Immunization adherence among children with sickle cell disease and sickle cell trait: Results of a population-based study.

INTRODUCTION: Despite the importance of timely vaccine completion for protection from infectious disease, there is limited knowledge of the immunization adherence rates of children with sickle cell disease (SCD). METHODS: This is a retrospective cohort study comparing the immunization rates of children with SCD to those with sickle cell trait between 2008 and 2019 in Georgia. Completion rates for each vaccine and the proportion of children with up-to-date status at 24 and 35 months were calculated and compared between the cohorts. Chi-square tests with odds ratios (OR) for differences and 95% confidence intervals (CIs) were reported on the overall up-to-date rates and rates for individual vaccines at 24 and 35 months for the two cohorts. RESULTS: Children with SCD had higher up-to-date rates than children with sickle cell trait at 24 and 35 months. At 35 months, the overall up-to-date rates (OR = 1.17; 95% CI, 1.04-1.31; p = .004) and the four-dose pneumococcal conjugate vaccine series (OR = 1.36; 95% CI, 1.18-1.57; p < .001) were significantly different between the groups. Both cohorts had the highest completion rates for the hepatitis B series and the lowest rates for the varicella vaccine. Doses of diphtheria, tetanus, and acellular pertussis vaccine; varicella; and pneumococcal conjugate vaccines were most commonly missed by children in both cohorts. CONCLUSIONS: Children with SCD have better immunization coverage than children with sickle cell trait, but there is an opportunity for improvement. Policymakers and healthcare professionals should focus on increasing access to care coordination services among children with SCD to ensure on-time and preventive healthcare services.

Septic arthritis of the native hip joint and septic pulmonary embolism in an adult with sickle cell trait after a complicated dental extraction.

Septic arthritis (SA) is a serious infection of the joint which can lead to irreversible destruction of the joint.We report a case of right hip SA with septic pulmonary embolism following a complicated dental extraction in a woman in her early 40s with sickle cell trait (SCT).The patient presented with severe right thigh pain and left jaw pain.Initial workup revealed raised C reactive protein and positive blood cultures. Right hip joint SA was confirmed following intraoperative joint aspiration. The patient had right hip debridement with long-term intravenous antibiotics.The incidence of SA in adults with sickle cell disease is low: 0.3% in a study in France and Brazil and 10.3% incidence of haematogenous osteoarticular infection in children with SCT in West Africa.

Update on the practice of premarital screening for sickle cell traits in Africa: a systematic review and meta-analysis.

BACKGROUND: Screening for sickle cell traits before marriage or producing children is one of the outstanding preventive measures for sickle cell disease (SCD).The disease is a collection of inherited blood disorders that impact millions globally, with a predominant 75% occurrence in the sub-Saharan region. With increasing burden of SCD on the continent amidst a cost effective prevention method, no study has systematically reviewed or presented meta-analytic uptake or practice of premarital sickle cell trait screening. METHODS: This review systematically explored the uptake or practice of premarital genotype screening in Africa. We searched PubMed and Scopus databases for African studies on premarital screening for sickle cell traits. RESULTS: Our results indicate that the pooled uptake of premarital sickle cell trait screening in Africa is 47.82% (95% CI: [46.53-49.11]; I2: 98.95% [98.74-99.13]). Our review observed, a significant relationship between the awareness of sickle cell disease and the uptake of genotype screening; F(1, 13) = 12.04, p = 0.004). The model explained approximately 48.08% of the variation in genotype screening (R² = 0.4808) and predicted a 0.729 increase in the likelihood of genotype screening uptake for every unit rise in sickle cell disease awareness (ß = 0.729, p = 0.004). Additionally, Pearson correlation (r = 0.6934) indicated a moderately strong positive correlation between the two variables. CONCLUSION: With over 75% of the global burden of sickle cell disease domiciled in Africa, the continent cannot overlook the cost of hemoglobinopathies. The uptake of sickle cell traits screening is suboptimal across the continent. To achieve the mandate of sustainable development goal number (3); to end preventable deaths of newborns and children under 5 years of age by 2030, there is need to intensify campaigns on premarital genetic screening through education and other health promotion tools.

Genome-Wide Analysis of Exertional Rhabdomyolysis in Sickle Cell Trait Positive African Americans.

Sickle cell trait (SCT), although generally a benign carrier state of hemoglobin S (HbAS), is a risk factor for exertional rhabdomyolysis (ERM), a rare but potentially fatal consequence of highly intense physical exercise, particularly among active-duty military personnel and high-performance athletes. The association between SCT and ERM is poorly understood. The objective of this study was to elucidate the genetic basis of ERM in an SCT-positive African American cohort. SCT-positive African Americans with a personal history of ERM (cases, n = 30) and without history of ERM (controls, n = 53) were enrolled in this study. Whole-genome sequencing was performed on DNA samples isolated from peripheral white blood cells. Participants' demographic, behavioral, and medical history information was obtained. An additional 131 controls were extracted from SCT-positive subjects of African descent from the 1000 Genomes Project. SCT carriers with ERM were characterized by myotoxicity features, significant muscle involvement dominated by muscle weakness, and severe pain and substantial increase in serum creatine kinase, with a mean value of 50,480 U/L. A distinctive feature of the SCT individuals with ERM was exertional collapse, which was reported in 53.3% of the cases in the study cohort. An important factor for the development of ERM was the duration and frequency of strenuous physical activity in the cases compared to the controls. Whole-genome sequencing identified 79,696 protein-coding variants. Genome-wide association analysis revealed that the p.C477R, rs115958260 variant in the SLC44A3 gene was significantly associated with ERM event in SCT-positive African Americans. The study results suggest that a combination of vigorous exercise and a genetic predisposing factor is involved in ERM.

Blood count changes in malaria patients according to blood groups (ABO/Rh) and sickle cell trait.

INTRODUCTION: Introduction: Malaria continues to be the leading cause of hospitalization and death in Angola, a country in sub- Saharan Africa. In 2023, in the first quarter, 2,744,682 cases were registered, and of these 2,673 patients died due to malaria disease. Previous studies have shown that the ABO blood group can affect the progression of malaria to severe conditions after P. falciparum infection, while the sickle cell gene offers relative protection. OBJECTIVE: We investigated changes in the blood count according to blood groups (ABO/Rh) and sickle cell trait in patients with malaria in Luanda, capital of Angola. METHODOLOGY: This was a longitudinal, prospective and observational study with 198 patients hospitalized for malaria. RESULTS: Of the 198 patients studied, 13(6.6%) were ABRh(+), 4(2.0%) were ARh(-), 49(24.7%) were ARh(+), 42(21, 2%) were BRh (+), 5(2.5%) were ORh(-) and 85(42.9%) were ORh(+). For sickle cell trait, 145(73.2%) were AA, 37(18.7%) were AS and 16(8.1%) were SS. No statistical relationship was observed between age group, sex, parasitemia, clinical picture, hematocrit, MCV, HCM, MCHC, leukocytes, NEUT, LINF and PTL values with blood groups (p<0.05), but there was a relationship between values of hemoglobin and ABO/Rh blood groups (p>0.05). There was no relationship between age, parasitemia, clinical condition, MCV, HCM and MCHC values, leukocytes, NEUT and LINF with sickle cell trait (p<0.05), but there was a relationship between sex, hemoglobin and PTL and sickle cell values. sickle cell trait (p>0.05). CONCLUSION: It is imperative to differentiate patients with malaria based on blood groups and sickle cell trait, taking into account mainly the blood count parameters that demonstrate that there are patients who, depending on blood group or sickle cell trait, may react weakly to malaria infection regardless of the degree of parasitemia and medical prognosis.

Splenic Subcapsular Hematoma from Commercial Air Travel: Case Report of a Unique Incident of Altitude-Associated Splenic Syndrome.

BACKGROUND: Sickle cell trait (SCT), the heterozygous form of sickle cell disease, is generally thought of as a benign condition. However, it is possible for those with SCT to have serious complications, especially when they are exposed to high altitudes where oxygen levels are low. CASE REPORT: We present a case of a 41-year-old man with a history of SCT who developed severe epigastric pain and nearly lost consciousness while traveling on a commercial airplane. His twin brother, who also has SCT, had a similar episode in the past and required a splenectomy. A splenic subcapsular hematoma was found in a computed tomography scan of the abdomen and pelvis with intravenous contrast. He was admitted and managed conservatively until his symptoms resolved. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Though SCT is prevalent in our population, the complications that can arise, such as altitude-associated splenic syndrome, have likely not been thoroughly investigated. Physicians should add this condition to their differential if they practice at locations near airports or in areas of higher altitude and if their patients have a past medical history of SCT.

Early-onset indicators of a hypercoagulable state and clinical complications in a cohort of children with sickle cell trait.

Adults with sickle cell trait (SCT) have a procoagulant state with increased risk of thromboembolism, but limited data are available for children. We compared the coagulation profile of children with SCT, different sickle cell disease (SCD) genotypes, and healthy controls. Compared to controls and similarly to HbSC patients, 41 SCT children (mean age 6.85 years; 20 males; 88% Africans) had a characteristic procoagulant profile: higher levels of factor VIII, von Willebrand factor (VWF) Ag and CBA, D-dimer; lower levels of ADAMTS 13 activity, ADAMTS13 activity: VWFAg, plasminogen activator inhibitor, tissue plasminogen activator. Moreover, 13/41 had clinical complications of SCD, five requiring hospitalization.

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.

Occlusive Retinal Vasculitis in a Pediatric Patient With Kikuchi-Fujimoto Disease and Sickle Cell Trait.

A 13-year-old Black male patient with a history of Kikuchi-Fujimoto disease (KFD) and sickle cell trait presented with acute painless vision loss and no light perception vision (NLP) in his left eye. The examination was indicative of occlusive retinal vasculitis with near total central retinal artery occlusion (CRAO). He was started on oral steroids with dramatic reperfusion and improvement of the retinal hemorrhages. However, his vision remained at NLP. Oral steroids were tapered, and rituximab infusion was initiated. While ocular involvement is uncommon in KFD, vision-limiting complications, such as occlusive retinal vasculitis, ophthalmic artery occlusion, and CRAO can occur. Early systemic immunosuppression is key in achieving rapid remission. [Ophthalmic Surg Lasers Imaging Retina 2024;55:235-239.].

Comparing Hearing Loss in Children with Adults Living with Sickle Cell Disease and Sickle Cell Traits.

BACKGROUND: Hearing loss is a neurological sequelae associated with sickle cell disease (SCD) and probably sickle cell trait (SCT) in children and adults but remains understudied. AIM: This study aimed to compare the hearing impairment among children and adults living with SCD or SCT. METHODS: A comparative cross-sectional study conducted in four departments with SCD outpatient clinic in a tertiary hospital in Nigeria. Participants with Sickle cell disease (HbSS) and Sickle cell trait (HbAS) (cohort) and HbAA (control) had comprehensive ear and hearing assessments for sensorineural hearing loss. Audiometric results were categorized according to WHO classifications and data analysed with Statistical Analysis System (SAS 9.4). RESULTS: A total of 212 participants (106 cohort and control, respectively), aged 6 months to 55 years, were enrolled. Of these, 35% of children with SCD and 25% with SCT had hearing impairment, while 30% of adults with SCD, 36.1% with SCT, and 11% with HbAA had hearing impairment. There was asymmetry in the hearing impairment, with the left ear more affected in children and the right ear in adults. The odds ratio (OD) of hearing impairment was higher in HbSS (2.48 (95% confidence interval (CI):1.51-4.14); P = 0.0004) and HbAS (2.28 (95% CI: 1.1-4.58); P = 0.02) participants compared with HbAA but was not statistically significant when adjusted for frequency of hospitalization, crises, blood transfusion and routine drugs in HbAS (P = 0.49) unlike HbSS (P = 0.03). CONCLUSION: The prevalence of hearing loss among children and adults with SCD is higher than in those with HbA genotype. The frequency of hospitalization, crises, blood transfusion and taking routine drugs may influence hearing impairment in SCT but may not in SCD.

Fatal Case of Exercise Collapse Associated with Sickle Cell Trait with Novel Underlying LAMA2 Mutation.

ABSTRACT: Sickle cell trait is typically thought to be an asymptomatic carrier state, but it is rarely associated with exertional rhabdomyolysis in cases termed Exercise Collapse Associated with Sickle Cell Trait (ECAST). In a subset of these cases, underlying disease contributes to the development and/or severity of the ensuing medical complications. We describe the first ever case of ECAST reported in a previously asymptomatic, multiply deployed, highly physically active service member with an underlying heterozygous LAMA2 mutation. Moreover, the mutation identified via whole exome sequencing is a novel, likely pathogenic variant that has yet to be described in the literature.

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.

Protocol for a comparative cross-sectional study on characterisation of auditory impairment in sickle cell disease and sickle cell trait and its impact on health-related quality of life in Nigeria.

INTRODUCTION: Sickle cell disease (SCD) and sickle cell traits (SCT) are genetically inherited red blood cell disorders common among people of African descent. Nigeria has a high prevalence of SCD, with a prevalence of 2.28%-3% and SCT, 25%-30%. Poorly managed SCD and SCT can lead to sensorineural hearing loss and health-related quality of life (HRQoL) issues. This research aims to assess these possible complications of SCD and SCT in Nigeria. METHODS AND ANALYSIS: The study will use a comparative cross-sectional design at study power 80% to investigate the association between SCD/SCT, hearing impairment and HRQoL. Participants will be divided into two groups: a cohort and a control group. Hearing levels will be assessed through audiometric assessments and categorised by type and severity of hearing impairments using WHO classifications. HRQoL will also be assessed using WHO Disability Assessment Schedule 2.0. Statistical analyses will be performed using the SAS V.9.4, with parametric or non-parametric analysis depending on the distribution. Relationship between key variables will be determined via correlational tests, χ2, Fisher's exact test and multivariable logistic regression analyses. ETHICS AND DISSEMINATION: The proposal has been fully reviewed and registered by the University of Cape Town's Faculty of Health Sciences Human Research Ethics Committee (HREC REF 228/2022) and the University of Abuja Teaching Hospital Human Research Ethics Committee (HREC/PR/2020/08/007). Information dissemination will be through conferences, peer-review publication and personal communications. The Strengthening the Reporting of Observational Studies in Epidemiology statement will be followed in writing the manuscript.

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.

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.

Delayed Plasmodium falciparum Malaria in Pregnant Patient with Sickle Cell Trait 11 Years after Exposure, Oregon, USA.

Delayed Plasmodium falciparum malaria in immigrants from disease-endemic countries is rare. Such cases pose a challenge for public health because mosquitoborne transmission must be rigorously investigated. We report a case of delayed P. falciparum malaria in a pregnant woman with sickle cell trait 11 years after immigration to the United States.

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.