Blood transfusion is an important element of health care which saves millions of lives each year but has life-threatening risks. In low-resource countries in Africa, a significant proportion of donated blood remains unsafe if blood units are not screened appropriately for all major transfusion-transmitted infections (TTIs). Syphilis, one of the TTIs, remains a public health problem in developing countries including Ghana if testing is not performed in a well-controlled manner. Thus, there is the possibility of infecting recipients with syphilis which may have long-term sequelae. The study investigated syphilis testing practices in transfusion facilities in Ghana, test cross-reactions between various techniques, and the potential infectivity of 'true' positive blood samples, in the Ghanaian blood donor population. The goal of the research was to guide transfusion policies and practices, and advance transfusion medicine research in Ghana by improving syphilis testing. Data collection was in three parts based on five specific objectives. The first part was a survey, carried out in 149 transfusion facilities in Ghana and found a syphilis seroprevalence of 3.7% for blood donors. The laboratories used predominantly non-approved test kits at variable costs. In the second part, using rapid diagnostic test, Fortress RDT, and rapid plasma reagin (RPR), syphilis testing was performed on 16,016 prospective blood donors who came to donate blood for the Komfo Anokye Teaching Hospital (KATH) blood bank. Positive predictive values of the RDT and RPR were found to be 90.9% and 97.1% respectively. The third part was a quality assessment to determine the performance of the frequently used syphilis test in Ghana, the ABON RDT, in four selected facilities. Sensitivity and specificity were found to be 99.2% and 82.5% respectively. Finally, we determined the relative proportions of confirmed syphilis antibody positive donors with clinical histories attributable to yaws rather than syphilis. Our data from the surveys showed a considerable mismatch between recommendations and practice of syphilis testing in Ghana, with potential serious consequences for blood safety and public health. This study found that the combination of syphilis RDT and RPR which have a relatively good PPV, as a novel strategy, could contribute to improving blood safety when screening blood donors for syphilis. It was confirmed that quality systems for syphilis testing are generally weak in Ghana, but are important for any laboratory or testing site to ensure accuracy, consistency, and reliability of test results which directly contributes to the safety of blood supply. Finally, the question, whether some of the syphilis positivity in blood donors could be attributable to yaws rather than syphilis remained speculative.

Background Asthma is a public health problem in Latin America, where asthmatic children are mainly treated at emergency rooms during acute attacks. These attacks result in loss of lung function and quality of life for the asthmatic child and family, risk of death and high direct and indirect economic costs. In order to improve paediatric asthma management in Esmeraldas, Ecuador, we aimed to identify predictors of recurrent asthma attacks requiring emergency care and to explore the caregivers’ (CGs) and health care workers’ (HCWs) perceptions of barriers and facilitators to asthma health and home care access. Methods First, a systematic review and meta-analysis of published studies analysing predictors for emergency department (ED) re-attendance or hospital readmission for acute asthma in children was performed. Second, a prospective cohort study of children treated for an asthma attack at an emergency room in Esmeraldas, Ecuador, was undertaken to define the characteristics of these children, determine the rate of ED re-attendance for acute asthma and identify the predictors for this to occur. Third, a qualitative study to explore acute asthma significance and perceived barriers and facilitators for health and home care access from the asthmatic children’s CGs’ and HCWs’ perspective was performed. Results In both the meta-analysis and prospective cohort study, children of a younger age and a history of severe asthma attacks during the previous year were at a greater risk of ED re-attendance for acute asthma. Forty six percent of the children recruited during the prospective cohort suffered a subsequent asthma attack requiring emergency care in the following 6 months. Other identified predictors of ED re-attendance for acute asthma were: existing asthma diagnosis (AOR: 2.17, 95% CI: 1.19-3.94; AHR: 1.66, 95% CI: 1.15-2.39); food triggers (AOR: 1.99, 95% CI: 1.11-3.55); existing eczema diagnosis (AOR: 4.22, 95% CI 1.02-17.54); and urban residence as protective (AHR: 0.69, 95% CI: 0.50-0.95). Twelve HCWs and 20 CGs participated in the in-depth interviews and focus group discussions, expressing a differing significance of asthma attacks. This difference was also observed between experienced and inexperienced HCWs. Multiple barriers and several facilitators were identified by HCWs and CGs that affect health and home care access for asthmatic children. When shown the predictors of ED-reattendance for acute asthma combined in a risk-assessment tool, both HCWs and CGs reported finding the tool easy to use and understand, as well as a useful aid in the decision-making process concerning asthma treatment and follow-up. Conclusion A combination of several question-based predictors may result in an effective and simple risk-assessment tool to be used at the ED to identify asthmatic children at a higher risk of recurrent severe asthma attacks. Increasing CGs’ and HCWs’ asthma knowledge as well as HCWs’ communication skills, to establish a patient centred approach with a shared decision-making process could mean a difference in the quality of the asthma care in this setting. The use of the described recurrent risk assessment tool could prove useful in this process, as reported by the participants in this study.

Devolution in Kenya was politically driven, motivated by the desire to share power and resources across regions, so as to remedy historical inequities. This led to transfer of planning, management and budgeting responsibilities for a range of services, including health, from central government to 47 new sub-national governments (known as counties), starting in 2013. This transition was driven by increasing frustration with inefficiencies and inequities associated with the former centralised government. Objectives for devolution are to strengthen democracy and accountability, increase community participation, improve efficiency and reduce inequities. However, global experiences have shown that transfer of powers does not always lead to achievement of these objectives. Rather, potential risks include that inefficiencies will multiply, inequities will widen and corruption will become more widespread. Health has been the most controversial of all devolved services in Kenya, contributing to recurring health worker strikes. Respondents described that ideally, priorities should be set following a series of consultations between local decision-making actors, guided by local evidence and community-generated priorities, bounded by available resources, using cost-effectiveness and equity principles to identify context-appropriate interventions which advance universal health coverage. This thesis which, to the best of our knowledge, is the first study of its kind, aims to explore priority-setting for community health and equity across counties and multiple health systems levels in Kenya post-devolution. It uses mixed qualitative approaches in ten counties including interviews, focus group discussions and participatory photography research conducted two to three years after devolution took place. It includes respondents from national to community level to analyse county health priority-setting processes, power dynamics and implications for health equity and community health services. This study shows that many respondents across health systems levels identify equity as a guiding principle, with devolution bringing positive ramifications for previously neglected counties, reducing inequities between counties. County decision-makers, who often hold greatest power compared with health workers and community members, perceive building health facilities as the most appropriate way to achieve health equity. Community members who have a more holistic understanding are not yet sufficiently empowered to understand the benefits and limitations of choices available to them or to reflect this within the priorities they identify. There is wide variation between counties, with emerging examples of stronger, more equitable health priority-setting, with inclusion of an illustrative case study. Overwhelmingly the findings from this study relate to power dynamics. We found a lack of clarity surrounding roles for decision-making actors, inadequate information, unclear criteria and processes for guiding priority-setting. Within the confusion created by the limited guidance and capacity, opportunistic actors have seized available power to manipulate priorities to align with personal objectives, such as political re-election. The resulting increase in complexity blurs lines of accountability creating a situation that makes progress beyond a single elected term challenging. This has led to increased focus on tangible curative services, stifling opportunities for strengthening quality and community-based primary health care. Devolution has brought a period of colossal upheaval with changes in roles and power locus within the health system. Clearer guidance, capacity building, stronger community empowerment, involving marginalised groups in priority-setting processes and accountability mechanisms are needed if devolution’s objectives are to be realised.

Cerebral malaria is one of the complications of the broad clinical syndrome named 'severe malaria'. The pathogenesis of cerebral malaria is thought to be due to the ability of infected red blood cell (iRBC) to sequester in the blood microvasculature of vital organs. Sequestration, resulting from the interaction (often called cytoadherence) between parasite proteins expressed on the surface of iRBC such as PfEMP-1, and host endothelial cell adhesion molecules such as ICAM-1, CD36 and EPCR, can modulate the downstream effects of several biological processes in the endothelial cells such as EC activation, intracellular signalling, endothelial cell permeability and endothelial apoptosis. The aim of this thesis is to gain a better understanding of how the P. falciparum parasite can modulate the gene expression of the host endothelial cells response to cytoadherence using the RNA-seq technique. We used an in vitro co-culture model of IT4var14 strain with HBMEC in the presence of 10ng/ml TNF. RNA-seq analysis of HBMEC transcriptome following co-culture showed significant differential regulation of genes which defined gene ontologies such as 'immune system' at 2 hours, 'immune response', 'arachidonic acid', 'positive and negative apoptotic pathways' at 6 hours, and 'immune response' and 'cell cycle pathways' at 20 hours of co-incubation. However, another co-culture model using IT4var37 isolate with HBMEC in the presence of TNF found that exposure of HBMEC to iRBC expressed genes in brain EC often in opposite levels compared to the IT4var14 strain under the same condition. These findings emphasize the ability of different PfEMP-1 variants from the same genetic background (IT4) to modulate different gene expression in host cells, and also the potential ability of the malaria parasite to use PfEMP-1 var gene switching technique to protect itself from the host defensive system. We conducted further co-culture experiments to assess the ability of IT4var14 parasite to modulate the transcriptional levels of different endothelial cells (HDMEC and HBMEC) that differentially express ICAM-1 and CD36 receptors; we demonstrated that there are similarities and differences in gene expression between TNF-stimulated HDMEC and HBMEC exposed to IT4var14 strain, which might be due to ICAM-1 expression in both ECs but the lack of CD36 on HBMEC, leading to the transduction of different signalling pathways in HDMEC and HBMEC. The ability of TNF stimulation in modulating the expression of genes in HBMEC exposed to IT4var14 parasite isolate, and uninfected erythrocytes on endothelium has also been examined in this study. It was found that the TNF plays a role in mediating the gene expression in human brain EC incubated with IT4var14 strain and uninfected RBC, this might be due to stimulation of TNF to HBMEC to induce expression of ICAM-1. These results are presented and discussed in the thesis with an aim to better understanding of the CM syndrome and the potential to lead to the discovery and development of new therapies for cerebral malaria.

Infections caused by Streptococcus pneumoniae are a major cause of morbidity and mortality globally: S. pneumoniae is the primary bacterial agent of pneumonia, the leading cause of death in children under 5 years of age and a major cause of invasive disease in the elderly. Currently licensed vaccination strategies target pneumococcal capsular polysaccharides of which there are 94 known types (serotypes). Antibodies against vaccine serotypes effectively protect against invasive pneumococcal disease, but less so against mucosal infections including pneumonia. New vaccine development efforts aim to overcome these hurdles by targeting conserved and immunogenic pneumococcal proteins. The Pneumococcal Surface Protein A (PspA) is a leading candidate due to its expression across all known clinically relevant pneumococcal strains, and ability to protect against infection across serotypes. However, PspA sequence heterogeneity necessitates identification of cross-protective protein constructs. In this doctoral research project, I investigated pneumococcal protein-specific humoral and CD4+ T-lymphocyte immune responses to S. pneumoniae utilising the platform of Experimental Human Pneumococcal Carriage (EHPC). With an emphasis on PspA, immune responses to nasopharyngeal carriage - the prerequisite to pneumococcal disease and proxy for infection - were evaluated. I present the first evidence of CD4+ T-cell responses specific to an individual pneumococcal purified protein in the blood of healthy adults both before and after carriage. PspA-specific CD4+ T-cell responses to S. pneumoniae in bronchoalveolar lavage of healthy adults after EHPC were detected at lower levels than in blood, indicating non-immunodominance of PspA as a T-cell antigen in the lung, and compartmentalisation of immune response. I also describe from preliminary data, a potential role of PspA in protection from pneumococcal carriage re- acquisition, and optimise an assay for the identification of linear pneumococcal protein epitopes with potential for inclusion in a multiple epitope protein. Unveiling protein-specific immune responses to S.pneumoniae using controlled and reproducible EHPC, may aid in our understanding of immunity towards selection of protein vaccine candidates for protection against human pneumococcal infection and disease.

Limited research has been conducted in the area of blood transfusion policy in Africa. Prior to this study, it was unclear how many countries had a national blood policy in place, if they differed from other policies and if so to what extent. The aim of this study was, therefore, to better understand the Ghanaian national blood policy in an African context, identify its strengths and weaknesses and make appropriate policy recommendations. Following a literature review, WHO policy documents and African national policies were obtained via a web search in French and English, and by contacting representatives of national blood services. Policy documents were analysed qualitatively, and a list of commonly accepted policies was generated and compared with the evidence. Guidelines relating to blood donation, blood screening, blood grouping and component usage were common to more than half of the national blood policies reviewed. The common recommendations listed above were compared to current blood transfusion service practices at the Komfo Anokye Teaching Hospital, and areas of policy requiring further research, to improve policy implementation and better meet the local population's needs, were identified. As a result, the following sub-objectives were identified: 1) Determine the most common reasons for donor deferral 2) Determine what information donors are interested in receiving during pre and post-donation counselling to improve donor satisfaction and potentially increase blood supply; 3) Better understand component demand and usage and its influencing factors as well as determine whether current component production rates are appropriate; 4) Understand the patient experience in obtaining a blood transfusion and securing a replacement donor. Results from this study showed that blood donors were most commonly deferred due to a low haemoglobin level or hepatitis B infection. Blood donors seek more information regarding their health and whether their blood is found to have any infections. In addition, they would like to know more about the blood donation process ahead of time, such as what steps are involved, if donating will be painful and how long the entire process will take. Based on interviews with clinicians and data obtained from the blood bank, while component production was found to be increasing at KATH, there were still instances when demand of blood components exceeded supply. In spite of this, patients did not find it difficult to obtain blood for their transfusion, but some expressed interest in learning more about the risks and benefits of transfusion. Clinicians and policy makers should therefore work together to determine whether certain biological criteria currently implemented can safely be adjusted to be more inclusive and maximise the number of blood units donated. Future donor counselling sessions should aim to better communicate with donors the blood donation process and reassure blood donors of their health status. Component production should continue to increase at KATH given its demand, but only providing the blood bank has the resources to maintain production without affecting supply and patient outcomes. Finally, clinicians should increase their efforts to maintain good communication with their patients regarding transfusions, their risks and benefits, and ensure consent is always sought.

No description available.

Background: Globally, there has been increasing interest to demonstrate value-for-money of interventions using various approaches including social return on investment, which is a form of social cost-benefit analysis. This study pioneered its application in maternal and newborn health. Specifically, the methodology was used to assess the social impact and value-for-money of an emergency obstetric care training intervention for health care providers in Kenya. Methods: Qualitative methods and literature review were used to identify key stakeholders who were direct beneficiaries of the training; and map, evidence and financially value its outcomes. These qualitative findings were triangulated with quantitative evidence from existing literature and programmatic data, which helped to establish impact. Quantitative methods were also used to account for the financial investment (input) used to implement the intervention and output produced. Both qualitative and quantitative findings were incorporated into the impact map, to estimate the social return on investment ratio. Sensitivity analyses were done to test assumptions and the pay-back period estimated. Stakeholders who were not deemed direct beneficiaries were engaged to establish strengths, weaknesses, opportunities and threats of the intervention. Results: Multiple numbers of key stakeholders of the training were engaged via 28 focus group discussions, 18 interviews, and three paired interviews. Trained health care providers, women who received care from them and their newborns are training primary beneficiaries. From the thematic analysis, key emerging themes were that training led to positive outcomes including improved knowledge, skills and attitude with patients. However, there were concomitant negative outcomes including increased workload because of new patient expectation and frustration from inability to practise what was learnt. Women had positive opinions concerning the quality of care that they received. They expected positive outcomes including avoiding maternal and newborn morbidity and mortality. However, women affirmed that negative outcomes could occur, attributable to health care providers, themselves or simply due to chance. These outcomes experienced by both health care providers and women who received care from them have been mostly reported in the literature and evidenced from programme data. However, ‘increased workload’ is reported as increased care provision in the literature and ‘increased frustration due to inability to practise what had been learnt following training’ had not been directly linked to training previously. Based on programmatic data, total implementation costs was £1,079,383 for the 2,965 HCPs that were trained across 93 courses. The cost per trained HCP per day was £72.80. The total social impact for one year was valued at £13,747,173.78, with women benefitting the most from the intervention (73%). For beneficiaries, estimation of attribution, duration, and financial value of these outcomes by the beneficiaries was difficult and variable. Though beneficiaries provided insight for subsequent literature search for values. SROI ratio was calculated as £11.02: £1 and net SROI was £10.02: £1. The payback period for the investment was about one month. Based on the multiple one-way sensitivity analyses, the intervention guaranteed VfM in all scenarios except when all the trainers were paid consultancy fees and the least amount of outcomes occurred. Implications for policy and research: SROI provides critical additional insight when used to assess value-for-money of EmOC training. However, there are methodological improvements required. In implementing and researching EmOC training, consideration needs to be given to both intended positive and unintended negative outcomes of the intervention. Evidently, to achieve the best results from training, other factors such as optimal human resource distribution and availability of equipment need to be addressed. Use of volunteer trainers, particularly those who work locally, to deliver the training is a critical driver in achieving value-for-money for investments made.

Background: Globally, 422 million adults have type 2 diabetes mellitus (T2DM), causing 1.5 million deaths per year. Kuwait has one of the highest T2DM prevalence in the world and determining the proportion of patients and relatives who have pre-diabetes (PDM), insulin resistance (IR) and T2DM is crucial to inform preventive activities and curative services. Study objectives: The study describes the prevalence and risk factors of PDM, IR and T2DM, in adult patients attending a primary health care facility in Kuwait and the prevalence and risk factors of the same conditions among the patients’ first-degree relatives. The study also describes the degree of glycaemic control achieved by patients with T2DM and risk factors for poor glycaemic control. Finally, we assessed the agreement of a point of care (POC) device to measure glycated haemoglobin (HbA1c) to monitor T2DM control. Methods We conducted cross-sectional surveys of patients and first-degree relatives attending Nuzha health care facility in Kuwait and case-control studies of participants attending Nuzha’s diabetic clinic. Diabetic participants were consecutively tested by the Quo-test (POC) device to compare its agreement with a reference test. Results The prevalence of T2DM, IR and PDM among patients attending the clinics were 29.6% (95% CI: 25.1%-34.1%), 34.6% (95% CI: 29.1%-40.2%) and 26.0% (95% CI: 21.6%-30.4%), respectively. The proportion of patients with T2DM increased with age (AOR=5.4), with the highest prevalence occurring at 60-69 years of age. T2DM was associated with hypertension (AOR=1.95) and being a widow (AOR=6.11). IR was associated with low HDL (AOR=1.96), overweight (OR=8.25), obesity (OR=18.33) and increased waist circumference (OR= 5.5). Sugar-sweetened beverages were associated with IR. The prevalence of T2DM, IR and PDM among first-degree relatives of T2DM patients were 29.1% (95%CI: 23.7%-34.5%), 32.8% (95%CI: 26.2%-39.4%), 20.4% (95%CI: 15.6%-25.2%). The risk factors for T2DM were similar among patients and first-degree relatives, but IR was associated with manual labour occupations (AOR=3.6). Only 30% of T2DM patients achieved good glycaemic. Poor control was associated with high triglycerides (AOR=2.2), smoking (AOR=4.1) and the number of years since diagnosis (AOR=4). The Quo-Test had comparable performance to the reference test, with a Coefficient of Variation of 2.1% (r2 = 935, Kappa 90% and 87% at HbA1c cut-offs of 7.0 and 9.0% respectively). The POC and the reference tests performed poorly in patients with haemoglobinopathies. Conclusion This study demonstrates that a high proportion of patients and first-degree relatives attending one of the main primary health care centres in Kuwait have T2DM. Many patients and relatives were unaware of their condition. There was also a very high prevalence of IR and PDM suggesting the burden of T2DM will increase further in the future. Major efforts are needed to upscale detection, and preventive programmes for IR, PDM and T2DM and the quality of T2DM management needs to improve. The POC device tested could provide timely information for the management of T2DM.

No description available.