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

The prognosis of sickle cell disease (SCD) in adults is determined primarily by damage to targeted organs such as the brain. Cognitive dysfunction in SCD is a common chronic neurological manifestation, but studies remain mostly descriptive in adults. The objective of this study was to better characterize the cognitive profile and the association between cognitive dysfunction and brain lesions. We included adult patients with SCD referred for a neurological assessment. An adapted battery of neuropsychological tests was used to assess cognitive deficits. Brain or arterial abnormalities were assessed using brain magnetic resonance imaging/magnetic resonance angiography and a cervical and transcranial Doppler ultrasound. The cognitive profile of 96 patients was characterized by deficits in processing speed (58%), short-term memory (34%), and working memory (24%). Brain infarcts were found in 56% of patients and intracranial vasculopathy in 49%. Twenty percent of patients had no brain abnormalities. Processing speed dysfunction was associated with territorial infarcts (odds ratio [OR], 3.1; P = .03) and education outside of France (OR, 4.7; P = .02). Short-term memory dysfunction was associated with territorial infarcts (OR, 3.4; P = .01) and a low educational level (OR, 8.2; P = .01). Working memory dysfunction was associated with a low educational level (OR, 4.3; P = .05) and vasculopathy (OR, 3.7; P = .03). Cognitive dysfunction appears to be a hallmark sign of SCD, particularly for adults with sickle cell-related stroke or suspected neurological morbidity. Assessment of such dysfunction could be used in longitudinal follow-up and clinical trials.

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

La drépanocytose est l'une des maladies génétiques les plus fréquentes au monde. Elle entraîne la production d'une hémoglobine (Hb) anormale, l'HbS, à l'origine d'une hémolyse périphérique chronique [1]. L'anémie a été identifiée comme un facteur de morbi-mortalité de la drépanocytose dans plusieurs études, à la fois dans des pays du Nord [2] et du Sud [3], mais peu d'études ont analysé les déterminants du taux d'Hb dans le contexte africain. L'objectif de notre étude était d'analyser les facteurs associés au taux d'Hb chez les patients drépanocytaires africains notamment les facteurs spécifiques de la maladie comme l'hémolyse mais aussi des facteurs non spécifiques comme l'inflammation ou les facteurs socioéconomiques. Nous avons réalisé une étude transversale nichée dans une cohorte prospective multinationale. Nous avons réalisé nos analyses dans 3 groupes de patients selon le phénotype drépanocytaire : SS/Sβ0, SC et Sβ+. Nous avons étudié l'association entre le taux d'Hb avec les facteurs démographiques (pays, sexe, âge), l'indice de masse corporelle (IMC), l'hémolyse (ictère clinique, bilirubine, LDH, réticulocytes) et l'inflammation (leucocytes, plaquettes) à l'aide de modèles de régression linéaire. Nous avons réalisé des analyses en sous-groupe : (1) au sein de la population avec des marqueurs biologiques d'hémolyse disponibles (LDH et/ou bilirubine) ; (2) chez les enfants et les adultes en ajustant sur le niveau d'éducation des patients chez les adultes et sur le niveau d'étude paternel chez les enfants. Les variables avec ≤ 20 % de données manquantes ont été imputées par la méthode des imputations multiples. Au total, 4206 patients ont été inclus avec différents phénotypes drépanocytaires : SS/Sβ0 (n = 3425, 81 %), SC (n = 600, 14 %) et Sβ+ (n = 181, 5 %) avec un taux d'Hb médian de 7,9, 11,3 et 11,2 g/dL respectivement. Parmi les patients, 56,3 % étaient originaires d'Afrique de l'Ouest (Mali, Sénégal et Côte d'Ivoire) tandis que 43,7 % étaient originaires d'Afrique Centrale (Cameroun, Gabon et République Démocratique du Congo). En analyse multivariée, chez les patients SS/Sβ0, être originaire d'un pays d'Afrique Centrale (β = −0,5, p < 0,001), un IMC plus faible (β = 0,15, p < 0,001), la présence d'un ictère clinique (β = −0,24, p < 0,001) et un taux plus élevé de leucocytes (β = −0,21, p < 0,001) étaient associés de façon négative et indépendante au taux d'Hb tandis que chez les patients SC et Sβ+, les facteurs associés de façon significative au taux d'Hb étaient le sexe féminin (p < 0,001), un IMC plus faible (p = 0,007 et p = 0,02), la présence d'un ictère clinique (p = 0,02 et p = 0,016) et un taux plus élevé de plaquettes (p < 0,001). Dans le sous-groupe de patients avec une évaluation biologique de l'hémolyse, les LDH et le taux de réticulocytes étaient associés de façon négative et indépendante au taux d'Hb dans tous les phénotypes mais de façon plus importante chez les patients SS/Sβ0 (β = −0,17 et −0,1 respectivement versus −0,09 et −0,07 chez les patients SC et, −0,09 et −0,04 chez les patients Sβ+). Dans le population adulte, un plus haut niveau d'éducation était associé de façon positive au taux d'Hb chez les patients SC seulement. Dans la population pédiatrique, le niveau d'éducation paternel n'était pas associé de façon significative au taux d'Hb quel que soit le phénotype. Nous avons identifié des interactions significatives entre : (1) le sexe et la classe d'âge avec un écart du taux d'Hb entre les hommes et les femmes plus important chez les adultes, et chez les patients SC et Sβ+ par rapport aux patients SS/Sβ0 ; (2) entre le pays d'origine et la présence d'un ictère clinique chez les patients SS/Sβ0 avec un impact négatif de l'ictère sur le taux d'Hb plus important chez les patients originaires d'Afrique Centrale par rapport aux patients originaires d'Afrique de l'Ouest. Nous avons pu montrer dans une large cohorte de patients drépanocytaires africains une association du taux d'Hb avec des facteurs liés à la drépanocytose comme l'hémolyse, mais aussi avec d'autres facteurs plus complexes et moins spécifiques de la maladie comme le pays d'origine et l'inflammation, et ce de façon indépendante de l'hémolyse. Nos résultats suggèrent aussi la présence de facteurs de confusion non mesurés associés à la région d'origine comme la malnutrition, la pression infectieuse et les facteurs génétiques autres que le phénotype comme les haplotypes de la β-globine.

Topic: 26. Sickle cell disease Background: Sickle cell disease (SCD) is one of the most frequent monogenic disease worldwide leading to the production of the abnormal haemoglobin (Hb) S that causes chronic peripheral haemolysis. Anaemia has been identified as a morbidity and mortality factor of SCD in several studies, in both developed and undeveloped countries, but few studies have analysed the determinants of Hb level in the African context. Aims: The aim of this study was to analyse the factors associated with Hb level in African patients with SCD, especially disease-specific factors such as haemolysis but also non-specific factors such as inflammation and socio-demographic factors. Methods: We conducted a cross-sectional study nested in the multinational prospective observational cohort CADRE, initiated to describe the natural history of SCD in sub-Saharan Africa. We conducted our analyses in 3 groups of patients according to their phenotype, SS/Sβ0, SC and Sβ+. We studied the association between Hb level with demographic factors (country, sex, age, educational level), body mass index (BMI), haemolysis assessed by clinical icterus, bilirubin or LDH levels and inflammation assessed by leukocytes and platelets count, using a linear regression model. We performed sub-group analyses: 1/in the population with haemolysis biomarkers available i.e. LDH and/or bilirubin; 2/in adults and children, adjusting for patient education level in adults and father education level in children. Variables with ≤20% missing data were imputed with multiple imputations by chained equations. Results: 4206 patients were included, with various SCD phenotypes: SS/Sβ0 (n=3425, 81%), SC (n=600, 14%) and Sβ+ (n=181, 5%) with median Hb level of 7.9, 11.3 and 11.2 g/dL respectively. 56.3% of the patients were from West Africa (Mali, Senegal and Ivory Coast) whereas 43.7% were from Central Africa (Cameroon, Gabon and Democratic Republic of Congo). In multivariate analysis in SS/Sβ0 patients, central African countries (β=-0.5, p<0.001), lower BMI (β=0.15, p<0.001), clinical icterus (β=-0.24, p<0.001) and higher leukocytes counts (β=-0.21, p<0.001) were independently negatively associated with Hb level whereas in SC and Sβ+ patients, female gender (p<0.001), lower BMI (p=0.007 and p=0.02), clinical icterus (p=0.02 and p=0.016) and higher platelets counts (p<0.001) were. In the sub-group of patients with biological haemolysis evaluation, LDH and reticulocytes count were independently negatively associated with Hb level in all SCD phenotypes but more importantly in SS/Sβ0 patients. In the adult population, a higher educational level was positively associated with Hb level in SC patients only. In the pediatric population, father educational level was not associated with Hb level in all phenotype groups. We found significant interactions between: 1/sex and age class in all the models with a Hb level gap between male and female more important in adult patients compared to children and in SC and Sβ+ patients compared to SS/Sβ0 patients; 2/country and clinical icterus in SS/Sβ0 patients with a negative effect of icterus on Hb level more important in central African countries.Summary/Conclusion: Our results show that anaemia in SCD African patients is the result of disease-specific factors such as haemolysis level and also non-specific factors such as inflammation and socio-demographic factors. They also suggest the presence of non-measured confounding factors associated to the African region such as malnutrition, infectious burden and genetic factors other than the SCD phenotype such as beta globin haplotypes. Keywords: Epidemiology, Anemia, Sickle cell disease

Abstract Background and Aims Chronic kidney disease (CKD) is associated with significant morbidity and mortality among patients with sickle cell anemia (SCA). Glomerular hyperfiltration (GHF) and albuminuria are known as early manifestations of kidney disease occurring in early childhood and can predict the progression to CKD in these patients. Studies reported the prevalence of these kidney abnormalities in SCA children using a single measure and their association with genetic risk factors, especially the co-inheritance of APOL1 risk variants (RVs). However, data on the prevalence of persistent kidney abnormalities (based on the KDIGO CKD definition) and their association with APOL1 RVs are limited in SCA children, particularly those living in sub-Saharan Africa. This study aimed: (i) to determine the prevalence of persistent kidney abnormalities (albuminuria and/or GHF) in SCA children living in the Democratic Republic of Congo (DRC); and (ii) to assess the association between persistent kidney abnormalities with clinical and genetic risk factors. Method From March 2021 to December 2022, we prospectively enrolled 585 steady state SCA children aged 2 to 18 years (male gender 278/585; 47.5%). The SCA status was confirmed through the molecular sequencing of beta-globin gene. Clinical and biological parameters were obtained. All participants were genotyped for apolipoprotein-L1 (APOL1) G1 (rs73885319, rs60910145) and G2 (rs71785313) variants. APOL1 high-risk genotype (HRG) was defined by the presence of 2 risk variants (G1/G1, G2/G2, and G1/G2), and low-risk genotype (LRG) by the presence of 0 or 1 risk variant. Albuminuria was defined as urinary albumin-to-creatinine ratio (ACR) ≥ 30mg/g. The estimated glomerular filtration rate (eGFRcr) was calculated using the original Schwartz formula and GHF was defined as eGFRcr ≥ 180 ml/min/1.73 m2 for children between 2-10 years of age and > 140 ml/min/1.73 m2 for children more than 10 years of age. All measurements were repeated at least three months later in participants who presented with kidney abnormalities at the first screening. The main outcome parameter was persistent albuminuria or persistent GHF for more than three months. Results At enrollment, 234/585 (40.0%) participants presented with kidney abnormalities, among which 80/585 (13.7%) with albuminuria and 171/585 (29.2%) with hyperfiltration. From participants found with kidney abnormalities at the first screening, 176/234 (75.2%) were available for repeated screening: 56/176 (31.8%) presented with persistent kidney abnormalities and 120/176 (68.2%) had a regression of kidney abnormalities without any treatment. Out of 176 participants who benefited from repeated screening, 57 had baseline albuminuria and 130 had baseline GHF. Persistent albuminuria and persistent GHF were found in 38.6% (22/57) and 28.5% (37/130), respectively. Multivariate logistic regression revealed that APOL1 HRG was significantly associated with persistent albuminuria (OR 3.4, 95CI 1.1-10.7, p = 0.037), while male gender was significantly associated with persistent GHF (OR 2.1, 95CI 1.0-4.2, p = 0.042). Conclusion A significant proportion (almost 70.0%) of SCA children who had kidney abnormalities at the first measure, presented regression of these abnormalities without any reno-protective drugs. This result emphasizes the importance of repeating screening at least three months later to confirm CKD, as recommended by the KDIGO Guidelines. This strategy will reduce the need for unnecessary treatment, which represents a high financial burden in a resource-limited area.

Background 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. Methods We did a retrospective, multicentre, case-control study in five countries in sub-Saharan Africa (Burkina Faso, Democratic Republic of the Congo, Cote 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. Findings 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 beta-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. Interpretation 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. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

En France comme dans les pays du nord, la quasi totalité des enfants drépanocytaires atteint désormais l’age adulte, mais la mortalité infanto-juvénile liée à la drépanocytose est inconnue en Afrique, où vivent pourtant 80 % des enfants atteints. L’absence de dépistage néonatal et de registre de décès y rendent les études de mortalité liées à la drépanocytose très difficiles. Étude multicentrique au Burkina Faso, au Sénégal, au Mali, en RDC et en Côte d’ivoire. Nous avons inclus des femmes en bonne santé ayant au moins un enfant drépanocytaire SS et des femmes témoins de phénotype AA (vérifié par test rapide), toutes ayant eu au moins 3 enfants nés il y a plus de 5 ans (vivants ou décédés) et issues du même milieu social. Durant un entretien mené par une professionnelle de santé étaient recueillies les caractéristiques socioéconomiques des familles (âge des parents et de leurs enfants, lieu d’habitation, niveau d’étude des parents, calcul de l’indice OMS multidimensionnel de pauvreté) et les données de mortalité infanto-juvénile (nombre d’enfants nés vivants, nombre d’enfants décédés, age de décès, drépanocytose (suspectée ou confirmée) ou non, circonstances et lieu de décès). Les taux de mortalité infanto-juvenile des familles drépanocytaires et témoins et leur intervalle de confiance, ont été calculés par la méthode de Kaplan Meier. Sachant que dans les familles avec un enfant drépanocytaire et des parents sains (hétérozygotes AS), 25 % en moyenne des nouveaux-nés sont drépanocytaires, les taux de mortalité des enfants drépanocytaires ont été estimés comme suit : (taux de mortalité des enfants des familles drépanocytaires × 4) - (taux de mortalité des enfants des familles témoins × 3). Un modèle de Cox multivarié a été utilisé pour décrire les facteurs socio-économiques et géographiques associés à la mortalité. 2559 familles ont été recrutées (1302 familles drépanocytaires et 1257 familles témoins) pour un total de 13199 enfants dont 1457 enfants décédés. Les caractéristiques sociodémographiques des familles étaient similaires dans les 2 groupes. L’âge moyen des enfants vivants était de 15,5 (± 10,2) ans chez les familles témoins et 14,6 (± 9,1) ans chez les familles drépanocytaires (p = 0,001). La première circonstance de décès était la fièvre : 53 % et 58 % dans les familles témoins et drépanocytaires, respectivement. Dans les familles drépanocytaires 65 % des enfants décédés avant 5 ans avaient une suspicion de drépanocytose mais seulement la moitié avaient reçu un diagnostic formel. L’estimation du taux de mortalité chez les enfants drépanocytaires était de 8 % [IC 95 % : 7-8] avant l’âge de 1 an, 19 % [18-19] avant 5 ans et 27 % [25-28] avant 10 ans. La mortalité observée dans les familles témoins était de 4 % [4-5], 7 % [6-8] et 7 % [7-8] à respectivement 1, 5 et 10 ans. Le risque relatif (RR) de mortalité liée à la drépanocytose augmentait avec l’âge : 2,0 avant 1 an, 2,7 avant 5 ans et 3,8 avant 10 ans. Toutefois, on observait de grandes disparités selon les pays. L’étude de survie multivariée a confirmé que le fait d’appartenir à une famille drépanocytaire était un facteur indépendant de mortalité avant 20 ans [HR 1,67(1,47-1,189), p < 0,001]. Les autres facteurs de risque indépendants étaient : l’âge élevé du père [HR1,11(1-1,2), p < 0,02] ou de la mère [1,71(1,57-1,88), p < 0,001] et un indice de pauvreté élevé [(1,37(1,32-1,43), p < 0,001], tandis que le fait de vivre au Sénégal [0,65(0,53-0,79), p < 0,001] plutôt que dans les 4 autres pays, et d’avoir une mère éduquée [0,65(0,44-0,96), p < 0,03] étaient des facteurs protecteurs de mortalité. Dans cette étude rétrospective nous avons estimé à 19 % la mortalité infanto-juvénile (avant 5 ans) liée à la drépanocytose en Afrique sub-saharienne centrale et de l’ouest par une méthode indirecte permettant de contourner l’absence dépistage néonatal -et donc le sous-diagnostic de la maladie- d’une part, et l’absence de registre de mortalité national d’autre part. Cette mortalité est bien supérieure à celle des enfants drépanocytaires vivant en Europe, où plus de 90 % d’entre eux atteignent l’âge adulte, mais est à pondérer par la mortalité observée dans les familles sans drépanocytose qui est également élevée. Toutefois, ces taux de mortalité liée à la drépanocytose sont très inférieurs à ceux rapportés dans la littérature où il est considéré que 90 % des enfants drépanocytaires nés en Afrique meurent avant l’âge de 5 ans. De toute évidence la survie des enfants drépanocytaire a bien évolué en Afrique, du moins dans les grandes villes. Nous avons également mis en évidence quelques facteurs de risques associé à la mortalité dans les familles, majoritairement socioéconomiques et non spécifiques à la drépanocytose.

Lung function in patients with sickle cell anaemia (SCA) living in sub-Saharan Africa is largely unknown. Anthropometry and spirometry were cross-sectionally evaluated in patients with SCA (HbSS) aged 6-18 years and in schoolchildren from the Democratic Republic of the Congo. The Global Lung Initiative 2012 spirometry reference values were used. A total of 112 patients and 377 controls were included. Twenty-six per cent of patients with SCA had spirometry findings suggestive of a restrictive pattern and 41% had a FEV1 z-score <5th percentile. Wasting, increasing age and female sex were independently associated with increased risk of restrictive spirometry pattern in patients with SCA. Longitudinal studies could clarify the prognostic meaning of these findings.

Despite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries. Following comprehensive training of local research teams, REACH was approved by local Ethics Committees and achieved full enrollment ahead of projections with 635 participants enrolled over a 30-month period, despite half of families living >12 km from their clinical site. At enrollment, study participants (age 5.4 ± 2.4 years) had substantial morbidity, including a history of vaso-occlusive pain (98%), transfusion (68%), malaria (85%), and stroke (6%). Significant differences in laboratory characteristics were noted across sites, with lower hemoglobin concentrations (P < .01) in Angola (7.2 ± 1.0 g/dL) and the DRC (7.0 ± 0.9 g/dL) compared to Kenya (7.4 ± 1.1 g/dL) and Uganda (7.5 ± 1.1 g/dL). Analysis of known genetic modifiers of SCA demonstrated a high frequency of α-thalassemia (58.4% with at least a single α-globin gene deletion) and G6PD deficiency (19.7% of males and 2.4% of females) across sites. The CAR β-globin haplotype was present in 99% of participants. The full enrollment to REACH confirms the feasibility of conducting high-quality SCA research in Africa; this study will provide vital information to guide safe and effective dosing of hydroxyurea for children with SCA living in Africa.

Background: Lung function in African children has been poorly investigated. Aims: To evaluate whether the Global Lung Initiative (GLI) Black spirometry reference (Quanjer,ERJ2012) fit Congolese children. Methods: Anthropometric and spirometric data were collected in 6-12 year old pupils from public and private schools in Kinshasa, D.R. Congo. Exclusion criteria: acute or chronic respiratory disease, non-repeatable test or abnormally shaped flow-volume curves. A portable spirometer (Pony FX©,Cosmed,IT) was used. Z-scores of anthropometric and spirometric data were derived from CDC2000 and GLI-Black equations, respectively. Results were compared to African American children from NHANES III. Results: Congolese children were smaller; FEV 1 and FVC, but not FEV 1 /FVC, were slightly smaller and had much less variability than in African Americans. School type, a proxy for affluence, was unrelated to respiratory outcomes. Conclusions: GLI equations for African Americans fit Congolese children despite a massive difference in socioeconomic conditions.