Sickle cell trait in São Tomé e Príncipe: a population-based prevalence study in women of reproductive age.

BACKGROUND: Sickle Cell Disorder is Africa's most prevalent genetic disease. Yet, it remains a neglected condition, with high mortality under-five, and a lack of population-based studies in the region. This is the first of its kind in São Tomé e Príncipe, aiming to estimate the prevalence of sickle cell trait and other haemoglobin variants in women of reproductive age and its associated factors. METHODS: We conducted a cluster survey in 35 neighbourhoods. Haemoglobin was assessed through point-of-care capillary electrophoresis or high-performance liquid chromatography, and sociodemographic data through questionnaires. The weighted prevalence of sickle cell trait (HbAS) and HbC carriers was estimated with a 95% confidence interval (95% CI). We calculated weighted prevalence ratios (95% CI) through robust Poisson regression for its association with age and individual and collective genetic heritage. FINDINGS: The prevalence of sickle cell trait in women of reproductive age in São Tomé e Príncipe (n = 376) was 13.45% (95% CI: 9.05-19.00). The prevalence of HbC carriers was 8.00% (95% CI: 4.71-12.00). Older age and speaking Forro or Angolar were positively associated with having sickle cell trait. INTERPRETATION: The prevalence of sickle cell trait in São Tomé e Príncipe ranks high in the West African region. The country should follow international guidelines, implementing newborn screening and comprehensive healthcare management.

Prevalence of sickle cell trait and needs assessment for uptake of sickle cell screening among secondary school students in Kampala City, Uganda.

BACKGROUND: Sickle cell disease (SCD) is one of the most frequent and traumatizing genetic disease in Uganda, with the prevalence of the sickle cell trait (SCT) estimated at 13.3% leading to serious psycho-social and economic impact on the patients and their families. AIM: This study aimed to determine the burden of SCT and factors influencing the uptake of screening services among secondary school students in Uganda. METHODS: We used an analytical cross-sectional design with a multi-stage sampling approach. A total of 399 students from four secondary schools in Kampala City were enrolled in this study. Data were gathered using semi-structured questionnaires and blood screening. We used the sickling test to determine the presence of sickle cell alleles among the participants and hemoglobin electrophoresis as a confirmatory test. Data gathered using the questionnaire were analyzed using descriptive and inferential statistics. RESULTS: In total, 5.8% of participants who were tested during this study had SCT. Most (80.2%) participants were not in an intimate relationship at the time of data collection. The majority (60.4%) had moderate knowledge about SCT screening and obtained information about screening from the school. Only 29 (7.3%) participants knew of a family member with sickle cell. Overall, participants had a negative attitude toward SCT screening (67%), although 41.6% believed that most people who were sickle cell carriers did not live long and were often sick. Statistically significant associations were found between testing for SCT and knowing a partner's sickle cell status (odds ratio [OR] 2.112, p = 0.043) and Anglican religion (OR 2.075, p = 0.047). CONCLUSION: Despite the moderate level of knowledge and negative attitudes, a relatively large number of participants had SCT. This highlights the need for a comprehensive health education package targeting adolescents to promote SCD/SCT screening.

Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa.

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that significantly contributes to childhood cancer burden in sub-Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria-such as the sickle cell trait variant, HBB-rs334(T)-also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome-scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB-rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628-0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533-0.885; p = .0037). ABO-rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379-0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.

Blood rheology and vascular function in sickle cell trait and sickle cell disease: From pathophysiological mechanisms to clinical usefulness.

Sickle cell disease (SCD) is an autosomal recessive disorder. Although the molecular mechanisms at the origin of SCD have been well characterized, its clinical expression is highly variable. SCD is characterized by blood rheological abnormalities, increased inflammation and oxidative stress, and vascular dysfunction. Individuals with only one copy of the mutated ß-globin gene have sickle cell trait (SCT) and are usually asymptomatic. The first part of this review focuses on the biological responses of SCT carriers during exercise and on the effects of combined SCT and diabetes on vascular function, several biomarkers and clinical complications. The second part of the review focuses on SCD and shows that the magnitude of red blood cell (RBC) rheological alterations is highly variable from one patient to another, and this variability reflects the clinical and hematological variability: patients with the less deformable RBCs have high hemolytic rate and severe anemia, and are prone to develop leg ulcers, priapism, cerebral vasculopathy, glomerulopathy or pulmonary hypertension. In contrast, SCD patients characterized by the presence of more deformable RBCs (but still rigid) are less anemic and may exhibit increased blood viscosity, which increases the risk for vaso-occlusive events. Several genetic and cellular factors may modulate RBC deformability in SCD: co-existence of α-thalassemia, fetal hemoglobin level, oxidative stress, the presence of residual mitochondria into mature RBCs, the activity of various non-selective cationic ion channels, etc. The last part of this review presents the effects of hydroxyurea and exercise training on RBC rheology and other biomarkers in SCD.

CHOICES for sickle cell reproductive health: A protocol of a randomized preconception intervention model for a single gene disorder.

Our long-term goal is to foster genetically informed reproductive health knowledge and behaviors among young adults with sickle cell disease (SCD) or sickle cell trait (SCT) with a web-based, tailored, multimedia intervention called CHOICES. CHOICES is designed to help young adults with SCD or SCT preconception to gain knowledge of genetic inheritance, specify their reproductive health intentions (their parenting plan), and engage in reproductive health behaviors concordant with their parenting plan. In a previous study, we found high acceptability of both the e-Book (usual care control) and CHOICES interventions. We also found sustained (24 months), significant effects on knowledge but not on behavior, most likely because half of the recruited group was not at risk for their children inheriting SCD. Hence, we propose an adequately powered randomized controlled trial with the CHOICES intervention and an e-Book control to compare their effects on genetic inheritance knowledge and at-risk reproductive health behaviors (immediate posttest and at 6, 12, 18, and 24 months). We will conduct subgroup analyses to provide insight into the baseline knowledge and behavior as well as the intervention effects in different demographic or acceptability groups. Given the scalability and low cost of CHOICES, if proved to be effective, it can reach the affected population at low cost.

Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait.

Sickle cell disease (SCD) is caused by the homozygous beta-globin gene mutation that can lead to ischemic multi-organ damage and consequently reduce life expectancy. On the other hand, sickle cell trait (SCT), the heterozygous beta-globin gene mutation, is still considered a benign condition. Although the mechanisms are not well understood, clinical evidence has recently shown that specific pathological symptoms can also be recognized in SCT carriers. So far, there are still scant data regarding the morphological modifications referable to possible multi-organ damage in the SCT condition. Therefore, after genotypic and hematological characterization, by conventional light microscopy and transmission electron microscopy (TEM), we investigated the presence of tissue alterations in 13 heterozygous Townes mice, one of the best-known animal models that, up to now, was used only for the study of the homozygous condition. We found that endothelial alterations, as among which the thickening of vessel basal lamina, are ubiquitous in the lung, liver, kidney, and spleen of SCT carrier mice. The lung shows the most significant alterations, with a distortion of the general tissue architecture, while the heart is the least affected. Collectively, our findings contribute novel data to the histopathological modifications at microscopic and ultrastructural levels, underlying the heterozygous beta-globin gene mutation, and indicate the translational suitability of the Townes model to characterize the features of multiple organ involvement in the SCT carriers.

Association of sickle cell trait with adverse pregnancy outcomes in a population-based cohort.

INTRODUCTION: Sickle cell trait (SCT) is common in African descendants. Its association with several adverse pregnancy outcomes (APOs) has been reported but remains inconsistent. The objectives of this study are to test associations of SCT with APOs in non-Hispanic Black women, including (1) validate the associations of SCT with previously reported APOs, (2) test novel associations of SCT with broad spectrum of APOs, and (3) estimate the attributable risk of SCT for implicated APOs. MATERIAL AND METHODS: This is a retrospective analysis of a prospectively designed population-based cohort. Women/participants were self-reported non-Hispanic Black women from the UK Biobank (UKB). SCT status was determined based on heterozygous Glu6Val in the HBB gene. Several APOs were studied, including four previously reported SCT-associated APOs (preeclampsia, bacteriuria, pregnancy loss, and preterm delivery), and broad conditions related to pregnancy, childbirth, and the puerperium. APOs were curated by experts' peer review and consensus processes. Associations of SCT with APOs were tested by estimating its relative risk and 95% confidence interval (95% CI), adjusting for number of live births and age at first birth. Attributable risk proportion (ARP) and population attributable risk proportion (PARP) of SCT to APOs were estimated. RESULTS: Among the 4057 self-reported non-Hispanic Black women with pregnancy records in the UKB, 581 (14.32%) were SCT carriers. For four previously reported SCT-associated APOs, two were confirmed at a nominal P < 0.05; relative risk (RR) was 2.39 (95% CI 1.09-5.23) for preeclampsia, and 4.85 (95% CI 1.77-13.27) for bacteriuria. SCT contributed substantially to these two APOs among SCT carriers, with attributable risk proportion estimated at 61.00% and 68.96% for preeclampsia and bacteriuria, respectively. SCT also contributed substantially to these two APOs in the population (self-reported Black UK women), with population attributable risk proportion estimated at 18.30% and 24.14% for preeclampsia and bacteriuria, respectively. In addition, novel associations were found for seven other APOs (nominal P < 0.05). CONCLUSIONS: SCT is significantly associated with APOs in this study and contributes substantially to APOs among self-reported Black women in the UK. Confirmation of these findings in independent study populations is required.

Effect of α+ Thalassemia on the Severity of Plasmodium falciparum Malaria in Different Sickle Cell Genotypes in Indian Adults: A Hospital-Based Study.

There is a paucity of literature on the association of α+-thalassemia, sickle-cell hemoglobin disorders, and malaria in India. This study aimed to understand the effect of α+-thalassemia on the severity of Plasmodium falciparum malaria in adults with respect to sickle-cell genotypes. The study subjects were categorized into 'severe-malaria' and 'uncomplicated-malaria' and age-gender matched 'control' groups. Sickle-cell and α+-thalassemia were investigated in all the recruited subjects. The effect of α+-thalassemia on the severity of malaria was analyzed in HbAA and sickle-cell genotypes (HbAS and HbSS) separately. The prevalence of α+-thalassemia in various groups ranged from 41.5% to 81.8%. The prevalence of α+-thalassemia was lower (OR = 1.64; p = 0.0013) in severe malaria (41.5%) as compared to healthy controls (53.8%) with HbAA genotype. In contrast, in HbAS genotype, the prevalence of α+-thalassemia was higher (OR = 4.11; p = 0.0002) in severe malaria (81.8%) compared to controls (52.2%). In severe malaria with HbAA genotype, there was a significantly higher hemoglobin level and low MCV and MCH level in patients with α+-thalassemia compared to the normal α-globin genotype. Further, the incidence of cerebral malaria, hepatopathy, and mortality was lower in patients (HbAA) with α+-thalassemia as compared to normal α-globin genotype (HbAA). In severe malaria with either HbAS or HbSS genotype, only a few parameters showed statistical differences with respect to α+-thalassemia. Low prevalence of α+-thalassemia in severe malaria with HbAA genotype compared to healthy controls with HbAA genotype indicates the protective effect of α+-thalassemia against severe malaria. However, the high prevalence of α+-thalassemia in patients with HbAS genotype depicts its interference in the protective effect of sickle-cell against severe malaria.

Influence of the sickle cell trait on Plasmodium falciparum infectivity from naturally infected gametocyte carriers.

BACKGROUND: Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the ß-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. METHODS: The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. RESULTS: Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29-1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. CONCLUSION: Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite's enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.

SMARCB1 regulates the hypoxic stress response in sickle cell trait.

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor SMARCB1. Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels of SMARCB1 and more aggressive growth in mice harboring the SCT mutation in human hemoglobin A (HbA) than in control mice harboring wild-type human HbA. Consistent with established clinical observations, SMARCB1-null renal tumors were refractory to hypoxia-inducing therapeutic inhibition of angiogenesis. Further, reconstitution of SMARCB1 restored renal tumor sensitivity to hypoxic stress in vitro and in vivo. Together, our results demonstrate a physiological role for SMARCB1 degradation in response to hypoxic stress, connect the renal medullary hypoxia induced by SCT with an increased risk of SMARCB1-negative RMC, and shed light into the mechanisms mediating the resistance of SMARCB1-null renal tumors against angiogenesis inhibition therapies.

COVID-19 Infection and Outcomes in Newborn Screening Cohorts of Sickle Cell Trait and Sickle Cell Disease in Michigan and Georgia.

The sickle cell mutation increases morbidity in those with sickle cell disease (SCD) and potentially sickle cell trait, impacting pulmonary, coagulation, renal, and other systems that are implicated in COVID-19 severity. There are no population-based registries for hemoglobinopathies, and they are not tracked in COVID-19 testing. We used COVID-19 test data from 2 states linked to newborn screening data to estimate COVID outcomes in people with SCD or trait compared with normal hemoglobin. We linked historical newborn screening data to COVID-19 tests, hospitalization, and mortality data and modeled the odds of hospitalization and mortality. Georgia's cohort aged 0 to 12 years; Michigan's, 0 to 33 years. Over 8% of those in Michigan were linked to positive COVID-19 results, and 4% in Georgia. Those with SCD showed significantly higher rates of COVID-19 hospitalization than the normal hemoglobin Black cohort, and Michigan had higher rates of mortality as well. Outcomes among those with the trait did not differ significantly from the normal hemoglobin Black group. People with SCD are at increased risk of COVID-19-related hospitalization and mortality and are encouraged to be vaccinated and avoid infection. Persons with the trait were not at higher risk of COVID-related severe outcomes.

Evaluation of Homocysteine Status and its Correlation with Disease Severity in Individuals with Sickle Cell Anaemia in Steady State.

INTRODUCTION: Sickle cell anaemia (SCA) is a genetic disorder associated with chronic inflammation and a hypercoagulable state. This study evaluated the serum homocysteine level and its correlation with disease severity and body mass index (BMI) among individuals with SCA in a steady state. METHODS: A cross-sectional study was carried out and the serum level of homocysteine was analysed using the ELISA method. Disease severity and BMI were also calculated. Data generated were analyzed using SPSS software, version 21. RESULTS: Ninety subjects participated in this study and were made up of 30 homozygous sickle cell (HbSS, SCA) subjects, 30 individuals with sickle cell trait (HbAS), and 30 individuals with normal adult haemoglobin (HbAA) with a mean age of 27.3 ± 6.4years, 26.0 ± 6.0years, and 27.2 ± 6.6years respectively. The mean serum level of homocysteine among HbSS was 26.2 ± 11.8umol/l which was significantly higher than 17.9 ± 8.0umol/l and 18.9 ± 7.9umol/l among HbAA or HbAS respectively (p< 0.05). Mean BMI of 21.9 ± 2.8kg/m2 among HbSS was significantly lower than those of HbAS (23.7 ± 2.5kg/m2) and HbAA (24.7 ± 2.4kg/m2) (p<0.05). There was a positive correlation between homocysteine level and disease severity in patients with HbSS, though not significant (r = 0.168; p>0.05). There was a significant negative correlation between homocysteine level and BMI(r = -0.0258; p = 0.021); and between disease severity and BMI (r = -0.400; p = 0.028). CONCLUSION: Individuals with HbSS have significantly higher mean serum homocysteine level and lower BMI compared to HbAS and HbAA. There was a positive correlation between homocysteine level and disease severity, though not significant but a strong negative correlation between homocysteine levels and BMI, and between disease severity and BMI among HbSS participants. A similar study should be carried out on a wide scale to determine the actual relationship between homocysteine level and disease severity in SCA and whether patients will benefit from routine administration of vitamin B12, vitamin B6, and folic acid.

INTRODUCTION: La drépanocytose est une maladie génétique associée à une inflammation chronique et à un état d'hypercoagulabilité. Cette étude a évalué le taux d'homocystéine sérique et sa corrélation avec la gravité de la maladie et l'indice de masse corporelle (IMC) chez les personnes atteintes d'anémie drépanocytaire à l'état stable. MÉTHODES: Une étude transversale a été réalisée et le taux sérique d'homocystéine a été analysé à l'aide de la méthode ELISA. La gravité de la maladie et l'IMC ont également été calculés. Les données générées ont été analysées à l'aide du logiciel SPSS, version 21. RÉSULTATS: Quatre-vingt-dix sujets ont participé à cette étude, dont 30 drépanocytaires homozygotes (HbSS, SCA), 30 drépanocytaires de trait (HbAS) et 30 personnes ayant une hémoglobine adulte normale (HbAA), âgés en moyenne de 27,3 ±6,4 ans, 26,0 ±6,0 ans et 27,2 ±6,6 ans, respectivement. Le taux sérique moyen d'homocystéine chez les HbSS était de 26,2 ±11,8 umol/l, ce qui était significativement plus élevé que 17,9 ±8,0umol/l et 18,9 ±7,9umol/l chez les HbAA ou HbAS respectivement (p< 0,05). L'IMC moyen de 21,9 ±2,8kg/m2 chez les HbSS était significativement inférieur à celui des HbAS (23,7±2,5kg/m2) et des HbAA (24,7 ±2,4kg/ m2) (p<0,05). Il y avait une corrélation positive entre le niveau d'homocystéine et la sévérité de la maladie chez les patients HbSS, bien que non significative (r= 0.168 ; p>0.05). Il existe une corrélation négative significative entre le taux d'homocystéine et l'IMC (r= - 0,0258 ; p = 0,021) ; et entre la gravité de la maladie et l'IMC (r = - 0,400 ; p = 0,028). CONCLUSION: Les personnes atteintes de HbSS ont un taux moyen d'homocystéine sérique significativement plus élevé et un IMC plus faible que les personnes atteintes de HbAS et de HbAA. Il existe une corrélation positive entre le taux d'homocystéine et la gravité de la maladie, une corrélation négative non significative mais forte entre le taux d'homocystéine et l'IMC, et entre la gravité de la maladie et l'IMC chez les participants HbSS. Une étude similaire devrait être menée à grande échelle pour déterminer la relation réelle entre le taux d'homocystéine et la gravité de la maladie dans le SCA et pour savoir si les patients bénéficieront de l'administration systématique de vitamine B12, de vitamine B6 et d'acide folique. Mots clés: Gravité de la maladie, homocystéine, anémie drépanocytaire.

Sickle Cell Hemoglobin Genotypes Affect Malaria Parasite Growth and Correlate with Exosomal miR-451a and let-7i-5p Levels.

Malaria affects a significant portion of the global population, with 247 million cases in 2021, primarily in Africa. However, certain hemoglobinopathies, such as sickle cell trait (SCT), have been linked to lower mortality rates in malaria patients. Hemoglobin (Hb) mutations, including HbS and HbC, can cause sickle cell disease (SCD) when both alleles are inherited (HbSS and HbSC). In SCT, one allele is inherited and paired with a normal allele (HbAS, HbAC). The high prevalence of these alleles in Africa may be attributed to their protective effect against malaria. Biomarkers are crucial for SCD and malaria diagnosis and prognosis. Studies indicate that miRNAs, specifically miR-451a and let-7i-5p, are differentially expressed in HbSS and HbAS compared to controls. Our research examined the levels of exosomal miR-451a and let-7i-5p in red blood cells (RBCs) and infected red blood cells (iRBCs) from multiple sickle Hb genotypes and their impact on parasite growth. We assessed exosomal miR-451a and let-7i-5p levels in vitro in RBC and iRBC supernatants. Exosomal miRNAs exhibited distinct expression patterns in iRBCs from individuals with different sickle Hb genotypes. Additionally, we discovered a correlation between let-7i-5p levels and trophozoite count. Exosomal miR-451a and let-7i-5p could modulate SCD and malaria severity and serve as potential biomarkers for malaria vaccines and therapies.

Variability in sickle cell knowledge by sickle cell status.

Disease-specific knowledge allows individuals with sickle cell disease, sickle cell trait, and unaffected family members alike to make informed decisions and support those affected by the condition. The current study assesses how sickle cell knowledge varies by disease status within families affected by sickle cell disease. One hundred seventy-nine participants from 84 families completed an online survey and telephone interview. Generalized linear models, with generalized estimating equations, were fitted to evaluate differences in both item-level responses and total scores on the Sickle Cell Knowledge Scale by sickle cell status. Those with negative or unknown sickle cell status scored significantly lower than those with sickle cell disease or trait, despite being related to someone with sickle cell disease (χ2 (2) = 9.72, p = 0.008). Overall, participants performed poorly on items related to sickle cell trait, with limited understanding of autosomal recessive inheritance patterns. The study's findings suggest a need to move beyond patient-centered approaches to family-centered education efforts that reach those with sickle cell traits and negative or unknown status. Findings point to knowledge gaps related to sickle cell trait and patterns of inheritance, representing key enhancement areas for future sickle cell education efforts.

Physiological jump in erythrocyte redox potential during Plasmodium falciparum development occurs independent of the sickle cell trait.

The redox state of the host-parasite unit has been hypothesized to play a central role for the fitness of the intraerythrocytic blood stages of the human malaria parasite Plasmodium falciparum. In particular, hemoglobinopathies have been suggested to cause a more oxidizing environment, thereby protecting from severe malaria. Here we determined the redox potential of infected wild-type (hemoglobin AA) or sickle trait (hemoglobin AS) erythrocytes using parasite-encoded variants of the redox-sensitive green-fluorescent protein 2 (roGFP2). Our non-invasive roGFP2 single-cell measurements revealed a reducing steady-state redox potential of -304 ± 11 mV for the erythrocyte cytosol during ring-stage development and a rather sudden oxidation to -278 ± 12 mV during trophozoite-stage development around 28 h post invasion. There was no significant difference between wild-type or sickle trait erythrocytes regarding the stage dependence and the detected increase of the redox potential during the intraerythrocytic life cycle. The steady-state redox potential of the parasite cytosol, between -304 and -313 mV, was highly reducing throughout the life cycle. The redox potential in the parasitophorous vacuole at the interface between the secretory pathway and the erythrocyte was -284 ± 10 mV and remained stable during trophozoite-stage development with implications for the export of disulfide-containing proteins. In summary, P. falciparum blood stage development from the late ring to the early trophozoite stage causes a physiological jump in erythrocyte redox potential irrespective of the presence or absence of hemoglobin S.

A Health Literate Approach to Address Health Disparities: a Virtual Program for Parents of Children with Sickle Cell Trait.

Background: Approximately 8% of African Americans born annually have sickle cell trait (SCT), a public health concern that may contribute to health disparities if individuals with SCT do not know it and lack access to understandable information about reproductive implications. Pre-pandemic, Ohio offered in-person SCT education for parents of SCT-affected children but many did not attend. Those with limited health literacy (HL) were less likely to achieve high knowledge. We used a HL-focused evaluation of this education to develop a virtual program (SCTaware) to communicate clear, actionable information and promote knowledge retention. Methods: Seven English-speaking parents, three with limited HL, were recruited in 2019 for in-person session videotaping and SCT knowledge assessments. Clinicians, HL experts, educators, genetic counselors, and parent stakeholders (evaluators) reviewed sessions, assessments, and accompanying visuals. Results: Evaluators: observed parents asked few questions; noted undefined technical terms, closed questions, key concept omission, and limited explanation of visuals scoring low for understandability, actionability, and clarity; and developed SCTaware for individual videoconference delivery (knowledge objectives; plain language guide; HL-informed communication strategies; new visuals scoring highly for understandability, actionability, and clarity; narrated post-education version; standardized educator training). Conclusions: Using a HL-focused evaluation, our diverse team created a promising virtual SCT education program addressing a common issue affecting populations at risk for disparities. Given virtual education will likely continue post-pandemic and limited HL is common, this approach may be essential and replicable for other public health education programs, especially those transitioning to virtual formats, to convey clear, actionable information and promote health equity.

Tailored Parenting Plans of Young Adults With Sickle Cell Disease or Sickle Cell Trait.

Our study purpose was to evaluate the variation and accuracy of tailored parenting plans individually generated as a supplement to reproductive health education on the genetic inheritance of sickle cell disease or sickle cell trait. We present a secondary data analysis of experimental group data from a randomized controlled trial. Participants completed the valid and reliable Internet-based Sickle Cell Reproductive Health Knowledge Parenting Intent Questionnaire. We created a computerized algorithm that used participants' responses to generate tailored parenting plans based on their parenting preferences and partner's sickle cell status. Thirty-one different parenting plans were generated to meet the variety in the participants' preferences. The most frequently generated plan was for participants with sickle cell disease who had a partner with hemoglobin AA, who wanted to be a parent, was not likely to be pregnant, and wanted their child to be sickle cell disease free. More than half of the participants required alteration in their reproductive behavior to achieve their parenting goals. Findings provide insight into the variety and accuracy of computer algorithm-generated parenting plans, which could further guide refinement of the algorithm to produce patient-centered, tailored parenting plans supplemental to Internet-based genetic inheritance education.

Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.

Importance: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the association of SCT with COVID-19 is unclear. Objective: To assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP) and to assess the severity and sequelae of COVID-19. Design, Setting, and Participants: COVID-19 clinical data include 2729 persons with SCT, of whom 353 had COVID-19, and 129 848 SCT-negative individuals, of whom 13 488 had COVID-19. Associations between SCT and COVID-19 outcomes were examined using firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification. Data for the study were collected between March 2020 and February 2021. Exposures: The hemoglobin beta S (HbS) allele (rs334-T). Main Outcomes and Measures: This study evaluated 4 COVID-19 outcomes derived from the World Health Organization severity scale and phenotypes derived from International Classification of Diseases codes in the electronic health records. Results: Of the 132 577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years. Sickle cell trait was present in 7.8% of individuals of African ancestry and associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among the 4 clinical outcomes of COVID-19, SCT was associated with an increased COVID-19 mortality in individuals of African ancestry (n = 3749; odds ratio, 1.77; 95% CI, 1.13 to 2.77; P = .01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. A counterfactual mediation framework estimated that on average, 20.7% (95% CI, -3.8% to 56.0%) of the total effect of SCT on COVID-19 fatalities was due to acute kidney failure. Conclusions and Relevance: In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity.

Incidence of hemoglobinopathies and spatialization of newborns with sickle cell trait in Mato Grosso do Sul, Brazil.

OBJECTIVE: To evaluate the incidence of variant hemoglobins of newborn samples from the Neonatal Screening Center in the state of Mato Grosso do Sul, Brazil, and to analyze the distribution and spatial autocorrelation of newborns with sickle cell trait. METHODS: Samples from 35,858 newborns screened by the Neonatal Screening Center. The samples with inconclusive diagnosis were submitted to electrophoretic, chromatographic, cytological and molecular analyses. The spatial distribution analysis of newborns with sickle cell trait was performed by spatial autocorrelation. RESULTS: A total of 919 newborns showed an abnormal hemoglobin profile; in that, ten genotypes had significant clinical impacts identified. Among the asymptomatic newborns, the sickle cell trait was the most frequent (incidence of 1.885 cases/100 newborns). The highest incidence rates were registered in the municipalities of Terenos, Figueirão, Corguinho and Selvíria. There was positive spatial autocorrelation between the proportion of declared individuals of black race/color and the incidence of newborns with sickle cell trait. CONCLUSION: The early diagnosis by neonatal screening and laboratory tests was very important to identify abnormal hemoglobin profiles and guide the spatial autocorrelation analysis of sickle cell trait newborns in Mato Grosso do Sul, serving as a support to anticipate health measures aimed to discuss efficient therapeutic behaviors and effective planning of municipalities with the greatest need for care, monitoring and orientations for affected families.

Sickle Cell Trait and Risk for Common Diseases: Evidence from the UK Biobank.

BACKGROUND: Sickle cell trait is typically considered benign. Although evidence remains inconsistent, recent studies suggest that it is associated with several common diseases. We systematically assessed associations of sickle cell trait with reported diseases in a large population-based cohort. METHODS: Study subjects were self-reported Blacks from the UK Biobank (UKB), a United Kingdom population-based cohort of subjects aged 40-69 years at recruitment in the United Kingdom. Sickle cell status was based on the International Classification of Diseases, Tenth Revision (ICD-10) or mutations in the HBB gene. Diagnoses of diseases were obtained from ICD-10 and self-reports. Associations of sickle cell trait and diseases were tested using logistic regression, adjusting for age at recruitment, sex, and genetic background (top 10 principal components). RESULTS: Among the 8019 Blacks in the UKB, 699 (8.72%) were sickle cell trait carriers; the rate was significantly higher in females (9.74%) than males (7.48%), P = .0005. Sickle cell trait was under-diagnosed; most heterozygous hemoglobin subunit beta (HBB) gene Glu6Val carriers did not have a sickle cell trait ICD-10 record. Compared with non-sickle cell trait, sickle cell trait carriers had significantly increased risk for type 2 diabetes; odds ratio 1.38; 95% confidence interval, 1.12-1.68; P = .002. Sickle cell trait was also significantly associated with increased risk for renal diseases (rhabdomyolysis, end-stage renal disease, chronic kidney disease, renal papillary necrosis) and vascular diseases (hypertension, retinopathy, non-ischemic stroke), P < .05. While most of these diseases are complications/comorbidities of diabetes, their associations with sickle cell trait remained significant after adjusting for diabetes. Association with end-stage renal disease was stronger in subjects without diabetes, odds ratio 6.45; 95% confidence interval, 1.93-19.61; P = .001. CONCLUSIONS: Sickle cell trait is significantly associated with increased risk for diabetes and diabetes-related complications/comorbidities.