Abstract only Background: Diabetes is a major cardiovascular disease (CVD) risk factor. There has been a epidemiological shift and chronic CVD is increasing in Sub-Saharan Africa, however, the extent ...is unknown. Methods: Data were collected between March and April 2013 from 3 regions of the Northern Senegal (i.e., Saint-Louis, Matam etand Louga) using a cluster sampling method and the survey base of the national statistical and demographical agency, we included subjects aged between 18 and 80 years old. Participants underwent a face-to-face questionnaire to collect demographics and data on cardiovascular history/risk factors. Blood pressure and anthropometric measurements were measured in addition to blood tests including fasting plasma glucose. Diabetes was defined as fasting plasma glucose >= 1.26 g/L. Continuous data were reported as mean ± standard deviation (SD). Comparisons used the chi-squared test for categorical variables and Student’s t test for continuous variables. Multivariable adjusted logistic regression was used to identify factors associated with diabetes. Covariates with significant association (P<0.05) in univariate analysis were included in the model. Results: Among the 2440 subjects in this study (mean age: 44 years old, SD: 15.99), 692 (28%) were male. Nearly half of the sample never attended school (48%, 95%CI: 46-50%). Body mass index (BMI) higher than 25 was present in 43% of the sample (95%CI: 29-35%), with a significant increase in women (51% vs 22%, p<0,001).. The prevalence of diabetes was 5.9% (95%CI: 5-6,9%). Among them, 93% had at least two cardiovascular diseases (95% CI: 87-96%), 71% had dyslipidemia (95%CI: 63-78%) and 67% had a BMI over 25 (95%CI: 58-74%). Conclusion: This community-based study revealed a low prevalence of diabetes. However, the prevalence of additional CVD risk factors in this population was high. Preventive measures should be implemented to avoid increasing rates of diabetes in Sub-Saharan Africa.
Summary
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.
Multivariate analysis revealed independent associations between Hb level and several factors, including the country of residence, gender, BMI, haemolysis parameters (LDH level, reticulocyte count) and platelet and leucocyte counts.
We explore in-situ fluorescence spectroscopy as an instantaneous indicator of total bacterial abundance and faecal contamination in drinking water. Eighty-four samples were collected outside of the ...recharge season from groundwater-derived water sources in Dakar, Senegal. Samples were analysed for tryptophan-like (TLF) and humic-like (HLF) fluorescence in-situ, total bacterial cells by flow cytometry, and potential indicators of faecal contamination such as thermotolerant coliforms (TTCs), nitrate, and in a subset of 22 samples, dissolved organic carbon (DOC). Significant single-predictor linear regression models demonstrated that total bacterial cells were the most effective predictor of TLF, followed by on-site sanitation density; TTCs were not a significant predictor. An optimum multiple-predictor model of TLF incorporated total bacterial cells, nitrate, nitrite, on-site sanitation density, and sulphate (r2 0.68). HLF was similarly related to the same parameters as TLF, with total bacterial cells being the best correlated (ρs 0.64). In the subset of 22 sources, DOC clustered with TLF, HLF, and total bacterial cells, and a linear regression model demonstrated HLF was the best predictor of DOC (r2 0.84). The intergranular nature of the aquifer, timing of the study, and/or non-uniqueness of the signal to TTCs can explain the significant associations between TLF/HLF and indicators of faecal contamination such as on-site sanitation density and nutrients but not TTCs. The bacterial population that relates to TLF/HLF is likely to be a subsurface community that develops in-situ based on the availability of organic matter originating from faecal sources. In-situ fluorescence spectroscopy instantly indicates a drinking water source is impacted by faecal contamination but it remains unclear how that relates specifically to microbial risk in this setting.
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•Total bacterial cells most related variable to tryptophan-like fluorescence (TLF)•TLF and humic-like fluorescence strongly correlate with dissolved organic carbon.•Thermotolerant coliforms are not strongly related to other variables.•TLF and HLF relate to faecal contamination.
Summary
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.
The prevalence of type 2 diabetes (T2D) is rapidly increasing in sub-Saharan Africa, where sickle cell trait (SCT) is also frequent. Although SCT is generally considered a benign condition, evidence ...suggests that SCT could exaggerate vascular dysfunction in T2D. However, it remains unclear whether SCT could increase the risk of the development of T2D complications. Therefore, this study was conducted to determine whether T2D complications were more prevalent among Senegalese individuals with SCT and T2D than among those with T2D only.
Rates of hypertension, retinopathy, peripheral neuropathy, peripheral artery disease, and impaired renal function as well as arterial stiffness, blood rheology, and concentrations of plasma advanced glycation end products (AGEs) and cytokines were compared between groups of Senegalese individuals with combined SCT and T2D (T2D-SCT) (
= 60), T2D (
= 52), SCT (
= 53), and neither T2D nor SCT (control) (
= 56). Human aortic endothelial cell (HAEC) expression of inflammatory and adhesion factors was measured after treatment with tumor necrosis factor-α and subjects' plasma. Effects of AGE inhibition or tiron on HAEC expression of E-selectin were measured.
Retinopathy, hypertension, and reduced renal function were more prevalent, and arterial stiffness, blood viscosity at high shear rates, and thixotropic index were higher, in the SCT group compared with the other groups. Multivariable analysis showed that plasma AGE concentration was significantly associated with arterial stiffness. E-selectin expression was elevated in HAECs treated with T2D-SCT plasma compared with the other groups, but AGE inhibition reversed this.
SCT could potentially augment the risk of the development of T2D-related complications, including retinopathy, nephropathy, and hypertension.
Summary
Although most individuals with sickle cell disease (SCD) live in sub‐Saharan Africa, the natural history of the disease on this continent remains largely unknown. Intravascular haemolysis ...results in activation of circulating blood cells and release of microparticles (MPs) that exert pro‐inflammatory effects and contribute to vascular damage. We designed a case‐control study nested in the CADRE cohort (Coeur‐Artère‐DRÉpanocytose, clinical trials.gov identifier NCTO3114137) and based on extreme phenotypes, to analyse blood cell‐derived MPs in 232 adult SS patients at steady state in Bamako and Dakar. Thirty‐six healthy adult controls matched by age and sex were recruited in Bamako. The MPs concentrations were higher in SS patients compared to AA controls with a predominance of erythrocyte‐ and reticulocyte‐derived MPs. These erythroid‐derived MPs were significantly lower in patients with retinopathy (P = 0·022). Reticulocyte‐derived MPs were significantly negatively and positively associated with a history of priapism (P = 0·020) and leg ulcers (P = 0·041) respectively. We describe for the first time the comparative patterns of plasma MPs in healthy subjects and
patients with SCD living in sub‐Saharan Africa and exhibiting various complications. Because our present results show no clear pattern of correlation between erythroid MPs and the classical hyper‐haemolytic complications, we hypothesise a weak relevance of the hyper‐haemolysis versus hyper‐viscous paradigm in Africa.
Introduction
Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the history of the disease on this continent remains largely unknown. SCD is characterized by the ...association of chronic hemolytic anemia with episodes of acute vaso-occlusive events and progressive vascular organ damage. Several pathophysiological pathways in SCD result in the activation of circulating blood cells and the release of microparticles (MPs). In the present study, we investigated cell-derived MPs in patients with SCD living in Africa and analyzed their relationship with clinical complications.
Patients and Methods
This cross-sectional case-control study is nested in the CADRE cohort (clinical trials.gov identifier NCTO3114137). We included 232 SS adults in two African centers: Bamako (Mali) and Dakar (Senegal). Patients were chosen depending on the absence or the presence of at least one of the following complications: tricuspid regurgitant jet velocity (TRJV) >3 m/s (which may indicate pulmonary hypertension), macroalbuminuria, leg ulcer, priapism, aseptic osteonecrosis, and retinopathy. Overall, 7 groups of 40 SS patients were constituted (20 in each center). Patients were investigated at steady state (i.e.,at least 15 days after a vaso-occlusive crisis, 8 days after fever or infectious disease, and 3 months after a transfusion). MPs were isolated in the African centers immediately after blood sampling by successive centrifugations at increasing speed: 2,500g x2 and 21,000g x2. MPs pellets were stored at -80 °C. The cellular origin of the MPs, erythrocyte, reticulocyte, endothelial, platelet, and leucocyte, was determined using antibodies directed against CD235a, CD71, CD106, CD41, and CD45, respectively, at the National Institute of Blood TransfusioninParis. To maintain the background at an acceptable level, events of 0.16 µm size were excluded (Fig 1A). Only MPs positive for Annexin V and the cell-type-specific labelling were retained. Potential associations between cell-derived MPs, hematological parameters, and vascular complications were assessed using logistic regression with adjustment for age, sex and country.
Results
The MP pellets of 106 SS patients from Bamako and 126 from Dakar were analyzed in Paris. In these patients, at a mean age of 29 years (+/- 11), high TRJV was present in 64, microalbuminuria in 84, leg ulcers in 33, priapism in 43, aseptic osteonecrosis in 45, and retinopathy in 31 patients whereas 28 patients had no complication at the time of sampling. As a typical result, Fig 1B shows erythrocyte-derived MPs labelled by Annexin V and CD235a (quarter Q2). The MPs distribution was as follows: erythroid 52% reticulocytes (CD235a+CD71+) 14%, erythrocytes (CD235a+ CD71-) 38%, leukocyte 18%, platelet 21%, and endothelial 9%. Neither erythrocyte- nor reticulocyte-derived MPs significantly correlated with hemolysis markers (LDH, unconjugated bilirubin or reticulocytes) or hemoglobin levels. Erythrocyte- and reticulocyte-derived MPs were significantly lower in patients with retinopathy (OR=0.48, p=0.003 and OR=0.68, p=0.005, respectively). Reticulocyte-derived MPs were negatively associated with a history of priapism (OR=0.76, p=0.020) and positively associated with a history of leg ulcers (OR=1.23, p=0.040). No correlation was found between MPs of other cellular origin and chronic complications, except for a negative association between endothelial-derived MPs and priapism (OR=0.76, p=0.036).
Conclusion
In our African patients with SCD, erythroid-derived MPs, although recognized cellular products of hemolysis, were not associated with other markers of hemolysis. We hypothesize that erythroid MPs are not only derived from hemolysis but also probably from the sickling process in this population. They were negatively associated with retinopathy and priapism and positively associated with leg ulcers, but not with the other complications classically associated with the hyperhemolytic sub-phenotype. The search for pertinent biomarkers of SCD complications in Africa is an essential challenge. To our best knowledge, this report is the first illustrating the feasibility of high-technology experiments in an African context.
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No relevant conflicts of interest to declare.
Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the history of the disease in this continent remains largely unknown. SCD is characterized by chronic hemolytic ...anemia, acute-vaso occlusive events and progressive vascular organ damage. The CADRE study is a large cohort of SCD patients in five countries of West and Central Africa aiming at studying SCD-related vascular complications. The inclusion data of this study did not match the hyper-hemolysis paradigm (Dubert et al. Blood 2018), but several methodological limitations were raised, including probable mortality bias and questionable reliability of classical hemolysis markers in Africa. For the 5-year follow-up of the CADRE study, we designed a case-control study nested in the cohort, based on extreme phenotypes, to look for new markers of vasculopathy, including new markers of hemolysis.
Patients and Methods
SS adult patients of the CADRE cohort were selected in the centres of Dakar (Senegal) and Bamako (Mali), depending on the presence of none or at least one of the following complications at inclusion: tricuspid regurgitant jet velocity (TRJV)>2,5 m/s (which may indicate pulmonary hypertension), albuminuria/creatininuria>100 mg/g, leg ulcer, priapism, aseptic osteonecrosis and retinopathy. We chose the youngest patients with a vascular complication and the oldest without any complication. Overall, 6 groups of 40 SS patients with extreme phenotypes were constituted (20 in each centre). Patients were called for a specific visit and investigated at steady state. Besides clinical examination, usual laboratory blood tests and albuminuria measure, additional plasma and saliva samples were collected. A trained investigator isolated microparticles immediately after blood sampling by successive centrifugations, measured blood and plasma viscosities and assessed microcirculation function using peripheral arterial tonometry. A cardio-echography was performed by a trained cardiologist. Plasma samples were stored at -80 °C and shipped to Paris. High technology tests were performed in Paris, including blood cell derived microparticles, free hemoglobin, inflammatory cytokines, neutrophile extracellular trap (NETs). Using saliva DNA, we also genotyped the known SCD genetic modifiers and new candidate genes implicated in the catabolism of hemoglobin. Potential associations between those markers, usual hematological parameters, and the vascular complications were assessed statistically .
Results
We recalled 240 selected patients 5 years after their first visit: 38 could not be retrieved, 21 had deceased, 62 had at least one new complication, and only 15 still had no complication. Therefore, we selected 56 more patients to obtain at least 30 patients in each group. 237 SS adults were eventually investigated and the plasma samples of 232 SS patients were analyzable in Paris (106 from Bamako and 126 from Dakar). In these patients, at a mean age of 29 years (+/- 11), high TRJV was present in 58, macroalbuminuria in 33, leg ulcers in 36, priapism in 43, aseptic osteonecrosis in 45 and retinopathy in 31 whereas 28 had no vascular complication. A principal component analysis found no cluster of complications. Among patients with one “hyper-viscous” complication (retinopathy or osteonecrosis) or more, 78% also had at least one “hyper-haemolytic” complication (high TRJV, albuminuria, leg ulcer or priapism) and 49% of patients with a “hyper-haemolytic” complication also had a “hyper-viscous” complication. The microvascular function was not associated with any of the complications, whereas higher blood viscosity was associated with retinopathy. The results of the associations between the vascular complications and specific biological tests are presented in other publications.
Conclusion
This study illustrates the feasibility of high-technology experiments in SCD patients living in sub-Saharan Africa, but was particularly challenging because of the difficulty to prepare, store and transport frozen plasma samples. Moreover, in agreement with previously published data from the CADRE study, we found that the dichotomization of vascular complications into hyperhemolytic and hyperviscous subgroups is not clinically relevant in Africa. Other simple predictive markers of vascular complication are needed to optimize the follow-up of African patients with SCD.
No relevant conflicts of interest to declare.
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