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    Risk Factors and Human coronaviruses Associated with Upper Respiratory Tract Infections in Three Rural Areas of Ghana.
    (2014.) Owusu, Michael
    Acute respiratory tract infections (ARI) are the leading cause of morbidity and mortality in developing countries, especially in Africa. In spite of its importance, information on the viral aetiology and risk factors associated with ARI are limited in Ghana. Even though human coronaviruses (HCoVs) are known to be associated with respiratory disease outbreaks and severe infections in some developed countries, their epidemiological role is understudied in many African countries including Ghana. It is therefore not known whether HCoVs are pathogenic viruses associated with ARI or only exist as normal commensals of the upper respiratory tract. The aim of this study was to find the association between HCoVs and ARIs, describe the sero-molecular epidemiology of HCoVs and identify the risk factors associated with upper respiratory tract infection. An unmatched case control study was conducted in Buoyem, Forikrom and Kwamang communities of Ghana. Subjects were interviewed on various socio-demographic factors and hygienic practices using structured questionnaires. Nasal/Nasopharyngeal swabs were taken from older children and adults, and tested for Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 using Reverse Transcriptase Real-Time Polymerase Chain Reaction. A total of 1272 subjects were recruited comprising of 662 (52%) controls and 610 (48%) cases. Risk factors associated with upper respiratory tract infections were school attendance to the level of Senior High and tertiary education, and being a health worker. Out of 322 subset of cases interviewed, 212 (66%) covered their nose with handkerchiefs when they sneezed, 52 (16%) covered with their hands upon xix sneezing and 79 (25%) sneezed in the open. Self-administered drugs such as herbs (2%), analgesics (25%) and antibiotics (16%) were used to manage upper respiratory tract infections. Out of the 1,272 subjects recruited, nasal swabs were taken from 1,213. Of the 1,213, 150 (12.4%) subjects were positive for one or more viruses. Of these, single virus detections occurred in 146 subjects (12.0%) and multiple detections occurred in 4 (0.3%). Compared with control subjects, infections with HCoV-229E (OR = 5.15, 95% CI = 2.24 – 11.78), HCoV-OC43 (OR = 6.16, 95% CI = 1.77 – 21.65) and combine HCoVs (OR = 2.36, 95% CI = 1.5 = 3.72) were associated with upper respiratory tract infections. Significant median virus concentration difference was observed for only HCoV- NL63 (cases: 2.41 x 106 copies per PCR reaction; IQR = 1.96 x 104 - 2.3 x 106 vrs controls: 1876.5 copies per PCR reaction; IQR =387.2 – 8.6 x 104, P=0.003) and the clinically relevant cut-off viral concentration was determined to be 7,510 copies per PCR reaction. HCoVs were found to be seasonally dependent with high proportions identified in the harmattan season (54/215, 25.1%) compared to the wet (80/516, 15.5%) seasons. The most frequent viruses detected in the harmattan and wet seasons were HCoV-229E and HCoV-NL63 respectively. HCoV-OC43 and HCoV-HKU1 were almost distributed equally throughout the year. Sequencing of the partial spike region was successful for 53 out of 146 samples (36.3%). Of the 53, 12 (22.6%) were HCoV-OC43, 14 (26.4%) were HCoV-NL63, 24 (45.3%) were HCoV-229E and 3 (5.7%) were HCoV-HKU1. A comparison of the obtained sequences resulted in no differences to sequences already published in GenBank. xx This study has identified risk factors of URTI and also demonstrated that HCoVs could play significant role in causing upper respiratory tract infections among adults and older children in rural arrears of Ghana. This information could be useful to policy makers, public health practitioners and other stakeholders in Ghana.
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    Bioactive constituents from the Ghanaian medicinal plant Chlorophora regia and its root endophytic fungus JK10.
    ( AUGUST, 2016 ) Kyekyeku, James Oppong
    The extracts of the Ghanaian medicinal plant Chlorophora regia A. Chev (Moraceae) has been used for the treatment of various ailments in traditional medicine including burns, wounds, snake bite, wasp bite. A search through the literature, however, revealed there were no available data on the phytochemical composition of the plant. Therefore, the main objective of this study was to isolate, characterize and evaluate some biological activities of secondary metabolites from the stem bark of the plant and further investigate the endophytic community harbored in the inner tissues of the plant. Extensive phytochemical investigation of the stem bark resulted in the isolation and characterization of four new metabolites, regiafuran A–C and 6–prenylated–3,5,7,4ʹ–tetrahydroxy–2ʹ–methoxyflavonol in addition to fifteen known compounds. The isolated compounds were tested for their free radical scavenging activities. Regiafuran A–B, mulberrofuran Y, kuwanol E and 5,7,4ʹ–trihydroxy–2ʹ–methoxyflavanone demonstrated significant free radical scavenging activities with IC50 values of 1.9 μg/ml, 2.4 μg/ml, 2.2 μg/ml, 2.1 μg/ml and 1.8 μg/ml respectively. An unidentified endophytic fungus, JK10, was isolated from the root of C. regia. Twelve compounds including seven new 7–desmethyl derivatives of fusarin C and five known compounds were isolated from the endophytic fungus, JK10. The planar and relative configurations of the new compounds were elucidated by combined spectroscopic analyses of their UV, IR, HRESI–MSn, ECD and NMR data. The absolute configuration of solaniol was established for the first time by X–ray diffraction analysis of a single crystal. The antibacterial activities of the isolated compounds were evaluated. 7–desmethyl fusarin C–22/23 and 7–desmethyl fusarin C–25 exhibited remarkable activity at concentrations of 10.0 μg/mL against the soil bacterium Acinetobacter sp. BD4 comparable to the reference standard streptomycin. All the tested compounds demonstrated activity against the environmental strain of E. coli. Based on the results it could be proposed that the endophytic fungus, whose origin is from the roots, contributes a chemical–mediated defensive mechanism to the host plant against iii invading specific soil and environmental bacterial pathogens. This may confirm the existence of a unique cost–benefit endophyte–plant association. The spatial distribution of three kaurane diterpenes, xylopic acid, ent–kaur–16–en–19–oic acid and 15–oxo–ent–kaur–16–en–19–oic acid, in the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) were visualized by MALDI–HRMS imaging techniques. The distribution of the compounds was predominantly in the pericarp region of the fruit with non-detectable levels in the seed.
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    Pathophysiological indicators of pregnancy-induced hypertension in Ghanaian women
    (OCTOBER, 2016) Pobee, Richard Orleans Samuel
    Pregnancy-Induced Hypertension (PIH) is the abnormal increase in blood pressure (BP) of pregnant women who do not have pre-gestational chronic hypertension or renal diseases or proteinuria before the final half of gestation, but present with high BP and proteinuria in the final half of pregnancy which normalizes postnatally. PIH ranges from high BP without proteinuria, through high BP with proteinuria and multiorgan dysfunction to high BP with proteinuria, multiorgan dysfunction with seizures. PIH is usually diagnosed when BP rises above 140/90 mmHg.Ten percent (10%) of complications of pregnancy are as a result of hypertension and this accounts for the increased risk of adverse foetal, neonatal and maternal outcomes. This necessitates early diagnosis to avert these fatal outcomes. This study sought to find the biomarkers that would assist in the early diagnosis of pregnancy-induced hypertension in Ghanaian women. To achieve this, the following specific objectives were set: The determination of the concentrations of biomarkers of systemic inflammation, endothelial injury and systemic oxidative stress in PIH and controls;the evaluation of the relationship of hepcidin levels with iron regulation and systemic inflammation in PIH and controls; the determination of the concentrations of Soluble urokinase plasminogen activator receptor, Interlukin-6 and C-reactive protein in PIH and healthy pregnancy were studied in order to evaluate the best marker for the characterization of the inflammatory status during pregnancy and the determination of serum lipids levels and its correlation with C-reactive protein, Interlukin-6, 8-iso-prostagladin F2α and fibronectin in PIH.This research took place at the antenatal clinics of Ridge Regional Hospital, Accra, La General Hospital, Accra and Lister Hospital and Fertility Centre, Accra, Ghana from June, 2014 to July, 2015. This study involved forty-eight (48) women with gestational hypertension, fifty-seven (57) with preeclampsia, eighteen (18) with eclampsia and forty-five (45) normotensive pregnant women (controls) in at least their second trimester of gestation. All participants were within 18yrs to 40 yrs of age and with singleton pregnancy based on ultra-sound results. After ethical approval and informed consent had been obtained, blood (ie. EDTA whole blood, heparinized-plasma and serum) and urine samples of participants were obtained for biochemical, haematological and urine analysis. There were significantly higher levels of markers of systemic inflammation : IL-6 (19.60±10.32pg/ml vs 13.85±2.80pg/ml, p=0.04), CRP (3.31±2.81ng/L vs 0.98±0.05ng/L, p<0.0001), suPAR (2.04±0.66pg/ml vs 1.57±0.56pg/ml, p=0.03), endothelial injury: FN (21.87±11.95ng/ml vs 13.85±2.80ng/ml, p=0.01) and systemic oxidative stress: 8-iso-PGF2α (43.03±27.29pg/ml vs 5.55±5.33pg/ml, p=0.03) in PIH women compared to controls respectively.The results of the level of hepcidin in relation to iron homeostasis and systemic inflammation among the participants indicates significant increase in the levels of hepcidin (7.72±1.07 vs 6.46±0.82, p<0.0001), ferritin (183.0±156.2 vs 37.1±30.5, p<0.0001), IL-6 (19.60±10.32 vs 13.85±2.80, p=0.04) and CRP (3.31±2.81 vs 0.98±0.05, p<0.0001) in the PIH women compared to the normotensive ones respectively. Whereas there was significantly lower iron (85±39.09 vs 138±30.33, p<0.0001) and TIBC (308.9±95.29 vs 360±68.0, p=0.0013) levels in the PIH compared to normotensive women respectively.
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    Effects of a computerised clinical decision support system and performance-based incentives on maternal healthcare providers in Northern Ghana.
    (NOVEMBER, 2016) Aninanya, Gifty Apiung
    Computerized clinical decision support system (CDSS) and performance-based incentive (PBI) have a potential to contribute to improving motivation and performance of healthcare providers in developing countries. However, there is currently a dearth of rigorous evidence on the effectiveness of these strategies in improving maternal health care in developing countries including Ghana. This study sought to evaluate the impact of CDSS and PBI on motivation and performance of healthcare providers in northern Ghana. The study employed a quasi-experimental design with an explanatory mixed-methods model to assess the effects of the social and technological interventions on motivation and performance of providers. The quantitative research component consisted of a controlled pre- and post-test design, which allowed the quantitative measure of motivation and performance of healthcare providers. To obtain explanatory descriptions of the effects of the interventions on motivation and performance of providers, 66 in-depth interviews (IDIs) with midwives, nurses and their supervisors were conducted in twelve health facilities in the Kassena-Nankana and Builsa districts at intervention endline. A difference-in-difference logistic regression analysis controlling for potential covariates compared variables across intervention and comparison facilities at baseline and endline. Nvivo version 10 was used to analyse qualitative data. CDSS and PBIs were associated with improvements in maternal healthcare providers’ motivation and performance in the intervention facilities compared with the comparison arm. At endline, constructs of motivation that improved were: job satisfaction, intrinsic motivation, organizational commitment, timeliness and attendance. Furthermore, CDSS vi and PBIs strategies improved providers’ management of antenatal and delivery clients. There was statistically significant increase in the proportion of anti-tetanus vaccinations, Human Imuno Deficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) testing compliance and hemoglobin examined during antenatal care consultations in the intervention sites. Additionally, perceptions of antenatal clients on providers’ technical performance, client-provider interaction and provider availability in the intervention arm at endline improved significantly. Furthermore, delivery clients’ perception of providers’ performance in terms of technical performance, healthcare provider availability and general satisfaction with delivery services significantly improved. Endline qualitative findings revealed that CDSS and PBIs interventions have enhanced providers’ knowledge and adherence to World Health Organisation (WHO) reproductive health treatment guidelines. CDSS prompted them on actions such as diagnosis, prescriptions, checking blood pressures of clients and use of partograph to monitor progress of labour. While the introduction of CDSS and PBIs interventions show positive improvement in healthcare delivery within these selected institutions, there is the need to provide evidence on sustainance mechanisms for large-scale implementation of this intervention. Therefore, future studies on the long-term effects of these interventions are required employing larger samples of different healthcare worker populations, including those of midwives, nurses as well as Medical Doctors.
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    Clinical, Metabolic and Immunological Characteristics of Ghanaian Patients with Diabetes Mellitus
    (Febuary, 2009) Titty, Felix-Val Kwaku
    Objectives: This study investigated the clinical characteristics of Ghanaian diabetic patients; prevalence of metabolic syndrome and its components in Ghanaian diabetic patients; and determinants of the metabolic syndrome diagnosed from Ghanaian diabetic patients. Further, association of metabolic syndrome with poor glycaemic control and occurrence and features of autoimmune diabetes and autoantibody-negative type 2 diabetes in Ghanaian diabetic patients were investigated. Research design and methods: This research was a prospective study covering a period of four years, from August 2004 to June 2008. The study was carried out at the Komfo Anokye Teaching Hospital and the Kwame Nkrumah University of Science and Technology, both in Kumasi on two study populations. For the first population, Ghanaian diabetic patients diagnosed by the WHO criteria were consecutively selected. The sample size was 456. Controls included 120 age- and sex-matched nondiabetic controls. For the second population, recently diagnosed (<1 year) Ghanaian diabetic patients were consecutively selected. The sample size was 120. Controls included 60 age- and sex-matched healthy nondiabetic controls. Socio-demographic and clinical characteristics of subjects were investigated using a standardized questionnaire. Blood pressure and anthropometric measurements (height, weight, waist circumference) of subjects were measured using mercury sphygmomanometer, physician standiometer and scale and a plastic tape respectively. Blood and serum samples from subjects were analysed for relevant biochemical indices using enzymatic methods and ATAC® 8000 Random Access Chemistry Analyzer and its reagent kits. Metabolic syndrome was diagnosed using the National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) criteria. HbA1C was analysed using an inhibition of latex agglutination test, DCA® 2000+ analyzer (Bayer model, USA) and its reagent kits. Insulin and autoantibodies were tested using an Enzyme linked immunosorbent assay (ELISA) technique, DRG International Inc. USA EIA reagent kits, ELISA reader (Tipo model, Italy) and washer (Murex, Great Britain). iii Results: The sex distribution of the Ghanaian diabetic patients of the first study population was 30.9% males and 69.1% females. Insulin-requiring diabetics were 24.6% and non-insulin requiring diabetics 75.4%. The mean age was 55.8 ± 12.3 years; 90.6% were ≥40 years of age. The mean age of onset was 49.7 ± 12.5 years; 89.5% had an age of onset ≥35 years or late onset diabetes. The mean diabetes duration was 6.0 ± 5.4 years and 60.5% had diabetes duration 1 – 9 years. Mean preprandial (fasting) glucose level was 9.4 ± 4.5 mmol/L with 62.1% having high preprandial glucose >7.2 mmol/L. The mean BMI was 25.1 ± 4.8 kg/m2; 44.5% were overweight and obese or had a BMI ≥25.0 kg/m2. The mean waist circumference was 87.0 ± 13.7 cm; 43.6% had central obesity. Diabetics with confirmed hypertension were 40.1%; hypertensives with inadequate blood pressure control ≥130/80 mmHg were 91.3%. The prevalence of the metabolic syndrome was 55.9% in the first population; prevalence in females (66.0%) was higher than males (33.3%). Low HDL cholesterol was the commonest component (47.4%) of the metabolic syndrome in the first population, followed by hypertension (46.9%). In females central obesity (57.1%) was the commonest component, followed by low HDL cholesterol (53.0%); in males, hypertension (39.7%) was the commonest component, followed by hypertriglyceridaemia (36.2%). Central obesity, hypertension and low HDL cholesterol prevalence was higher in females than males, while hypertriglyceridaemia prevalence was comparable in females and males. Female diabetics individually carried more metabolic syndrome factors than males. The major determinant of the metabolic syndrome diagnosed from Ghanaian diabetics was central obesity (69.4%) followed by hypertension (67.5%). In females the major determinant was central obesity (76.9%), followed by hypertension (67.3%), while in males the major determinant was hypertriglyceridaemia (74.5%), followed by hypertension (68.1%). The most frequent combination of different components was hyperglycaemia, central obesity and hypertension (46.3%). For the second population, the prevalence of the metabolic syndrome in patients with poor glycaemic control was 50.0% and patients with good glycaemic control 33.3%. The prevalence of autoimmunty in the insulin-requiring recently diagnosed diabetic patients was 35.3% and in the non-insulin requiring patients 16.5%. The prevalence of LADA in the non-insulin requiring diabetic patients was iv 13.5%. The prevalence of LADA and autoimmune type 1 diabetes in the second population were 11.7% and 7.5% respectively, giving total autoimmune diabetes prevalence of 19.2%; single autoantibody positivity was 77.3% and multiple autoantibody positivity 22.7% in the autoimmune diabetic patients. Most of the clinical and metabolic parameters of autoimmune diabetes and type 2 diabetes did not differ. The exceptions were hypertension and central obesity which were more likely in type 2 diabetes than autoimmune diabetes and HbA1C which was higher in autoimmune diabetes than type 2 diabetes. Conclusion: There were more Ghanaian females with diabetes mellitus than males and more non-insulin requiring than insulin requiring patients. Majority of the diabetic patients were 40 years and above and had late onset diabetes. More than half had diabetes disease duration of 1-9 years and carry clinical modifiable risk factors for microvascular and macrovascular disease. Less than half of the subjects had clinical modifiable risk factors for cardiovascular disease. The metabolic syndrome was frequent in Ghanaian diabetic patients, especially females, and was present at an prevalence slightly less than that in developed countries. Future prevention and control strategies should not overlook the importance of metabolic disease risk factors in Ghana. Interventions that address obesity and hypertension in females and hypertriglyceridaemia and hypertension in males and reduce waist circumference, blood pressure and hypertriglyceridaemia, may reduce the prevalence of the metabolic syndrome, and hence cardiovascular disease in Ghanaian diabetic patients. The major determinants of the metabolic syndrome were not necessarily the commonest metabolic syndrome components of the population under consideration. The metabolic syndrome was associated with poor glycaemic control. However, metabolic syndrome and poor glycaemic control are independent risk factors for cardiovascular disease. Autoimmune diabetes, including autoimmune type 1 diabetes and LADA, occurs in recently diagnosed Ghanaian diabetic patients. Both ICA and GAD autoantibody tests are required to identify autoimmune diabetes, and distinguish it from autoantibody-negative type 2 diabetes. Clinical and metabolic markers cannot be used for this purpose.