Sickle cell disease clinical phenotypes in Nigeria: A preliminary analysis of the Sickle Pan Africa Research Consortium Nigeria database.

BACKGROUND/OBJECTIVE: Sickle cell disease (SCD) is a monogenic disease with multiple phenotypic expressions. Previous studies describing SCD clinical phenotypes in Nigeria were localized, with limited data, hence the need to understand how SCD varies across Nigeria. METHOD: The Sickle Pan African Research Consortium (SPARCO) with a hub in Tanzania and collaborative sites in Tanzania, Ghana and Nigeria, is establishing a single patient-consented electronic database with a target of 13,000 SCD patients. In collaboration with the Sickle Cell Support Society of Nigeria, 20 hospitals, with paediatric and adult SCD clinics, are participating in patient recruitment. Demographic and clinical information, collected with uniform case report forms, were entered into Excel spreadsheets and uploaded into Research Electronic Data Capture software by trained data clerks and frequency tables generated. RESULT: Data were available on 3622 patients enrolled in the database, comprising 1889 (52.9%) females and 1434 (39.6%) children ≤15 years. The frequencies of Hb SS, Hb SC and Hb Sß thalassemia in this data set were 97.5%, 2.5% and 0% respectively. Sixty percent, 23.8%, 5.9%, 4.8% and 2.5% have had bone pain crisis, dactylitis, acute chest syndrome, priapism and stroke respectively. The most frequent chronic complications were: leg ulcers (6.5%), avascular necrosis of bone (6.0%), renal (6.3%) and pulmonary hypertension (1.1%). Only 13.2% had been hospitalized while 67.5% had received blood transfusion. CONCLUSION: These data on the spectrum of clinical phenotypes of SCD are useful for planning, improving the management of SCD across Nigeria and provide a foundation for genomic research on SCD.

Effectiveness and Safety of Hydroxyurea in the Treatment of Sickle Cell Anaemia Children in Jos, North Central Nigeria.

BACKGROUND: Hydroxyurea has been shown to positively modify sickle cell disease pathogenesis, but its use is low among Nigerian sickle cell anaemia (SCA) patients because of effectiveness and safety concerns. METHODS: We conducted a quasi-experimental study to evaluate the effectiveness and safety of hydroxyurea in 54 SCA children aged 4-17 years. Clinical and haematological parameters were compared at baseline and 12 months after hydroxyurea therapy. The participants were monitored for adverse events. The parameters were compared using relative risk and Wilcoxon Signed-Rank Test. RESULTS: The number of subjects who had more than two episodes of painful crises reduced from 27 (50%) to 2 (2.7%) (p < 0.001), while those who had acute chest syndrome reduced from 6 (11.1%) to 0 (0.0%; p < 0.001). The risk of being transfused more than once was 0.11 times the risk in the 12 months period preceding therapy (95% CI = 0.02-0.85; p = 0.016). Similarly, the risk of hospital stay >7 days was 0.08 times the risk at the baseline (95% CI = 0.02-0.24; p < 0.0001). The median haematocrit and percentage foetal haemoglobin increased from 26 to 28% and 7.8 to 14%, respectively (p < 0.0001). A dose-dependent but reversible leucopenia was observed among six children (11.1%), otherwise, hydroxyurea was safe in the study population. CONCLUSION: Hydroxyurea is effective and safe in SCA children in Jos, Nigeria. The findings could strengthen educational programme aimed at improving the utilization of hydroxyurea among SCA children.

HemoTypeSC, a low-cost point-of-care testing device for sickle cell disease: Promises and challenges.

BACKGROUND: Sickle cell disease (SCD) is a neglected burden of growing importance. >312,000 births are affected annually by sickle cell anaemia (SCA). Early interventions such as newborn screening, penicillin prophylaxis and hydroxyurea can substantially reduce the mortality and morbidity associated with SCD. Nevertheless, their implementation in African countries has been mostly limited to pilot projects. Recent development of low-cost point-of-care testing (POCT) devices for sickle haemoglobin (HbS) could greatly facilitate the diagnosis of those affected. METHODS: We conducted the first multi-centre, real-world assessment of a low-cost POCT device, HemoTypeSC, in a low-income country. Between September and November 2017, we screened 1121 babies using both HemoTypeSC and HPLC and confirmed discordant samples by molecular diagnosis. FINDINGS: We found that, in optimal field conditions, the sensitivity and specificity of the test for SCA were 93.4% and 99.9%, respectively. All 14 carriers of haemoglobin C were successfully identified. Our study reveals an overall accuracy of 99.1%, but also highlights the importance of rigorous data collection, staff training and accurate confirmatory testing. It suggests that HPLC results might not be as reliable in a resource-poor setting as usually considered. INTERPRETATION: The use of such a POCT device can be scaled up and routinely used across multiple healthcare centres in sub-Saharan Africa, which would offer great potential for the identification and management of vast numbers of individuals affected by SCD who are currently undiagnosed. FUNDING US: Imperial College London's Wellcome Trust Centre for Global Health Research (grant #WMNP P43370).

Preliminary Evaluation of a Point-of-Care Testing Device (SickleSCAN™) in Screening for Sickle Cell Disease.

Sickle cell disease affects about 150,000 births annually in Nigeria. Early diagnosis is hampered by factors such as centralized and urban localization of laboratories, high cost of diagnostic equipment and inadequate skilled manpower to operate them. The need for a low-cost, portable, easy-to-use diagnostic test for sickle cell disease is critical, especially in resource-poor countries. In this study, we evaluated the performance characteristics of a novel point-of-care testing device (SickleSCAN™), and its acceptability and feasibility, as a possible screening tool for sickle cell disease. In the first phase, we assessed the performance characteristics of SickleSCAN™ by evaluating 57 subjects comprising both children and adults attending a primary health center, for Hb SS (ßS/ßS; HBB: c.20A>T), Hb SC (ßS/ßC; HBB: c.19G>A) and Hb AS (ßA/ßS) using SickleSCAN™, cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC). Performance characteristics such as diagnostic sensitivity and specificity were compared to HPLC as a standard method. We subsequently undertook a second phase wherein the acceptability and feasibility of the device for sickle cell disease screening, was evaluated using semi-structured and structured questionnaires among 197 healthcare personnel and 221 subjects, respectively. Sickle cell disease was carried by 3.4% of the subjects. The diagnostic sensitivity, specificity and test efficiency of SickleSCAN™ for sickle cell disease (Hb SS and Hb SC), were 100.0, 98.2 and 98.2%, respectively. Findings from this study showed SickleSCAN™ to be a viable screening tool that can easily be applied in community-based screening for early diagnosis of sickle cell disease with little expertise and low cost.

Health related quality of life and perception of stigmatisation in adolescents living with sickle cell disease in Nigeria: A cross sectional study.

BACKGROUND: Sickle cell disease impacts the physical, emotional and psychological aspects of life of the affected persons, often times exposing them to disease associated stigma from the society and alters the health related quality of life (HRQoL). This study compared the HRQoL of adolescents with sickle cell disease with their healthy peers, identified socio-demographic and clinical factors impacting HRQoL, and determined the extent and effects of SCD related stigma on quality of life. PROCEDURE: We conducted a cross-sectional survey among 160 adolescents, 80 with SCD and 80 adolescents without SCD. Socio-demographic and clinical data were collected using a pre-tested questionnaire. HRQoL was investigated using the Short Form (SF-36v2) Health Survey. SCD perceived stigma was measured using an adaptation of a perceived stigma questionnaire. RESULTS: Adolescents with SCD have significantly worse HRQoL than their peers in all of the most important dimensions of HRQoL (physical functioning, physical roles limitation, emotional roles limitation, social functioning, bodily pain, vitality and general health perception) except mental health. Recent hospital admission and SCD related complication further lowered HRQoL scores. Over seventy percent of adolescents with SCD have moderate to high level of perception of stigmatisation. Hospitalisation, SCD complication, SCD stigma were inversely, and significantly associated with HRQoL. CONCLUSIONS: Adolescents living with SCD in Nigeria have lower health related quality of life compared to their healthy peers. They also experience stigma that impacts their HRQoL. Complications of SCD and hospital admissions contribute significantly to this impairment.

Evaluation of arm span and sitting height as proxy for height in children with sickle cell anemia in Lagos, Nigeria.

BACKGROUND: Sickle cell anemia may affect linear growth, and complications like avascular necrosis of femoral head may make direct measurement of height difficult. OBJECTIVE: To determine the relationship between height and arm span as well as between height and sitting height among children with sickle cell anemia in Lagos, Nigeria. METHODOLOGY: A random sample of 200 children aged 8 months to 15 years were studied-100 with hemoglobin genotype SS and 100 with hemoglobin genotype AA, matched for age and sex. Height/length, sitting height, and arm span were measured. Correlations and regression analysis were performed to test the relationship between height as a dependent variable and the sitting height and arm span as independent variables. RESULTS: Height, arm span, and sitting height were slightly but not significantly lower in subjects with sickle cell anemia. Strong correlations (R ≥ 0.95) were observed between height and other measurements in both subgroups. Regression analysis with height as the independent variable showed that arm span had a higher coefficient of determination than sitting height in both subjects (R(2) = 0.94 vs 0.899) and controls (R(2) = 0.942 vs 0.940). On the other hand, sitting height had a lower mean difference between observed and predicted height (0.04 and -0.11, respectively). CONCLUSION: Sitting height may be the preferred proxy for height in children with sickle cell anemia.

Strategies to improve healthcare services for patients with sickle cell disease in Nigeria: The perspectives of stakeholders.

Background: Sickle cell disease (SCD) continues to pose physical and psychosocial burdens to patients, caregivers and health workers. Stakeholder engagement in the processes of policy making and implementation is increasingly becoming the cornerstone of best practices in healthcare. Aim and Objectives: To engage stakeholders with a view to assessing the knowledge of SCD; ascertain the challenges associated with accessibility and affordability of healthcare services; improve the quality of care, and thereby effect behavioral change through increasing attendance and follow-up of patients in the clinics. Methodology: A Stakeholders' Engagement meeting organized by the Sickle Pan Africa Research Consortium Nigeria Network (SPARC-NEt) was attended by patients, caregivers and members of patient support groups, healthcare providers and management/policymakers. The engagement was through PowerPoint presentations, structured questionnaires and an interactive session. The structured questionnaire assessed the knowledge of stakeholders about SCD; the quality of healthcare services; challenges with access and affordability; and SCD-related government policies. Results: Three hundred and twelve stakeholders attended the engagement meeting. Of the 133 that participated in the study, medical workers were the most represented. The majority had good knowledge of what causes SCD (96.2%) and the best place to get help during SCD crisis (98.5%). However, knowledge of the specific preventive measures of SCD and its crisis was not optimal. In terms of the role of community engagement and education, only about one-quarter of the study participants, 34 (25.6%) knew about their positive role in reducing the prevalence of SCD and alleviating SCD crises. Challenges identified include inadequate healthcare personnel and facilities, delay in obtaining laboratory results, long waiting time in the clinic, poor communication, absence of holistic consultation, uncoordinated healthcare services, high cost of care, ignorance, non-prioritization of SCD by government, lack of multisectoral collaboration and partnership with NGOs and international organizations. Strategies proffered to improve healthcare services include, community/stakeholder engagement and health education, sickle cell daycare services, access to a willing and dedicated multidisciplinary workforce, collaboration with support groups and government policies and programs. Conclusion: There is need for regular stakeholder engagement to improve access to healthcare services for SCD patients in Nigeria.

Obesity--does it occur in Nigerian children with sickle cell anemia.

Children with sickle cell anemia are vulnerable to growth deficits; thus, it would be thought that obesity would be rare among them. The objective of the study is to examine the prevalence of obesity in a sickle cell anemia population in Lagos. A random sample of children with sickle cell anemia aged 2-15 years was interviewed and anthropometric measurements including weight and height were taken. Their body mass index (BMI) was calculated. Participants were classified as obese or not obese by their BMI or weight-for-height-for-age using World Health Organization standard definitions. The overall prevalence of obesity was 2.5% and 3.8% among hemoglobin genotype SS subjects and hemoglobin genotype AA controls, respectively. The age-specific prevalence for obesity was highest among the adolescent age category in hemoglobin genotype AA controls and the childhood age category in subjects with sickle cell anemia. All the obese subjects with sickle cell anemia were from upper socioeconomic strata, while two and one of the three subjects with hemoglobin genotype AA were from upper and middle socioeconomic strata, respectively. Obesity does exist among children with sickle cell anemia in Lagos, Nigeria. Public health programs aimed at prevention and control of obesity must include children with sickle cell anemia.

Helicobacter pylori infection among a pediatric population with sickle cell disease.

OBJECTIVES: Recurrent abdominal pain (RAP) is a common presenting symptom in children with sickle cell disease (SCD). This may be as a result of complications of the disease, surgical problems, or Helicobacter pylori gastritis. The prevalence of H pylori infection in SCD children is not known. This study aimed to determine the prevalence and association of H pylori infection with RAP in SCD children. METHODS: This was a prospective case-control study conducted at the Lagos State University Teaching Hospital, Nigeria, involving SCD children (subject, n = 118) and non-SCD children (control, n = 118) matched for age, sex, and socioeconomic status. Seroprevalence status of the children was determined by measuring immunoglobulin G antibodies against H pylori using enzyme-linked immunosorbent assay that had been validated for pediatric use. RESULTS: The overall prevalence of H pylori infection was 155 of 236 (SCD, 67.8%; non-SCD, 63.6%; OR, 1.1; 95% CI, 0.89-1.28; p = .493). The prevalence increased with age in both SCD and non-SCD children and was significantly highest at the age of 6 to 10 years (p < .001 in each case). H pylori infection was significantly associated with socioeconomic status of the parents (OR, 4.25; 95% CI, 1.49-12.1; p = .004) but not significantly associated with RAP in SCD children (OR, 1.21: 95% CI, 0.55-2.66; p = .632). CONCLUSIONS: Prevalence of H pylori infection is high in SCD and non-SCD children in Lagos, Nigeria. There was no significant association between H pylori infection and recurrent abdominal pain in SCD children.

Paediatric to adult transition care for patients with sickle cell disease: a global perspective.

Sickle cell disease is a life-threatening inherited condition designated as a public health priority by WHO. Increased longevity of patients with sickle cell disease in high-income, middle-income, and low-income countries present unprecedented challenges for all settings; however, a globally standardised solution for patient transition from paediatric to adult sickle cell disease health care is unlikely to address the challenges. We established a task force of experts from a multicountry (the USA, Europe, Middle East, and Africa) consortium. We combined themes from the literature with viewpoints from members of the task force and invited experts to provide a global overview of transition care practice, highlighting barriers to effective transition care and provide baseline recommendations that can be adapted to local needs. We highlighted priorities to consider for any young person with sickle cell disease transitioning from paediatric to adult health care: skills transfer, increasing self-efficacy, coordination, knowledge transfer, linking to adult services, and evaluating readiness (the SICKLE recommendations). These recommendations aim to ensure appropriate benchmarking of transition programming, but multisite prospective studies are needed to address this growing public health need.

Unprepared and Misinformed Parents of Children with Sickle Cell Disease: Time to Rethink Awareness Campaigns.

Worldwide, sickle cell disease (SCD) poses a significant public health concern. It causes recurrent morbidity, and premature death is a distinct possibility, especially in Nigeria, which bears half the world's burden of SCD patients. Nigeria has yet to establish a newborn screening program; consequently, most affected children are diagnosed between one and three years of age when a health problem arises. Parents are unprepared to identify SCD and seek comprehensive management early enough for the best outcome. Awareness of carrier status and knowledge of SCD would ensure informed reproductive choices. Questionnaires were employed to conduct a prospective, cross-sectional study of the occurrence of missed carrier status of one biological parent of children enrolled at the pediatric sickle cell disease clinic of a teaching hospital. The institution's ethics committee approved the study. Of 133 respondents, 53% of the parents were unaware of being sickle cell carriers and did not expect to have children with SCD. Among families in which one or both parents proactively sought to know their genotype, 35% of all parents received incorrect genotyping results regarding the SCD risk of their offspring. The majority of incorrectly assigned hemoglobin AA results occurred in private laboratories. More than 60% of the respondents reported gaining awareness regarding SCD through antenatal care (51%) and schools (17%), as opposed to public awareness campaigns (8%). Many parents in our study population were unprepared for their children's SCD diagnosis. Awareness campaigns need to be revisited as a major potential modality to increase outreach about SCD. Standardization and improved quality control of laboratory testing involving screening of the sickle cell trait could reduce the frequency of wrong genotype assignment.

A Multi-centre Survey of Acceptability of Newborn Screening for Sickle Cell Disease in Nigeria.

Background Sickle cell disease (SCD) is a major genetic disease that manifests early in life and may lead to significant morbidities. One of the health care services that have been effective in reducing the burden of SCD in developed countries is newborn screening (NBS) followed by pneumococcal vaccines, penicillin prophylaxis, and hydroxyurea treatment. Yet, in sub-Saharan African countries, where about 75% of annual affected babies worldwide are born, NBS programmes are largely unavailable. It is not clear whether this is due to technical challenges associated with setting up such programmes, or significant cultural and social barriers to its acceptance in such settings. Objective Our aim was to ascertain the attitudes to and acceptability of NBS in Nigeria among various socio-demographic groups including health professionals, undergraduate students, parents of children with SCD and SCD patients. Methods Data on socio-demographic characteristics, knowledge of SCD and attitude towards NBS were collected using a semi-structured pre-tested questionnaire from April to July 2014 across 15 health institutions and university campuses in Nigeria. Data were collected from 1,301 respondents across Nigeria. Results There was good knowledge of SCD as an inherited blood disorder. Although 86% of respondents (n = 1,119) supported NBS, there was a statistically significant relationship between support for NBS and age (p = 003), educational status (p = 000) and religion (p = 000). Conclusion This study suggests that there is a good acceptability of NBS across Nigeria. The main barriers to its use are likely to be financial and practical, rather than social or cultural.

Pattern of Cerebral Blood Flow Velocity Using Transcranial Doppler Ultrasonography in Children with Sickle Cell Disorder in Lagos State, Nigeria.

Cerebrovascular accident (CVA) is a common, devastating neurological complication of sickle cell disorder (SCD) with a high recurrent and mortality rate. The Stroke Prevention Trial in Sickle Cell Anaemia study (STOP) recommends routine screening with transcranial Doppler ultrasonography in children aged two to sixteen years with SCD. The present study assessed cerebral blood flow velocities of children with SCD in accordance with the recommendation of routine screening by the STOP study. METHODS: Transcranial Doppler ultrasonography was done for children with SCD that attended Sickle Cell Foundation, Nigeria between July and November 2015. RESULTS: In all, 388 subjects were screened within the study period (360 HbSS and 28 HbSC). The prevalence of abnormal Time-Averaged Maximum Mean Velocity (TAMMV) of at least 200 cm/second was 10.8%: this was seen solely in HbSS subjects. The mean Time-averaged mean of the maximum (TAMM) velocity were 163±25 cm/sec, 162±30 cm/sec and 150±30 cm/sec for children less than five years, five to ten years and eleven to sixteen years respectively. CONCLUSION: The prevalence of abnormal TAMM velocity in children with HbSS is 10.8%. Identification of subjects at risk helped in primary CVA prevention by prompt therapy institution.

Head circumference of children with sickle cell disease in Lagos, Nigeria.

INTRODUCTION: Growth retardation and under-nutrition are common in children with sickle cell disease (SCD). The aim of this study was to compare the head circumference (HC) of SCD children and non-SCD children and to determine the effect of malnutrition on head circumference of children with SCD. METHODS: This was a prospective case-control study conducted at the Lagos State University Teaching Hospital, Nigeria, involving SCD children (subject, n = 118) and non-SCD children (control, n = 118) matched for age, sex, and socioeconomic status. Weight, height and HC were measured using standard techniques. RESULTS: The mean ages of children with and without SCD were 7.46 ± 3.69 years and 7.01 ± 3.58 years, respectively. The HC increased significantly with age in both males and females (r = 0.75, p = < 0.001; r = 0.70, p < 0.001 respectively). There was no significant difference in HC between males and females (p > 0.05). At all ages, the mean head circumference of SCD children was not significantly (p > 0.05) different from non-SCD children. The In the age group 11-15 years, the prevalence of stunting was significantly higher among SCD children than non-SCD children. The mean HC of SCD children with stunting was significantly lower than those not stunted (51.7 vs. 53.5; P= 0.006) in age group 11.15 years. CONCLUSION: The head circumference of children with SCD is not significantly different from that of non-SCD children. Therefore, the HC chart for the general population is also applicable for monitoring head growth in children with SCD. The effect of malnutrition on head circumference of SCD children is most marked in age group 11-15 years.

Blood transfusion services for patients with sickle cell disease in Nigeria.

BACKGROUND: Safe, timely red blood cell transfusion saves lives and chronic transfusion therapy (CTT) prevents or limits morbidities such as stroke, therefore improving quality of life of patients with sickle cell disease (SCD). METHODS: This questionnaire-based study assessed the ability of sickle cell centers in Nigeria to provide safe blood to patients with SCD between March and August 2014. RESULTS: Out of the 73 hospitals contacted, responses were obtained from 31. Twenty four (78%) hospitals were unable to transfuse patients regularly due to blood scarcity. Packed red blood cells were available in 14 (45%), while only one provided leukocyte-depletion. Most centers assessed donor risk and screened for HIV in 30 (97%), hepatitis B in 31(100%) and hepatitis C in 27 (87%) hospitals. Extended phenotyping and alloantibody screening were not available in any center. A quarter of the hospitals could monitor iron overload, but only using serum ferritin. Access to iron chelators was limited and expensive. Seventeen (55%) tertiary hospitals offered CTT by top-up or manual exchange transfusion; previous stroke was the most common indication. CONCLUSION: Current efforts of Nigerian public hospitals to provide safe blood and CTT fall short of best practice. Provision of apheresis machines, improvement of voluntary non-remunerated donor drive, screening for red cell antigens and antibodies, and availability of iron chelators would significantly improve SCD care in Nigeria.

Acute soft head syndrome in children with sickle cell anaemia in lagos, Nigeria.

Acute soft head syndrome is rare complications seen in children with sickle cell anaemia. A case report of a child with sickle cell anaemia who developed acute soft head syndrome. A 12-year old known sickle cell anaemia patient presented with acute, rapidly progressive skull pain and swelling, manifestations indicative of the rare complication of SCD which is called acute soft head syndrome. Conservative treatment with intravenous fluids and analgesics and empirical use of broad-spectrum antibiotics resulted in recovery. Acute soft head syndrome is a rare complication in children with sickle cell anaemia probably related to skull infarction. It further draws attention to the importance of acute soft head syndrome as a differential to be considered for pains in the head and skull swellings in children with sickle cell anaemia.

Iron Deficiency Anaemia among Pre-School Children with Sickle Cell Anaemia: Still a Rare Diagnosis?

BACKGROUND: The frequent need for blood transfusion in children with SCA creates the impression that IDA is rare in this class of children. OBJECTIVES: The objective of the study is to determine the prevalence of IDA in a population of under-five children with SCA in Lagos, Nigeria. METHODOLOGY: Serum iron, total iron binding capacity, transferrin saturation and serum ferritin were assayed in 97 under-five children with SCAand 97 age/sex matched controls. THE DIAGNOSIS OF IDA WAS ESTABLISHED BASED ON THE FOLLOWING CRITERIA: haemoglobin <11.0 g/dl plus two or more of the following: MCV <70fl, transferrin saturation (Ts) <16% or serum ferritin (SF) <25ng/dL. RESULTS: Overall prevalence of IDA was significantly higher among AA controls. In the younger age group, the prevalence of IDA was significantly higher among HbAA controls while in the older age group the odds of having IDA was three times higher among HbSS subjects but the difference was not statistically significant. Two of the three SCA children with IDA have history of previous blood transfusion. CONCLUSION: IDA is uncommon in pre-school aged children with SCA. A multi-centre study is necessary to yield large number of transfused subjects to examine the effects of blood transfusion on prevalence of IDA.