Cell Disease In sub-Saharan Africa Research Articles

Current challenges and new approaches to implementing optimal management of sickle cell disease in sub-Saharan Africa

Sickle cell disease (SCD) is the most common life-threatening monogenic disorder in the world. The disease is highly prevalent in malaria endemic areas with over 75% of patients residing in Sub-Saharan Africa (SSA). It is estimated that, without proper care, up to 90% of children with SCD will not celebrate their fifth birthday. Early identification and enrolment into comprehensive care has been shown to reduce the morbidity and mortality related with SCD complications. However, due to resource constraints, the SSA is yet to implement universal newborn screening programs for SCD. Furthermore, care for patients with SCD in the region is hampered by the shortage of qualified healthcare workers, lack of guidelines for the clinical management of SCD, limited infrastructure for inpatient and outpatient care, and limited access to blood and disease modifying drugs such as Hydroxyurea which contribute to poor clinical outcomes. Curative options such as bone marrow transplant and gene therapy are expensive and not available in many SSA countries. In addressing these challenges, various initiatives are ongoing in SSA which aim to enhance awareness on SCD, improve patient identification and retention to care, harmonize the standards of care for SCD, improve the skills of healthcare workers and conduct research on pertinent areas in SCD in the SSA context. Fortifying these measures is paramount to improving the outcomes of SCD in SSA.

Association of haemolysis markers, blood viscosity and microcirculation function with organ damage in sickle cell disease in sub-Saharan Africa (the BIOCADRE study).

Sickle cell anaemia (SCA) is a monogenic disease with a highly variable clinical course. We aimed to investigate associations between microvascular function, haemolysis markers, blood viscosity and various types of SCA-related organ damage in a multicentric sub-Saharan African cohort of patients with SCA. In a cross-sectional study, we selected seven groups of adult patients with SS phenotype in Dakar and Bamako based on the following complications: leg ulcer, priapism, osteonecrosis, retinopathy, high tricuspid regurgitant jet velocity (TRV), macro-albuminuria or none. Clinical assessment, echocardiography, peripheral arterial tonometry, laboratory tests and blood viscosity measurement were performed. We explored statistical associations between the biological parameters and the six studied complications. Among 235 patients, 58 had high TRV, 46 osteonecrosis, 43 priapism, 33 leg ulcers, 31 retinopathy and 22 macroalbuminuria, whereas 36 had none of these complications. Multiple correspondence analysis revealed no cluster of complications. Lactate dehydrogenase levels were associated with high TRV, and blood viscosity was associated with retinopathy and the absence of macroalbuminuria. Despite extensive phenotyping of patients, no specific pattern of SCA-related complications was identified. New biomarkers are needed to predict SCA clinical expression to adapt patient management, especially in Africa, where healthcare resources are scarce.

Treatment of Sickle Cell Disease in Sub-Saharan Africa: We have come a long way, but still have far to go

Treatment of Sickle Cell Disease in Sub-Saharan Africa: We have come a long way, but still have far to go

PI-09: LESSONS LEARNED FROM ONE DECADE EXPERIENCE OF THE « CENTRE DE RECHERCHE ET DE LUTTE CONTRE LA DRÉPANOCYTOSE (CRLD) » IN BAMAKO, MALI.

Purpose: In 2006, WHO declared sickle cell disease (SCD) as a global public health priority and recommended the development of Reference Centers in the sub-Saharan African region where the disease affects 1 to 2% of births. In Mali, the birth rate was estimated at 714,000 per year and the incidence of sickle cell anemia (homozygous SS + S/β-thalassemia + SC), at 0.8% of live births. To begin to adress the issue of reducing the burden of the SCD in Mali, a Sickle Cell Research and Control Center was established in Bamako in 2010. This presentation, reports the experience of the first decade of operation of this Center. Materials and methods: Through the circumstances of its creation, the principle of operation and the results acquired by the Center in ten years of functioning, we make an analysis on the possible future orientations to optimize the management of sickle cell disease in sub-Saharan Africa by the Reference Centers. Results: The « Centre de Recherche et de Lutte contre la Drépanocytose (CRLD) » was established as a result of coordinated efforts by the Government of Mali, SCD patients association, and a consortium of partners led by Pierre Fabre foundation. The assigned objectives were: to support access to quality care with equity, to develop medical research on sickle cell disease, to train medical personnel on sickle cell disease, to develop education, information and communication on the disease, to promote national and international collaboration (South-South, North-South). In order to ensure an equitable access to care, the center provides treatment with no consideration of the financial status of the family. Since March 2010, when the Center began its activities, 956 patients from the first year to 10745 sickle cell patients in 2019 have been recruited and are being provided with regular follow-up and access to treatment. Sickle cell mortality assessed in 2016 was estimated at 0.035 per 100 person-years (0.040 per 100 person-years before 5 years). In terms of research, 44 research protocol have been conducted and 26 scientific papers were published. Within the framework of an university degree, the Center has trained 126 physicians from 12 French-speaking countries in East and West Africa, Madagascar and Haiti. More than 300 communications relays were trained. Conclusion: If the growing increase in patients recruitment has shown the validity of the creation of the Center with satisfactory results in the support of specific care, the results of some of its asigned objectives have remained below expectations. We propose a new approach for the management of sickle cell disease in sub-Saharan Africa that follows a pyramid-schape of healthcare services. The authors do not declare any conflict of interest

Barriers to Therapeutic Use of Hydroxyurea for Sickle Cell Disease in Nigeria: A Cross-Sectional Survey.

Background: Sickle cell disease, the inherited blood disorder characterized by anemia, severe pain and other vaso-occlusive complications, acute chest syndrome, disproportionate hospitalization, and early mortality, has significant financial, social, and psychosocial impacts and drains individuals, families, and health systems globally. Hydroxyurea could improve the health of the 300,000 individuals born each year with sickle cell disease in sub-Saharan Africa; however, challenges to adoption and adherence persist. This study assessed the barriers to therapeutic use of hydroxyurea for sickle cell disease within the Nigerian healthcare system, specifically from the level of the patient, provider, and health system. Methods: We used purposive sampling to recruit participants from 13 regions in Nigeria. A cross-sectional survey was administered to physicians (n = 70), nurses or counselors (n = 17), and patients or their caregivers (n = 33) at 13 health centers. Findings were mapped onto the appropriate Consolidated Framework for Implementation Research (CFIR) domains. Results: This study was able to identify factors that mapped onto the inner setting, outer setting, and characteristics of individuals domains of CFIR. The majority of physicians (74.3%) prescribe hydroxyurea, and half stated hydroxyurea is the standard of care. Among clinicians, barriers included limited knowledge of the drug, as well as low self-efficacy to prescribe among physicians and to counsel among nurses; perceived side effects; perceived patient preference for traditional medicine; cost for patient and expense of accompanying laboratory monitoring; and limited availability of the drug and equipment for laboratory monitoring. Among patients and caregivers, barriers included lack of knowledge; perceived side effects; cost; religious beliefs of disease causation; and lack of pediatric formulation. Conclusions: Findings suggest that patient, provider, and health systems-level interventions are needed to improve hydroxyurea uptake among providers and adherence among patients with sickle cell disease in Nigeria. Interventions such as patient education, provider training, and policy change could address the disproportionate burden of sickle cell disease in sub-Saharan Africa and thus improve health equity.

Child mortality from sickle cell disease in Nigeria: a model-estimated, population-level analysis of data from the 2018 Demographic and Health Survey

SummaryBackgroundChild mortality from sickle cell disease in sub-Saharan Africa is presumed to be high but is not well quantified. This uncertainty contributes to the neglect of sickle cell disease and delays the prioritisation of interventions. In this study, we estimated the mortality of children in Nigeria with sickle cell disease, and the proportion of national under-5 mortality attributable to sickle cell disease.MethodsWe did a model-estimated, population-level analysis of data from Nigeria's 2018 Demographic and Health Survey (DHS) to estimate the prevalence and geographical distribution of HbSS and HbSC genotypes assuming Hardy-Weinberg equilibrium near birth. Interviews for the survey were done between Aug 14 and Dec 29, 2018, and the embedded sickle cell disease survey was done in a randomly selected third of the overall survey's households. We developed an approach for estimating child mortality from sickle cell disease by combining information on tested children and their untested siblings. Tested children were aged 6–59 months at the time of the survey. Untested siblings born 0–14 years before the survey were also included in analyses. Testing as part of the DHS was done without regard to disease status. We analysed mortality differences using the inheritance-derived genotypic distribution of untested siblings older than the tested cohort, enabling us to estimate excess mortality from sickle cell disease for the older-sibling cohort (ie, those born between 2003 and 2013).FindingsWe analysed test results for 11 186 children aged 6–59 months from 7411 households in Nigeria. The estimated average birth prevalence of HbSS was 1·21% (95% CI 1·09–1·37) and was 0·24% (0·19–0·31) for HbSC. We obtained data for estimating child mortality from 10 195 tested children (who could be matched to the individual mother survey) and 17 205 of their untested siblings. 15 227 of the siblings were in the older-sibling cohort. The group of children with sickle cell disease born between 2003 and 2013 with at least one younger sibling in the survey had about 370 excess under-5 deaths per 1000 livebirths (95% CI 150–580; p=0·0008) than children with HbAA. The estimated national average under-5 mortality for children with sickle cell disease born between 2003 and 2013 was 490 per 1000 livebirths (95% CI 270–700), 4·0 times higher (95% CI 2·1–6·0) than children with HbAA. About 4·2% (95% CI 1·7–6·9) of national under-5 mortality was attributable to excess mortality from sickle cell disease.InterpretationThe burden of child mortality from sickle cell disease in Nigeria continues to be disproportionately higher than the burden of mortality of children without sickle cell disease. Most of these deaths could be prevented if adequate resources were allocated and available focused interventions were implemented. The methods developed in this study could be used to estimate the burden of sickle cell disease elsewhere in Africa and south Asia.FundingSickle Pan African Research Consortium, and the Bill & Melinda Gates Foundation.

Stroke in Pediatric Sickle Cell Disease in Sub-Saharan Africa: Systematic Review and Estimated Prevalence

Background: Most people with sickle cell disease (SCD) live in Sub-Saharan Africa (SSA); many do not survive to adulthood (Grosse et al. Am J Prev Med 2011). Stroke is a common complication of SCD in the region (Ohene-Frempong et al.Blood 1998), yet the region's burden of pediatric SCD stroke is unknown. This systematic review aims to describe what is known, and to estimate the number of children affected by SCD stroke in SSA.Methods: Systematic reviews using Pubmed, Embase, and Web of Science were performed for all studies reporting pediatric SCD stroke prevalence data. Keyword search strategy included these or related terms: “stroke” or “brain” and “sickle cell” and “Africa” or each country in SSA available in English or French. Publication dates were selected between 1980 and December 13, 2016. Using pre-selected inclusion criteria, titles and abstracts were screened and full-text articles were reviewed. For publications meeting inclusion criteria, extracted data included: study and participant characteristics, number of patients with stroke, diagnostic criteria, imaging, management, recurrence. The number of children affected by SCD stroke in SSA was estimated based on current estimates of national population and S allele frequency (Piel et al. Lancet 2013) and the stroke prevalence in the extracted studies. The stroke prevalence in SSA was estimated based on both fixed-effect analysis and random-effect analysis.Results: After duplicates were removed, 133 individual articles remained. Ten full text articles met review selection criteria, including one in French. In all, papers reported data from seven countries in the region, including four reports from Nigeria. Cross-sectional SCD clinic-based data, with a sample size of 6,289 patients, reported pediatric stroke prevalence of 2.9-16.9%. Diagnostic criteria of stroke varied by site and were limited by access to brain imaging, which was reported in only half of the included studies. Treatment for stroke included packed red blood cell transfusion, exchange transfusion, or hyperhydration. Secondary stroke prevention with chronic blood transfusion or hydroxyurea was offered at two of 10 sites. Recurrence data was limited by variable study follow-up and limited reporting times. Using available sickle gene frequencies by country, estimated births affected by SCD per country in SSA, and a linear- or random-effects model, pediatric stroke prevalence in SSA was projected as 279,908 (95% CI: 240,335-319,481) and 561,746 (347,472-775,056), respectively. Estimates do not include stroke- or disease-associated mortality.Conclusion: This meta-analysis estimates prevalence of pediatric SCD stroke in SSA, underscoring the region's high stroke burden. Multiple clinic-based cross-sectional studies reported stroke prevalence comparable to data from high income countries prior to implementation of standardized prevention strategies. Accuracy is limited by different approaches to stroke diagnosis, paucity of population-based data on disease prevalence and mortality, regional variation in disease prevalence and severity, and overall high rates of early death in children with SCD. Available data would skew towards surviving patients, leading to possible underreporting of people at risk for SCD stroke. Improved diagnostic specificity with standardized criteria and imaging would be useful for identification of strokes. Understanding the large numbers affected by SCD stroke is critical for focusing public health efforts to introduce preventive measures to reduce stroke risk and to implement rehabilitative strategies. Adopting standardized primary and secondary stroke prevention measures in SSA may decrease the burden of SCD-associated stroke.This work was supported by funding from the National Institutes of Health (5R21HD089791, PIs Idro, Green). DisclosuresNo relevant conflicts of interest to declare.

Systemic complications and imaging challenges of sickle cell disease in sub-saharan Africa

With improved life expectancy of people living with sickle cell disease (SCD) as a result of modern interventions, chronic problems such as pulmonary, abdominal, cardiovascular, musculoskeletal, and obstetric challenges are more often encountered. The need for radiological examination is, therefore, growing for the early diagnosis of these complications and improved prognosis. The emphasis, therefore, should be toward safer diagnostic options such as ultrasonography, transcranial Doppler ultrasound, and echocardiography as repeated radiation is counterproductive. This review is aimed at highlighting the imaging challenges encountered in the management of SCD in sub-Saharan Africa and possible ways of mitigating them. We reviewed available electronic literature in the last 20 years, especially articles from Google Scholar and PubMed with search keywords of imaging challenges, sickle cell disease, and sub-Saharan Africa. The challenges identified in this review include lack of institutional infrastructure, poor equipment availability, weak health and imaging personnel capacity, treatment affordability, service accessibility, and poor research and training facilities. With the increasing longevity of SCD individuals in sub-Saharan Africa, imaging requirements are rising. Repeated exposure to radiation should be minimized as much as possible. Engagement of the private sector through public-private partnership in equipping health institutions with radiological equipment, as well as training of appropriate personnel for their deployment is strongly recommended to enhance care, prevent complications, and improve outcomes for SCD in sub-Saharan Africa.

Low- Versus Moderate-Dose Hydroxyurea for Secondary Stroke Prevention in Children with Sickle Cell Disease in Sub-Saharan Africa: Final Results of a Randomized Controlled Trial, Sprint Trial

Introduction Strokes are a preventable cause of neurological morbidity and premature death, particularly in children with sickle cell anemia (SCA) living in low-resource countries. If untreated, 50% of children with SCA their first overt ischemic stroke will have a recurrent stroke within two years of the event. In high-income countries, ASH 2020 guidelines recommend indefinite regular blood transfusion therapy for secondary stroke prevention (Blood Adv. 2020). Unfortunately, regular blood transfusion therapy is not a feasible option for children with SCA in sub-Saharan Africa due to the high cost of monthly blood transfusion, limited blood supply, and unsafe transfusion practices. Also, children who receive regular blood transfusions will ultimately require daily iron chelation at a cost that is prohibitive to most families in low-income settings. One randomized controlled trial provided evidence that HU therapy may be an effective therapy for secondary prevention of strokes when compared to no therapy (Blood. 2012;119(17):3925-3932). In the SWiTCH trial, the incidence rate of stroke recurrence in the group randomly allocated to receive maximum tolerated dose HU therapy was significantly higher than the group randomly assigned to receive blood transfusion therapy (5.6 and 0 events per 100 person-years, respectively, but considerably lower when compared to children not treated with any treatment, approximately 28 events per 100 person-years (Niger Postgrad Med J. 2013;20(3):181-187). Given the practical limitations for regular blood transfusion therapy, we tested the hypothesis that for secondary stroke prevention among children with SCA and acute overt ischemic stroke, fixed moderated dose HU therapy (~20 mg/kg/day) results in 80% relative risk reduction when compared to fixed low-dose HU therapy (10 mg/kg/day) in a randomized controlled trial (SPRINT Trial; NCT02675790). Methodology In phase III controlled trial, partially blind d controlled trial, we randomly assigned children 1 - 16 years of age with SCA and a new-onset of ischemic stroke (within 1 month) to receive fixed moderate-dose HU therapy at 20 mg/kg/day or fixed-low dose HU therapy at 10 mg/kg/day) with a monthly follow-up for at least 36 months. The primary endpoint was a recurrence of overt stroke or transient ischemic attack. Myelosuppression was assessed with monthly CBCs. Adherence to hydroxyurea was based on an increase in MCV from baseline and monthly pill count return, as a percent of dispensed pills. Results A total of 101 children with SCA were randomly assigned to fixed low- (~10 mg/kg/day) or moderate- (~20 mg/kg/day) dose hydroxyurea. The mean age was 6.6 years; 55.4% were males, and the median follow up was 1.6 years (IQR 1.0 - 2.3). The DSMB stopped the trial early due to the futility of the primary endpoint. In the fixed low- and moderate-dose groups, the incidence rates of recurrent strokes per 100 person-years were 7.1 and 6.0, respectively, incidence rate ratio of 0.85 (95% CI: 0.20 - 3.34), p=0.999. The incidence rates of mortality per 100 person-years in the fixed low dose and moderate- fixed-dose groups were 2.38 and 3.63, respectively, with an incidence rate ratio of 1.53 (95% CI: 0.18 - 18.30), p=0.98. No participant had hydroxyurea therapy stopped because of myelosuppression. As a measure of adherence, MCV from baseline to endpoint increased 6.2 fl and 13.3 fl in the fixed low- and moderate-dose groups, respectively, p=0.025; returned pills during the trial were 3.3% and 3.5% in the fixed low- and moderate-dose groups, respectively, p= 0.76. Conclusion For secondary stroke prevention, in a randomized controlled trial in children with SCA and new onset of ischemic strokes, fixed low-dose, when compared to fixed moderate-dose hydroxyurea therapy, demonstrated no difference in the incidence rate of stroke recurrence. Fixed low-dose hydroxyurea for secondary prevention of strokes in Nigeria provided similar stroke recurrence rate, when compared to the SWiTCH Trial (Blood. 2012;119(17):3925-3932) with the maximum tolerated dose of hydroxyurea of 7.0 and 5.7 events per 100 person-years, respectively. For secondary stroke prevention, in low-income settings without access to indefinite regular blood transfusion therapy, fixed low-dose hydroxyurea of at least 10 mg/kg/day with biannual CBC is a new evidence-based strategy to prevent strokes and minimize unnecessary laboratory testing. Disclosures DeBaun: Global Blood Therapeutics (GBT): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: fixed low and moderate dose hydroxyurea for primary stroke prevention in sickle cell

Screening infants for sickle cell disease in sub-Saharan Africa: starting the journey to a sustainable model in primary care

Screening infants for sickle cell disease in sub-Saharan Africa: starting the journey to a sustainable model in primary care

Red Blood Cell Alloimmunization in Transfused Patients With Sickle Cell Disease in Sub-Saharan Africa; a Systematic Review and Meta-Analysis.

Sickle cell disease (SCD) is the most common monogenic disorder in sub-Saharan Africa (SSA). Blood transfusion to increase the oxygen carrying capacity of blood is vital in the management of many patients with SCD. However, red blood cell (RBC) alloimmunization is a major challenge to transfusions in these patients. Commonly in SSA, pretransfusion tests only involve ABO D grouping and compatibility without RBC antibody testing. Data on the frequency of RBC alloimmunization in patients with SCD in SSA are limited. We performed a systematic review and meta-analysis on available data on alloimmunization in transfused patients with SCD to determine the published prevalence of RBC alloimmunization in SCD patients in SSA. Six databases were systematically searched to identify relevant studies, without year or language restrictions. In all, 249 articles were identified and 15 met our selection criteria. The overall proportion of alloimmunization was 7.4 (95% confidence interval: 5.1-10.0) per 100 transfused patients. Antibodies against E, D, C, and K antigens accounted for almost half of antibody specificities, and antibodies to low- and high-frequency antigens were also common and represented almost 30% (20% to low-frequency antigens and 9% to high-frequency antigens) of specificities. Heterogeneity between studies was moderate, and meta-analysis found region of Africa as the major contributor to the heterogeneity. We also observed inconsistencies across studies in reporting of factors that may influence alloimmunization. This review provides an overview of the extent of the alloimmunization problem in SSA and provides a baseline against which to compare the effect of any interventions to reduce the alloimmunization risk.

Health-related quality of life of adolescents with sickle cell disease in sub-Saharan Africa: a cross-sectional study

BackgroundSickle cell disease (SCD) is a chronic hematologic disease associated with increased morbidity and mortality. Hemoglobinopathies are the most prevalent genetic disease globally, and SCD is estimated to affect 0.7% of Ugandan. The disease may adversely impact on the quality of life of sickle cell patients. This study aimed to evaluate the health related quality of life (HRoL) of adolescents with SCD.MethodsThis was a mixed-methods study of adolescents with sickle cell disease and their caretakers living in Kampala city, Uganda. All children aged 8–17 years with homozygous sickle cell disease attending the sickle cell clinic at Mulago Hospital during the study period were included in this study. Participants completed the PedsQL™ generic core scales parent-proxy and child self-report questionnaire during a routine clinic visit. HRQoL was the primary outcome measured. Socio-demographics and disease related data were obtained through personal interview with caretakers and reviewing patients’ medical records. Mean scores were used for HRQoL and linear regression for associated factors.ResultsOf the 140 adolescents with SCD included in the study, 40% were male. A total of 95 adolescents (68%) were between the age of 8–12 years with a mean age of 14.25 years. The physical function was assessed slightly higher by adolescents with a mean score of57.5 ± 20.3 compare to caretakers with 52.8 ± 22.1(p < 0.001). As assessed by caretakers, physical HRQoL scores were negatively associated with pain about-10.02 CI [− 19.22, − 0.81](p = 0.033), whereas it was positively associated with Pneumococcal vaccine with the score of 28.43 CI [16.78,40.09](p < 0.001) as assessed by adolescents and 31.37CI [22.22,40.51](p < 0.001) by caretakers. Pneumococcal vaccination impacted positively the psychosocial functioning with a score of 8.67CI [1.51,15.84] (p = 0.018) as assessed by children and 15.94 CI [5.50,26.38](p = 0.003) as assessed by the caretakers.ConclusionsThis study highlighted that pain was negatively associated with both physical and psychosocial functioning; whereas getting Pneumococcal vaccine was positively associated with both physical and psychosocial functioning as reported by children and caretakers.

Stroke Prevalence in Children With Sickle Cell Disease in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Objectives. The prevalence of stroke among children with sickle cell disease (SCD) in sub-Saharan Africa was systematically reviewed. Methods. Comprehensive searches of PubMed, Embase, and Web of Science were performed for articles published between 1980 and 2016 (English or French) reporting stroke prevalence. Using preselected inclusion criteria, titles and abstracts were screened and full-text articles were reviewed. Results. Ten full-text articles met selection criteria. Cross-sectional clinic-based data reported 2.9% to 16.9% stroke prevalence among children with SCD. Using available sickle gene frequencies by country, estimated pediatric mortality, and fixed- and random-effects model, the number of affected individuals is projected as 29 800 (95% confidence interval = 25 571-34 027) and 59 732 (37 004-82 460), respectively. Conclusion. Systematic review enabled the estimation of the number of children with SCD stroke in sub-Saharan Africa. High disease mortality, inaccurate diagnosis, and regional variability of risk hamper more precise estimates. Adopting standardized stroke assessments may provide more accurate determination of numbers affected to inform preventive interventions.

White Paper: Pathways to Progress in Newborn Screening for Sickle Cell Disease in Sub-Saharan Africa.

Sickle Cell Disease (SCD) is among the most common single-gene diseases in the world but evidence-based comprehensive health care has not been implemented where the highest prevalence of SCD occurs, in sub-Saharan Africa (SSA). It represents an urgent health burden, both in terms of mortality and morbidity with an estimated mortality of 8–16% in children under 5 years in SSA. Addressing the high mortality of SCD in SSA and for effective management of SCD, newborn screening (NBS) should be incorporated with prevention of infections (including pneumococcal septicaemia and malaria), parental education and support at all levels of healthcare provision to enable timely recognition. The NBS working group of the Africa Sickle Cell Research Network (AfroSickleNet) collaboration surveyed current projects in NBS in SSA, and current conditions that hinder more widespread implementation of NBS for SCD. Solutions based on new point-of-care testing technology to disseminate education, and implementation science approaches that leverage existing resources are proposed.

Haemoglobin F, A2, and S levels in subjects with or without sickle cell trait in south-eastern Gabon

ABSTRACTBackground: Infant mortality due to sickle cell disease in sub-Saharan Africa is high, necessitating a better understanding of the modulating factors of the disease in this region.Methods: We assessed the hereditary persistence of foetal haemoglobin and α-thalassemia. We diagnosed 787 subjects, with or without sickle cell trait, by capillary electrophoresis in the Medical Diagnostic Laboratory of the CIRMF (Franceville, Gabon).Results: Heterocellular and pancellular forms of hereditary persistence of foetal haemoglobin occurred at low rates of 10.9 and 2.3%, respectively. The distribution of HbS levels in individuals with sickle cell trait was trimodal, showing a high percentage (52.4%) of heterozygous subjects with α-thalassemia. The distribution of HbA2 levels was bimodal in individuals without sickle cell trait, estimated to be comprised of 12 and 15% of α and β-thalassemic heterozygous subjects, respectively.Conclusions: In sub-Saharan Africa, α-thalassemia is a far more prevalent modulating factor than hereditary persistence of foetal haemoglobin. Our study highlights the need for further investigation of thalassemia, haemoglobinopathies that are neglected in sub-Saharan Africa.

Is integrating sickle cell disease and HIV screening logical?

Is integrating sickle cell disease and HIV screening logical?

Sickle cell disease in Sub-Saharan Africa: Molecular mechanisms underlying episodic crises, current and emerging therapeutic strategies in treatment

Sickle cell disease (SCD) is a haematological disease that affects multiple organs, thus eliciting episodes of chronic pain, acute anaemia and infection, due to a single nucleotide mutation in the β-globin gene, which results in the substitution of a glutamic acid residue in place of valine on the β-globin chain of the resultant haemoglobin protein molecule, the sickle haemoglobin (HbS). SCD is a major cause of morbidity and mortality characterized by episodes of vaso-occlusivecrises, pain syndromes and end organ dysfunctions. Its global prevalence is highest in Sub-Saharan Africa with 75% of global births living in this region, of which Nigeria has the highest number of SCD patients with about 100.000 births each year. The burden of SCD in the sub-Saharan region of Africa is enormous. Emotional, financial and total healthcare costs are monumental. An understanding of the mechanism underlying the vaso-occlusive crises, pain syndromes, inflammatoryconditions and other sequelae of SCD appears to be essential in providing more rational treatments. The present review discuses the prevalence of SCD in Africa, molecular mechanisms underlying SCD episodic crises including vaso-occlusive syndrome, anaemia and infection. Current available treatments modalities in Sub-Saharan Africa and possible new treatment methods that cure SCD are re-examined in light of these mechanisms.

To begin at the beginning: sickle cell disease in Africa

Sickle cell disease is one of the most common severe inherited disorders in the world, with numbers projected to increase substantially in the next 40 years. 1 Piel FB Hay SI Gupta S Weatherall DJ Williams TN Global burden of sickle cell anaemia in children under five, 2010–2050: modelling based on demographics, excess mortality, and interventions. PLoS Med. 2013; 10: e1001484 Crossref PubMed Scopus (509) Google Scholar It is characterised by unpredictable episodes of acute illness, and chronic organ damage. Sickle cell disease has been studied in high-income countries for about 100 years, but treatment options are few and life expectancy is still reduced by about 30 years compared with those without the disease. 2 Brousse V Makani J Rees DC Management of sickle cell disease in the community. BMJ. 2014; 348: g1765 Crossref PubMed Scopus (42) Google Scholar Early renal damage in patients with sickle cell disease in sub-Saharan Africa: a multinational, prospective, cross-sectional studyHyperhaemolysis is associated with albuminuria, with an age-dependent effect, in the SS and Sβ0 phenotypes only, suggesting a different pathological mechanism for glomerular disease in the patients with SC and Sβ+ phenotypes. However, both phenotypes are associated with a high prevalence of albuminuria in childhood. Therefore, screening for albuminuria is advised in African children with sickle cell disease to detect early renal damage. Full-Text PDF

Early renal damage in patients with sickle cell disease in sub-Saharan Africa: a multinational, prospective, cross-sectional study

Chronic kidney disease is one of the leading causes of mortality in patients with sickle cell disease. However, it has been almost exclusively studied in patients with the SS phenotype and in high-income countries, despite more than 80% of patients living in Africa. We looked for the determinants of glomerulopathy in a multinational cohort of patients with sickle cell disease of different phenotypes in sub-Saharan Africa. In the CADRE cohort, we prospectively included patients 3 years and older with sickle cell disease of all haemoglobin phenotypes in Cameroon, Côte d'Ivoire, Mali, and Senegal. All individuals were assessed at steady state. The main outcome of interest was albuminuria defined as a urine albumin-to-creatinine ratio of greater than 30 mg/g. We investigated the clinical and biological determinants (including haemolysis markers) of albuminuria in two main phenotype groups (SS and Sβ(0); SC and Sβ(+)) with further stratification by age and country. The study is ongoing because of follow-up. 2582 patients with sickle cell disease were included (1776 SS, 136 Sβ(0), 511 SC, and 159 Sβ(+)). 644 patients with the SS and Sβ(0) phenotypes (33·7%, 95% CI 31·6-35·8) and 110 with the SC and Sβ(+) phenotypes (16·4%, 13·6-19·2) had albuminuria. In the SS and Sβ(0) group, albuminuria was detected in 144 (27%) of 527 children younger than 10 years and its frequency increased with age (29 [48%] of 60 patients aged >40 years). Multivariable analysis showed that albuminuria was associated with age (odds ratio 1·43, 95% CI 1·20-1·71; p<0·0001), female sex (1·35, 1·02-1·82; p=0·045), low haemoglobin (0·79, 0·66-0·93; p=0·006), high lactate dehydrogenase concentrations (1·33, 1·14-1·58; p=0·0009), and, using Côte d'Ivoire as the reference, Mali (2·49, 1·64-3·79; p=0·042) and Cameroon (1·59, 1·01-2·51; p=0·0007) in patients with the SS and Sβ(0) phenotypes. The magnitude of the association of albuminuria with haemoglobin and lactate dehydrogenase concentrations increased with age. In the SC and Sβ(+) patients, only low haemoglobin (0·69, 0·48-0·97; p=0·029), high blood pressure (1·63, 1·17-2·27; p=0·0017), and Mali (3·75, 1·75-8·04; p<0·0001) were associated with albuminuria. Hyperhaemolysis is associated with albuminuria, with an age-dependent effect, in the SS and Sβ(0) phenotypes only, suggesting a different pathological mechanism for glomerular disease in the patients with SC and Sβ(+) phenotypes. However, both phenotypes are associated with a high prevalence of albuminuria in childhood. Therefore, screening for albuminuria is advised in African children with sickle cell disease to detect early renal damage. Paris Cité Sorbonne University (GrEX project) and Cardiology and Development.

Sickle cell disease in sub-Saharan Africa

In the late 1990s publications on cohorts of sickle cell disease (SCD) patients, followed since birth, showed that the life expectancy of SCD patients in developed countries could approach that of those without SCD, when managed appropriately. Between 2005 and 2008, SCD was declared as a public health priority issue worldwide. In 2006, the WHO recommended that African states should include the fight against SCD in their health policies. Nevertheless, there are, as of yet, no data on effective strategies to implement SCD control in these countries. This review discusses the stakes and proposes strategies for SCD management and research in sub-Saharan Africa. This work is a review of the recent literature on the burden of SCD in sub-Saharan Africa; on approaches that resulted in improved survival and comfort for SCD patients in developed countries; and, in contrast, on the inadequacies of most issues relating to the fight against SCD in Africa. Multiple constraints require an organization based on a network of health professionals working in sickle cell referral centers with specific missions of research, communication, teaching, establishment of guidelines for diagnosis, treatment, and prevention, and the centers of competence that will focus primarily on the screening, diagnosis, and management of SCD patients favoring equity in access to care.