Using dried blood spot on HemoTypeSC™, a new frontier for newborn screening for sickle cell disease in Nigeria.

Background: HemoTypeSC is a rapid, point-of-care testing (POCT) device for sickle cell disease (SCD) that traditionally uses the capillary blood from heel stick collected at the point of testing, a procedure that makes mass screening cumbersome and less cost-effective. Using dried blood spots (DBS) on HemoTypeSC could mitigate this challenge. Therefore, this study aimed to determine the feasibility of eluting blood from DBS to read on HemoTypeSC. Methods: DBS and fresh samples from heel sticks were collected from 511 newborns at the immunization clinics of six Primary Health Centers in Abuja, Nigeria. The two samples from each newborn were analyzed using HemoType SC and then compared with the result of the isoelectric focusing (IEF) test. Results: Of the 511 newborns, 241 were males and 270 were females. Standard HemoTypeSC (using fresh samples collected from heel sticks) and HemoTypeSC using DBS identified 404 (79.0%) HbAA, 100 (19.6%) HbAS, 6 (1.2%) HbSS, and 1 (0.2%) HbAC phenotypes. The IEF tests identified 370 (72.4%) HbAA, 133 (26.0%) HbAS, 5 (1.0%) HbSS, and 3 (0.6%) HbAC phenotypes. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of HemoTypeSC using DBS, compared to standard HemoTypeSC POCT was 100%. IEF method showed for AA, AS, AC phenotypes; sensitivity; 84.7%, 67%,100% respectively, specificity; 67.6%, 86%, 99% respectively, PPV; 91.2%, 53%, 50% respectively, NPV; 52.7%, 91%, 100% respectively. For SS phenotype, IEF showed 100% specificity, sensitivity, PPV and NPV. Conclusion: HemoTypeSC test using dried blood spot is as accurate as the standard point-of-care HemoTypeSC test. The use of DBS on HemoTypeSC could ensure better efficiency and cost-effectiveness in mass newborn screening for SCD.

Determinants of hydroxyurea use among doctors, nurses and sickle cell disease patients in Nigeria.

BACKGROUND: Hydroxyurea (HU) is an evidence-based therapy that is currently the most effective drug for sickle cell disease (SCD). HU is widely used in high-income countries with consequent reduction of morbidity and mortality. In Nigeria, HU is prescribed by physicians while nurses are mainly involved in counseling the patients to ensure adherence. The extent of utilization and the determinant factors have not been sufficiently evaluated in Nigeria. OBJECTIVE: To assess the frequency of use of HU and factors affecting utilization among healthcare providers, patients, and caregivers for SCD. METHODS: A questionnaire was administered online and in- person to assess the frequency of HU use and the factors that promote and limit its use. The data were analyzed by descriptive statistics using IBM SPSS software version 23 and the result was presented in frequency tables and percentages. RESULT: A total of 137 physicians, 137 nurses, and 237 patients/caregivers responded to the survey. The rate of prescription of HU by doctors in the past 6 months was 64 (46.7%), 43 (31.4%) nurses provided counseling and 36 (15.6%) patients were on HU. Among doctors, adequate knowledge (91.3%), clinical benefits and safety (94.8%), and inclusion of HU in management guidelines (86.9%) were motivators for prescribing it while inadequate knowledge (60.9%) and unawareness of treatment guidelines (68.6%) constituted barriers. Among nurses, reduction of crisis (91.6%) and safety (64.8%) were the major motivators while barriers were high cost (79.1%) and intensive monitoring (63.1%) of HU treatment. Among the patients, the major motivator was the reduction of crises (80.3%) while poor knowledge (93.2%), high cost of the drug (92.2%) while monitoring (91.2%), non-availability (87.7%) and side effects (83.9%) were the major barriers for the utilization of HU. CONCLUSION: HU prescription and utilization are still poor among healthcare providers and patients. Inadequate knowledge, non-availability and high cost of HU as well as unawareness of treatment guidelines constitute major barriers to prescription and utilization.

Utilization of Pneumococcal Vaccine and Penicillin Prophylaxis in Sickle Cell Disease in Three African Countries: Assessment among Healthcare Providers in SickleInAfrica.

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers' behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of Streptococcus pneumoniae in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.

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.

Nigerian Population Research on Environment, Gene and Health (NIPREGH) - objectives and protocol.

Sub-Saharan Africa is currently undergoing an epidemiological transition from a disease burden largely attributable to communicable diseases to that resulting from a combination of both communicable and chronic non-communicable diseases. Data on chronic disease incidence, lifestyle, environmental and genetic risk factors are sparse in this region. This report aimed at providing relevant information in respect to risk factors that increase blood pressure and lead to development of intermediate cardiovascular phenotypes. We presented the rationale, objectives and key methodological features of the Nigerian Population Research on Environment, Gene and Health (NIPREGH) study. The challenges encountered in carrying out population study in this part of the world and the approaches at surmounting them were also presented. The preliminary data as at 20 November 2013 showed that out of the 205 individuals invited starting from early April 2013, 160 (72 women) consented and were enrolled; giving a response rate of 78%. Participants' age ranged from 18 to 80 years, with a mean (SD) of 39.8 (12.4) years and they were of 34 different ethnic groups spread over 24 states out of the 36 states that constitute Nigeria. The mean (SD) of office and home blood pressures were 113.0 (15.2) mm Hg systolic, 73.5 (12.5) mm Hg diastolic and 117.3 (15.0) mm Hg systolic, and 76.0 (9.6) mm Hg diastolic, respectively. Forty-three (26.8%) participants were hypertensive and 8 (5.0%) were diabetic. In addition to having the unique potential of recruiting a cohort that is a true representative of the entire Nigerian population, NIPREGH is feasible and the objectives realisable.

Calcaneal measurement in estimation of stature of South African blacks.

Stature (height) is an important factor in establishing the identity of a person in the living as well as in the skeletonized state. When stature is estimated from the bones of the limbs, regression equations, which estimate the ratios of the lengths of bones to the height of the individual, are generated. The majority of bones that were used previously were the long bones. The calcaneus was used for estimating stature only in American whites and blacks (Holland [1995] Am. J. Phys. Anthropol. 96:315-320). The regression equations that he generated were found to be useful for stature estimation in these population groups. Since the calcaneus has not been used for the same purpose in South Africa, the aim of this study was to derive regression equations that will allow this bone to be used for stature estimation in South African blacks. In total, 116 complete skeletons (60 males and 56 females) were selected from the Raymond A. Dart Collection of Human Skeletons, School of Anatomical Sciences, University of the Witwatersrand (Johannesburg, South Africa). The skeletal heights of these sets of skeletons were calculated using the anatomical method of Fully ([1956] Ann. Med. Leg. 35:266-273). Nine parameters of the calcaneus were measured and matched against skeletal heights, using univariate and multivariate regression methods. Regression equations were obtained for estimation of the stature of the South African black population from the calcaneus. The standard error of estimate that was obtained with univariate regression analysis was higher than the corresponding values using multivariate regression analysis. In both cases, the standard errors of estimate compared well with the values obtained for fragmentary long bones by previous authors.

Sexual dimorphism of the calcaneus of South African blacks.

Forensic anthropology is a rapidly growing field in South Africa and skeletal biologists are often called upon by the police to assist in personal identification from skeletal remains, which are recovered in suspected cases of homicide and suicide and in mass disaster. Measurements of the calcaneus have been shown to be sexually dimorphic in South African whites. Since the validity of discriminant function equations in sex determination is population specific, the aim of the present study was to derive similar equations for the calcanei of the South African blacks. The bones that were used in this study were obtained from the Raymond A. Dart Collection of Human Skeletons, School of Anatomical Sciences, University of the Witwatersrand, Johannesburg. One hundred and sixteen (116) intact and non-pathological calcanei, consisting of 58 males and 58 females and belonging to individuals whose age at death ranged between 22 and 75 years, were selected by the simple random sampling technique. The measured variables included the maximum length, the load arm length, the dorsal articular facet length, the body height, the maximum height, the cuboidal facet height, the middle breadth, the dorsal articular facet breadth and the maximum breadth. Discriminant function analyses were done using the Statistical Product and Service Solutions (SPSS) program. All measured parameters of the calcaneus showed significant sexual differences. Length measurements were found to be the most sexually dimorphic. Combinations of variables provided better estimate of sex (79%-86%) than individual variables (64%-79%).

Discriminant function sexing of the calcaneus of the South African whites.

The skull and some postcranial elements, such as the humerus, femur, and tibia, have been used in their intact states for sex determination in forensic and archaeological cases. But, in practice, these bones are often recovered in fragmented states, which render them unsuitable for use in sex determination. The calcaneus is a compact bone that is able to withstand high tensile forces. Some of its parameters have been used for sex determination in American whites and blacks (1) and Italians (2). This bone has not been used for sex determination in the South African white population. Therefore, the aim of this study was to assess the degree of sexual dimorphism of the calcaneus of the South African white population sample, derive discriminant function score equations for use in sex determination, and determine the level of accuracy of its sex-determining ability. Nine parameters were measured on each pair of 53 male and 60 female calcanei of known South African white skeletons, obtained by a random sampling technique from the Raymond A. Dart Collection of Human Skeletons, School of Anatomical Sciences, University of the Witwatersrand, Johannesburg. Basic statistic and discriminant function analysis was performed on the acquired data. The basic statistics showed that all measured parameters were sexually dimorphic. Discriminant function score equations were generated for use in sex determination. The average accuracy of sex classification ranged from 73 to 86% for the univariate method, 81 to 91% for the stepwise method, and 82 to 92% for the direct method. It is concluded that the calcaneus is useful for sex determination in the South African white population.

The efficiency of the demarking point of the femoral head as a sex determining parameter.

The percentage of skeletal remains that can be sexed depends on the degree of completeness of the skeleton, the parameters that are used and the type of statistical analysis that is done. The objective of the present study was to assess the accuracy of the demarking point in sexing the femur of South African whites and blacks. One hundred pairs of femurs were randomly selected from the bone collections of each of the two racial groups. The bones were sexed by measuring the head diameters and comparing them with the corresponding demarking point values that had been previously determined. The sex that was so allocated to each bone was compared with its documented sex in the database in order to assess the accuracy of the method. The overall success rate of sex identification was 32% for both white and black populations, but the accuracy of sexing was 100%.