Incidence Of Sickle Cell Disease Research Articles

Cost-effectiveness of newborn screening for sickle cell disease: a systematic review protocol.

The purpose of this systematic review is to assess the cost-effectiveness of targeted/selective newborn screening compared with universal screening for sickle cell disease across various countries and settings. The incidence of sickle cell disease is a widespread and potentially fatal hematologic disorder that affects thousands of newborns worldwide. The cost of newborn screening creates a burden on households and the economy. Studies will be eligible for inclusion in the review if they focus on the cost-effectiveness of newborn screening for sickle cell disease, comparing targeted/selective screening with universal screening. A preliminary search of MEDLINE (PubMed) was undertaken using MeSH terms, such as sickle cell disease, newborn , and economic evaluations . Two reviewers will screen the titles, abstracts, and full text independently against the inclusion criteria. Disagreements will be resolved by discussion or with a third reviewer. To assess methodological quality, the JBI checklist for economic evaluation will be used. Data will be extracted by 2 reviewers using a modified JBI data extraction form. The JBI dominance ranking matrix for economic evaluations will be used to summarize and compare the results. Cost-effectiveness will be measured on the basis of cost per test/case detected, quality-adjusted life years gained, or disability-adjusted life years averted. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment will be conducted to evaluate the certainty of economic evidence, such as use of resources and expenditures, and to incorporate the results into the decision-making process. PROSPERO CRD42017057963.

Factors Associated with Sickle Cell Crisis Among Sickle Cell Disease Patients Aged ≤15 Years in Three Kenyan Health Facilities

In view of the dearth of definitive therapeutic measures for sickle cell disease (SCD) and its associated crises, the resulting financial burden on parents and caregivers, coupled with psychological distress, social stigma, and other far-reaching consequences, remains incalculable. This research assessed the determinants of sickle cell crises among individuals with SCD aged 15 years and below, focusing on three healthcare facilities in Nairobi County. Using a descriptive cross-sectional design, the study aimed to establish the correlation between SCD crises and various variables in this specific age group within the selected health facilities. Structured interviewer-administered questionnaires, featuring both open-ended and dichotomous questions, were meticulously validated, optimized, and employed to gather pertinent data from the participants. The findings revealed that a majority of SCD patients below 15 years in sampled hospitals were female (52.85%), and the highest incidence of SCD occurred in the age range of 0-5 years (46.63%). Educational attainment among patients predominantly peaked at the primary school level (65.80%), with a minimal 7.77% reaching a secondary school level. Moreover, female caregivers (92.23%) were prevalent among those responsible for SCD patients aged 15 years and below. Primary caregivers, aged between 26- 30 years (37.82%) and 31-35 years (26.42%) were predominately married (75.13%) and engaged in agricultural activities (63.73%). This study revealed that out of the sampled SCD patients under 15 years old, a staggering 83.94% experienced crises related to their sickle cell disease, manifesting as abdominal pains for nearly 70 %, joint discomfort for over 72.22%, acute chest pain occurring approximately 25 %, with bone ache accounting about 32 %. Multiple logistic regression analysis demonstrated that female gender, the age group of 6-10 years, and frequent hospital visits (more than twice a month) significantly increased the log odds for severe SCD crises. Therefore, this study underscores the impact of patient and caregiver factors on the severity of SCD and its crises. Modifying these factors appropriately holds the potential to enhance the prognosis and wellbeing of both patients and caregivers, and strategic interventions must be devised to improve adherence to treatment protocols for SCD patients aged 15 years and below, thereby enhancing prognosis and overall quality of life.

Awareness of sickle cell disease among nursing undergraduates in Farasan: Its interference with malaria.

The present study was conducted to generate data on awareness and incidence of sickle cell disease (SCD) and also to adduce the widespread myths peddled about SCD. Students studying in the Department of Nursing were recruited. A pretested, self-administered sickle cell assessment questionnaire was distributed electronically through WhatsApp group to collect necessary data. Participants were screened for malaria by thin blood smear analyses, and their hemoglobin (Hb) contents (g/dL) were determined by Sahli's haemoglobinometer. Statistical analyses were done using Origin (version 8.1, USA). A reliability study was performed for the validity of questionnaire data. Study participants had significantly high awareness regarding SCDs (89.9%, P < 0.001). Most participants (96.3%) were aware about government policy regarding premarital screening for genetic disorders and replied that the government has strict health policies backed by equally robust laboratory diagnostics. Moreover, none of the participants had SCDs, although their parents had a consanguineous marriage. Thin blood smear analyses of participants did not reveal any cases of Plasmodium falciparum. However, significant percentages (33.1%) were found to be anemic, probably due to their dietary habits and lifestyles, as has been reflected by questionnaire analyses. Furthermore, a very less number of students had knowledge about genetic variations that might occur in malaria-endemic regions after long exposure to offer protection from malaria. Knowledge about management practices was also lacking among study participants (29%). This research points to the necessity that the nursing study plan should focus on providing specific training on management skills and preventive measures for SCDs, which is of paramount importance.

New Insights into VOC Incidence By Analyzing the Single Cell Quantification of HbF per RBC and Mchbs

Vaso-occlusive crisis (VOC), the main complication of sickle cell disease (SCD), is responsible for more than 50% of the associated deaths. The effect of hydroxyurea, the cornerstone treatment for SCD, on the occurrence of VOC is mainly mediated by increasing HbF levels, which is a protective factor by inhibiting hemoglobin S (HbS) polymerization. 1,2 However, HbF level is variable between patients, and its expression is heterogeneous among the red blood cell (RBC) population. 3 As a result, while an increase in HbF levels is associated with better survival, %HbF only partially explains patients' clinical manifestations. The protective effect of HbF is also related to the HbS content; the more HbS, the more HbF is needed to inhibit its polymerization. In this study, we wondered if the single-cell quantification of HbF that we developed could better explain the VOC incidence of SCD compared to %HbF. Patients and method We analyzed data from the FCDREP1 protocol, aiming to obtain a predictive score for VOC at 1 year. Inclusion criteria were SS and S- S-b 0 Thal SCD patients, more than 1 month after a vaso-occlusive crisis, 3 months after a transfusion, and on a stable dose of hydroxyurea (HU) for at least 3 months. After giving their consent (IRB no. 00003835) during a routine blood sampling visit, an additional sample was taken for HbF single cell quantification, providing HbF/cell distribution. VOC were collected prospectively for 1 year. HbF single cell quantification was measured by flow cytometry using a previously published protocol, 4 data are expressed as histograms representing % RBC in each HbF range in pg for the whole cluster. K-means clustering was performed on different combination of variables containing ranges of HbF/cell distribution versus %HbF, with MCHbS (MCH x %HbS) using UMAP for dimensionality reduction (into 2), after we applied Min-Max scaling to preprocess the features, with python 3 on sklearn and umap library. This clustering approach can group data points based on their similarity, providing insights into distinct patterns or subgroups within the dataset. Results One hundred two patients were included with a mean age of 38 ± 11 years, a sex ratio F/M of 0.56, 63% of patients were on HU. Patients had a total of 74 VOC with a mean of 0.71 ± 1.4 VOC per patient in the year. Analyses were performed finding 4 different clusters in different 2 groups. Group 1: clusters identified by the association of HbF/cell distribution and MCHbS (HbF/Cell) and Group 2: clusters identified by %HbF and MCHbS (%HbF). Clusters were numbered according to increasing HbF levels (Figure 1A and B). There was no significant difference in age or sex ratio between the groups whereas the percentage of patients on HU differed between groups (Figure 1F). The number of patients by cluster was also similar. Cluster analysis of Group 1 showed a decrease in VOC incidence (Figure 1E, blue bars) associated with an increase in HbF level per RBC (Figure 1A). If clusters 1 and 2 are similar regarding the % of HU-treated patients, cluster 1 shows a lower HbF/cell content (Figure 1A) but lower MCHbS and MCH (Figure 1C and 1D), possibly explaining a similar VOC incidence in the 2 clusters. With a higher % of HU-treated (Figure 1F), Cluster 3 and 4 stand out from each other by different HbF expression patterns and VOC incidence (Figure 1A). The clusters of group 2 does not show the same increasing incidence of VOC as a function of median %HbF (Figure 1B and E). If cluster 4, mostly treated with HU, corresponds to patients with high %HbF and low VOC; cluster 1, with little HU treatment and very low %HbF, has few VOCs, not explained by MCHbS. The difference in severity between clusters 2 and 3, which have the same percentage of HU, could be explained by the greater difference in %HbF distribution, with median %HbF values of 11.8 [5-14] and 13.8 [11-15] (p=0.06) respectively, as well as by the low MCHbS of cluster 3. Conclusion : Single cell quantification of HbF in RBC in association with MCHbS could help improve to better understand VOC incidence.

Sickle cell disease in Sudanese children & psychosocial problems faced by children and parents – a two-scale study

ABSTRACT Sickle cell disease (SCD) is an inherited red blood cell (RBC) disorder transmitted to the child through the parental genes. SCD is a serious public health problem in Sudan, ranging from 18.2% to 30.4%, with the sickle cell anemia gene known to be prevalent in the Khartoum area. This study aimed to explore the psychosocial impact of SCD on affected children and parents and to identify the relationship between psychosocial problems experienced by children and parents with the use of two scales. To address the research aim, the Strengths and Difficulties Questionnaire (SDQ) was administered among n = 170 SCD children aged 6–12 years. In addition, the Depression, Anxiety, Stress Scale-21 (DASS-21) was used to measure levels of depression, anxiety, and stress in parents of children with SCD. Most of the children experienced substantially high emotional symptoms (n = 113), with conduct problems (n = 113), hyperactivity (n = 100), and peer problems (n = 86) being close to average. Most of the parents had the normal level of depression (n = 78), anxiety (n = 92), and stress (n = 85), with severe and extremely severe cases being the least recorded. Further analysis of the association between the SDQ scale and DASS-21 showed a significant association between parental stress and children’s conduct problems (p = 0.009), hyperactivity (p = 0.03), and the pro-social behavior of the child (p = 0.03). No association was found between parental anxiety, depression, and emotional symptoms, conduct problems, hyperactivity, and peer problems. Future research is recommended to explore the incidence of SCD in children at birth and parental actions after diagnosis.

Increasing Visibility of Sickle Cell Disease in Indiana: Establishing Baseline Prevalence Using Integrated Data From Multiple Sources.

The Indiana Sickle Cell Data Collection (IN-SCDC) program aims to provide timely, reliable, and locally relevant information on the sickle cell disease (SCD) population in Indiana to inform public health interventions, research, and policy development. We describe the development of the IN-SCDC program and report the prevalence and geographic distribution of people with SCD in Indiana using an integrated data collection approach. Using multiple integrated data sources and case definitions established by the Centers for Disease Control and Prevention, we classified cases of SCD in Indiana during 2015-2019. We calculated the prevalence and incidence of SCD and described characteristics of people with SCD. We identified 1695 people living with SCD in Indiana during the study period. The median age of people living with SCD was 21 years, and 1474 (87.0%) were Black or African American. Most (n = 1596, 91%) resided in metropolitan counties. The age-adjusted prevalence of SCD was 24.7 cases per 100 000 people. The prevalence of SCD among Black or African American people was 209.3 per 100 000 people. The incidence was 1 in 2608 live births overall and 1 in 446 live births among Black or African American people. Eighty-six deaths were confirmed in this population during 2015-2019. Our results establish a baseline for the IN-SCDC program. Baseline and future surveillance program efforts will help accurately inform standards of care for treatments, identify gaps in coverage and access to care, and provide guidance for legislators and community-based organizations.

Newborn screening for sickle cell disease in Kisangani, Democratic Republic of the Congo: an update

ABSTRACTBackgroundNeonatal screening is the first action necessary to identify children with sickle cell disease (SCD) and thus ensure their care. Using rapid tests to give an immediate result to families is a new resilient approach of great interest. These two aspects are essential for establishing an adequate health policy for this disease. This study was undertaken in Kisangani to update the current incidence of neonatal SCD.MethodsHeel prick blood samples of 1432 babies born from different racial groups of parents living in Kisangani were collected at birth and screened using a point of care test, i.e. the HemoTypeSCTM.ResultsThe incidence at birth was 2.2% (n = 31; 95% CI: [1.5%−3.1%]) for HbSS homozygosity and 21% (n = 303; 95% CI: [19%−23%]) for HbAS heterozygosity. Compared to a previous study in 2010; the incidence at the birth of the HbSS form has doubled, while that of the heterozygous form HbAS remained almost unchanged. The inter-ethnic incidence of HbSS among the five top-represented ethnic groups was significant (<0.001).ConclusionThe prevalence of homozygote form has doubled compared to the 0.96% reported in 2010. Setting up a neonatal screening program and an awareness unit is necessary to assess the need for care services correctly.

5567917 COST COMPARISON OF TRANSFUSION CHOICES IN OMAN FOR PATIENTS SUFFERING FROM SICKLE CELL DISEASE

Background: Sickle cell disease(SCD) management can be challenging, requiring different therapeutic approaches because SCD could induce multiple complications. Red blood cell(RBC) transfusion is well known as one of the disease-modifying therapies available for long-term management. It’s supported by multiple randomized clinical trials for the prevention of disease complications such as stroke in adults and children with SCD.RBCs can be delivered via three methods: Simple transfusion(ST), manual exchange(ME) and automated red blood cell exchange(aRBCX). In ST, patients receive additional units of blood. The purpose is to raise the haemoglobin (Hb) to a steady state and maintain the oxygen-carrying capacity of blood. ME transfusion consists of removing the patient’s sickle-shaped RBCs and replacing them with healthy ones— lowering the concentration of sickled cells without increasing blood viscosity. This is performed using repeated alternating isovolumetric phlebotomy and blood transfusion. aRBCX involves removing sickled RBCs from the patient and rapid replacement with healthy RBCs while maintaining isovolemia. An advantage of aRBCX is the avoidance or minimization of costly iron chelation therapy to treat iron overload. Aim: SCD management is an important cost driver for health systems. The intent of this research was to compare the cost-effectiveness of different transfusion modalities. We wanted to compare the all-inclusive costs. and wanted to perform this evaluation in Oman, as the incidence of SCD ranges between 0.2% and 0.07%. This disease is considered one of Oman’s most common genetic blood disorders. Method: In-depth data about variables that drive costs have been collected to populate a de novo cost model. We collected data from the Royal Hospital and Sultan Qaboos University Hospital. Cost drivers that we took into consideration were disease incidence, cost of blood transfusion, medical equipment, disposables, cost of staff, complications, iron chelation therapy, hospitalization, and lives lost. The assessment took place in June 2020. The cost of the treatment intervention, cost of disease-related complications and the yearly cost of treatment imputable to each transfusion modality represented the most significant differences across the three transfusion choices. By populating the model with resources provided by the two above-mentioned hospitals, we could demonstrate the cost differences between transfusion choices and the potential benefits that healthcare providers can experience. The results demonstrate significant differences across cost parameters, such as Cost of treatment, Cost of treatment-related potential effect, Cost of complications, Cost of life years lost, and Estimated total yearly cost per patient. Results and conclusion: aRBCX promotes a reduction in overall resource utilization and improved patient outcomes. aRBCX is approximately 47% less costly than ST, and is approximately 23% less costly when compared to ME. By highlighting the consequence of treatment choice and its financial impact, we aim to support the adoption of aRBCX in comparison to alternative transfusion choices and validate future reimbursement considerations. aRBCX cost savings may lead to better adoption. We recommend researchers rerun these calculations with the model on an individual hospital basis.

The Next Step in Telehealth Education in a Low-Income Setting: Implementing a Project Echo for Sickle Cell Disease

Background and Aims: Sickle Cell Disease affects nearly 100 million people worldwide and disease complications are responsible for over 50% of deaths among those affected with the most severe form. It is estimated that each year, over 300,000 children are born annually with this disease and over 70% of these births occur in Sub-Saharan Africa. In Kenya, approximately 14,000 children are born with Sickle Cell Disease each year with a greater incidence in malaria endemic areas including lake-region, western, and coastal regions. Advances have been made in the United States to reduce the disease related mortality at 5 years of age to 3%. However, in developing countries of Sub-Saharan Africa, this number is greater than 50%. Since 2011, hematologists from North American institutions have partnered with Kenyan specialists to deliver educational seminars in African counties with a high incidence of Sickle Cell Disease. As an expansion of these efforts, a telehealth educational platform has been developed, capable of providing ongoing collaboration and mentorship for high risk communities. Methods: The combined team of Kenyans and North American providers collaborated to launch a Project ECHO program focusing on Sickle Cell Disease. The virtual educational platform - a hub and spokes teaching model - was implemented based on previous success with other chronic diseases in the region. A complete panel of experts consisting of pediatric and adult hematologists from Kenya and the United States, nursing leadership, patient advocates, social workers, and local physician leaders was assembled as the hub team. Recruitment for the ECHO began in April 2022 in Western Kenya and consisted of participants from prior educational workshops and participants from other ECHO programs at county referral hospitals. A curriculum was built focusing on infant screening, infection prevention, and utilization of Hydroxyurea, with expanding topics based on community needs. The ECHO program occurred at monthly intervals utilizing the Zoom platform. The sessions consisted of both a scheduled didactic and a case-based discussion. The didactic was given by a Kenyan expert while the cases were submitted by ECHO participants from the community. Attendance was tracked by the ECHO platform automatically including recurrent attendance and participant county. Surveys were utilized on a semi-annual basis to further assess educational impact. Results: The program launched in June 2022 with initial success. Participation at early sessions averaged 60 attendees with participants attending from 24 of the 47 total counties in Kenya. ECHO leadership maintained fidelity to the model with an emphasis on dialogue, collaboration, and mentorship. The ECHO community has also flourished outside of the virtual sessions as evidenced by increased dialogue amongst participants via electronic messaging and an increase in Sickle Cell Disease referral patterns. Conclusions: Significant morbidity and mortality persists for sickle cell disease in low- and middle-income countries such as Kenya and education at the community level is a key mechanism to address these disparities. The utilization of a telehealth education program such as Project ECHO represents a strong mechanism to continue building local, regional, and international partnerships to improve care together.

P-086: POINT-OF-CARE SCREENING FOR SICKLE CELL DISEASE IN RURAL AFRICAN COMMUNITY HEALTHCARE CENTERS

Purpose: Over 200 000 babies are born with sickle cell disease (SCD) annually in sub-Saharan Africa. In many African nations, however, 50% to 90% of children with SCD will not survive until their fifth birthday and will die due to susceptibility to malaria, sepsis, anemia, and infection without being diagnosed with SCD. The incidence of SCD and trait in newborns in Sierra Leone is unknown. Early diagnosis of SCD and treatment can greatly improve patient outcomes. The purpose of this study was to assess the feasibility of a Nurse Champion sickle cell disease point of care testing (SCD-POCT) model in community healthcare centers using a novel microtechnology diagnostic device. Materials and methods: This cross-sectional study was conducted at a regional government hospital in a rural district in Sierra Leone. Immediate, free screening was offered to newborns over 24 hours old delivered at the maternity ward. We used a validated, low-cost, point-of-care, lateral flow immunoassay (SickleSCAN®) device to screen for SCD and trait. The screening tests were conducted by 12 nurse-midwives. A brief questionnaire was used to record the test evaluators’ experience with the device. Results: Fifty-two (30 males/22 females) newborns screened within 24-48 hours of birth over four weeks. Two newborns were identified with sickle cell disease (HbSS). The test identified 13 newborns with sickle cell trait (HbAS). Thirty-seven newborns had the normal HbAA genotype. The heterozygous HbSC genotype was not observed in the study cohort. 12 nurse-midwives evaluators rated the acceptability and feasibility of screening for SCD at the bedside as very good. None of the evaluators deemed the device to be inappropriate for SCD screening. Conclusion: Our study demonstrates a practical method of instituting SCD screening in maternity wards with nurses and midwives as frontline implementers. Our study is a “real world” confirmation that the SickleSCAN device produces reliable results; that nurses are uniquely positioned to educate and advocate for newborn screening, and serves as a “proof of concept” for service delivery, particularly in settings where access is limited and point-of-care testing is less well studied. The authors do not declare any conflict of interest

No child left behind: Building a comprehensive sickle cell disease care oasis in the Lake County, Indiana care desert.

Sickle cell disease (SCD) leads to end-organ damage and shortened life expectancy. The second highest incidence of SCD in Indiana is in Lake County, but until 2017, there was no SCD expert within 65 miles. The Indiana Hemophilia and Thrombosis Center (IHTC) developed the Sickle Care coordination OutReach and Education (SCORE) program in 2017 to bring high-quality, guideline-based care to children with SCD. The St. Vincent IRB deemed this retrospective analysis of SCORE clinic care from 2017 to 2020 exempt. Data on the number of transcranial Dopplers (TCD) performed, HU dosing escalation, and vaccine rates were collected along with the number of school and home visits completed. Fifty-three children, adolescents, and young adults completed 288 SCORE clinic visits during the study period; over 75% completed at least three clinic visits. Mean HU dose increased significantly with SCORE clinic care. TCD screening rates increased every year starting in 2018 through 2020 when we added local care coordination. One hundred seventy-three vaccines were administered in SCORE outreach clinics. The PPSV23 vaccines had a 100% acceptance rate, and seasonal influenza had a 75.8% acceptance rate. Access to care coordination services and local hematology specialty care alleviates barriers to care and enables comprehensive SCD care delivery to children in need. Prior to the establishment of the SCORE clinic, 75% of children in Lake County were not receiving recommended stroke screening. The SCORE clinic model demonstrates feasibility and impact when delivering on the promise of high-quality care for children with SCD.

Premarital Genotype Screening for Sickle Cell Disease: Knowledge Gaps, Perception and Determinants of Uptake among Final Year Undergraduates of a Tertiary Institution in South-West Nigeria.

Strategies involved in the prevention and management of sickle cell disease include premarital genotype screening and counselling as well as efforts at increasing the knowledge of the population about the condition. This is a cross-sectional descriptive study which assessed the knowledge of sickle cell disease and premarital genotype screening, attitudes towards screening and factors associated with uptake of premarital genotype screening among 326 final year students at the University of Ibadan, Oyo State, Nigeria. Respondents were within the age range of 18-24 with a mean age of 23. Majority of the respondents had AA genotype (68.71%). Only 15.95% of the respondents had good knowledge of sickle cell disease. Mean knowledge score was 14 out of 26 with a standard deviation of 4.31. 75.77% of the respondents had good knowledge of premarital genotype screening. 76.07% of the respondents had good attitudes to premarital genotype screening. Mean attitude score was 9.5 out of 12 with a standard deviation of 2.15. Respondents' current level of study (P=0.000) and marital status (P=0.042) were significantly associated with knowledge of sickle cell disease. There was significant association between knowledge of sickle cell disease and knowledge of premarital genotype screening (Fisher's P= 0.000). Knowledge of premarital genotype screening was significantly associated with respondents' current level of study (P=0.004) and attitudes to premarital genotype screening (Fisher's P= 0.000). Significant knowledge gaps were identified in the study population. There is need for continuous assessment of knowledge gaps and educational intervention to decrease the incidence of sickle cell disease.

Incidence of Sickle Cell Disease and Other Hemoglobinopathies in Burkina Faso: Results of a Five-Year Systematic Neonatal Screening (2015-2019) in Four Urban Hospitals

Hemoglobinopathies, mainly Sickle cell disease (SCD), are the most common monogenic disorders in Africa. In Burkina Faso, data on these diseases are scarce, mainly hospital-based in Ouagadougou and its surroundings. In order to assess the incidence and allelic frequencies of the main hemoglobinopathies in newborns in Burkina Faso, we conducted a cross-sectional study from 2015 to 2019 in four hospitals. The study included babies of both sexes, regardless of ethnic group and parents’ hemoglobin status. It was a newborn screening and hemoglobin variants were detected using isoelectric focusing on cord blood samples and confirmed using hemoglobin electrophoresis by high-performance liquid chromatography. The proportions and cumulative incidences of the different hemoglobinopathies were computed. Hardy-Weinberg equilibrium law was applied to calculate genotypic and allelic frequencies. The significant level was p ere from Bobo-Dioulasso. Abnormal hemoglobin was found in 27.1%, representing a cumulative incidence of 1:4 newborns. The incidence of SCD was 1.9% (1:53 newborns) with 27.9% of homozygous SS. Homozygous CC and compound heterozygous Cβ-Thalassemia accounted for 1.1%. SCD cases were 1.51 times higher in Bobo-Dioulasso (OR = 1.51; 95% CI [1.09 - 2.10]: p = 0.013). The observed genotype frequencies were significantly different from the expected ones (p 0.001). The βS and βC alleles represented 5.1 and 9.9%, respectively. This study showed a high incidence of hemoglobinopathies. Such results raise the question of control strategies for these hemoglobinopathies in our country.

Awareness and Incidence of Sickle Cell Disease Among Nursing Undergraduates in Farasan Island, KSA: Its Interference with Malaria

Awareness and Incidence of Sickle Cell Disease Among Nursing Undergraduates in Farasan Island, KSA: Its Interference with Malaria

Comparison of Sickle SCAN and Hemotype SC As Point-of-Care Newborn Screening Diagnostics for Sickle Cell Disease in Luanda, Angola

Background: Sickle cell disease (SCD) is among the most common, lethal and poorly recognized diseases globally. Over 300,000 children are born each year with SCA and most die by five years, primarily due to the lack of timely and accurate diagnosis. In high-resource countries, early identification of SCD through newborn screening (NBS) is routine and subsequent delivery of preventive measures and comprehensive care is highly effective in reducing morbidity and early mortality. In lower-resource settings, where the incidence of SCD is much higher, NBS is limited to only a few pilot programs. Despite the proven efficacy of NBS, large-scale implementation remains infeasible in many sub-Saharan countries due to inadequate financial, laboratory, and technical resources. In the pilot NBS program in Angola, only 56% of infants with SCD were able to be contacted to relay results due to delays in traditional laboratory diagnostic methods, lack of traditional mailing system or primary care providers, and inconsistent telephone numbers. The development and deployment of low-cost, rapid, user-friendly, and accurate diagnostic testing for SCD is imperative.There are two promising point-of-care (POC) tests (Sickle SCAN and HemoTypeSC) that may allow for a simplified approach to newborn screening for SCD. There have been few real-world studies that compare these tests head to head, particularly in the setting of NBS, where accurate diagnosis amidst high levels of fetal hemoglobin is critical. We performed a study at maternity centers and immunization centers in Luanda, Angola to evaluate the real-world accuracy of these tests.Methods: The study was a prospective evaluation of two rapid, POC tests (Sickle SCANÔ or HemoTypeSCÔ) ain Luanda, Angola, with laboratory confirmation using a dried blood spot (DBS) by isoelectric focusing (IEF), defined as the gold standard. To evaluate the real-world feasibility and accuracy, with the guidance of the Angolan Ministry of Health, we selected 10 sites, including both birth hospitals and vaccination sites, to screen infants < 6 months of age. Due to the complexity of performing more than one POC at once, we focused on one POC test at a time and planned to test 100 infants with each test at each site, for a total of 2,000 infants tested overall. The study was designed to mimic a real-world setting with all POC testing performed and interpreted by local healthcare staff (nurses, students, and laboratory technicians) with basic instructions as to the use of each test.Results: Blood samples were collected from 2,000 infants from age 0 to 6 months of age, including 1,000 with Sickle SCAN and 1,000 with HemoTypeSC. 42 HemoTypeSC samples (4.2%) and 6 Sickle SCAN results (0.6%) were not included in the final analysis, as results were not interpreted in the recommended time frame (5 minutes for Sickle SCAN an 10 minutes for HemoTypeSC). Consistent with prior studies in Angola, the burden of sickle cell trait (AS, 21.9%) and sickle cell anemia (HbSS, 1.7%) was high. 63% of the tests were performed in maternity wards at the time/day of birth and 37% were performed in immunization centers through the first 6 months of life. The HemoTypeSCÔ took an average of 15 minutes to obtain a result, was repeated 68 times (6.8%) due to invalid results, and was read incorrectly 4 times (0.4%). The SickleScanÔ took an average of 7 minutes to run, was repeated 2 times (0.2%) due to invalid results, and read incorrectly 11 times (1.1%). All results were compared to the gold standard IEF and both tests correlated perfectly (100%) with the IEF results, excluding 12 samples that had inconclusive IEF results.Conclusions: This study demonstrates the feasibility and accuracy of both HemoTypeSC and Sickle SCAN for diagnosing SCD in newborns in a limited-resource setting of Luanda, Angola. Given the complexities of testing in the newborn period at busy maternity hospitals, it appears that testing at immunization centers may be a more practical solution to early infant diagnosis programs for SCD. While both HemoTypeSC and Sickle SCAN were accurate, Sickle SCAN was preferred by local staff likely due to the shorter time to interpretation and reduced need for repeating the test. Further implementation studies are needed, including careful analysis of end-user cost, to determine the appropriate strategy for these POC tests in low-resource setting of sub-Saharan Africa. DisclosuresNo relevant conflicts of interest to declare.

L-Glutamine and Crizanlizumab for Adults with Sickle Cell Disease (SCD) in Qatar: A Cost Effectiveness Analysis

Background :Sickle cell disease (SCD) is a hereditary disease that is caused by autosomal recessive gene fault in the beta (β) allele of the hemoglobin (Hb) gene. As a result, sickled cells are characterized by easy and abnormal hemolysis with resultant varying degrees of anemia. Globally, the incidence of SCD is estimated to reach 400,000 persons per year, and in the United States alone, for example, the prevalence estimation is approximately 100,000 patients. Possible clinical presentations of SCD may come from different pathophysiologic mechanisms: the disfiguration of the RBC with subsequent loss of function can lead to vascular occlusion and a short lifetime of these RBCs that leads to hemolysis. The most severe and serious manifestation of SCD is the recurrent acute pain, or better known as vaso-occlusive crisis (VOC). Additionally, other clinical manifestations that SCD patients may show are acute complications such as acute chest syndrome (ACS), recurrent infections, kidney necrosis, and stroke. Such complications may affect multiple organs and can result in early death. Acute pain crisis is another common complication of SCD and is usually managed with pain medications, especially opioids,This is the first study to address two of novel therapies in patients with SCD in the Middle East. Our study was comprehensive in terms of outcome mostly encountered by SCD patients which is VOC and inclusivity of interventions mostly used for its management and was focused on the target population of in one of areas of high prevalence of SCD in the world. Our analysis tracked the CHEERS guidelines and checklist for reporting. To be also complete, we used only RCT evidence in our analysis. Additionally, in considering VOC, we ensured only studies with a definition compatible with that of the principal Crizanlizumab study were analyzed.Objectives:Treatment options for preventing vaso-occlusive crises (VOC) among sickle cell disease (SCD) patients are on the rise, especially if hydroxyurea treatment has failed. This economic analysis is conducted to assess the comparative clinical effectiveness, safety and acquisition cost of L-glutamine and Crizanlizumab for older adolescent and adults (≥16 years old) SCD in Qatar, with an emphasis on treatment costs and acute pain crises.Methods:We conduct a decision tree model, where we compare the clinical and economic outcomes of two novel FDA-approved medications which are available in Qatar; L-glutamine and Crizanlizumab over a time horizon of one year in a hypothetical cohort of adult SCD patients from a Qatar healthcare perspective. The main outcome is incremental cost per SCD-related acute pain crises averted. Model clinical parameters were derived from individual drug randomized trials, published literature, whereas cost parameters from Qatar healthcare payer system. A sensitivity analysis was carried out, and the study results were robust around model inputs. Costs were converted to 2020 US dollars.Results:Study results showed that both treatment modalities' costs were the main driver of this analysis, with average annual cost of the treatments per patient being $189,014 for Crizanlizumab (5mg/Kg), $143,798 Crizanlizumab (2.5mg/Kg) and $74,323 for L-glutamine. The probability of no first time SCD-related VOC averted were 0.001/year for Glutamine, 0.26/year for Crizanlizumab (5mg/Kg) and 0.34/year for Crizanlizumab (2.5mg/Kg). Lower dose Crizanlizumab (2.5mg/Kg) dominated the higher one (5mg/Kg). The ICER of Crizanlizumab (2.5mg/Kg), when compared to L-Glutamine was $81,265 per SCD-related VOC averted. When comparing Crizanlizumab (5mg/Kg) and L-Glutamine, Crizanlizumab (5mg/Kg) showed higher efficacy, yet the Crizanlizumab ICER was at $459,620 than L-glutamine.Conclusions:Crizanlizumab (2.5mg/Kg) may be cost-effective interventions yet it is not the approved dose for preventing VOC in adolescents and adults with sickle cell disease. Crizanlizumab (5mg/Kg) was more cost effective than the approved L-glutamine per SCD vaso-occlusive crisis prevented. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparative Study of Haiti and Miami Cohorts of Sickle Cell Disease (CSHSCD): Methods, Accomplishments, and Implementation

▪Background: There are significant limitations in Haiti for the diagnosis and management of sickle cell disease (SCD), including the non-availability of universal newborn screening (NBS) and transcranial Doppler (TCD) ultrasound screening, and the lack of diagnostic laboratory resources, oral penicillin and hydroxyurea (HU).Methods: Beginning in September 2019, CSHSCD (R01HL149121), a 5-year NIH-sponsored observational comparative study of children with SCD from Haitian ethnicity in Miami and in Haiti compared to children of African American ethnicity with SCD, was designed to increase access to care in Haiti. The study aims are 1) to compare the incidence of SCD among newborns from Haitian and African American ethnicity in Miami, 2) to establish NBS programs for hemoglobinopathies in Haiti, and 3) to compare cohorts of children in SCD at the study sites. The participating sites are the University of Miami (UM, Miami, Florida), Hôpital Saint Damien (HSD, Tabarre, Haiti), Hôpital de l'Université d'Etat d'Haïti (HUEH, Port-au-Prince, Haiti), Hôpital Universitaire Justinien (HUJ, Cap Haitien, Haiti), and Hôpital Sacré Coeur (HSC, Milot, Haiti). HUJ and HSC use two NBS screening methods (isoelectric focusing and Sickle SCAN rapid test) and HSD and HUEH use isoelectric focusing only. CSHSCD supplies penicillin and HU and trains TCD examiners to implement stroke risk screening. Data are collected in REDCap.Results: During the first 2 years and despite the COVID-19 pandemic, we established NBS sites with a cohesive network of physicians and nurses trained in the care of children with SCD in Haiti. This capacity building will support sustainability of the program. We successfully identified at least 15 new cases of SCD via newborn screening, trained six TCD examiners, and enrolled 130 children with SCD in follow up, providing them with penicillin prophylaxis and hydroxyurea for severe cases according to local protocols . Implementation activities which have helped are close communications between the investigators, monthly Zoom meetings to coordinate efforts with enrollment updates every month, the availability of rapid tests (Sickle SCAN and Gazelle miniature cellulose acetate electrophoresis) for the diagnosis of SCD, especially when there is no laboratory equipment on site. Implementation challenges we have faced are mostly two. The first is the timely completion of DUNS and SAM registration for the two public hospitals, with one site achieving this after 9 months and the other site taking 18 months to complete. The reasons for the delay are the inability for the UM site to direct these efforts, following strict rules, and the Haitian hospital officers' lack of familiarity with website requirements. We were able to achieve these registrations with the assistance of one Haitian study staff who is very acquainted with internet navigation and became familiarized with requirements. Outsourcing materials to Haiti is another major challenge, with either gaps in the delivery of supplies because of multiple steps involved in ordering and shipping or with delays in releasing equipment once it is at the Port-au-Prince customs, resulting in gaps in NBS in one of the sites for 8 weeks. We have minimized these issues by opening a one-year ticket to order materials from the different companies involved. Also, Haiti's lack of infrastructure, available materials and medications, and political instability limit health care delivery.Conclusion: Since its inception, we have achieved major milestones, including capacity building and implementation of NBS, TCD training, and enrollment of children with SCD into the prospective cohorts despite the current COVID-19 pandemic. Material outsourcing challenges have been the major implementation problem we have faced due to systemic factors. We anticipate that these factors will be corrected or minimized as we have learned how to handle them. These problems were expected as part of conducting an international study in a low-resource setting.Acknowledgment: We acknowledge NHLBI for supporting this work. DisclosuresAlvarez: Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; GBT: Membership on an entity's Board of Directors or advisory committees. Romano: Genentech: Research Funding; Vycor: Current holder of individual stocks in a privately-held company; NovaVision: Consultancy.

A Cross Sectional Study of Association of HLA typing with Haemoglobin Level in Sickle Cell Anaemia

Background: Sickle-cell Disease (SCD) is the most common blood cell disorder affecting millions of people. In severe cases, regular blood transfusion is an essential practice to relieve clinical symptoms. However, since regular blood transfusion can lead to alloimmunization to foreign human leukocyte antigens (HLA), this may result in severe anemia due to red blood cell destruction. Therefore, this study aimed to determine the association between the hemoglobin level and the presence of HLA genotypes among Sickle Cell Anemia patients. &#x0D; Methodology: A total of 64 SCD patients and 21 healthy donors seen at King Abdulaziz hospital between November 2019 and February 2021 were recruited for this study. Demographic data including ABO/Rhesus blood groups, hemoglobin concentration, were among the clinical information obtained. HLA genotyping was performed using Polymerase Chain Reaction-Sequence Specific Oligonucleotide (PCR-SSO). The data were cleaned using the Microsoft Excel and analysed using the statistical packages for Social Sciences (SPSS) version 24.&#x0D; Results: The incidence of SCD is not strictly gender-related because of its transmission as an autosomal recessive disorder. Sixty-four individuals (33 females; 31 males) having SCD were analyzed. O blood group recorded the highest prevalence compared to other ABO blood groups in SCD patients. After analysing allelic association, HLA-A*02 was more frequent in SCD patients compared to control. After further allelic combination analysis of patients and compared with the control group, HLA-DQB1*02 was majorly involved in overexpression and decreasing hemoglobin level and significantly different among control and experimental groups.&#x0D; Conclusion: Rhesus-positive blood types were more associated with the SCA. HLA- type II alleles could influence the clinical course of sickle cell disease and HLA-DQB1*02 was significantly different among SCD group and control individuals, which signifies the concept that the allele was overexpressed among patients resulting in low Hb level.

Living with sickle cell disease: voices from sub-Saharan Africa

Sickle cell disease is sometimes wrongly considered as an African crisis or, at best, a disease affecting minority ethnic groups. However, it is a global crisis affecting millions of people throughout the world, irrespective of race or continent of origin, although it is common in people of African descent (including African Americans), people from Asia, including India, and Hispanic Americans. Globally, about 305 000 children are born with sickle cell disease every year, a quarter of sickle cell disease births worldwide are reported in Nigeria, and Tanzania records about 10 000 sickle cell disease births annually. In Ghana, about 15 000 newborns are diagnosed with sickle cell disease every year. South Africa has a low incidence of sickle cell disease compared with Nigeria, Ghana, and Tanzania, but this might be gradually changing due to immigration patterns from countries where sickle cell disease is more prevalent. SickleInAfricaOver the past 20 years, organised efforts in Africa have described and addressed the burden of sickle cell disease, with commendable achievements. However, there have been four limiting factors. First, there have been few multi-site, well described cohort studies of sickle cell disease in Africa. Second, there is no evidence yet that consistent standards of care are applied across Africa. Third, there are insufficient human resources, both in numbers and skills. Finally, there are few programmes exploring pertinent research questions related to sickle cell disease in Africa to guide locally appropriate interventions. Full-Text PDF

Newborn screening for sickle cell disease in France

Newborn screening (NBS) for sickle cell disease (SCD) in France has allowed the identification of 9,260 children with SCD since 1989, including 583 in 2019. In mainland France, however, SCD screening is targeted to newborns identified at risk of SCD, i.e born from parents originating from countries with a high SCD prevalence. This screening program, combined to prophylactic measures and a well-organized social and health network in France, has demonstrated considerable efficacy in reducing childhood mortality as well as severe infectious, anemic and neurovascular complications in childhood. SCD NBS has additionally allowed the identification of 180,687 heterozygous (AS) children since 1989. The increasing incidence of SCD (1/1,303 new-borns identified in 2019 versus 1/2,089 in 2009) now pleads for universal NBS and strong advocacy regarding SCD, the most frequent disease identified by NBS in France, and a major public health issue.