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.

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.

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.

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.

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.

Closing knowledge gaps among parents of children with sickle cell trait.

BACKGROUND: Despite needing to be informed about sickle cell trait (SCT) status to make informed reproductive decisions, more than 80% of adults with SCT, including parents of children with SCT who have a high prevalence of SCT, do not know their status. PROCEDURE: This was a prospective study of parents who received SCT telephone education from the state department of health and then completed SCTaware, a videoconference-administered SCT education program. The objectives were to evaluate knowledge after telephone education and explore if SCTaware closes knowledge gaps. Participants completed a demographic survey, a health literacy assessment, and reported their SCT status. They completed the Sickle Cell Trait Knowledge Assessment before receiving SCTaware, immediately after, and at follow-up visits; high knowledge was a score of 75% or higher correct. RESULTS: SCTaware and the initial surveys were completed by 61 parents; 45 completed the 6-month surveys. Only 43% of participants had high SCT knowledge after telephone education; 92% achieved high knowledge immediately after, and 84% continued with high knowledge at 6 months. Most parents reported they were aware of their SCT status after telephone education; 12 changed their response after receiving SCTaware. CONCLUSIONS: Our findings suggest that over half of parents have low SCT knowledge following telephone education, and many may be unaware of their status. SCTaware closes knowledge gaps, leads to high sustained knowledge, and is a potentially scalable tool. Future studies should refine SCTaware and determine if parents use their knowledge to inform their children and reproductive decisions.

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.

Association of Sickle Cell Trait on Career and Operational Outcomes in the United States Air Force.

INTRODUCTION: Sickle cell trait (SCT) is a heterozygotic state defined by having one normal hemoglobin gene and one sickle hemoglobin gene. Individuals with SCT are at increased risk for negative health outcomes during intense physical exertion, especially in hot climates and high-elevation locations, or when dehydrated. The U.S. Air Force mitigates this risk through universal screening after accession followed by education of SCT-positive airmen. Airmen who are SCT positive but remain asymptomatic are not restricted in occupation choice or deployment/duty locations based on their SCT status. Previous studies have analyzed the relationship between SCT and health and fitness outcomes. The objective of this study was to analyze the relationship between SCT and career and operational outcomes in a large cohort of airmen and secondarily to analyze the relationship between hemoglobin S (HgbS) percentage and these outcomes. METHODS: This is a retrospective cohort study of all recruits who entered U.S. Air Force (USAF) Basic Military Training (BMT) between January 2009 and December 2013. The SCT status was assessed through a sickle solubility test. Hemoglobin electrophoresis permitted subgroup analysis of SCT-positive individuals by HgbS percentage. The following career and operational outcomes were assessed: BMT graduation; retention at 4 and 6 years; promotion to the rank of staff sergeant by 4 and 6 years; overseas deployment and number of deployments within 6 years; and high-elevation assignment and cumulative months at a high-elevation assignment within 6 years. Multivariable logistic regression was used to assess all binary outcomes, controlling for age, sex, and race, to produce adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Multivariable Poisson regression was used to assess cumulative count outcomes and to produce adjusted incidence rate ratios (aIRRs) with 95% CIs. Attrition from BMT by SCT status was also assessed as a hazards function using the Kaplan-Meier approach with Cox proportional hazards. RESULTS: A total of 180,355 civilians entered USAF BMT during the 5-year surveillance period, of whom 169,837 graduated and had data available for analysis. Compared to their SCT-negative peers, SCT-positive airmen (n = 1,697) had 26% lower adjusted odds of promotion to staff sergeant within 4 years of BMT graduation (aOR = 0.74; 95% CI: 0.59-0.92) and served less time at a high-elevation assignment during their first 6 years (aIRR = 0.88; 95% CI: 0.85-0.91). The SCT status was not associated with statistically significant differences in BMT graduation, retention at 4 and 6 years, promotion to staff sergeant by 6 years, likelihood or number of overseas deployments, and likelihood of ever working at a high-elevation assignment. Retention at 4 and 6 years was inversely associated with HgbS percentage. CONCLUSIONS: SCT-positive and SCT-negative airmen had similar career and operational outcomes, with two exceptions: SCT-positive airmen were less likely to be promoted to staff sergeant within 4 years, and they spent less time at a high-elevation location during their first 6 years of service. The underlying explanation of these findings should be explored with an aim to support SCT-positive airmen and to reduce potentially unwarranted discrepancies. Efforts should continue to reduce the stigma associated with SCT.

Sickle cell trait screening in students in a Ugandan university: a cross-sectional study.

OBJECTIVE: To determine the uptake, knowledge level and attitude towards sickle cell trait screening in students aged 18 to 35 years in a Ugandan university. METHODS: This was a university-based, cross-sectional study of students aged 18 to 35 years who were students at the Busitema University Faculty of Health Sciences. We used a simple random sampling technique to recruit participants. We conducted multivariable logistic regression to establish the association between factors such as age, year of study, marital status and uptake of sickle cell trait screening (SCTS) services. RESULTS: A total of 315 students participated in the study. The uptake rate of SCTS was 24.4%. The knowledge level regarding sickle cell disease/SCTS was 93.7%, and 73.3% of respondents had a positive attitude towards SCTS, with a mean score of 23.32 ± 5.84. A multivariate analysis showed that those aged 25 to 29 years were 7.8 times more likely to have SCTS, while married respondents were 1.3 times more likely to be screened. CONCLUSION: The uptake of SCTS services was low relative to the total number of participants recruited in this study. Therefore, the uptake of SCTS needs to be encouraged in students at universities.

Optical absorbance-based rapid test for the detection of sickle cell trait and sickle cell disease at the point-of-care.

People afflicted with sickle cell disease (SCD) experience severe deterioration in quality of life. The disease is characterized by debilitating pain, anemia, and increased susceptibility to life threatening infections. This genetic disorder is endemic to many parts of the world. Extensive and accurate screening of individuals with sickle cell trait (SCT) in the population, coupled with genetic counselling can inhibit the propagation of the disease. The gold-standard techniques for the detection of sickle hemoglobin, such as capillary electrophoresis, HPLC, and genetic testing, are prohibitively expensive and time-consuming. Mass screening is usually conducted with a low-cost test called the solubility test, which does not offer high specificity. This study proposes a game-changing single-step low-cost method for rapidly yet accurately screening and diagnosing SCD and SCT. This method relies on the hitherto unexplored differences in the optical absorbance between diseased, trait, and normal blood samples, under deoxygenated conditions. The proposed method was tested in two phases of clinical validation: a pilot study and a blind study. A total of 438 patient samples were tested using the proposed method across the two phases. The proposed method offers an average accuracy, sensitivity, and specificity of 97.6%, 96.9%, and 98.6%, respectively. The proposed test has the potential to obliviate the conventional two-step process of screening and diagnostic tests as it can be used at the point-of-care with minimal training and yet yield results reliable enough to assess disability benefit claims.

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.

Sudden Death in Diabetic Ketoacidosis Complicated by Sickle Cell Trait.

ABSTRACT: In a sudden death investigation of a service member with sickle cell trait (SCT), evidence of sickle cell crisis further complicated by coexisting, undiagnosed diabetic ketoacidosis called into question the synergistic effects of diabetic ketoacidosis on red blood cell sickling. Sickle cell trait affects more than 4 million people in the United States (US) with the highest prevalence in non-Hispanic Blacks (7%-9%; Mil Med 2017;182(3):e1819-e1824). The heterozygous state of sickled hemoglobin was previously considered a benign condition causing sickling during hypoxic, high-stress conditions such as exercise and high altitude ( Am Assoc Clin Chem 2017). However, research within the last decade shows evidence of sudden death among SCT patients ( J Forensic Sci 2011;56(5):1352-1360). It has been shown that the presence of sickled hemoglobin artificially lowers levels of hemoglobin A1c making it a less effective biomarker for red blood cell glycosylation over time in sickle cell patients ( JAMA 2017;317(5):507-515). The limited scope of medical understanding of the effects of SCT in combination with other comorbidities requires further investigation and better diagnostic criteria. The uniqueness of the US Military and its screening program for sickle cell disease (SCD) and SCT allows for more detection. Since May 2006, newborn screening for SCD/SCT has been a national requirement; however, anyone older than 14 years may not know their SCD/SCT status ( Semin Perinatol 2010;34(2):134-44). The previous absence of such national screening makes it more challenging to identify SCT and SCD patients even within high-risk populations. Furthermore, patients may not know or understand the results of their SCD/SCT status testing. International standards for the autopsy of decedents with SCD and SCT exist ( R Coll Pathol 2017). Within the US, testing of vitreous electrolytes is a common practice in suspected natural death cases, but a review of the US literature did not demonstrate any autopsy standards or recommendations for persons with SCT or high-risk persons for sickling pathologies. The identification of a new diagnosis of type 2 diabetes mellitus, as the cause of death, is not uncommon; however, this case indicates that type 2 diabetes mellitus was not the sole contributing factor. It further illustrates that the US may be underestimating the impact of SCD and SCT as a cause of death, a contributing factor to death, and its synergistic effects with other pathologic processes. We propose a stringent literature review in conjunction with a review of international autopsy standards to develop national autopsy standards and possible SCT/SCD screening recommendations for high-risk persons at the time of autopsy.

Outcomes of kidney donors with sickle cell trait: A preliminary analysis.

Most transplant centers do not screen kidney donor candidates for sickle cell trait (SCT) and many decline candidates with SCT since it may associate with kidney disease. We compared 17 kidney donors with SCT to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure. The prevalence of SCT in African American (AA) donors was 11 per 1000 compared to 73 per 1000 in non-donor AA. Donors with SCT were younger; 33 versus 35 years in controls, nine were AA, six were White, and two were listed as other or unknown ethnicities. After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive, developed hypertension or cardiovascular disease were similar. No donor with SCT developed an eGFR <30 mL/min/1.73 m2 or kidney failure. SCT was, however, associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 - 22.7), P = .01. This small and preliminary case series suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort of donors with SCT.

Newborn Screening and Clinical Profile of Children With Sickle Cell Disease in a Tribal Area of Gujarat.

OBJECTIVE: To present the result of newborn sickle cell disease (SCD) screening and clinical profile of SCD newborns in a tribal area of Gujarat. METHODS: We screened all newborns of sickle cell trait (SCT) and SCD mothers for SCD using high-performance liquid chromatography (HPLC) within two days of birth at a secondary care hospital in a tribal area in Gujarat from 2014 to 2019. Newborns with SCD were registered under an information technology based platform for hospital-based comprehensive care. Neonates were followed prospectively every 3 months. If they missed the clinic visit, a medical counsellor visited them at home to collect the required information. RESULTS: Out of 2492 newborns screened, 87 (3.5%) were diagnosed with SCD. Among the 67 newborns screened for alpha-thalassemia deletion, 64 (95.4%) of babies had alpha-thalassemia deletion. We recorded total 554 clinic visits over the period of 221.5 person-years. The rates of acute febrile illness, painful crisis, hospitalization and severe anemia were 42.9, 14.9, 14.9 and 4.5 per 100 person-year, respectively. Two deaths were recorded, and 5 babies (5.7%) had severe SCD. CONCLUSION: We found a high prevalence of alpha thalassemia deletion among newborn SCD cohort in tribal area of Gujarat, and 70% babies had atleast one clinical complication on follow-up.