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Many children with sickle cell disease living in sub-Saharan Africa die before reaching age 5 years. We estimate the child mortality associated with sickle cell anaemia using an indirect approach to overcome the absence of systematic screening at birth.We did a retrospective, multicentre, case-control study in five countries in sub-Saharan Africa (Burkina Faso, Democratic Republic of the Congo, Côte d'Ivoire, Mali, and Senegal). Women with at least one child with a confirmed SS haemoglobin phenotype (sickle cell anaemia) and who had at least three (alive or deceased) children from the same father born more than 5 years ago were recruited at an outpatient consultation in a sickle cell disease care centre. Women who had children without sickle cell disease (control group) were recruited from the same area, with inclusion criteria of being a neighbour or relative of one of the mothers included in the study who had a child with sickle cell anaemia, having no child or other first-degree relative with major sickle cell syndrome, having at least three children (alive or deceased) born more than 5 years ago, and having a confirmed haemoglobin AA phenotype. During the mothers' interview, we collected data concerning the mortality of siblings from the same father of a child with sickle cell anaemia and characteristics of the family, such as age at the time of the survey and the level of education of both parents. Mortality rates were calculated for children younger than 1, 5, and 10 years using the Kaplan-Meier method after excluding the index children. We assumed, as per Mendel law, that in families who have a child with sickle cell anaemia and healthy heterozygous parents, 25% of children born on average have sickle cell anaemia. A multivariate Cox model was used to describe socioeconomic and geographical factors associated with mortality.Between Sept 1, 2017, and Nov 30, 2020, 1563 women who had at least one child with sickle cell anaemia and 4972 women from the same neighbourhood who had children without sickle cell disease were assessed for eligibility. Of 1563 women, 248 were excluded because the genotype of the index child was SC or S β-thalassaemia. 1315 families with cases of sickle cell anaemia and 1243 control families were included in the study. The median age of children (alive) was 14 years (IQR 8-20) in control families and 13 years (8-19) in families with cases of sickle cell anaemia. 5532 [50·6%] of 10 924 children were male. Mortality rates were 15·3% (95% CI 13·3-17·3) for children with sickle cell anaemia younger than 1 year, 36·4% (33·4-39·4) for those younger than 5 years, and 43·3% (39·3-47·3) for those younger than 10 years. Multivariate Cox survival analysis showed that belonging to a family with sickle cell anaemia (hazard ratio [HR] 2·23, 95% CI 1·96-2·54), living in the Democratic Republic of the Congo (HR 1·64, 1·34-2·01), having an older parent (father or mother age had similar effect; HR 1·12, 1·05-1·19 per 10 years of age), or a significantly higher global Multidimensional Poverty Index (HR 1·09, 1·03-1·14), independently increased the risk of mortality. Whereas, living in Senegal (HR 0·70, 95% CI 0·57-0·86) or having a mother with higher education (high school HR 0·66, 0·55-0·80 or advanced HR 0·41, 0·28-0·61) independently decreased the risk of mortality.Although higher than in high-income countries and affected by non-specific socioeconomic factors, the estimated mortality in children with sickle cell anaemia living in sub-Saharan African cities was substantially lower than previous estimates, suggesting an improvement of sickle cell anaemia care in this setting.Fondation Pierre Fabre.For the French translation of the abstract see Supplementary Materials section.

Sickle cell disease (SCD), the most common monogenic disease worldwide, is marked by a phenotypic variability that is, to date, only partially understood. Because inflammation plays a major role in SCD pathophysiology, we hypothesized that single nucleotide polymorphisms (SNP) in genes encoding functionally important inflammatory proteins might modulate the occurrence of SCD complications. We assessed the association between 20 SNPs in genes encoding Toll-like receptors (TLR), NK cell receptors (NKG), histocompatibility leukocyte antigens (HLA), major histocompatibility complex class I polypeptide-related sequence A (MICA) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and the occurrence of six SCD clinical complications (stroke, acute chest syndrome (ACS), leg ulcers, cholelithiasis, osteonecrosis, or retinopathy). This study was performed in a cohort of 500 patients. We found that the

Background Treatment of acute malnutrition in infants under 6 months is a relevant topic regarding the global problem of maternal and child malnutrition. While treatment for older age groups has shifted more towards an outpatient, community based approach, young infants are mostly treated in hospital. This study aims to describe barriers and facilitators for outpatient and inpatient treatment of malnourished infants under 6 months in Senegal. Methods This qualitative descriptive study uses in-depth interviews with health workers and focus group discussions with mothers of malnourished infants, conducted from June to September 2015 in two case clinics. In data analysis, Collins’ 3 key factors for a successful nutrition program were used as a theoretical framework: access, quality of care and community engagement. Results Within Collins’ 3 key factors, 9 facilitators and barriers have emerged from the data. Key factor access: Outpatient care was perceived as more accessible than inpatient concerning distance and cost, given that there is a milk supplement available. Trust could be more easily generated in an outpatient setting. Key factor quality of care: The cup and spoon re-lactation technique was efficiently used in outpatient setting, but needed close supervision. Basic medical care could be offered to outpatients provided that referral of complicated cases was adequate. Health education was more intensive with inpatients, but could be done with outpatients. Key factor community engagement: The community appeared to play a key role in treating malnourished young infants because of its influence on health seeking behaviour, peer support and breastfeeding practices. Conclusions Outpatient care does facilitate access, provided that an affordable milk supplement is available. Quality of care can be guaranteed using an appropriate re-lactation technique and a referral system for complications. The community has the potential to be much engaged, though more attention is required for breastfeeding education. In view of the magnitude of the health problem of young infant malnutrition and its strong relationship with breastfeeding practices, an outpatient community-based treatment approach needs to be considered.

International audience; BACKGROUND: Our objective was to investigate the combined and differential effects of alpha-thalassemia -3.7 kb deletion and HbF-promoting quantitative trait loci (HbF-QTL) in Senegalese hydroxyurea (HU)-free children and young adults with sickle cell anemia (SCA).PROCEDURE: Steady-state biological parameters and vaso-occlusive crises (VOC) requiring emergency admission were recorded over a 2-year period in 301 children with SCA. The age of the first hospitalized VOC was also recorded. These data were correlated with the alpha-globin and HbF-QTL genotypes. For the latter, three different genetic loci were studied (XmnI, rs7482144; BCL11A, rs1427407; and the HBS1L-MYB region, rs28384513) and a composite score was calculated, ranging from zero (none of these three polymorphisms) to six (all three polymorphisms at the homozygous state).RESULTS: A positive clinical impact of the HbF-QTL score on VOC rate, HbF, leucocytes, and C-reactive protein levels was observed only for patients without alpha-thalassemia deletion. Conversely, combination of homozygous -3.7 kb deletion with three to six HbF-QTL was associated with a higher VOC rate. The age of the first hospitalized VOC was delayed for patients with one or two alpha-thalassemia deletions and at least two HbF-QTL.CONCLUSION: Alpha-thalassemia -3.7 kb deletion and HbF-QTL are modulating factors of SCA clinical severity that interact with each other. They should be studied and interpreted together and not separately, at least in HU-free children.

Le syndrome de résistance à l'Adrénocorticotrophine Hormone (ACTH) est l'une des rares causes d'insuffisance surrénalienne chez l'enfant. Toutes les formes d'insensibilité héréditaire à l'ACTH décrites à ce jour sont d'origine autosomique récessive. Dans nos pays à ressources limitées, bon nombre de ces pathologies rares sont méconnues ou non diagnostiquées, en raison des plateaux techniques insuffisants. Nous rapportons l'observation d'un nourrisson de 4 mois hospitalisé pour des hypoglycémies réfractaires et chez qui; malgré la présence d'une mélanodermie généralisée et importante, des troubles digestifs, et des troubles ioniques, le diagnostic d'insuffisance cortisolique n'a été évoqué que rétrospectivement au décours d'un arrêt respiratoire avec une évolution favorable et dépendante de l'hydrocortisone. L'objectif de ce travail est donc, de mettre en exergue les particularités, cliniques, biologiques et thérapeutiques des déficits périphériques en cortisol, en dehors des blocs enzymatiques, notamment ce syndrome de résistance à l'ACTH.

Growth failure (GF) in children with sickle cell disease (SCD) tends to decline in high-income countries, but data are lacking in sub-Saharan Africa. We performed a cross-sectional study nested in the CADRE (Cœur, Arteres et DREpanocytose) cohort in Mali, Senegal, Cameroon, Gabon and the Ivory Coast. SCD patients and healthy controls aged 5-21 years old were recruited (n = 2583). Frequency of GF, defined as a height, weight or body mass index below the 5th percentile on World health Organization growth charts, was calculated. We assessed associations between GF and SCD phenotypic group, clinical and biological characteristics and history of SCD-related complications. GF was diagnosed in 51% of HbSS, 58% of HbSβ0 , 44% of HbSC, 38% of HbSβ+ patients and 32% of controls. GF in patients was positively associated with parents' lower education level, male sex, age 12-14 years, lower blood pressure, HbSS or HbSβ0 phenotypes, icterus, lower haemoglobin level, higher leucocyte count and microalbuminuria. No association was found between GF and clinical SCD-related complications. In sub-Saharan Africa, GF is still frequent in children with SCD, especially in males and during adolescence. GF is associated with haemolysis and microalbuminuria, but not with the history of SCD-related clinical complications.

La drépanocytose pose un problème de santé publique au Sénégal. Elle concerne principalement les enfants et les adolescents. L'objectif de notre travail était de déterminer les profils épidémiologiques, cliniques et hématologiques de la drépanocytose homozygote SS dans une cohorte d'enfants suivis à l'hôpital de la paix de Ziguinchor. Il s'agit d'une étude rétrospective portant sur des dossiers d'enfants drépanocytaires. Etaient inclus, les drépanocytaires SS âgés entre 2mois et 21ans, reçus en phase inter critique durant la période d'étude allant du 1er Janvier 2015 au 31 Août 2017. N'étaient pas inclus dans l'étude les hétérozygotes composites (SC, S béta thalassémie). Nous avons colligé 46 dossiers de drépanocytaires SS (20 filles et 26 garçons). L'âge moyen des enfants était de 8,0ans [11mois-21ans]. Environ 1/3 des enfants (39,1%) avaient un âge inférieur ou égal à 5 ans. Il y avait une diversité ethnique avec une prédominance de diola (30,2%) suivi de mandingue (27,9%) et de poular (25,6%). L'âge moyen des enfants à la 1ére crise était de 35,5mois [7-192 mois]. Plus de 1/3 des enfants (41,3%) avaient fait une 1ére crise avant le deuxième anniversaire. Le type de la 1ére crise, qu'avait présenté l'enfant, était dominé par la crise vaso-occlusive (32,6%) suivi du syndrome pied-main (30,4%). Les signes cliniques en phase inter critique étaient la pâleur 95,6%); l'ictère (36,9%) et la splénomégalie (21,7%). A l'hémogramme, le nombre de globules blancs moyen était de 12465 leucocytes/mm3 [5340-26900]. L'hyperleucocytose, supérieure à 10 000 leucocytes/mm3 était retrouvée chez 34 malades (73,9%). La totalité des malades présentait une anémie avec une moyenne 08,6 g/dl [05,7-11,8]. Le taux d'hémoglobine S variait entre 54,6 et 98,4%. Le diagnostic et la prise en charge médicale de la drépanocytose SS sont tardifs à Ziguinchor. Le dépistage néonatal pourrait favoriser une prise en charge précoce dans la région.

Sickle cell disease is a genetic disorder with a large variability in the pattern and severity of clinical manifestations. Different genetic modulators have been identified but very few epidemiologic data are available on these modifier genes in Senegal. This study aimed to determine their prevalence in a Senegalese sickle cell disease pediatric population. The following genetic parameters were genotyped in 295 sickle cell disease children of the Dakar pediatric hospital: sickle cell disease genotype [βS/βS (HBB: c.20A>T), βS/βC (HBB: c.19G>A), βS/β0-thalassemia (β0-thal)], XmnI polymorphism, the five most common α-thalassemia (α-thal) deletions and the A(-) and Betica glucose-6-phosphate-dehydrogenase (G6PD) deficient variants. Despite very few βS/βC and βS/β0-thal children (1.0% each), a novel frameshift β0-thal mutation was characterized: HBB: c.265_266del; p.Leu89Glufs*2. The -α3.7 (rightward) deletion was the only α-thal deletion identified in this cohort (12.0% allelic frequency). Most of βS/βS patients (61.9%) were homozygous for the XmnI polymorphism and assumed to carry a Senegal/Senegal βS haplotype. The remaining haplotypes were predominantly of the Benin type. While the Betica G6PD variant was quite frequent (13.0%), a low frequency of the A(-) variant was detected (1.0-2.0%). The systematic genotyping of the -α3.7 deletion and of the G6PD Betica variant in sickle cell disease patients from Senegal could be useful to identify patients at risk for several complications, such as cerebral vasculopathy, where it has been demonstrated that a normal α-globin genotype and G6PD deficiency are predisposing factors. These patients should be eligible for a transcranial Doppler examination that is not routinely offered in Senegal.

Introduction Expanded programme on immunizations in resource-limited settings currently measure vaccination coverage defined as the proportion of children aged 12-23 months that have completed their vaccination. However, this indicator does not address the important question of when the scheduled vaccines were administered. We assessed the determinants of timely immunization to help the national EPI program manage vaccine-preventable diseases and impact positively on child survival in Senegal. Methods Vaccination data were obtained from the Demographic and Health Survey (DHS) carried out across the 14 regions in the country. Children were aged between 12-23 months. The assessment of vaccination coverage was done with the health card and/or by the mother's recall of the vaccination act. For each vaccine, an assessment of delay in age-appropriate vaccination was done following WHO recommendations. Additionally, Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and cox-proportional hazards models were used to examine risk factors for delays. Results A total of 2444 living children between 12-23 months of age were included in the analysis. The country vaccination was below the WHO recommended coverage level and, there was a gap in timeliness of children immunization. While BCG vaccine uptake was over 95%, coverage decreased with increasing number of Pentavalent vaccine doses (Penta 1: 95.6%, Penta 2: 93.5%: Penta 3: 89.2%). Median delay for BCG was 1.7 weeks. For polio at birth, the median delay was 5 days; all other vaccine doses had median delays of 2-4 weeks. For Penta 1 and Penta 3, 23.5% and 15.7% were given late respectively. A quarter of measles vaccines were not administered or were scheduled after the recommended age. Vaccinations that were not administered within the recommended age ranges were associated with mothers' poor education level, multiple siblings, low socio-economic status and living in rural areas. Conclusion A significant delay in receipt of infant vaccines is found in Senegal while vaccine coverage is suboptimal. The national expanded program on immunization should consider measuring age at immunization or using seroepidemiological data to better monitor its impact.

The hyperhemolysis paradigm that describes overlapping "hyperhemolytic-endothelial dysfunction" and "high hemoglobin-hyperviscous" subphenotypes of sickle cell disease (SCD) patients is based on North American studies. We performed a transversal study nested in the CADRE cohort to analyze the association between steady-state hemolysis and vascular complications of SCD among sub-Saharan African patients. In Mali, Cameroon, and Ivory Coast, 2407 SCD patients (1751 SS or sickle β-zero-thalassemia [Sβ0], 495 SC, and 161 sickle β+-thalassemia [Sβ+]), aged 3 years old and over, were included at steady state. Relative hemolytic intensity was estimated from a composite index derived from principal component analysis, which included bilirubin levels or clinical icterus, and lactate dehydrogenase levels. We assessed vascular complications (elevated tricuspid regurgitant jet velocity [TRV], microalbuminuria, leg ulcers, priapism, stroke, and osteonecrosis) by clinical examination, laboratory tests, and echocardiography. After adjustment for age, sex, country, and SCD phenotype, a low hemoglobin level was significantly associated with TRV and microalbuminuria in the whole population and with leg ulcers in SS-Sβ0 adults. A high hemolysis index was associated with microalbuminuria in the whole population and with elevated TRV, microalbuminuria, and leg ulcers in SS-Sβ0 adults, but these associations were no longer significant after adjustment for hemoglobin level. In conclusion, severe anemia at steady state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy.

Le syndrome hémolytique et urémique (SHU) est une cause fréquente d’insuffisance rénale aiguë (IRA) organique chez l’enfant. C’est une complication évolutive des gastroentérites aiguës (GEA) en particulier à Escherichia coli de l’enfant. Notre objectif était de décrire les aspects cliniques, thérapeutiques et évolutifs de cette affection chez quatre enfants. Nous avions colligé quatre cas de SHU. L’âge moyen était de 10,5 mois (5-15mois) exclusivement des garçons. L’examen clinique retrouvait une anémie de type hémolytique (pâleur et ictére), un syndrome oedémateux avec oligo-anurie (2 cas), une hypertension artérielle (1 patient), une GEA avec déshydratation sévère et choc hypovolémique (2 patients), des troubles de conscience. L’IRA était notée chez tous les patients de même que la thrombopénie et les schizocytes au frottis. Le Coombs direct était négatif. Il y avait une hyperkaliémie (3patients) dont 1 patient supérieure à 9,2 mmol/l, une hyponatrémie à 129mmol/l(1 patient) et une hypernatrémie à 153mmol/l (1 patient). Le shu était secondaire à une pneumonie à pneumocoque (1 patient), une GEA à E. coli (1 patient). Le traitement était essentiellement symptomatique et comprenait la restriction hydrique, la transfusion de concentrés érythrocytaires, les diurétiques, la dialyse péritonéale et l’hémodialyse. L’évolution était marquée par la survenue d’une insuffisance rénale chronique (1 patient) après 6 mois de suivi et la guérison (1 cas). Nous avions noté 3décés.Le SHU est la cause la plus fréquente d’IRA organique du nourrisson. Le diagnostic est essentiellement biologique, le traitement est surtout symptomatique. The Pan African Medical Journal 2016;24

Background: Although a blood genetic disease, sickle cell disease (SCD) leads to a chronic vasculopathy with multiple organ involvement. We assessed arterial stiffness in SCD patients and looked for associations between arterial stiffness and SCD-related vascular complications. Methods: The CADRE (Coeur Artères et Drepanocytose, ie, Heart Arteries and Sickle Cell Disease) study prospectively recruited pediatric and adult SCD patients and healthy controls in Cameroon, Ivory Coast, Gabon, Mali, and Senegal. Patients underwent clinical examination, routine laboratory tests (complete blood count, serum creatinine level), urine albumin/creatinine ratio measure, and a measure of carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AI) at a steady state. The clinical and biological correlates of cf-PWV and AI were investigated by using a multivariable multilevel linear regression analysis with individuals nested in families further nested in countries. Results: Included were 3627 patients with SCD and 943 controls. Mean cf-PWV was lower in SCD patients (7.5±2.0 m/s) than in controls (9.1±2.4 m/s, P 0 than in SC-Sβ + phenotypes. AI, corrected for heart rate, increased more rapidly with age in SCD patients and was higher in SCD than in control adults. cf-PWV and AI were independently associated with age, sex, height, heart rate, mean blood pressure, hemoglobin level, country, and hemoglobin phenotype. After adjustment for these correlates, cf-PWV and AI were associated with the glomerular filtration rate and osteonecrosis. AI was also associated with stroke, pulmonary hypertension, and priapism, and cf-PWV was associated with microalbuminuria. Conclusions: PWV and AI are deeply modified in SCD patients in comparison with healthy controls. These changes are independently associated with a lower blood pressure and a higher heart rate but also with the hemoglobin phenotype. Moreover, PWV and AI are associated with several SCD clinical complications. Their prognostic value will be assessed at follow-up of the patients.