outcomes compared to those in high-income countries. AREAS COVERED: This manuscript provides an in-depth review of the cornerstones of basic SCD care, the barriers to implementing these in LMICs, and strategies to increase access in these regions. Publications in English language, peer-reviewed, and edited from 2000 to 2021 were identified on PubMed. Google search was used for gray literature. EXPERT OPINION: Outcomes for patients with SCD in high-income countries have improved over the last few decades due to the implementation of universal newborn screening programs and use of routine antimicrobial prophylaxis, increase in therapeutic and curative options, and the adoption of specific measures to decrease risk of stroke. This success has not translated to LMICs due to several reasons including resource constraints. A combination of several strategies is needed to increase access to basic SCD care for patients in these settings.

Primary Prevention of Stroke in Children With Sickle Cell Anemia in Nigeria: Protocol for a Mixed Methods Implementation Study in a Community Hospital.

BACKGROUND: In Nigeria, approximately 150,000 children with sickle cell anemia (SCA) are born annually, accounting for more than half of all SCA births worldwide. Without intervention, about 11% of children with SCA will develop a stroke before their 20th birthday. Evidence-based practices for primary stroke prevention include screening for abnormal transcranial Doppler (TCD) measurements coupled with regular blood transfusion therapy for at least one year, followed by hydroxyurea (HU) therapy indefinitely. In high-resource countries, this strategy contributes to a 92% decrease in stroke incidence rates. In 2016, as part of a capacity building objective of the Stroke Prevention Trial in Nigeria (1R01NS094041: SPRING), TCD screening was adopted as standard care at Barau Dikko Teaching Hospital in Kaduna. However, with just 70 radiologists and only 3 certified in TCD screening in the state, just 5.49% (1101/20,040) of eligible children with SCA were screened. Thus, there is a need to explore alternate implementation strategies to ensure children with SCA receive standard care TCD screening to decrease stroke incidence. OBJECTIVE: This protocol describes a study to create a stroke prevention program in a community hospital in Kaduna through task shifting TCD screening to nurses and training medical officers to initiate and monitor HU utilization for stroke prevention. METHODS: This study will be conducted at 2 sites (teaching hospital and community hospital) over a period of 3 years (November 2020 to November 2023), in 3 phases using both quasi-experimental and effectiveness-implementation study designs. In the needs assessment phase, focus groups and structured interviews will be conducted with health care providers and hospital administrators to identify barriers and facilitators to evidence-based stroke prevention practices. Results from the needs assessment will inform intervention strategies and a process plan to fit the needs of the community hospital. In the capacity building phase, nurses and medical officers at the community hospital will be trained on TCD screening and HU initiation and monitoring. In the implementation phase, children with SCA aged 2-16 years will be recruited into a nonrandomized single-arm prospective trial to determine the feasibility of initiating a task-shifted stroke prevention program by recording recruitment, retention, and adherence rates. The Reach and Effectiveness components of the RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework will be used to evaluate implementation outcomes between the community and teaching hospitals. RESULTS: The needs assessment phase of the study was completed in February 2021. Manuscript on findings is currently in preparation. Capacity building is ongoing with TCD training and sickle cell disease and stroke education sessions for nurses and doctors in the community hospital. Recruitment for the implementation trial is expected to commence in July 2022. CONCLUSIONS: This study proposes a structured, theory-driven approach to create a stroke prevention program in a community hospital in Kaduna, Nigeria, to decrease stroke incidence among children with SCA. Results will provide preliminary data for a definitive randomized clinical trial in implementation science. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37927.

Translating research to usual care of children with sickle cell disease in Northern Nigeria: lessons learned from the SPRING Trial Team.

OBJECTIVES: Evidence-based practice for stroke prevention in high-income countries involves screening for abnormal transcranial Doppler (TCD) velocity and initiating regular blood transfusions for at least 1 year, followed by treatment with hydroxyurea. This practice has not been transferred to low-resource settings like Nigeria, the country with the highest global population density of SCD. Following a multi-center randomized controlled trial among children with SCA in northern Nigeria, screening for stroke and initiation of hydroxyurea was established as standard of care at the clinical trial sites and other locations. We aim to describe the critical steps we took in translating research into practice for stroke prevention in SCA in Nigeria. Guided by the PRISM framework, we describe how we translated results from a randomized controlled trial for primary prevention of stroke in children with sickle cell anemia into usual care for children with SCA in Kaduna, Nigeria. RESULTS: Findings from this study demonstrate the importance of organizational support and stakeholder involvement from the onset of a clinical trial. Having the dual objective of conducting an efficacy trial while simultaneously focusing on strategies for future implementation can significantly decrease the lag time between discovery and routine practice.

Biomass fuel use and birth weight among term births in Nigeria.

Despite the high burden of household air pollution from biomass fuel in sub-Saharan Africa, the association of prenatal biomass fuel exposure and birth weight as a continuous variable among term births has not been extensively studied. In this study, our primary aim is to estimate the association between biomass cooking fuel and birth weight among term births in Kaduna, northwestern Nigeria. For replication, we also evaluated this association in a larger and nationally representative sample from the 2018 Nigerian Demographic and Health Survey (DHS). Our primary analysis included 1,514 mother-child pairs recruited from Kaduna, in northwestern Nigeria, using the Child Electronic Growth Monitoring System (CEGROMS). Replication analysis was conducted using data from 6,975 mother-child pairs enrolled in 2018 Nigerian DHS. The outcome variable was birth weight, and the exposure was cooking fuel type, categorized in CEGROMS as liquefied petroleum gas, kerosene, or biomass fuel, and in the DHS as low pollution fuel, kerosene, or biomass fuel. We estimated covariate adjusted associations between birth weight and biomass fuel exposure in CEGROMS using linear regression and using linear mixed model in the DHS. In CEGROMS, adjusting for maternal age, education, parity, BMI at birth, and child sex, mothers exposed to biomass fuel gave birth to infants who were on average 113g lighter (95% CI -196 to -29), than those using liquified petroleum gas. In the 2018 Nigeria DHS data, compared to low pollution fuel users, mothers using biomass had infants weighing 50g (95% CI -103 to 2) lower at birth. Exposure to biomass cooking fuel was associated with lower birth weight in our study of term newborns in Kaduna, Nigeria. Data from the nationally representative DHS provide some support for these findings.

Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): a double-blind, multicentre, randomised, phase 3 trial.

BACKGROUND: In high-income countries, standard care for primary stroke prevention in children with sickle cell anaemia and abnormal transcranial Doppler velocities results in a 92% relative risk reduction of strokes but mandates initial monthly blood transfusion. In Africa, where regular blood transfusion is not feasible for most children, we tested the hypothesis that initial moderate-dose compared with low-dose hydroxyurea decreases the incidence of strokes for children with abnormal transcranial Doppler velocities. METHODS: SPRING is a double-blind, parallel-group, randomised, controlled, phase 3 trial of children aged 5-12 years with sickle cell anaemia with abnormal transcranial Doppler velocities conducted at three teaching hospitals in Nigeria. For randomisation, we used a permuted block allocation scheme with block sizes of four, stratified by sex and site. Allocation was concealed from all but the pharmacists and statisticians. Participants were assigned in a 1:1 ratio to low-dose (10 mg/kg per day) or moderate-dose (20 mg/kg per day) oral hydroxyurea taken once daily with monthly clinical evaluation and laboratory monitoring. The primary outcome was initial stroke or transient ischaemic attack, centrally adjudicated. The secondary outcome was all-cause hospitalisation. We used the intention-to-treat population for data analysis. The trial was stopped early for futility after a planned minimum follow-up of 3·0 years to follow-up for participants. This trial was registered with ClinicalTrials.gov, number NCT02560935. FINDINGS: Between Aug 2, 2016, and June 14, 2018, 220 participants (median age 7·2 years [IQR 5·5-8·9]; 114 [52%] female) were randomly allocated and followed for a median of 2·4 years (IQR 2·0-2·8). All participants were Nigerian and were from the following ethnic groups: 179 (82%) people were Hausa, 25 (11%) were Fulani, and 16 (7%) identified as another ethnicity. In the low-dose hydroxyurea group, three (3%) of 109 participants had strokes, with an incidence rate of 1·19 per 100 person-years and in the moderate-dose hydroxyurea group five (5%) of 111 had strokes with an incidence rate of 1·92 per 100 person-years (incidence rate ratio 0·62 [95% CI 0·10-3·20], p=0·77). The incidence rate ratio of hospitalisation for any reason was 1·71 (95% CI 1·15-2·57, p=0·0071), with higher incidence rates per 100 person-years in the low-dose group versus the moderate-dose group (27·43 vs 16·08). No participant had hydroxyurea treatment stopped for myelosuppression. INTERPRETATION: Compared with low-dose hydroxyurea therapy, participants treated with moderate-dose hydroxyurea had no difference in the stroke incidence rate. However, secondary analyses suggest that the moderate-dose group could lower incidence rates for all-cause hospitalisations. These findings provide an evidence-based guideline for the use of low-dose hydroxyurea therapy for children with sickle cell anaemia at risk of stroke. FUNDING: National Institute of Neurological Disorders and Stroke.

Menstrual characteristics of sickle cell disease patients seen at a tertiary institution in North Western Nigeria.

Introduction: The burden of sickle cell disease (SCD) is high in Sub-Saharan Africa, including Nigeria, and with improved care and survival, reproductive health issues, including menstruation, have become increasingly important and may impact on long-term health and social wellbeing. Objectives: This study was carried out to characterize the menstrual characteristics of SCD patients. Methodology: Using a cross-sectional study design, a semi-structured questionnaire was administered and information collected on bio-demographic data, medical history of SCD, reproductive, and menstrual history. Results: One hundred and sixty female patients participated in the study. The mean age was 24.9 years (standard deviation [SD] ± 8.8). The mean age at menarche was 15.6 years (SD ± 2.7) for those menstruating. Most respondents had regular menstrual cycles 120 (82%); normal menstrual cycle lengths 120 (81%) significantly associated with respondent's age (P < 0.05); normal duration of flow 140 (97%); light menstrual flow 104 (71%) significantly associated with body mass index BMI (P < 0.05). Overall, however, 114 (78%) had abnormal menses and 32 (22%) had normal menses. Eighty-one respondents (56%) experienced menstrual pain, which was severe in only 28 cases (35%). The presence of menstrual pain did not significantly affect the annual frequency of crisis (P > 0.05). Conclusion: The mean age at menarche was high at 15.6 years. Most respondents had light menstrual flow and overall abnormal menstrual patterns. Menstrual pain was common but was not significantly associated with the frequency of crisis.

RésuméIntroduction: Le taux d'infection de la drépanocytose est élevé en Afrique Sub-Saharien, inclus le Nigéria. Avec les avancements en soin et survie, les problèmes de santé de reproductions, ci inclus le cycle menstruel, sont devenus très préoccupants et peuvent avoir un impact à longue terme sur la santé et le bien-être du patient. Objectifs: Cette étude a pour but de décrire les caractéristiques du cycle menstruel des drépanocytaires. Méthodologie: Utilisant la conception de l'étude transversale, un questionnaire semi-structuré a été administré pour collectionner les informations sur les données biodémographiques, les antécédents médicaux de la drépanocytose ainsi que l'histoire de reproduction et de menstruation des drépanocytaires. Résultats: Cent soixante (160) drépanocytaires de sexe féminin ont pris part à l'étude comme échantillons. La moyenne d'âge était de 24,9 ans (Écart-Type de ±8,8). La moyenne d'âge à ménarche était de 15,6 ans (Écart-Type de ±2,7) pour celles qui sont en cycle menstruel. La plupart des participantes avaient un cycle menstruel régulier (120 sur 160) donc un taux de 82% ; 120 avaient un cycle menstruel de durée normale (81%) qui correspondait significativement très bien à l'âge des participantes (P- Probabilité <0,05) ; 140 avaient une durée d'écoulement normal donc (97%) ; 104 avaient un écoulement léger c'est- à-dire 71% qui correspondait significativement à l'indice de masse corporelle (P<0,05). En totalité, 114 dont 78% ont eu des cycles menstruels anormaux et 32 (22%) ont eu des cycles menstruels douloureux avec 28 cas sévères donc 35%. La présence du cycle menstruel douloureux n'a pas eu d'effet significatif sur la fréquence de crises annuelles (P>0,05). Conclusion: La moyenne d'âge à ménarche était élevée à 15,6 ans. La plupart des participantes ont eu des écoulements légers et globalement, des cycles anormaux. Les cycles douloureux étaient fréquents, mais n'étaient significativement pas liés à la fréquence de crise. Mots-clés: Caractéristiques menstruelles, Menstruation (règles), Nord-Ouest du Nigéria, Drépanocytose.

Capacity Building for Primary Stroke Prevention Teams in Children Living With Sickle Cell Anemia in Africa.

BACKGROUND: Nigeria has the highest proportion of children with sickle cell anemia (SCA) globally; an estimated 150,000 infants with SCA are born annually. Primary stroke prevention in children with SCA must include Nigeria. We describe capacity-building strategies in conjunction with two National Institutes of Health-funded primary stroke prevention trials (a feasibility trial and phase III randomized controlled trial) with initial hydroxyurea treatment for children with SCA and abnormal transcranial Doppler (TCD) velocities in Nigeria. We anticipated challenges to conducting clinical trials in a low-resource setting with a local team that had not previously been involved in clinical research and sought a sustainable strategy for primary stroke prevention. METHODS: This is a descriptive, prospective study of challenges, solutions, and research teams in two trials that enrolled a total of 679 children with SCA. RESULTS: As part of the capacity-building component of the trials, over eight years, 23 research personnel (physicians, nurses, research coordinators, a statistician, and a pharmacist) completed a one-month research governance and ethics training program at Vanderbilt University Medical Center, USA. A lead research coordinator for each site completed the Society of Clinical Research Professionals certification. TCD machines were donated; radiologists and nonradiologists were trained and certified to perform TCD. A scalable E-prescription was implemented to track hydroxyurea treatment. We worked with regional government officials to support ongoing TCD-based screening and funding for hydroxyurea for children with SCA at a high risk of stroke. CONCLUSIONS: Our trials and capacity building demonstrate a sustainable strategy to initiate and maintain pediatric SCA primary stroke prevention programs in Africa.

World Health Organization's Growth Reference Overestimates the Prevalence of Severe Malnutrition in Children with Sickle Cell Anemia in Africa.

Anthropometric indices are widely used to assess the health and nutritional status of children. We tested the hypothesis that the 2007 World Health Organization (WHO) reference for assessment of malnutrition in children with sickle cell anemia (SCA) overestimates the prevalence of severe malnutrition when compared to a previously constructed SCA-specific reference. We applied the WHO and SCA-specific references to children with SCA aged 5-12 years living in northern Nigeria (Primary Prevention of Stroke in Children with SCA in sub-Saharan Africa (SPRING) trial) to determine the difference in prevalence of severe malnutrition defined as body mass index (BMI) Z-score <-3 and whether severe malnutrition was associated with lower mean hemoglobin levels or abnormal transcranial Doppler measurements (>200 cm/s). A total of 799 children were included in the final analysis (median age 8.2 years (interquartile range (IQR) 6.4-10.4)). The application of the WHO reference resulted in lower mean BMI than the SCA-specific reference (-2.3 versus -1.2; p < 0.001, respectively). The use of the WHO reference when compared to the SCA-specific reference population also resulted in a higher prevalence of severe malnutrition (28.6% vs. 6.4%; p < 0.001). The WHO reference significantly overestimates the prevalence of severe malnutrition in children with SCA when compared to an SCA-specific reference. Regardless of the reference population, severe malnutrition was not associated with lower mean hemoglobin levels or abnormal transcranial Doppler (TCD) measurements.

Epidemiology and treatment of relative anemia in children with sickle cell disease in sub-Saharan Africa.

INTRODUCTION: Sickle cell disease (SCD) is the most common inherited hemoglobinopathy in the world, with the majority of cases in sub-Saharan Africa. Concomitant nutritional deficiencies, infections or exposure to environmental toxins exacerbate chronic anemia in children with SCD. The resulting relative anemia is associated with increased risk of strokes, poor cognitive function and impaired growth. It may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa. This review will focus on the epidemiology, clinical sequelae, and treatment of relative anemia in children with SCD living in low and middle-income countries in sub-Saharan Africa. Areas covered: The causes and treatment of relative anemia in children with SCD in sub-Saharan Africa. The MEDLINE database was searched using medical subject headings (MeSH) and keywords for articles regarding relative anemia in children with SCD in sub-Saharan Africa. Expert commentary: Anemia due to nutritional deficiencies and infectious diseases such as helminthiasis and malaria are prevalent in sub-Saharan Africa. Their co-existence in children with SCD increases morbidity and mortality. Therefore, preventing, diagnosing and treating the underlying cause of this relative anemia will improve SCD-related outcomes in children in sub-Saharan Africa.