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.

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.

Non-invasive estimation of pulmonary artery pressures in patients with sickle cell anaemia in Ibadan, Nigeria: an echocardiographic study.

INTRODUCTION: Pulmonary hypertension is emerging as one of the causes of morbidity and mortality in adults with sickle cell disease. The prevalence of pulmonary hypertension in Nigerian adults with sickle cell anaemia is unknown. We decided to estimate the pulmonary artery systolic and diastolic pressures in subjects with sickle cell anaemia seen at the University College Hospital, Ibadan, Nigeria, and to determine the frequency of pulmonary hypertension among them. METHODS: Ninety patients (38 males and 52 females) with sickle cell anaemia in steady state and comparable age- and sex-matched normal controls had a clinical evaluation and echocardiographic examination. RESULTS: The mean age of the subjects with sickle cell anaemia was 24.0 (9.00) years while the mean age for the control group was 24.0 (7.00) years. The frequency of pulmonary hypertension as assessed by a tricuspid regurgitant jet velocity of > 2.5 m/s in this study was 12.2%. Larger left ventricular dimensions and volumes, higher stroke volume and increased left ventricular mass indexed by body surface area were found to be associated with pulmonary hypertension. A multivariate analysis of the potential predictors of pulmonary hypertension in this study showed that male sex and lower packed cell volume (PCV) were independent predictors of pulmonary hypertension in patients with sickle cell anaemia. CONCLUSION: We conclude that pulmonary artery systolic and diastolic pressures are higher in subjects with sickle cell disease than normal controls. Male sex and low PCV are independent determinants of pulmonary arterial pressure in subjects with sickle cell anaemia in Nigeria.

Blood donation practices, processing and utilisation of blood components in government tertiary hospitals in Nigeria: a multicentre cooperative study.

BACKGROUND: Timely access to safe blood and blood components is still a challenge in Nigeria. This study aimed to determine blood donation practices, processing and utilization of blood components across government tertiary hospitals (THs) in Nigeria. METHODS: This was a descriptive cross-sectional study done in Nigeria in June-July 2020. Data were analysed with SPSS version 21.0. RESULTS: Data were collected from 50 THs. The majority (68%) of the THs lack facilities for blood component preparation and only 18% and 32% provide cryoprecipitate and platelet concentrate, respectively. Whole blood was most commonly requested (57.04%). All facilities tested blood for HIV, HBV and HCV, but the majority (23 [46%]) employed rapid screening tests alone and nucleic acid testing was not available in any hospitals. The manual method was the most common method of compatibility testing in 90% (45/50) and none of the THs routinely perform extended red cell typing. The average time to process routine, emergency and uncross-matched requests were a mean of 109.58±79.76 min (range 45.00-360.00), 41.62±25.23 (10.00-240.00) and 11.09±4.92 (2.00-20.00), respectively. CONCLUSION: Facilities for blood component preparation were not widely available. Concerned government authorities should provide facilities for blood component preparation.

A fifteen-year review of lymphomas in a Nigerian tertiary healthcare centre.

In Africa, epidemiological data on the effect of the HIV epidemic on the occurrence of lymphomas are scanty. The 1990s witnessed the alarming rates of HIV/AIDS in Nigeria. The prevalence of HIV/AIDS in Nigeria increased from 1.8% in 1991 to 4.4% in 2005. The aim of this study was to determine whether there have been any changes in the frequency and pattern of lymphomas in view of the HIV/AIDS epidemic in the country. This is a retrospective study of all lymphoma cases diagnosed during 1991-2005. The prevalence of lymphomas declined from 1.4% to 0.7% of surgical biopsies during 1991-2005. There was a decline in the proportion of high-grade non-Hodgkin lymphoma and Burkitt's lymphoma from 79.1% and 45.8% respectively to 21.1% and 13.6% respectively. There is a suggestion that the HIV/AIDS epidemic in the country may not have influenced the pattern of occurrence of both major histomorphological types of lymphoma in Ibadan.

Acute leukemia in sickle cell disease patients in a tertiary health facility in Nigeria: a case series.

BACKGROUND AND OBJECTIVES: Sickle cell disease(SCD) is a disorder of red cells resulting from the co-inheritance of haemoglobin S (HbS) with another abnormal haemoglobin. The diagnosis of acute leukaemia is uncommon in our patients with sickle cell disease more so the patients have high morbidity and mortality due to the sickling process. Acute leukemia is a malignant clonal disorder of haemopoietic precursor cells resulting in accumulation of immature blood cells in the bone marrow and blood. The objective of the case series was to highlight the challenges of diagnosis and management of SCD patients with acute leukaemia, the importance of peripheral blood film review and propound a possible risk factor. METHODS: Records of 58 patients diagnosed and managed for acute leukaemia over a 7 year period at the University College Hospital, Ibadan were reviewed. The diagnosis of acute leukaemia was based on clinical features in addition to peripheral and bone marrow smears findings. Microsoft excel version 2013 was used for statistical analysis. RESULTS: Five (8.6%) of the patients with acute leukaemia also had sickle cell disease: 3 males and 2 females were described. Recurrent fever and anaemia were the most consistent presenting features in the patients. All the patients were not on any routine medications meant for SCD patients and had poor history of clinic attendance prior to the diagnosis of acute leukaemia. The diagnosis of acute leukaemia was not made until the patients were seen by a haematologist. The principal tool of diagnosis in all the patients was peripheral blood film review. Two patients were discharged against medical advice. The treatment period ranged between one month and one year in the remaining three patients. CONCLUSION: SCD patients are not exempted from developing acute leukaemias and the diagnoses of the two conditions overwhelms the social and economic support of patients and care givers. The study also underscores the relevance of high level of suspicion and prompt review of peripheral blood film of SCD patients particularly when patients present with unremitting symptoms associated with anaemia and fever.

Immunoglobulin A Myeloma in a Newly Diagnosed Sickle Cell Disease Patient.

Several neoplasms including hematological malignancies occurring in very few patients with sickle cell syndromes have been reported in literature, particularly as survival among these patients and diagnostic accuracy have continued to improve. Multiple myeloma (MM) has rarely been reported in patients with hemoglobin (Hb) S + C. We report a 65-year-old retired banker who was recently diagnosed with HbS + C. This patient developed MM with markedly elevated erythrocyte sedimentation rate, mild anemia, 80% bone marrow plasmacytosis, and elevated serum immunoglobulin A level, while plain X-ray of the lumbosacral spine showed multilevel vertebral collapse.

Adult Sickle Cell Anaemia Patients in Bone Pain Crisis have Elevated Pro-Inflammatory Cytokines.

BACKGROUND AND OBJECTIVES: Inflammatory markers that influence bone pain crisis (BPC) and other complications of sickle cell anaemia (SCA) are numerous and play various roles. This study determined the plasma levels of tumour necrosis factor (TNF) - α, interleukin - 8 (IL-8), and endothelin - 1 (ET-1) in adult SCA patients during BPC and in steady state. In addition, the plasma levels of these cytokines were correlated with the severity of BPC of the patients. METHODS AND MATERIALS: Sixty adult SCA patients (30 during BPC and 30 during steady state) and 30 haemoglobin A controls were enrolled for this cross-sectional study. The severity of BPC was assessed clinically, and questionnaires were filled. Plasma levels of TNF- α, IL-8 and ET-1 were quantified by ELISA, and haematological parameters were determined using a 5-part auto-analyzer. Plasma levels were correlated with the severity of bone pain crisis. Results were considered statistically significant if p<0.05. RESULTS: Plasma TNF-α, IL-8, and ET-1 were significantly elevated in the BPC group than in the steady state group and the controls. Plasma TNF-α, IL-8 and ET-1 were markedly higher in the severe BPC groups than the steady state and control groups, There was a positive correlation between TNF-α and ET-1 in the bone pain crisis group. CONCLUSION: Elevated levels of plasma TNF-α, IL-8, and ET-1 further establish the chronic inflammatory state in SCA and equally affirm their significant contribution, not only to pathogenesis but also to the severity of pain in SCA.

Insulin Sensitivity, Inflammation, and Basal Metabolic Rate in Adults with Sickle Cell Anemia.

BACKGROUND: Chronic inflammation and elevated basal metabolic rate (BMR) are established features of sickle-cell anemia (SCA). However, there is little information on the possible impacts of these afore-mentioned features on glycemia and insulin sensitivity status of this group of people. AIM: This study aims to determine the insulin sensitivity status as well the effect of BMR on glycemia in adults with SCA in steady state. MATERIALS AND METHODS: Fifty participants comprising 30 adults with SCA in steady state and 20 age- and gender-matched apparently healthy adults with hemoglobin genotype AA (HbAA) genotype that served as controls. Anthropometric and clinical indices were obtained using standard methods. After an overnight fast, fasting plasma glucose (FPG), and serum insulin levels were determined using the glucose oxidase method and ELISA, respectively. Indices of insulin sensitivity and ß-cell function as well as BMR were appropriately calculated. RESULTS: The mean fasting insulin resistance (IR) index, homeostatic model of assessment of IR (HOMA-IR) and of ß-cell function (HOMA2-ß%), and mean insulin level were significantly lower while the mean HOMA of insulin sensitivity (HOMA2-S%), quantitative insulin sensitivity check index, inverse of insulin sensitivity (1/FI), glucose-insulin ratio, C-reactive protein (CRP), and BMR was significantly higher in patients with SCA compared with the controls. The mean FPG and insulin levels and the mean values of indices of insulin sensitivity and secretion were not significantly different in SCA patients with elevated BMR compared with SCA patients with lower BMR. In addition, BMR had no significant correlation with FPG and HOMA-IR in patients with SCA. CONCLUSION: Despite the established chronic inflammation in SCA patients in steady state, they seem to have better insulin sensitivity status but impaired ß-cell activity when compared with adults with HbAA. Furthermore, BMR does not have any pronounced effect on glycemic and insulin sensitivity status in SCA patients in steady state.

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.

Male Sexual Dysfunction, Leptin, Pituitary and Gonadal Hormones in Nigerian Males with Metabolic Syndrome and Type 2 Diabetes Mellitus.

BACKGROUND: Pituitary and gonadal dysfunctions resulting from increased adiposity leading to disturbances of sexual and reproductive functions have been reported in males with metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). The aim of this study was to evaluate sexual dysfunction, leptin, and reproductive hormones in Nigerian males with MS and DM2. METHODS: Participants were 104 men (34 males with DM2, 17 men with MS and 53 men with normal body mass index (18.5-24.9 Kg/m (2)) without MS (controls)). The International Diabetes Federation (2005) criteria were used for MS diagnosis. Reproductive history, anthropometry, blood pressure (BP) and 10 ml fasting blood samples were obtained by standard methods. Fasting plasma glucose, total cholesterol, triglycerides and high density lipoprotein cholesterol were determined by enzymatic methods while low density lipoprotein cholesterol was calculated. Leptin, follicle stimulating hormone (FSH), luteinising hormone (LH), prolactin, testosterone and oestrogen were determined by enzyme immunoassay (leptin by Diagnostic Automation, Inc.; others by Immunometrics (UK) Ltd.) while oestrogen-testosterone ratio was calculated. Data analyzed using ANOVA, Chi square and multiple regression were statistically significant at p<0.05. RESULTS: Testosterone was significantly lower in MS than controls while oestradiol and ETR were significantly higher in MS compared with controls and DM2 group (p<0.05). ETR significantly predicted testosterone in all groups (p<0.05). Significantly lower libido was observed in men in MS than controls and DM2 groups (p<0.05). CONCLUSION: Sexual and reproductive dysfunction may be related to increased conversion of testosterone to oestrogen in increased adipose mass in men with metabolic syndrome and type 2 diabetes mellitus.

Defective lipid metabolism in sickle cell anaemia subjects in vaso-occlusive crisis.

BACKGROUND: Abnormal lipid homeostasis has been reported in sickle cell anaemia (SCA) as well as in other haematological disorders. However, there is little information on the lipid profile of SCA subjects in vaso-occlusive crisis (VOC). This study determined the lipid profile of adult SCA subjects in VOC and in steady state (SSCA). MATERIALS AND METHODS: Fifty-eight (58) adults with HbSS (30 in steady state and 28 in vaso-occlusive crisis) and 24 age-matched healthy individuals with HbAA genotype were recruited into this study. Standard methods were used for the determination of blood pressure (BP), packed cell volume (PCV), total white blood cell count (WBC) and haemoglobin phenotype. After an overnight fast, 5 ml of venous blood was obtained from each SSCA and the controls while samples were collected upon admission in the VOC group. Plasma lipid profile was determined using enzymatic method. Differences between two groups were determined using independent Student's t-test or Man-Whitney U as appropriate. P-values less than 0.05 were considered significant. RESULTS: Plasma total cholesterol (TC) and high density lipoprotein (HDL) were significantly lower while the ratio of triglyceride (TG) to HDL (TG/HDL) was significantly higher in SSCA compared with the controls. Low density lipoprotein (LDL) and TC were significantly lower in SCA subjects in VOC compared with controls. However, TC, TG, LDL and TG/HDL were significantly lower while HDL was significantly higher in VOC compared with SSCA. CONCLUSION: Sickle cell anaemia subjects have defective fasting lipid metabolism which becomes pronounced with VOC.

Serum copeptin and cortisol do not accurately predict sickle cell anaemia vaso-occlusive crisis as C-reactive protein.

OBJECTIVE: This study assessed the diagnostic performance and prognostic properties of C-reactive protein (CRP), copeptin and cortisol in individuals with sickle cell anaemia (SCA). DESIGN: Prospective case-control study. METHODS: Sixty consecutive SCA subjects (18-40 years) comprising 30 subjects in the steady state and 30 subjects in vaso-occlusive crisis (VOC) were recruited into this study. Thirty (30) apparently healthy individuals with HbAA genotype served as controls. ELISA was used for the determination of serum levels of copeptin, CRP and cortisol. Data obtained were statistically analyzed using the Student's t-test and Mann Whitney U as appropriate and P<0.05 was considered significant. RESULTS: SCA subjects in VOC had significantly lower copeptin level and significantly higher CRP level compared with controls. However, serum levels of copeptin, cortisol and CRP were significantly higher in SCA subjects in VOC compared with SCA subjects in steady state. Furthermore, CRP had the widest Area under the ROC curve (AUROC) than copeptin and cortisol. No significant difference was observed in the levels of copeptin, CRP and cortisol when SCA subjects in VOC who were hospitalized for less ≤ 5 days were compared with subjects who had longer stays. CONCLUSION: It could be concluded that C-reactive protein has a superior diagnostic performance for vaso-occlusive crisis in individuals with sickle cell anaemia and that C-reactive protein, cortisol and copeptin are not good prognostic markers in SCA subjects in vaso-occlusive crisis.

Multiple bone and joint diseases in a nigerian sickle cell anaemia: a case report.

This case highlights the fact that bone involvement is the commonest clinical manifestation of Sickle Cell Disease (SCD) both in the acute settings such as painful vaso-occlusive crisis (VOC) and as a source of chronic, progressive debility such as avascular necrosis (AVN), chronic osteomyelitis and fixed flexion deformity of joints.Protracted multiple bone involvement i.e. bilateral femoral and left humeral chronic osteomyelitis, Left elbow, Left knee and right humeral septic arthritis together with avascular necrosis of both femoral and right humeral heads, coupled with urinary tract infection (UTI) and decubitus ulcer in a young adult SCD patient is an unusual occurrence. This morbidities resulted into an uninterrupted 29 weeks of hospitalization for the patient who had previously enjoyed fairly good health.Various micro-organisms were sequentially cultured at various times and sites; these include E coli and Klebsiella in urine and klebsiella spp in the aspirates of the affected knee joint, elbow joint and femoral osteomyelitis. A screen for HIV 1 and 2 were non-reactive.Multidisciplinary approach was applied to the patient who was finally discharged home on a wheelchair. This case reflects not only the high susceptibility of SCD patients to infection, but also the morbidity and the attendant complications. It also highlights the need to forestall VOC which often predisposes to osteomyelitis. There is a need to have a highly organized, well-equipped and highly subsidized Sickle Cell and rehabilitation center in Nigeria in order to improve the medical care for SCD patients.