Haemoglobin Genotype Research Articles

Ethical issues in denial of church wedding based on couple\u2019s hemoglobin genotype in Enugu, south eastern Nigeria

BackgroundSickle cell anemia (SCA) is a major genetic disease with the greatest burden in sub-Saharan Africa. To try to help reduce this burden, some churches in Nigeria conduct premarital sickle cell hemoglobin screening and refuse to conduct weddings when both individuals are identified as carriers of sickle cell trait.Main bodyThis paper explores the ethical challenges involved in such denials. We assess whether churches have the right to decline to marry adults who understand the risks and still prefer to get married, and whether couples should be denied church weddings based on the risk that their child may suffer from sickle cell anemia. We examine the moral and ethical dimensions of such denials and explore the underlying socio-cultural context involving the purpose of marriage and the meaning of the wedding ceremony in societies where premarital screening is one of the few tools available to reduce the risk of having children with SCA. The potential role of the church is also examined against the background of church beliefs, the duty of the church to its members and its role in reducing the suffering of its members and /or their children.ConclusionWe argue that the church should impose these burdens on couples only if doing so promotes a sufficiently compelling goal and there is no less burdensome way to achieve it. We then argue that the goal of reducing the number of individuals in Nigeria who have SCA is compelling. However, testing earlier in life offers a less burdensome and potentially even more effective means of achieving this goal. This suggests that, advocating for earlier screening and helping to support these programs, would likely better promote the church’s own goals of helping its parishioners, increasing the number of church weddings, and reducing the burden of SCA in Nigeria.

Impact of Hemoglobin S Trait on Cell Surface Antibody Recognition of Plasmodium falciparum-Infected Erythrocytes in Pregnancy-Associated Malaria.

BackgroundSickle cell trait (HbAS) confers partial protection against malaria by reducing the adhesion of Plasmodium falciparum-infected erythrocytes to host receptors, but little is known about its potential protection against placental malaria. MethodsUsing flow cytometry, we assessed the recognition of HbAA and HbAS VAR2CSA-expressing infected erythrocytes, by plasma from 159 Beninese pregnant women with either HbAA (normal) or HbAS. Using multivariate linear models adjusted for gravidity, parasite infection at delivery, glucose-6-phosphate dehydrogenase deficiency, and α-thalassemia carriage, we observed significantly reduced cell surface antibody binding of HbAS-infected erythrocytes by plasma from HbAS compared with HbAA women (P < 10–3).ResultsThe difference in cell surface antibody binding was only observed when infected erythrocytes and plasma were associated according to the same hemoglobin genotype. Similar levels of VAR2CSA-specific antibody were measured by enzyme-linked immunosorbent assay in the 2 groups, suggesting that the altered interaction between VAR2CSA and HbAS women’s antibodies could reflect abnormal display of VAR2CSA on HbAS erythrocytes.ConclusionsOur data stress the need for assessments of erythrocyte disorders such as the sickle cell trait in a population group when studying immunological responses to P falciparum.

The Sub-Phenotypes of Sickle Cell Disease in Kuwait

Kuwaiti patients with sickle cell disease generally have a mild phenotype, but exhibit considerable heterogeneity, in spite of high Hb F levels. We have carried out a cross-sectional study of patients with sickle cell disease in the five major hospitals in Kuwait. Details of their hemoglobin (Hb) genotypes, clinical presentations and complications are presented. The study was over a span of 3 years and involved 396 patients, made up of 351 (88.6%) Kuwaitis and 45 (11.4%) expatriates. They were aged <1 to 73 years. Hb SS (βS/βS) was the most common (in 246 patients, i.e. 62.1%) followed by Hb S (HBB: c.20A>T)-β-thalassemia (Hb S-β-thal) in 138 (34.8%) and 11 (2.8%) Hb S/Hb D-Punjab (HBB: c.364G>C). Hb F ranged from 1.0 to 55.0%, with a mean of 21.2 ± 9.8%. The most common presentation was vaso-occlusive crises (VOCs), with 230 (54.8%) having had at least one prior to the study with 54 (13.2%) and 74 (18.9%) having between 2-3 and >3 VOCs, respectively. Hydroxyurea (HU) was prescribed to 157 (39.6%) patients. The most common complication was gallstones in 131 (33.1%), followed by acute splenic sequestration in 26.8% and avascular necrosis of the femoral head in 21.2% patients, respectively. Stroke, priapism and leg ulcers were rare. Gallstones, splenic sequestration and osteonecrosis were significantly more common in patients aged >16 years. Patients with Hb S-β-thal were similar to those with Hb SS in their clinical profiles. The phenotypic expression of sickle cell disease in Kuwaitis is unique in many respects. The role(s) of Hb F and other genetic modifiers require further elucidation.

The p.H63D allele of the HFE gene protects against low iron stores in Sri Lanka

In hereditary hemochromatosis, iron overload is associated with homozygosity for the p.C282Y mutation. A second mutation, p.H63D, occurs at significant frequencies in Europe, North Africa, the Middle East and Asia. Early studies in Sri Lanka indicated that the variant had arisen independently, suggesting that it had been the subject of selective pressure. However, its role in iron absorption is unclear.In a survey of 7526 Sri Lankan secondary school students, we determined hemoglobin genotype and measured red cell indices, serum ferritin, transferrin receptor, iron zinc protoporphyrin and hepcidin. These variables were compared according to the presence or absence of the p.H63D variant in a subset of 1313 students for whom DNA samples were available. Students were classified as having low red cell indices if they had an MCV <80 fl and/or MCH <27 pg.Hetero and/or homozygosity for the p.H63D variant was more common in students with normal than low red cell indices (16.4% and 11.9% respectively; p = 0.019). Iron biomarkers and red cell indices were greater in children with the p.H63D variant than in normal and this was statistically significant for MCV (p = 0.046).Our findings suggest that selective pressure by mild iron deficiency contributes to the high frequencies of the p.H63D variant.

Study of association between sickle cell trait and renal dysfunction among young adults in South-west Nigeria.

Although sickle cell disease has become a recognized etiology of chronic kidney disease (CKD), the sickle cell trait (SCT) variant was until recently believed to be a benign carrier state with little or no effect on the health of affected individuals. However, recent studies now appear to suggest an association between SCT and CKD. The objective of the study is to determine the association between SCT (hemoglobin AS) and renal dysfunction among young Nigerian adults. This was a cross-sectional, descriptive study among apparently healthy undergraduates of Adeyemi College of Education, Ondo, southwest Nigeria. Their hemoglobin genotypes were determined using standard alkaline electrophoresis; their blood pressure, anthropometry, serum total cholesterol (TC), creatinine, and estimated glomerular filtration rate (eGFR) were determined. Data analyzed using Statistical Package for Social Sciences (SPSS) 20 were significant at P < 0.05. Six hundred and two subjects with HbAS (SCT, n = 465) and HbAA (non-SCT, n = 137) were studied. Their age range was 18-30 years with male-to-female ratio 1:3.8. There was no difference in the prevalence of renal dysfunction between SCT and non-SCT subjects (5.1% vs. 5.2%, P = 0.591). There was no increased risk of CKD among subjects with SCT (PR, 0.99 at 95% CI [0.417-2.348]). SCT was not associated with increased risk of renal dysfunction among young adults in Nigeria. Further studies are needed to clarify the controversy, especially in Nigeria, with a relatively higher prevalence of SCT.

Seroreactivity of Populations Living in Endemic Area of Burkina Faso to Plasmodium falciparum Alpha-Helical Coiled Coil Proteins Motifs by Protein Microarray

The naturally acquired immunity is one of the models of immunity that is exploited for malaria antigens discovery. We have used multiplex protein microarrays of 92 P. falciparum alpha-helical coiled coil protein motifs to screen plasma samples obtained from 1113 children and adults belonging to three sympatric ethnic groups from malaria endemic area of Burkina Faso. We have investigated the influence of some factors such as age, ethnicity, hemoglobin genotype and sex on the antigens reactivity and the IgG antibody level. We also investigated specifically, the influence of the factors mentioned above on the 36 antigens with the highest antibody prevalence and intensity. As expected, the findings of the study confirmed the positive correlation between age, antigens reactivity and IgG antibody level. Except for three antigens (MSP2_3D7, MR260, and As182.20), the IgG level was higher in adults compared to children. The Fulani ethnic group recognized more antigens with the highest IgG values compared to the sympatric groups of Mossi and Rimaibé, except for six antigens (LR166, LR146, AS182.15, MR214, MR236A, and MSP3). In General, the hemoglobin type and sex did not have any influence on the IgG antibody reactivity and intensity. Except for four antigens (MR232, MR261A, MSP2_3D7, and NANP) 10), there was statistically no IgG intensity difference between people with normal hemoglobin genotype (AA) and the non-(AA) volunteers. Our study has demonstrated that protein microarrays of alpha-helical coiled-coil proteins motifs are suitable to screen the naturally acquired immunity. The findings of the study should be considered in any strategy for new antigen related to alpha-helical coiled coil protein segments discovery for a potential vaccine clinical development.

Assessment of Genetic Diversity at the Heamoglobin Locus in Selected West African Dwarf Goat Populations in Nigeria

Blood samples were collected from 40 (forty) goats in Kwande Local Government Area, of Benue State, Nigeria. Blood samples collected were subjected to electrophoresis to study haemoglobin polymorphism and its distribution in West African Dwarf goat populations in Kwande. Data on Haemoglobin genotypes were subjected to sample variance (S2) population genetics simulation software for the analysis. Three heamoglobin genotypes (HbAA, HbAB and HbBB) were observed in the West African dwarf goat populations. The haemoglobin gynotypes (HbAA, HbAB and HbBB) were controlled by two co-dominant haemoglobin alleles HbA and HbB. The genotypic frequencies were 0.24, 0.57 and 0.19 for HbAA, HbAB and HbBB respectively. Genotypic frequencies at the haemoglobin locus in West African Dwarf goat were in hardy-weinberg equilibrium. The gene frequencies of HbA and HbB observed were 0.52 and 0.48 respectively with HbA being the most frequent. The low allelic variation may have occur when populations are separated but only for a short time, that the processes of genetic drift and mutation that leads to differentiations of allelic frequencies at selected loci are yet to occur. As the amount of time in which two isolated populations increases, the differences in allelic frequencies will also increase until each population is completely fixed for a number of alleles. These factors may have accounted for the low variation in the heamoglobin allelic frequencies observed in this study. There was also gene-controlled diversity at the haemoglobin locus in the WAD goat populations with heterozygosity (He) value of 0.49, which indicated a moderate level of genetic diversity at the haemoglobin locus in WAD goat populations in Kwande Local Government Area of Benue State, Nigeria.

The impact of sickle cell anemia on the quality of life of sicklers at school age.

Background:Sickle cell anemia (SCA) is prevalent in Sudan in general, and in particular in the western part of the country among Misseria tribe. School absence, depressive symptoms, embarrassment, social disturbances, and emotional disturbance present negative impact for sicklers. Therefore, an urgent call for improving the quality of life of sicklers is needed.Objectives:To examine the impact of SCA on the quality of life of school-age children affected by the disease from the perspective of three dimensions: psychological, social, and schooling.Materials and Methods:This is a prospective, cross-sectional, observational study carried out over 2 weeks’ period in April 2011 in Western Sudan, Gineana District. This study included 107 patients within the age group of 7–15 years with confirmed diagnosis of SCA in a steady state. A sickler with SCA who had hemoglobin genotype “SS” on hemoglobin electrophoresis without crises over the past 4 weeks was considered to be in steady state. Questionnaires designed by expert covering social and psychological aspects of the disease were filled by the authors.Results:Of 107 patients with confirmed diagnosis of SCA in steady state, 54.2% of them were male. About 17.8%, 29.6%, 23.4%, 48.6%, 16.8%, and 45.8% of the patients suffered from school absence, teasing, embarrassment due to bedwetting, embarrassment due to jaundice, failure to contribute to school activities such as sport, and depressive symptoms, respectively. Around 8.4% of the patients repeated classes. Divorce and anxiety among sicklers’ families were found in 6.5% and 8.4%, respectively. Twenty-one (19.6%) families had less interest in social activities in the community.Conclusion:Sickle cell disease has many social and psychological problems which need to be addressed. Enuresis, depressive symptoms, school absentees, and deterioration in school performance were the common problems encountered.

Sickle Cell Anemia in Cuba: Prevention and Management, 1982-2018.

Sickle cell anemia is the most common hereditary disease in Cuba. On average, 1 in 33 Cubans is a carrier of this severe hemolytic anemia that can cause early death. In early 1980, its incidence in Cuba was calculated at 1 in 1600 births. In 1982, the Cuban public health system established the Sickle Cell Anemia Prevention Program, which aims to prevent the disease through identification of carrier couples and antenatal diagnosis of fetuses with disease-associated genotypes. In 1982-2018, hemoglobin genotypes were tested in 4,847,239 pregnant women. Of these, 168,865 (3.5%) were found to be carriers or to have sickle cell disease. During the same period, 8180 at-risk couples were identified, of whom 79.2% agreed to an antenatal study for detection of the sickle cell gene in the fetus. Among fetuses diagnosed, 20.1% had the SS genotype, the most clinically severe; 76.2% of the associated couples decided to interrupt the pregnancy. This program has resulted in a 3-fold reduction in prevalence of sickle cell disease in Cuba, a 10-fold reduction in the number of infants born with it each year, and a 16-year average increase in life expectancy of sickle cell disease patients of both sexes. Key contributors to these results have been universal screening of pregnant women in primary care, installation of diagnostic laboratories in every province, genetic counseling for couples, testing of fetal DNA (allowing couples to decide whether to continue the pregnancy if the fetus tests positive for the disease) and guaranteed multidisciplinary clinical care for patients. The Cuban experience shows that a middle-income country can mitigate the impact of a genetic disease through a universal preventive program based in primary care, which also pays particular attention to afflicted patients. KEYWORDS Sickle cell anemia, sickle cell disease, sickle cell disorders, hemolytic anemia, sickle cell trait, sickle cell hemoglobin C disease, HbS disease, prevention, antenatal screening, preventive health services, Cuba.

Hemoglobin S and Glucose-6-Phosphate Dehydrogenase Deficiency Coinheritance in AS and SS Individuals in Malaria-Endemic Region: A Study in Calabar, Nigeria.

Background:Malaria placed a huge burden on human life and has been reported to be a key health problem affecting developing countries. This study was designed to assay for glucose-6-phosphate dehydrogenase (G6PD) status and malaria parasite density of individuals with sickle cell gene in University of Calabar Teaching Hospital, Calabar.Subjects and Methods:The methemoglobin method was used to determine the G6PD status. Thick blood films were used to ascertain the malaria parasite density while hemoglobin genotype was determined using cellulose acetate paper electrophoresis with tris ethylenediaminetetracetic acid borate buffer (pH 8.6). Thirty hemoglobin SS (HbSS) and 30 hemoglobin AS (HbAS) individuals were recruited for the study while 30 hemoglobin AA (HbAA) individuals were recruited as control.Results:The study showed a high frequency of G6PD deficiency (17.78%) in the study area while G6PD deficiency was significantly (P < 0.05) higher in HbAA individuals (33.33%) when compared to HbSS (10.00%) and HbAS (10.00%) individuals. The prevalence of malaria parasitemia and parasite density was comparable in the three hemoglobin variants. The distribution of malaria parasitemia and parasite density in both gender among the various hemoglobin variants showed no association (P > 0.05). G6PD deficiency distribution in both gender were found to be comparable (P > 0.05). The distribution of malaria parasitemia in the various hemoglobin variants in the G6PD-deficient individuals showed no significant difference (P > 0.5). However, the parasite density of the HbAS (3100 ± 1828.48 μL) and HbSS (2400 ± 1687.06 μL) were significantly lower than that of HbAA (4040 ± 1529.44 μL).Conclusion:The result of this study supports the hypothesis that inheriting the G6PD deficiency gene and sickle cell gene (both in homozygous and heterozygous form) reduces the severity of malaria parasite infection and hence protects against severe acute malaria while having less effect on infection.

Sickle Cell and α+-Thalassemia Traits Influence the Association between Ferritin and Hepcidin in Rural Kenyan Children Aged 14–26 Months

The relation between subclinical hemoglobinopathies and concentrations of the iron-regulatory hormone hepcidin is not well characterized. We investigated the relation of hepcidin concentration with hemoglobinopathies among young children in Kenya. We quantified serum hepcidin and ferritin in 435 Kenyan children aged 14-20 mo in a subsample of the Water, Sanitation, and Handwashing (WASH) Benefits Trial. Blood samples were genotyped for α+-thalassemia and for sickle cell disorder. Hepcidin was compared across sickle cell and α+-thalassemia genotypes separately by using generalized linear models, and children who were normozygous for both conditions were also compared with those who had either of these conditions. In the association between hepcidin and ferritin, we assessed effect modification by genotype. In this population, we found that 16.2% had sickle cell trait and 0.2% had sickle cell disorder, whereas 40.0% were heterozygous for α+-thalassemia and 8.2% were homozygous. Hepcidin concentration did not differ by genotype, but effect modification was found by genotype in the association between hepcidin and ferritin (P<0.1). Among normozygous sickle cell children (HbAA), there was an association between hepcidin and ferritin (β=0.92; 95% CI: 0.72, 1.10). However, among those with sickle cell trait (HbAS), the association was no longer significant (β=0.31; 95% CI: -0.04, 0.66). Similarly, among children who were normozygous (αα/αα) or heterozygous (-α/αα) for α+-thalassemia, hepcidin and ferritin were significantly associated [β=0.94 (95% CI: 0.68, 1.20) and β=0.77 (95% CI: 0.51, 1.03), respectively]; however, in children who were homozygous for α+-thalassemia (-α/-α), there was no longer a significant association (β=0.45; 95% CI: -0.10, 1.00). Hepcidin was not associated with hemoglobin genotype, but there may be a difference in the way hepcidin responds to iron status among those with either sickle cell trait or homozygous α+-thalassemia in young Kenyan children. This trial was registered at clinicaltrials.gov as NCT01704105.

Differences in Protein S, Protein C, and Antithrombin Levels and Risk of Venous Thromboembolism Among American Black and White Enrollees in the Gate Study

Introduction: Black Americans have been reported to have a higher incidence of venous thromboembolism (VTE) compared to white Americans. The underlying cause of this disparity is not well characterized. Protein S, protein C, and antithrombin deficiency are known risk factors for VTE. There is inconsistent data regarding racial variation on the effect of protein S, protein C, and antithrombin levels and/or deficiency and risk of VTE. Most prior studies have not included a large black study population. The aim of this investigation is to compare levels of protein C, protein S, and antithrombin between VTE cases and controls by race among enrollees in the Genetic Attributes and Thrombosis Epidemiology (GATE) study, accounting for genetic differences such as hemoglobin genotype that may contribute to differences in protein levels by race.Methods: Testing for protein S, protein C, and antithrombin deficiency was performed on a subset of participants enrolled in the GATE study, a case-control study comprised of VTE cases and controls frequency-matched on age, sex, and race (self-identified). Controls had no history of VTE and did not receive anticoagulant therapy. Antigen and activity levels in cases were measured at least one month after completion of anticoagulation therapy. A priori cutoff levels for determining deficiency status were standardized per Centers for Disease Control Hemostasis Laboratory reference ranges. Beta hemoglobin genotype was determined by either a multiplex genotyping assay or sequencing of the beta hemoglobin gene. Differences in protein levels between cases and controls were compared using the Wilcoxon rank sum test. Conditional logistic regression analysis was performed to evaluate the association between protein S, protein C, or antithrombin deficiency and VTE. Crude models were conditioned on the matching factors, and adjusted models were conditioned on the matching factors and controlled for patient characteristics found to be associated with VTE and protein S, protein C, or antithrombin deficiency. Potential effect modification was assessed using likelihood ratio tests.Results: Among 2,454 subjects enrolled in the GATE study, 1,436 subjects (63.6%) had samples available for analysis. Protein S activity and total protein S antigen levels were significantly lower among VTE cases compared to controls in both white and black participants; however, antithrombin levels were higher among VTE cases compared to controls in white participants only. (Table 1) The prevalence of protein S and protein C deficiency was higher among VTE cases compared to controls in both white and black participants in the GATE study (Table 2). The prevalence of antithrombin deficiency was similar between VTE cases compared to controls. Adjusting for the effect of family history of VTE, history of cancer, and hemoglobin genotype, the effect of protein S and protein C deficiency on odds of VTE was stronger among black participants compared to white participants (Table 2).Conclusions: The effects of protein S and protein C deficiency on the odds of being a VTE case were higher among black participants in the GATE study, controlling for confounding variables including hemoglobin genotype. While these results indicate protein S and protein C deficiency may be important contributors to disparities in VTE occurrence, additional investigations using a larger study populations and different study designs are warranted. [Display omitted] DisclosuresPatel:Daiichi Sankyo: Other: DSMB member. Payne:Bioverativ: Other: treatment product donation; Novo Nordisk: Other: treatment product donation; Shire: Other: treatment product donation; Genentech: Membership on an entity's Board of Directors or advisory committees; Bayer: Other: treatment product donation.

A comparative study of carbohydrate antigen 19-9 in sickle cell disease subjects and controls in Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria

Sickle cell disease is characterized by chronic complications that affect almost all body organs. Pancreatic disease is rare in SCD. CA 19-9 is a non-specific surrogate marker for pancreatic disease especially carcinoma. CA 19-9 levels have not been evaluated in SCD patients in our environment. The study aimed to compare the levels of CA 19-9 in homozygous sickle cell disease subjects in steady state with those of (Hb AS) and normal healthy subjects (Hb AA). Seventy nine subjects including 39 Hb SS, 19 Hb AS and 21 Hb AA subjects were recruited in a cross-sectional study in Nnamdi Azikiwe University and Teaching Hospital. Haemoglobin genotype and CA 19-9 estimation were done using Hb electrophoresis and enzyme linked immunosorbent assay respectively. Data was analyzed with IBM SPSS 21. P value was set at 0.05. The mean CA 19-9 (U/ml) level in Hb SS, Hb AS and Hb AA were 13.6 ± 7.6, 15.3 ± 9.9, and 20.0 ± 15.9 respectively. [Reference value <37U/ml] CA 19-9 was significantly lower in Hb SS compared to Hb AA subjects (p = 0.035). Low levels of CA 19-9 in Hb SS may suggest reduced pancreatic disorders in SCA.

Modifiable Cardiovascular Risk Factors in Adults with Sickle Cell Disease

Introduction:Body composition, cardiorespiratory fitness (CRF) and muscular strength(MusS) are important predictors of cardiovascular (CV) mortality and morbidity. Poor CRF, body composition and MusS are each associated with higher rates of musculoskeletal injury, inflammation, heart disease, and all-cause mortality. Fortunately, these parameters in the general population, are partly influenced by lifestyle habits and can improve with modifying unhealthy behaviors such as increasing activity levels. Few studies have examined fitness parameters, in particularly MusS, in adults with sickle cell disease (SCD). As cardiopulmonary disease is a leading cause of death in SCD, we sought to better characterize fitness and body composition in adults with SCD. The objective of this study is to describe modifiable CV risk factors of fitness along with other risk factors of smoking, hypertension, and cholesterol in a population of adults with SCD.Methods:Forty-six participants (ages 21-66 yrs.; 74% female; sickle cell anemia n =29, sickle variant genotype n=17) were recruited from a comprehensive adult sickle center. Non-pregnant adults in steady-state SCD disease without an absolute contraindications to exercise were eligible to participate. CRF was measured using symptom-limited exercise testing performed on a cycle ergometer following an incremental ramp protocol. Maximal oxygen uptake (VO2 max), a key measure of CRF, was calculated during exercise testing. MusS was assessed using an isokinetic dynamometer, the Biodex system 3, the gold standard to measure MusS in rehabilitative medicine. Peak isokinetic torques of knee extension and flexion were determined at 60 degrees per second, and adjusted for body weight on the Biodex system 3. A medical history, fitness assessments, anthropometric testing, and laboratory testing were completed on all SCD participants. Sixteen SCD participants had dual energy x-ray absorptiometry imaging to assess fat, lean, and bone mass. The remaining 30 SCD patients underwent isokinetic CRF and MusS testing. Lean muscle mass and body fat of participants were compared to US national guidelines, VO2max was compared to predicted norms. As there are no well-established normative values for MusS, we compared values to a cohort of 60 adults without SCD (age 21-40 yrs.; 63% female) who underwent MusS testing as a part of a separate study. For muscle strength, multivariate regression was performed to control for the effects of age, BMI, gender, and SCD status on peak torques.Results:All SCD and control participants were able to complete testing safely without any adverse events. 34.7% of SCD participants (n=16) had a smoking history with a mean pack year history of 9 years (Table 1). 18% of participants (n=10) received medical treatment for hypertension (Table 1). 64% (n=32) of participants had reduced HDL levels and 8% (n=3) had elevated triglycerides. Median (IQR) waist-hip circumference (F=0.89(0.14), M=0.93 (0.11)) and total percent body fat (F=37.7(11.5), M=22.3(11.5)) for SCD participants were higher than national normative values and 66% were classified as obese (Table 1). SCD participants had reduced mean (SD) VO2max, 16.77 (3.29) and 19.56 (7.27) ml/min/kg for females and males respectively compared with norms. In 90% of SCD participants (n=28), percent-predicted VO2max was less than normal (i.e. < 84 percent-predicted) with 4 adults having markedly reduced VO2max with a percent-predicted value less than 50%. Hemoglobin, hydroxyurea use and SCD genotype were not predictive of VO2max. Compared to controls, mean (SD) peak torque values for knee extension (82.7 Nm (19) vs 44.33 Nm (18.85), p<0.0001) and flexion ( 38.6 Nm (9.03)vs 19.19 Nm (13.2), p<0.0001) at 60 degrees were lower in SCD participants even after adjusting for age, sex, and body mass index (BMI) (Table1).Limitations: Study limitations include a small sample size, and the lack of controls matched for race, age, BMI, and hemoglobin.Conclusion:In this pilot study we show that both CRF and MusS are decreased in adults with SCD. Additionally, this cohort had a number of CV risk factors including smoking, hypertension and reduced HDL levels. As we know these are important predictors of poor CV outcomes additional research is needed to determine whether a carefully designed exercise and diet program can improve these modifiable CV risk factors and ultimately health status in adults living with SCD. [Display omitted] DisclosuresWang:PCORI: Research Funding. Lanzkron:Pfizer: Consultancy, Research Funding; NHLBI: Research Funding; Ironwood: Research Funding; PCORI: Research Funding; GBT: Consultancy, Research Funding; Selexys: Research Funding; Prolong: Research Funding.

Haemoglobin Genotype, ABO and Rhesus Blood Group Distribution in Briggs Family of Abonnema, Rivers State, Nigeria

Haemoglobin Genotype, ABO and Rhesus Blood Group Distribution in Briggs Family of Abonnema, Rivers State, Nigeria

Biochemical and hematological changes among anemic and non-anemic pregnant women attending antenatal clinic at the Bolgatanga regional hospital, Ghana

BackgroundAnemia in pregnancy may not only be associated with maternal morbidity and mortality but can also be detrimental to the fetus. A definitive diagnosis of anemia is a pre-requisite to unravelling possible cause(s), to allow appropriate treatment intervention. It is hypothesised that measured hemoglobin (HGB), complemented by biochemical and other hematological parameters would enhance anemia diagnosis.MethodsThis was a cross-sectional study among 400 pregnant women comprising 253 anemic and 147 non-anemic pregnant women, attending an antenatal clinic at Bolgatanga Regional Hospital, Ghana. Venous blood was collected and hemoglobin genotype, complete blood count and biochemical parameters [ferritin, iron, total iron binding capacity (TIBC), transferrin saturation (TfS), C-reactive protein (CRP) and bilirubin] were determined. Thick blood films were prepared for malaria parasitemia, while early morning stool and midstream urine samples were examined for enteric and urogenital parasites, respectively.ResultsThere were significantly reduced levels of HGB (p < 0.0001), HCT (p < 0.0001), MCV (p < 0.0001), iron (0.0273), ferritin (p = 0.018) and transferrin saturation (0.0391) and increased WBC (p = 0.006), RDW (p = 0.0480), TIBC (p = 0.0438) and positivity of CRP in anemic, compared to non-anemic pregnant women. Anemic women were associated with increased proportion of hemoglobinopathies (AS, SS and SC), Plasmodium falciparum, Schistosoma hematobium and intestinal parasite infections.ConclusionAnemic pregnant women are associated with a significant derangement in hematological and iron indices that implicate iron deficiency. This was influenced by hemoglobinopathies and parasitic infections.

Enuresis in children and adolescents with sickle cell anaemia is more frequent and substantially different from the general population

BackgroundNo large studies have examined the prevalence of enuresis, its various forms and risk factors in children with sickle cell anaemia (SCA) in Sub-Saharan Africa using standardised definitions. We determined age and gender-specific prevalence of enuresis and compared the nature of enuresis in children with and without SCA. We also identified predictors of enuresis in children with SCA.MethodsCaregivers of children with SCA attending a tertiary centre haematology clinic in Nigeria were interviewed using a questionnaire. In addition, a separate questionnaire was completed for every sibling aged 5–17 years whose haemoglobin genotype was known. Enuresis and its various forms were defined using the definitions of the International Children’s Continence Society.ResultsThe study involved 243 children with SCA and 243 controls matched for age and sex. The mean age of the study cohort was 9.9 (3.4). Females made up 45.7% of the cohorts. The prevalence of enuresis was 49.4% and 29.6% in children with and without SCA, respectively (p = 0.009). In both groups, the prevalence of enuresis declined with age but remained five times higher at 25% in children with SCA aged 14–17 years compared with controls. Also, children with SCA and enuresis were older, more likely to have non-monosymptomatic enuresis and wet at least three nights per week than controls. Independent predictors of enuresis in children with SCA were a family history of enuresis and young age.ConclusionChildren with SCA had more frequent and more severe enuresis which persisted to late adolescence than age and sex-matched controls. These features indicate a subset of enuresis that is difficult to treat in the general population. Young age and enuresis in a family member define a subset of children with SCA more likely to have enuresis. Healthcare workers need to discuss enuresis with parents of children with SCA and offer referral to continence services.

Gene Frequencies of Haemoglobin Genotype, ABO and Rhesus Blood Groups among Students Population of a Private University in Nigeria-Implications for Blood Banking

Gene Frequencies of Haemoglobin Genotype, ABO and Rhesus Blood Groups among Students Population of a Private University in Nigeria-Implications for Blood Banking

Transcranial Doppler Ultrasound in Peninsular Arab Patients With Sickle Cell Disease.

Transcranial Doppler ultrasound is used to identify patients with sickle cell disease (SCD) at risk for stroke. We performed transcranial Doppler studies in patients from 4 countries in the Arabian Peninsula (Kuwait, Oman, Iraq, and United Arab Emirates) to document the prevalence of abnormal transcranial Doppler findings. The patients were recruited from outpatient clinics and studied in a steady state. Transcranial Doppler examinations were performed with standard equipment by experienced operators. The time-averaged maximum mean velocity (TAMMV) was documented in the arteries of the circle of Willis. The hemoglobin (Hb) genotype was confirmed, and the fetal Hb level and complete blood counts were determined. There were 415 patients in the study, aged 2 to 18 years (mean ± SD, 8.6 ± 3.5 years). None of the patients had an abnormal TAMMV (ie, > 200 cm/s), whereas only 13 (3.1%), all from Iraq, had conditional values (170-200 cm/s) in the right middle cerebral artery and 7 (1.7%) in the left middle cerebral artery. There were no consistent TAMMV differences among male and female patients or in patients with different Hb genotypes (sickle cell anemia, sickle cell β0- thalassemia, and sickle D). The use of hydroxyurea was associated with a lower TAMMV, whereas a blood transfusion history had no influence. Total hemoglobin, reticulocyte count, serum bilirubin, and fetal Hb values showed varying degrees of association with the TAMMV in the different vessels. This study has demonstrated the rarity of abnormal transcranial Doppler findings among Peninsular Arab patients with SCD. The guidelines for transcranial Doppler screening in this population need further studies and recommendations.

Plasmodium falciparum merozoite protein-1 genetic diversity and multiplicity of infection in isolates from Congolese children consulting in a pediatric hospital in Brazzaville

As in many sub-Saharan African countries, the burden of malaria has been reduced in the Republic of Congo as a result of massive deployment of insecticide treated nets and availability of artemisinin-combinations therapies (ACTs). High to moderate genetic diversity of msp-1 gene of Plasmodium falciparum (P. falciparum) has been reported from different parts of the world but limited data are available from Central Africa including the Republic of Congo. For this reason, the aim of study was to investigate the P. falciparum genetic diversity and to determine the multiplicity of infection in P. falciparum isolates from Congolese children in order to dispose of an additional parameter to measure the impact malaria control intervention. A total of 229 blood samples were collected from September 2014 to February 2015 in children aged from one to ten years presenting a paediatric hospital Marien NGOUABI located in Northern part of Brazzaville. Inclusion criterion was fever (axillary temperature ≥ 37.5 °C) or history of fever in the preceding 48 h before inclusion in this study. Then thick and thin blood smears were done to detect malaria parasites, to determine parasite density and to identify plasmodial species. Sub-microscopic infection was detected by PCR using the P. falciparum msp-1 gene as molecular marker. The prevalence of microscopic and sub-microscopic infection in this cohort was 10% and 27.5%, respectively. The K1 allelic family was predominant (45% of isolates) whereas the RO33 and MAD20 represented 35% and 20%, respectively of isolates. In this study 48% (38/79) of isolates harbored more than one parasite clone.Overall the multiplicity of infection (MOI) was 1.7. According to type of infection, the MOI was significantly higher in children with microscopic infection (2.5 vs 1.4 for submicroscopic infection, P = .001). When considering age, hemoglobin genotype (AA or AS) and level and parasite density, no association was observed with the MOI. This study reveals that the P. falciparum genetic diversity in isolates from Congolese children is high but with low multiplicity of infection.