Centre for Tropical, Clinical Pharmacology & Therapeutics
Permanent URI for this collectionhttp://197.255.125.131:4000/handle/123456789/25482
Browse
91 results
Search Results
Item Considerations for unblinding individual study participants during vaccine trials(Vaccine, 2023) Halsey, H.; Evans, S.; Dodoo, A.; et al.Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or ‘‘pseudo unblinding,” in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.Item Hypertension and associated factors among patients attending HIV clinic at Korle-Bu Teaching Hospital(Ghana Medical Journal, 2023) Nartey, E.t; Tetteh, R.A.; Anto, F.; Sarfo, B.; Kudzi, W.; Adanu, R.M.Objectives: This study determined the prevalence of hypertension and its associated factors among patients attending the HIV clinic at the Korle-Bu Teaching Hospital (KBTH). Design: A hospital-based cross-sectional study was conducted at KBTH. The prevalence of hypertension was estimated among study participants, and socio-demographic, lifestyle, anthropometric, metabolic and HIV/ART-related factors associated with hypertension were determined by logistic regression modelling. Setting: Study participants were recruited from the HIV clinic at the KBTH. Participants: A total of 311 Persons Living with HIV were recruited as study participants Interventions: Simple random sampling technique was used to recruit study participants. A questionnaire adapted from the WHO STEPwise approach to chronic disease risk-factor surveillance was used to collect study participants' data. Results: The prevalence of hypertension was 36.7%, and the factors associated with hypertension were increasing age, positive family history of hypertension, minimal exercising, current BMI ≥25.0 kg/m2 , total cholesterol level ≥5.17 mmol/L, exposure to anti-retroviral therapy (ART) and increasing duration of ART exposure. Conclusions: This study shows a high prevalence of hypertension among patients attending the HIV clinic at KBTH, associated with exposure to ART and increasing duration of this exposure. Blood pressure monitoring should move from routine to a more purposeful screening of patients for hypertension. Patients with the identified risk factors should be encouraged to have regular blood pressure measurements at home and not only when they visit the HIV clinic.Item Treatment of COVID-19 with Chloroquine: Implication for Malaria Chemotherapy Using ACTs in Disease Endemic Countries(Oxford University Press, 2021) Quashie, N.B.; Duah-Quashie, N.O.Based on reports of parasite resistance and on World Health Organization recommendation, chloroquine was replaced with the artemisinin-based combination therapies (ACTs) as the first choice of drugs for the treatment of uncomplicated malaria. Disuse of chloroquine led to restoration of drug-sensitive para site to some extent in certain countries. Ever since chloroquine and hydroxychloroquine were touted as potential treatment for coronavirus disease 2019 (COVID-19), there has been a dramatic surge in de mand for the drugs. Even in areas where chloroquine is proscribed, there has been an unexpected in crease in demand and supply of the drug. This situation is quite worrying as the indiscriminate use of chloroquine may produce drug-resistant parasites which may impact negatively on the efficacy of amo diaquine due to cross-resistance. Amodiaquine is a partner drug in one of the ACTs and in some of the drugs used for intermittent preventive treatment. We herein discuss the consequences of the escalated use of chloroquine in the management of COVID-19 on chemotherapy or chemoprevention of malaria and offer an advice. We speculate that parasite strains resistant to chloroquine will escalate due to the increased and indiscriminate use of the drug and consequently lead to cross-resistance with amodiaquine which is present in some drug schemes aforementioned. Under the circumstance, the anticipated hope of reverting to the use of the ‘resurrected chloroquine’ to manage malaria in future is likely to diminish. The use of chloroquine and its derivatives for the management of COVID-19 should be controlled.Item High Prevalence of Molecular Markers of Plasmodium falciparum Resistance to Sulphadoxine–Pyrimethamine in Parts of Ghana: A Threat to ITPTp-SP?(Oxford University Press, 2021) Afutu, L.L.; Boampong, J.N.; Quashie, N.B.Malaria in pregnancy is a huge public health problem as it is the cause of maternal anaemia, still birth, premature delivery, low birth weight among others. To tackle this problem, WHO recom mended the administration, during pregnancy, of intermittent preventive treatment with sulphadox ine–pyrimethamine (IPTp-SP). The introduction of this policy is likely to create SP drug pressure which may lead to the emergence of parasite strains resistant to the drug. This study investigated the prevalence of the molecular markers of SP resistance as pointers to potential failure of IPTp-SP among pregnant women attending antenatal clinic, women at the point of baby delivery and out patients department (OPD) attendees. The study was conducted in health facilities located in parts of Ghana. Prevalence of mutations in dhfr and dhps genes of Plasmodium falciparum was determined using the method described by Duraisingh et al. The outcome of the study indicated the presence of high prevalence of strains of P.falciparum with the resistant alleles of the dhfr or dhps genes in the three categories of participants. There was a high prevalence of triple mutations (IRN) in the dhfr gene of P.falciparum isolates: 71.4% in peripheral blood of antenatal attendees; 74.1% in placenta cord blood of delivering mothers and 71.1% in OPD attendees. Quintuple mutations were only found in 2 (0.5%) isolates from OPD attendees. This observation might have occurred due to the increased use of SP for IPTp among others. There is the need for an interventional measure in order to protect pregnant women and their unborn children.Item Knowledge of Pharmacogenetics among Healthcare Professionals and Faculty Members of Health Training Institutions in Ghana(Ghana Medical Journal, 2015-03) Kudzi, W.; Addy, B.S.; Dzudzor, B.Background: Pharmacogenetics has a potential for optimizing drug response and identifying risk of toxicity for patients. Pharmacogenetics knowledge of healthcare professionals and the unmet need for pharmacogenetics education in health training institutions are some of the challenges of integrating pharmacogenetics into routine medical practice. Aim: To assess pharmacogenetics knowledge among healthcare professionals and faculty members of health training institutions in Ghana. Method: Semi-structured questionnaires were used to interview healthcare professionals from selected public and private hospitals. Faculty members from health training institutions were also interviewed. Results: The respondents were Medical doctors 42 (46.7%), Pharmacists 29 (32.2%) and Nurses 19 (21.1%). Healthcare professionals rated their knowledge of Pharmacogenetics as Excellent 5 (5.6%), Very Good 10 (11.2%), Good 53 (60%) and Poor 19 (21.4%). Thirty-two faculty members from health training institutions were also interviewed. Faculty members rated their knowledge of pharmacogenetics as Excellent 2 (6.3%), Very Good 3 (9.4%), Good 9 (28.1%), Fair 12 (37.5%) and Poor 6 (18.8%). Thirty seven percent (12) of these faculty members said pharmacogenetics was not part of their institutions’ curriculum, 7 (22%) did not know if pharmacogenetics was part of their curriculum and only 13 (40.6%) said it was part of their curriculum. Conclusion: Few healthcare professionals and faculty members of training institutions are aware of the discipline of pharmacogenetics. There is the need for continuous professional education on pharmacogenetics and development of competency standards for all healthcare professionals in Ghana.Item Willingness to pay for small solar powered bed net fans: Results of a Becker-DeGroot-Marschak auction in Ghana(Malaria Journal, 2017) Yukich, J.O.; Briët, O.J.T.; Ahorlu, C.K.; Nardini, P.; Keating, J.Background and methods: Long-lasting insecticidal nets (LLINs) are one of the main interventions recommended by the World Health Organization for malaria vector control. LLINs are ineffective if they are not being used. Subsequent to the completion of a cluster randomized cross over trial conducted in rural Greater Accra where participants were provided with the 'Bokoo System' - a set of solar powered net fan and light consoles with a solar panel and battery - or alternative household water filters, all trial participants were invited to participate in a Becker-DeGroot-Marschak auction to determine the mean willingness to pay (WTP) for the fan and light consoles and to estimate the demand curve for the units. Results, discussion and conclusions: Results demonstraed a mean WTP of approximately 55 Cedis (~13 USD). Demand results suggested that at a price which would support full manufacturing cost recovery, a majority of households in the area would be willing to purchase at least one such unit. © 2017 The Author(s).Item Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing(Antimicrobial Agents and Chemotherapy, 2018-09) Ali, A.M.; Penny, M.A.; Smith, T.A.; Workman, L.; Sasi, P.; Adjei, G.O.; Aweeka, F.; Kiechel, J.R.; Jullien, V.; Rijken, M.J.; McGready, R.; Mwesigwa, J.et.al.Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and >62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation.Item Population Pharmacokinetic Estimates Suggest Elevated Clearance and Distribution Volume of Desethylamodiaquine in Paediatric Sickle Cell Disease Patients Treated with Artesunate-Amodiaquine(Current Therapeutic Research - Clinical and Experimental, 2019-01) Adjei, G.O.; Amponsah, S.K.; Goka, B.Q.; Enweronu-Laryea, C.; Renner, L.; Sulley, A.M.; Alifrangis, M.; Kurtzhals, J.A.L.Background There is limited information on the safety or efficacy of currently recommended antimalarial drugs in patients with sickle cell disease (SCD), a population predisposed to worse outcomes if affected by acute malaria. Artesunate-amodiaquine (ASAQ) is the first-line treatment for uncomplicated malaria (UM) in many malaria-endemic countries and is also used for treatment of UM in SCD patients. There is, however, no information to date, on the pharmacokinetics (PK) of amodiaquine or artesunate or the metabolites of these drugs in SCD patients. Objectives This study sought to determine the PK of desethylamodiaquine (DEAQ), the main active metabolite of amodiaquine, among paediatric SCD patients with UM treated with artesunate-amodiaquine (ASAQ). Methods Plasma concentration-time data (median DEAQ levels) of SCD children (n = 16) was initially compared with those of concurrently recruited non-SCD paediatric patients with acute UM (n = 13). A population PK modelling approach was then used to analyze plasma DEAQ concentrations obtained between 64 and 169 hours after oral administration of ASAQ in paediatric SCD patients with acute UM (n = 16). To improve PK modeling, DEAQ concentration-time data (n = 21) from SCD was merged with DEAQ concentration-time data (n = 169) of a historical paediatric population treated with ASAQ (n = 103) from the same study setting. Results The median DEAQ concentrations on days 3 and 7 were comparatively lower in the SCD patients compared to the non-SCD patients. A two-compartment model best described the plasma DEAQ concentration-time data of the merged data (current SCD data and historical data). The estimated population clearance of DEAQ was higher in the SCD patients (67 L/h, 21% relative standard error (RSE) compared with the non-SCD population (15.5 L/h, 32% RSE). The central volume of distribution was larger in the SCD patients compared with the non-SCD patients (4400 L, 43% RSE vs. 368 L, 34% RSE). Conclusions The data shows a tendency towards lower DEAQ concentration in SCD patients and the exploratory population PK estimates suggest altered DEAQ disposition in SCD patients with acute UM. These findings, which if confirmed, may reflect pathophysiological changes associated with SCD on DEAQ disposition, have implications for therapeutic response to amodiaquine in SCD patients. The limited number of recruited SCD patients and sparse sampling approach however, limits extrapolation of the data, and calls for further studies in a larger population.Item Factors contributing to the development of anaemia in Plasmodium falciparum malaria: What about drug-resistant parasites?(Journal of Tropical Pediatrics, 2006-09) Quashie, N.B.; Akanmori, B.D.; Ofori-Adjei, D.; Goka, B.Q.; Kurtzhals, J.A.L.A major manifestation of complicated malaria especially among children is severe anaemia, the pathogenesis of which is not well understood. Among other factors, suppression of the bone marrow's response to erythropoietin, which is rapidly reversed after successful treatment of the malaria, has been implicated in its pathogenesis. Since resolution of malaria restores erythropoiesis, we hypothesized that drug-resistant strains of Plasmodium falciparum would increase the risk of severe anaemia developing from initially uncomplicated malaria. Using both in vivo and in vitro drug-sensitivity tests we compared the prevalence of drug-resistant malaria between severe malarial anaemia (SA) and non-anaemic malaria (NAM) patients. Assessment of treatment outcome using the WHO in vivo criteria showed no significant difference in parasite resistance between the two groups. The mean parasite clearance time was also comparable. Treatment failures of about 14 per cent and 12 percent were observed between SA and NAM patients respectively. The in vitro drug susceptibility test showed overall mean IC 50 values of 0.41×10-6 mol/l and 0.32×10-6 mol/l blood for SA and NAM groups respectively. Geometric mean pre-treatment blood levels of chloroquine did not differ much between the two groups. Findings from this study could not therefore implicate drug-resistant parasites in the pathogenesis of severe malarial anaemia. © 2006 Oxford University Press.Item The selection and use of essential medicines(World Health Organization - Technical Report Series, 2003) De Buschiazzo, P.M.; Helali, A.; Laing, R.; Laporte, J.R.; Ofori-Adjei, D.et.alThis report presents the recommendations of the WHO Expert Committee responsible for updating the WHO Model List of Essential Medicines. The first part contains a summary of the Committee's considerations and justifications for additions and changes to the Model List, including its recommendations. Annexes to the main report include the revised version of the WHO Model List of Essential Medicines (the 15th) and a list of all items on the Model List sorted according to their 5-level Anatomical Therapeutic Chemical (ATC) classification codes. Other annexes cover the proposed procedure for updating and disseminating the WHO Model List of Essential Medicines, and the revised procedure for updating the content of the Interagency Emergency Health Kit.