Detection of Transversions and Transitions in HBG2 Cis-Elements Associated with Sickle Cell Allele in Ghanaians.

Short tandem repeats located 5' prime to the ß-globin gene, have been observed to be in linkage disequilibrium with the HbS allele, and thought to affect the severity of sickle cell disease. Here, we report on new mutants within the HBG2 region that may impact sickle cell disease. To determine the cis-acting elements microsatellites, indels and single nucleotide polymorphisms (SNPs), within the HBG2 region by sequencing, in subjects with sickle cell disease. The case-control study was located at the Center for Clinical Genetics, Sickle cell unit, Korle-Bu Teaching Hospital. A questionnaire was used for demographic data and clinical information. Hematological profile (red blood cell, white blood cell, platelet, hemoglobin and mean corpuscular volume) were assessed in 83 subjects. A set of 45 samples comprising amplified DNA on the HBG2 gene from HbSS (22), HbSC (17) and 6 controls (HbAA) were sequenced. Differences in the microsatellite region between sickle cell disease (SCD) (HbSS and HbSC) genotypes and control subjects were identified by counting and assessed by Chi-square analysis. Red blood cells, hematocrit, platelets, white blood cells and hemoglobin indices differed in genotypic groups. HbSS subjects were affirmed to have severer hemolytic anemia than HbSC subjects. Two indels (T1824 and C905) were seen in both SS and SC genotypes. Two peculiar SNPs: G:T1860 (transition) and A:G1872 transversions were found within the HBG2 gene that were significantly associated with the HbSS genotype (Fisher's exact test, p = 0.006) and HbS allele respectively (Fisher's exact test, p = 0.006). Cis-acting elements in HbSS and HbSC were different and may contribute to the phenotype seen in the disease state.

Further observations on hydrogen peroxide antisepsis and COVID-19 cases among healthcare workers and inpatients.

BACKGROUND: The use of prophylactic antisepsis to protect against coronavirus disease 2019 (COVID-19) has been suggested. This study investigated hydrogen peroxide antisepsis (HPA) at two hospitals in Ghana. METHODS: Cases of COVID-19 among healthcare workers (HCWs) using hydrogen peroxide (HP-HCWs) or not using hydrogen peroxide (NHP-HCWs), vaccinated or unvaccinated, were recorded at Shai-Osudoku Hospital (SODH), Dodowa, and Mount Olives Hospital (MOH), Techiman, between May 2020 and December 2021. The effect of HPA in all inpatients at MOH was also observed. Permutation tests were used to determine P values. FINDINGS: At SODH, there were 62 (13.5%) cases of COVID-19 among 458 NHP-HCWs but no cases among eight HP-HCWs (P=0.622) from May to December 2020. Between January and March 2021, 10 (2.7%) of 372 NHP-HCWs had COVID-19, but there were no cases among 94 HP-HCWs (P=0.206). At MOH, prior to HPA, 17 (20.2%) of 84 HCWs and five (1.4%) of 370 inpatients had COVID-19 in July 2020. From August 2020 to March 2021, two of 54 (3.7%) HCWs who stopped HPA had COVID-19; none of 32 NHP-HCWs contracted COVID-19. At SODH, none of 23 unvaccinated HP-HCWs and 35 (64%) of 55 unvaccinated NHP-HCWs had COVID-19 from April to December 2021 (P<0.0001). None of 34 vaccinated HP-HCWs and 53 (13.6%) of 390 vaccinated NHP-HCWs had COVID-19 (P=0.015). No inpatients on prophylactic HPA (total 7736) contracted COVID-19. CONCLUSION: Regular, daily HPA protects HCWs from COVID-19, and curtails nosocomial spread of SARS-CoV-2.

The effect of electronic reminders on risk management among diabetic patients in low resourced settings.

BACKGROUND: Information technology has potential to improve health care delivery particularly among individuals with chronic diseases such as diabetes in low and middle-income countries (LMIC). Research on the usefulness of information technology to manage persons living with chronic diseases is scarce in LMIC. We sought to evaluate the effect of an electronic reminder system on cardiovascular risk factors (blood pressure, heart rate, and fasting plasma glucose) and adherence to clinical appointments among persons living with diabetes. RESEARCH DESIGN AND METHODS: A randomized controlled design was used to recruit 200 diabetic patients (intervention n=100, control n=100) from the National Diabetes Management Research Centre, Accra. All patients received usual diabetes care. The intervention group was given electronic reminders for their clinical appointments and their physicians were prompted with abnormal laboratory results for six months. RESULTS: Baseline characteristics were largely similar for both groups. At six months follow up, the mean reductions of all the cardiovascular risk factors in the intervention group were significantly greater than in the control group: -1.7 kg/m(2) versus -1.1 kg/m(2)(p=0.002) for BMI; -4.7 mmHg versus -2.8 mmHg (p=0.002) for SBP; -5.3 mmH versus -3.1 mmHg (p=0.001) for DBP; -1.7 bpm versus -0.1 bpm (p=0.001) for heart rate and -2.3 mmol/L versus -1.6 mmol/L (p=0.001) for fasting plasma glucose, respectively. Adherence to appointment schedules was also significantly higher in the intervention group compared with the control group (97.8% versus 89.4%, p=0.010). CONCLUSIONS: Locally developed electronic initiatives such as this resulted in improved cardiovascular risk factors and effective compliance to clinical practices and improved quality of care for persons living with diabetes.

Feasibility of thyroid ultrasonography in field studies in a developing country, Ghana.

This study was carried out to determine the feasibility of using ultrasonography for goitre estimation in the field situation. It is a cross sectional study that was conducted using community based cluster sample. Thyroid sonography was performed on 112 randomly selected school children aged 10 -15 years from two districts in the Greater Accra area of Ghana, using normative values for thyroid volume recommended by WHO/ICCIDD. The mean age of all subjects was 13.5 years+/-0.13 SEM. The male to female ratio was 1:1. The mean height and weight of the children were 1.5 metres+/-0.9 SEM and 38.1 Kg+/-0.7 SEM, respectively. The mean body surface area was 1.27 m2+/-0.2. There were no significant gender differences in their ages (13.6yrs+/-0.2 SEM, 13.4yrs+/-0.1 SEM, respectively) and height (1.50m+/-1.6 SEM, 1.46m+/-1.7 SEM, respectively). The girls (40.0kg+/-1.2 SEM) weighed more than the boys (35.6kg+/-1.1). The mean and median urinary iodine concentration were 82.4+/-8.5 SEM and 67.9 ug/l, respectively. All the children examined had normal thyroid sonogram. The thyroid volumes ranged from 3.6 ml to 15.3ml. The mean thyroid volume was 7.0ml+/-0.2 SEM and the thyroid volume was higher in the girls (7.5ml+/-0.3 SEM) than the boys (6.5ml+/-0.2 SEM). The criteria of thyroid volume per age and sex yielded a goitre prevalence of 1.8 %. In contrast, the criteria of thyroid volume by surface area yielded a goitre prevalence of 8 %. Our study has shown that it is feasible to employ ultrasonography for field studies to determine goitre prevalence in school children in a developing country such as Ghana. However, the best criteria for goitre in children in Ghana, requires to be confirmed in future studies.

A-61C and C-101G Hp gene promoter polymorphisms are, respectively, associated with ahaptoglobinaemia and hypohaptoglobinaemia in Ghana.

We have investigated the genetic basis for the Hp0 phenotype amongst 123 randomly selected Ghanaians. A total of 17 individuals were determined to be Hp0 phenotype, based on the classical method for Hp phenotyping of Hb-supplemented plasma. Out of the 17 Hp0 individuals, nine subjects were further classified as ahaptoglobinaemic and eight as hypohaptoglobinaemic by Western blots and double immunodiffusion. We identified three previously known base substitutions (A-55G, A-61C and T-104A) and three new ones (C-101G, T-191G and C-242T) within the 5' flanking region of the Hp gene. The A-61C base substitution significantly decreased transcriptional activity and was associated strongly with Hp2 allele and ahaptoglobinaemia. The C-101G substitution was similar in transcriptional activity to the wild-type and was associated with Hp1S allele and hypohaptoglobinaemia. The Hpdel allele seen in Asian populations was absent. We conclude that the Hp0 phenotype in Ghana has a genetic basis that differs significantly from that seen in Asia.

Insulin sensitivity and cardiovascular risk factors in hypertensive and normotensive native Ghanaians.

AIMS/HYPOTHESIS: The objective of this study was to examine the relationships among insulin and insulin sensitivity and risk factors for cardiovascular diseases in native Ghanaians with and without hypertension. METHODS: We measured the anthropometric parameters, systolic and diastolic blood pressure, fasting serum triglycerides, cholesterol and high-density lipoprotein cholesterol and fasting and stimulated glucose, insulin and C-peptide of 200 Ghanaian subjects, who were between 25 to 74 years of age, and residing in the Accra Metropolitan area. Serum glucose, C-peptide and insulin concentrations were measured at baseline (fasting) and also 2 h after 75 gm oral glucose drink. Homeostasis model assessment was used to measure insulin resistance. Hypertension was defined as a blood pressure higher than 140/90 mmHg. RESULTS: There were 53 subjects with hypertension (HBP) and 147 subjects with normal blood pressure (NBP). The mean BMI, waist circumference and waist-to-hip circumference ratio for HBP and NBP subjects were 27.4+/-0.8, 24.8+/-0.4 kg/m(2); 89.8+/-11.7, 81.1+/-0.9 cm; and 0.87+/-0.08, 0.82+/-0.08 respectively, (p<0.05). The fasting and 2-h plasma glucose concentrations in HBP and NBP subjects were 5.5+/-0.2, 7.2+/-0.3 mmol/l and 5.2+/-01, 6.8+/-0.2 mmol/l respectively (p>0.05). The corresponding fasting and 2-h insulin concentrations were 10.0+/-0.7, 8.0+/-0.4 uU/ml and 47.3+/-3.7, 37.3+/-2.5 uU/ml respectively (p<0.05). The insulin resistance index (HOMA-IR) in the HBP and the NBP groups were 2.49+/-0.2 and 1.95+/-0.13 (p<0.05). The two groups had similar fasting and stimulated C-peptide, lipids and HDL concentrations. Correlations were found between blood pressure and the concentrations of lipids, HDL, fasting and stimulated insulin and C-peptide, and between fasting insulin and HOMA-IR with lipids and HDL concentrations. On multiple regression analysis, fasting insulin and HOMA-IR did not influence blood pressure variations significantly. CONCLUSIONS/INTERPRETATION: We found clustering of hyperinsulinaemia, insulin resistance and truncal obesity in hypertensive Ghanaian subjects but dissociation between insulin resistance, hypertension and atherogenic lipid and lipoprotein profile.

Undiagnosed diabetes and impaired glucose regulation in adult Ghanaians using the ADA and WHO diagnostic criteria.

Fasting glucose and oral glucose tolerance test (OGTT) criteria for glucose homeostasis were compared in a cross-sectional cluster, community study in Accra, Ghana. A total of 4636 subjects without prior diagnosis of diabetes had fasting plasma glucose, 2-hour OGTT and measurement of cardiovascular risk factors. Mean age of subjects was 44.2 years: 39.1% of subjects were males. The overall prevalence of undiagnosed diabetes ascertained with both criteria was 4.5% (n=209). The prevalence of undiagnosed diabetes by fasting (3.2%) and OGTT (3.1%) criteria were similar (p>0.05). The prevalence of impaired glucose tolerance (IGT) (15.8%) was higher than that of impaired fasting glucose (IFG) (10.7%). Only 56.5% (n=83) of subjects with diabetes by fasting criteria also had diabetes by OGTT criteria. Sixty-two subjects (42.8%) with diabetes by OGTT had normal or impaired fasting glucose. There was poor agreement between the two diagnostic criteria (kappa=0.31). The concordant normoglycaemic group was the youngest and had the lowest body-mass index (BMI), waist girth, waist-hip ratio (WHR), total cholesterol, and systolic and diastolic blood pressures. The concordant diabetic group, in contrast, had the highest BMI, waist girth, WHR, total cholesterol and triglyceride levels. Both systems gave similar undiagnosed diabetes rates but dissimilar IFG and IGT rates. There was poor agreement between the two diagnostic criteria. Diagnostic criteria influenced cardiovascular risk factors. A case may be made for using both criteria in order to ascertain all "diabetes" and all "at-risk" subjects.