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Competing Interests: We declare no competing interests.

In high-income countries, premarital genetic counseling for Sickle Cell Disease (SCD) is a standard practice. However, in Nigeria, there is no formal premarital genetic counseling program available for SCD. We conducted a series of focus group discussions with health care professionals, patients with SCD, and parents of the patients with or without SCD to gain an understanding of their attitudes and beliefs towards SCD/Sickle Cell Trait and premarital genetic counseling for SCD. Data were analyzed using Charmaz's constructivist grounded theory approach. Two themes were highlighted in the analysis as follows: (1) the difference between the perception of premarital sickle cell screening among individuals with SCD versus the general population, and (2) the personal beliefs and physical challenges that could lead to the avoidance of premarital screening within the general community. Lack of disease-related knowledge, testing facilities, transportation, and stigma associated with the disease were the most commonly perceived barriers to premarital testing. Also, a willingness to receive premarital testing for SCD exists within our community to reduce the spread of the disease and advocate for improved health-related quality of life of patients with SCD. The content and structure of a premarital genetic counseling program in Kano, Northern Nigeria, needs to be developed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Cardiopulmonary complications remain a leading cause of morbidity and mortality in sickle cell disease (SCD). The overall goals of this study were to evaluate the relationship between left ventricular hypertrophy (LVH) and laboratory markers of hemolysis and determine the association between LVH and SCD-specific therapies (hydroxyurea and chronic red cell transfusion). Data from the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study cohort was used. LVH was defined based on the left ventricular mass indexed to the body surface area as left ventricular mass index >103.0 g/m2 for males and >84.2 g/m2 for females. There were 1,409 children included in the analysis and 20.3% had LVH. Results of multivariable analysis of LVH showed baseline hemoglobin levels were associated with the lower odds of having LVH (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.60- 0.84). The odds of LVH increases for every 1-year increase in age (OR: 1.07, 95% CI: 1.02-1.13). Similarly, the odds of LVH were lower among males than females (OR: 0.59, 95% CI: 0.38-0.93). The odds of LVH were higher among those on hydroxyurea compared to no therapy (OR: 1.83, 95% CI: 1.41-2.37). Overall results of the study showed that LVH occurs early in children with SCD and the risk increases with increasing age and with lower hemoglobin. Further, we found higher use of hydroxyurea among those with LVH, suggesting that the need for hydroxyurea conveys a risk of cardiovascular remodeling.

Reduced growth and delayed maturation have been described in children with sickle cell disease (SCD). This study investigated growth and hemolysis in children with SCD in the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) cohort. The database includes 5287 children, of which, 3305 had at least 2 growth measurements over a 5-year period. Body mass index was converted to z-scores (zBMI), and 19.8%, 66.1%, 14.2% of children were classified as underweight, normal, and overweight/obese, respectively. Multivariable analysis of growth was conducted and included variables: age, sex, blood pressure, hemoglobin, reticulocyte count, treatment with chronic red cell transfusion therapy (CRCT), or hydroxyurea therapy. Baseline hemoglobin levels were associated with the lower odds of being underweight (odds ratio [OR]=0.93, 95% confidence interval [CI]: 0.86-0.99), and higher odds of being overweight/obese (OR: 1.26, 95% CI: 1.17-1.36) compared with normal zBMI. CRCT was associated with being overweight/obese at baseline (OR: 1.85, 95% CI: 1.31-2.60). Overall, results showed that children who were underweight improved regardless of therapy over the 2-year time period. However, children on CRCT are at higher risk for being overweight and should be monitored closely., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Ischemic stroke is one of the most devastating complications of sickle cell anemia (SCA). Previous studies have shown that intracardiac shunting including patent foramen ovale (PFO) can be a potential risk factor for stroke in children with SCA. This study investigates the association between PFO and overt ischemic stroke in the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study cohort of 5,247 children with SCA of whom 1,414 had at least one clinical non-contrast transthoracic echocardiogram. Presence of PFO was taken from the clinical report. Further, we assessed the association between PFO and other clinical and hemolytic factors in children with SCA such as history of abnormal sickle stroke screen [elevated Transcranial Doppler ultrasound (TCD) velocity] and patient's baseline hemoglobin. In 642 children for whom all data were available, the adjusted odds ratio (OR) for overt stroke was higher in those with PFO but this was not statistically significant (OR: 1.49, 95% CI: 0.20-11.03, p = 0.6994). With an OR of 0.85, the study suggested less PFOs in those with abnormal TCD, but this was not statistically significant (95% CI: 0.17-4.25, p = 0.8463). Overall, the prevalence of PFO in this large sub study of non-contrast echocardiography amongst children with SCA is much lower than previous smaller studies using bubble contrast echocardiography. Overt stroke was non-statistically more common in children with SCA and PFO, but there was no evidence that PFO was more common in those with abnormal TCD, the most important pediatric sickle stroke screen., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Galadanci, Johnson, Carson, Hellemann, Howard and Kanter.)

Objectives: To provide lay information about genetics and sickle cell disease (SCD) and to identify and address ethical issues concerning the Sickle Cell Disease Genomics of Africa Network covering autonomy and research decision-making, risk of SCD complications and organ damage, returning of genomic findings, biorepository, data sharing, and healthcare provision for patients with SCD., Design: Focus groups using qualitative methods., Setting: Six cities in Ghana, Nigeria and Tanzania within communities and secondary care., Participants: Patients, parents/caregivers, healthcare professionals, community leaders and government healthcare representatives., Results: Results from 112 participants revealed similar sensitivities and aspirations around genomic research, an inclination towards autonomous decision-making for research, concerns about biobanking, anonymity in data sharing, and a preference for receiving individual genomic results. Furthermore, inadequate healthcare for patients with SCD was emphasised., Conclusions: Our findings revealed the eagerness of patients and parents/caregivers to participate in genomics research in Africa, with advice from community leaders and reassurance from health professionals and policy-makers, despite their apprehensions regarding healthcare systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Sickle cell disease is often complicated by retinopathy, which can be proliferative or non proliferative. Proliferative sickle cell retinopathy potentially leads to blindness. There is a paucity of data on sickle cell disease-related retinopathy from Africa, where the disease is most prevalent. We aimed to determine the clinical, ophthalmic, and laboratory predictors of sickle cell retinopathy in an African population. We conducted a cross-sectional study of 262 participants, aged 13 years and above, with sickle cell disease. Demographic and clinical data were collected using a structured questionnaire and standard physical examinations. Vitreo-retinal specialists performed eye examinations on all the participants. Hematological and biochemical assessments were conducted using standard methods. A multivariate stepwise forward logistic regression was performed to determine the predictors of retinopathy. The median age of the participants was 20 years (interquartile range: 17-25 years). Most of the participants had a homozygous Hb S ( HBB : c.20A>T) genotype (96.9%), with 3.1% who carried a Hb S/Hb C ( HBB : c.19G>A) genotype. The prevalence of non proliferative sickle cell retinopathy was 24.4%. Only 1.9% had proliferative sickle cell retinopathy (PSCR). Elevated systolic blood pressure (BP) [odds ratio (OR): 6.85, 95% confidence interval (95% CI): 1.05-44.45, p  = 0.059], moderate visual impairment (OR: 5.2, 95% CI: 1.39-19.63, p  = 0.015), and anterior segment changes (OR: 2.21, 95% CI: 1.19-4.13, p  = 0.012) were independently predictive of retinopathy. This study provides new insight into predictors of retinopathy in sickle cell disease, with implications on early screening and prevention.

Background: HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to CKD in HIV positive patients, and the pathophysiology of progression to ESKD., Objectives: We will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria., Methods: We will consecutively screen 150 HIV-positive adults (≥18 years of age) attending the HIV clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral (ARV) regimen. In the first group (n = 16), we will determine differential gene expression markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases., Results: Our exploratory study will provide valuable information on the potential roles of differential expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population. The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches., Conclusion: Validated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine., Competing Interests: The authors have declared that no competing interests exist.

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 [ S troke Pr evention i n N i g eria (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.

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 HbSβ 0 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., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Children with sickle cell anemia (SCA) have elevated cerebral blood velocity relative to healthy peers. The primary aim of this study was to evaluate the association between cerebral blood velocity, measured by transcranial Doppler (TCD) ultrasound, age, and gender with cognitive function in children with SCA in Nigeria. Eighty-three children (M age  = 9.10, SD = 1.90 years; 55% female) with SCA in Nigeria completed cognitive assessments and a TCD ultrasound. The association between TCD velocity and measures of perceptual reasoning (Raven's Progressive Matrices), working memory (WISC-IV Digit Span), and executive planning (Tower of London, TOL) were assessed. Results showed that elevated TCD velocity significantly predicted lower scores on TOL Time Violations and Total Problem-Solving Time when controlling for BMI, hemoglobin level, and parent education, suggesting that TCD velocity is related to the efficiency of executive function. Further, age was negatively related to children's performance on the Ravens Matrices and TOL Total Correct, and boys showed greater deficits on the TOL Total Correct relative to girls. Moderation analyses for gender showed that there was a conditional negative association between TCD velocity and Digit Span for boys, but not for girls. Findings suggest that children with SCA in Nigeria with elevated TCD velocity are at risk for deficits in efficiency of executive planning, and boys with elevated TCD velocity are particularly at increased risk for deficits in auditory working memory. Implications of this study are important for interventions to reduce cerebral blood velocity and the use of TCD in this population.

Introduction: Sickle Cell Disease (SCD) is one of the most common genetic diseases in the world affecting every organ. The major challenge in the medical care of children with SCD is preventing end-organ dysfunction, particularly the brain. Major neurologic complications in children less than five years with SCD include, but are not limited to, Silent cerebral infarct, cerebral sinus thrombosis, epilepsy, reversible encephalopathy syndrome, and ischemic and hemorrhagic stroke. Recurrent headaches and migraine are not rare in children under five years with SCD. This review will focus on the neurologic complications and the description of the modifiable risk factors in children less than 5 years of age with emphasis on differences between high and low resource settings., Areas Covered: Neurologic complications of children under 5 years of age and the modifiable risk factors. The PUBMED database was searched using medical subject headings (MeSH) and keywords for articles regarding neurologic complications in children under 5 years of age., Conclusion: Neurologic complications in children under five years of age with SCD may be more frequent than currently reported, among which Silent cerebral infarct and cognitive impairment are the most common., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: To improve the quality of care for children with sickle cell anemia in Kano, Nigeria, we initiated a standard care protocol in 2014 to manage children with strokes at Aminu Kano Teaching Hospital., Methods: The standard care protocol requires that children with acute strokes be treated with hydroxyurea at a fixed dose of 20 mg/kg/day within two months of the stroke., Results: Twenty-nine children with sickle cell anemia and initial stroke were identified based on clinical World Health Organization criteria from 2014 to 2017. Follow-up was a median of 1.04 years (interquartile range 0.43 to 1.83 years) to either July 2017 or a second stroke, corresponding to an initial stroke incidence rate of 0.88 per 100 patient-years. Eight children had a recurrent stroke, six of whom were prescribed hydroxyurea 20 mg/kg/day by two months after initial stroke. Two children died. Six of the recurrent strokes occurred within six months of the initial stroke, two before hydroxyurea prescription. The stroke recurrence rate was 17.4 events per 100 patient-years. Adherence was approximately 60%, partly because families had to pay for hydroxyurea. Stroke incidence is probably underestimated because despite formal training for stroke detection during the quality improvement period, no participant had assessment using a standardized pediatric stroke scale and neuroimaging was not available., Conclusions: In children with sickle cell anemia, a high rate of initial and recurrent strokes exists in a low-resource setting. Ongoing needs include training to detect strokes with an objective stroke assessment and government-supported free access to hydroxyurea for stroke prevention., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cardiopulmonary disease is a major cause of morbidity and mortality in persons with sickle cell disease (SCD). Tricuspid regurgitant jet velocity (TRJV) and predicted forced expiratory volume in 1 s (FEV1%) predicted are independently associated with death in SCD. The goal of this study was to determine the prevalence of elevated TRJV and the association, if any, between TRJV and FEV1% predicted among persons with sickle cell anaemia (SCA) in Nigeria., Methods: Using a cross-sectional design, we enrolled 100 adult Nigerians (≥15 y) with SCA. We screened participants using Doppler echocardiogram to determine their TRJV and assessed their lung function with spirometry., Results: The prevalence of elevated TRJV was 6%, with 74% of participants having low FEV1% predicted (<70%). TRJV was negatively correlated with FEV1%, but this finding was not statistically significant (Spearman's ρ=-0.0263, p=0.8058)., Conclusions: We found a low prevalence of elevated TRJV and a trend in association between TRJV and FEV1% predicted in Nigerian adults with SCA. Our findings underscore the need to explore further the relationship between SCD and cardiopulmonary disease in adults.

Background: Successful tuberculosis (TB) treatment is essential to effective TB control. TB-HIV coinfection, social determinants and access to services influenced by rural residence can affect treatment outcome. We examined the separate and joint effects of rural residence and HIV infection on poor treatment outcome among patients enrolled in a large TB treatment centre in Kano, Nigeria., Methods: We retrospectively analysed a cohort of patients with TB enrolled in a large urban TB clinic in northern Nigeria, from January 2010 to December 2014. Poor treatment outcome was defined as death, default or treatment failure. We used Poisson regression to model rates and determine the relative risks (and 95% confidence intervals, CI) of poor treatment outcomes., Results: Among 1381 patients included in the analysis, 28.4% were rural residents; 39.8% were HIV-positive; and 46.1% had a poor treatment outcome. Approximately 65 and 38% of rural and urban residents, respectively, had a poor treatment outcome. Rural residents had 2.74 times (95% CI: 2.27-3.29) the risk of having a poor treatment outcome compared to urban residents. HIV-positive patients had 1.4 times (95% CI: 1.16-1.69) the risk of poor treatment outcome compared to HIV-negative patients. The proportion of poor treatment outcome attributable to rural residence (population attributable fraction, PAF) was 25.6%. The PAF for HIV infection was 11.9%. The effect of rural residence on poor treatment outcome among HIV-negative patients (aRR:4.07; 95%CI:3.15-5.25) was more than twice that among HIV-positive patients (aRR:1.99; 95%CI:1.49-2.64)., Conclusion: Rural residents attending a large Nigerian TB clinic are at increased risk of having poor treatment outcomes, and this risk is amplified among those that are HIV-negative. Our findings indicate that rural coverage of HIV services may be better than TB services. These findings highlight the importance of expanding coverage of TB services to ensure prompt diagnosis and commencement of treatment, especially among rural-dwellers in resource-limited settings.

Background: Multidrug resistant tuberculosis (MDR-TB), is an emerging public health problem in sub-Saharan Africa (SSA). This study aims to determine the trends in prevalence of MDR-TB among new TB cases in sub-Saharan Africa over two decades., Methods: We searched electronic data bases and accessed all prevalence studies of MDR-TB within SSA between 2007 and 2017. We determined pooled prevalence estimates using random effects models and determined trends using meta-regression., Results: Results: We identified 915 studies satisfying inclusion criteria. Cumulatively, studies reported on MDR-TB culture of 34,652 persons. The pooled prevalence of MDR-TB in new cases was 2.1% (95% CI; 1.7-2.5%). There was a non-significant decline in prevalence by 0.12% per year., Conclusion: We found a low prevalence estimate of MDR-TB, and a slight temporal decline over the study period. There is a need for continuous MDR-TB surveillance among patients with TB.

Background: Despite availability of effective cure, tuberculosis (TB) remains a leading cause of death in children. In many high-burden countries, childhood TB is underdiagnosed and underreported, and care is often accessed too late, resulting in adverse treatment outcomes. In this study, we examined the time to death and its associated factors among a cohort of children that commenced TB treatment in a large treatment centre in northern Nigeria., Methods: This is a retrospective cohort study of children that started TB treatment between 2010 and 2014. We determined mortality rates per 100 person-months of treatment, as well as across treatment and calendar periods. We used Cox proportional hazards regression to determine adjusted hazard ratios (aHR) for factors associated with mortality., Results: Among 299 children with a median age 4 years and HIV prevalence of 33.4%; 85 (28.4%) died after 1,383 months of follow-up. Overall mortality rate was 6.1 per 100 person-months. Deaths occurred early during treatment and declined from 42.4 per 100 person-months in the 1st week of treatment to 2.2 per 100 person-months after at the 3rd month of treatment. Mortality was highest between October to December period (9.1 per 100 pm) and lowest between July and September (2.8 per 100 pm). Risk factors for mortality included previous TB treatment (aHR 2.04:95%CI;1.09-3.84); HIV infection (aHR 1.66:95%CI;1.02-2.71), having either extra-pulmonary disease (aHR 2.21:95%CI;1.26-3.89) or both pulmonary and extrapulmonary disease (aHR 3.03:95%CI;1.70-5.40)., Conclusions: Mortality was high and occurred early during treatment in this cohort, likely indicative of poor access to prompt TB diagnosis and treatment. A redoubling of efforts at improving universal health coverage are required to achieve the End TB Strategy target of zero deaths from TB.

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., (© 2017 Wiley Periodicals, Inc.)

Background and Objective: Respiratory symptoms including wheezing are common in adults with sickle cell anaemia (SCA), even in the absence of asthma. However, the prevalence of spirometry changes and respiratory symptoms in adults with SCA is unknown., Methods: Using a cross-sectional study design, we tested the hypothesis that adults with SCA (cases) would have higher rates of lower airway obstruction and wheezing than those without SCA (controls) using the American Thoracic Society Division of Lung Diseases' questionnaire. Patients were adults with SCA aged between 18 and 65 years. Controls were consecutive unselected individuals without SCA who presented to an outpatient general medicine clinic., Results: We enrolled 150 adults with SCA and 287 consecutive controls without SCA. The median age was 23.0 and 27.0 years for adults with and without SCA, respectively. Cases were more likely to report cough without a cold (35.0% vs 18.6%, P < 0.001), lower forced expiratory volume in 1 s (FEV 1 ) % predicted (70.1% vs 82.1%, P = 0.001) and lower forced vital capacity (FVC) % predicted (67.4% vs 74.9%, P = 0.001) than controls. In the multivariable model, wheezing was significantly associated with SCA status (OR = 1.69, 95% CI = 1.08-2.65, P = 0.024). Similarly, FEV 1 % predicted was significantly associated with SCA status and wheezing (P = 0.001 for both)., Conclusion: Adults with SCA experience a higher rate of wheezing and impaired respiratory functions compared with controls from the same region., (© 2016 Asian Pacific Society of Respirology.)

Elevated tricuspid regurgitant jet velocity (TRJV) is a surrogate measure of pulmonary hypertension (PH) in persons with sickle cell disease (SCD). We sought to estimate the burden of PH in people living with sickle cell disease based on TRJV. From 2000 to 2015, we searched electronic databases for eligible publications and included 29 studies (n = 5358 persons). We used random effects modeling to determine the pooled estimate of elevated TRJV. The overall pooled prevalence of elevated TRJV was 23.5 %(95 % CI 19.5-27.4) in persons with SCD. The pooled prevalence of elevated TRJV in children and adults with SCD was 20.7 % (95 % CI 15.7--25.6) and 24.4 % (95 % CI 18.4-30.4), respectively. TRJV is prevalent among adults and children with SCD. Our finding support international recommendations that call for screening for PH in SCD patients.

In the United States, primary stroke prevention in children with sickle cell anemia (SCA) is now the standard of care and includes annual transcranial Doppler ultrasound evaluation to detect elevated intracranial velocities; and for those at risk, monthly blood transfusion therapy for at least a year followed by the option of hydroxyurea therapy. This strategy has decreased stroke prevalence in children with SCA from approximately 11% to 1%. In Africa, where 80% of all children with SCA are born, no systematic approach exists for primary stroke prevention. The two main challenges for primary stroke prevention in children with SCA in Africa include: 1) identifying an alternative to blood transfusion therapy, because safe monthly blood transfusion therapy is not feasible; and 2) assembling a health care team to implement and expand this effort. We will emphasize early triumphs and challenges to decreasing the incidence of strokes in African children with SCA., Competing Interests: Potential Conflicts of Interest: None disclosed.

Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ∼11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in SCD., (© 2015 by The American Society of Hematology.)

Background: The majority of children with sickle cell disease (SCD), approximately 75%, are born in sub-Saharan Africa. For children with elevated transcranial Doppler (TCD) velocity, regular blood transfusion therapy for primary stroke prevention is standard care in high income countries, but is not feasible in sub-Saharan Africa., Procedure: In the first U.S. National Institute of Health (NIH) sponsored SCD clinical trial in sub-Saharan Africa, we describe the protocol and challenges unique to starting a clinical trial in this region. We are conducting a single arm pilot trial of hydroxyurea therapy in children with TCD velocity ≥200 cm/sec in the middle cerebral arteries. Eligible children will be placed on hydroxyurea (n = 40) and followed for 3 years at Aminu Kano Teaching Hospital, Nigeria. Adherence will be measured via the Morisky Scale and adverse events will be determined based on hospitalization., Results: Originally, a randomized placebo trial was planned; however, placebo was not approved by the local Ethics Committee. Hence a single arm trial of hydroxyurea will be conducted and five controls per patient with normal TCD measurements will be followed to compare the rate of adverse events to those with abnormal TCD measurements taking hydroxyurea. Using non-NIH funding, over 9 months, multiple face-to-face investigator meetings were conducted to facilitate training., Conclusion: A hydroxyurea trial (NCT01801423) for children with SCD is feasible in sub-Saharan Africa; however, extensive training and resources are needed to build a global patient oriented multi-disciplinary research team with a common purpose., (© 2014 Wiley Periodicals, Inc.)

In children with sickle cell disease (SCD), wheezing may occur in the absence of asthma. However, the prevalence of wheezing in children with SCD when compared with children without SCD (controls) in the same setting is unknown. Using a case-control study design, we tested the hypothesis that children with SCD would have a higher rate of wheezing than those without SCD. We enrolled 163 children with SCD (cases) and 96 children without SCD (controls) from a community hospital in Nigeria. Parent reports of respiratory symptoms were identified based on responses to questions taken from the American Thoracic Society Division of Lung Diseases' Questionnaire. The median age was 8.5 years for children with SCD and 7.7 years for controls. Cases were more likely than controls to report wheezing both with colds (17.3% vs. 2.1%, P<0.01) and without colds (4.9% vs. 0%, P=0.03). Cases had 9.8 times greater odds of wheezing (95% confidence interval, 2.3-42.2). In the multivariable model, the only variable associated with wheezing was SCD status (odds ratio=18.7, 95% confidence interval, 2.5-142; P=0.005). Children with SCD experience a significantly higher rate of wheezing when compared with children of similar age without SCD.