Thesis (M.Arch.)--University of Hong Kong, 1999. / Includes bibliographical references. Also available in print.

Background: The global policy focus of today’s HIV efforts and strategies is to reverse the spread of HIV/AIDS and provide care, treatment and support. A key component of this strategy is to increase individual HIV status awareness through expansion of HIV testing and counselling (HTC). However, the numbers tested still remain low and evidence suggests that there are significant missed opportunities for HIV testing in clinical settings. One key strategy to expand HTC in clinical settings has been to implement a policy of ‘provider initiated counselling and testing’ (PITC) in which all patients accessing health facilities for treatment are routinely offered a HIV test. The introduction of PITC has brought with it a ‘dilution’ of the previously lengthy and stringent testing process by doing away with signed informed consent and extensive pre and post test counselling. The previous process was recognised as a barrier to public health gains of HIV testing expansion, particularly as it differentiated an HIV test from other routine medical tests resulting in a sense of HIV exceptionalism. In its place, the PITC policy recommends an opt-out approach and replaces the extensive pre test counselling with an information giving session placing more emphasis on post test counselling in cases where the result is positive. This change has given rise to debates about the potential for PITC to infringe patients’ rights to informed consent and counselling especially in developing countries. Emerging evidence from the exploration of the PITC process within antenatal settings in the Sub Saharan Africa has revealed some of the complexities of implementing PITC guidelines in different cultural and healthcare contexts. These studies suggest that information giving and consent are difficult to apply in contexts characterized by healthcare worker dominance, lack of sufficient resources and time constraints. This study aimed to specifically investigate how patients and counsellors co-construct informed consent and perform counselling during the PITC consultation. It examined ‘real time’ patient-counsellor interaction within hospital outpatient and inpatient settings in Kenya, explored the patient’s experience of a routine HIV test and evaluated how stigma and patient – provider interaction norms influence the PITC process in this context. Methods: In order to explore the context of the routine testing consultation and the way the interaction played out, a qualitative research approach was adopted, utilizing multiple data collection methods (interviews, observations and audio recording of consultations). The study was carried out in two government run health facilities in Kenya’s capital, Nairobi. The intention was to follow patients through the PITC process, i.e. before testing, during the HIV test and (whenever possible) after the HIV test. To get a broader picture of the events during the routine HIV testing consultation, additional interviews were conducted with five nurse-counsellors whose consultations had been observed. Ethical approval was obtained from the Kenya National Research Council, Kenya Medical Research Institute and the Aga Khan University Ethics Committee. The data were analysed using Charmaz’s constructivist grounded theory approach which allowed for a systematic yet flexible approach to analysis. This method facilitated immersion and engagement with the data, and provided a means of managing the different data sets in the study and undertaking a process of constant comparison within and between data sets. Findings: Results from the study suggest that HIV remains a highly stigmatised illness in Kenyan society and is associated with death and immorality. This is still the case in spite of years of health promotion and high profile media campaigns raising awareness about HIV and the availability and effectiveness of treatment. The context of stigma shaped the consultation so that both patients and counsellors worked together to help patients to maintain a ‘moral face’. Patients tended to withhold information on risky sexual behaviour whilst the counsellors avoided inquiring into this domain. The PITC consultation was characterised by a counsellor dominated approach to communication and health promotion. Counsellor inputs were generic, highly scripted and didactic rather than patient-centred. As a result, the counsellors’ style of communication allowed little space for personalised risk assessment or for patients to ask questions or to express concerns. The findings suggest that informed consent enabling explicit refusal of the test offer was difficult to achieve in an environment where the HIV test was not framed as a choice and patients came to the health facility expecting to be told what to do. Nevertheless, in spite of the obvious lack of explicit informed consent and the counsellor dominated interaction, post test interviews revealed that patients were satisfied with the nature of the interaction. The study concludes that there is a considerable distance between the policy recommendations and their implementation on the ground due to the complexity of real world practice. Lay constructions about HIV (HIV stigma) and the existing norms of patient-provider interaction that are characterised by a passive patient and a dominant health care provider shape the way the consultation unfolds. PITC training programs and manuals need to include skills and strategies that can support counsellors manage an uncomfortable interaction and emphasis the need to ensure an individualized post test counselling is carried out. The thesis makes several contributions to knowledge. The study pays attention to the operationalization of PITC recommendations thus illuminating how the PITC policy is translated into practice within a developing country like Kenya. It informs the existing debates on how informed consent and counselling should be implemented. The study findings suggest that in spite of the global debates on what constitutes ideal informed consent and counselling, in practice, sociocultural norms shape how these issues are translated and implemented. However, the study indicates that diversion from the PITC policy recommendations does not necessarily constitute a disregard for the recommendations but, rather, is an attempt to adapt to the prevailing environment. The study methodology enabled unique insights to be gained on how counselling and consent are constructed and managed in the PITC setting through the use of observations / audio recording to examine ‘real time’ interactions. The research study has been able to illuminate barriers that are posed by sociocultural and organisational structures in the real world implementation of the PITC policy. Therefore, my study suggests that the national PITC policy needs to consider the practical problems faced on the ground in developing contextually appropriate recommendations for the conduct of PITC and implementation of key guidelines.

Background: The 2009-10 influenza A(H1N1) pandemic was the first pandemic influenza of the twenty-first century and presented the first major opportunity for the use of influenza vaccines en-masse during a pandemic scenario. National anticipatory policies of pandemic influenza vaccine preparedness were implemented, and vaccine guarantee agreements were activated. Large quantities of vaccines were purchased and made available to identified citizens over the course of the pandemic. The use of pandemic influenza vaccines has been examined in this research. Methods: A comparative health policy approach in five study countries (Sweden, New Zealand, Japan, Singapore, and Canada) was conducted. Qualitative interviews (n= 36) were undertaken in each country with key pandemic influenza response personnel (n = 39). Participants included public health officials, policy makers and clinicians engaged at national country response level. Interviews facilitated discussions surrounding the 2009-10 influenza A(H1N1) pandemic response and use of vaccines. Documentary examination of available records supplemented the analysis of the interview data. Results: Several interview themes were identified following data analysis of the use of pandemic vaccines in the study countries. Themes of the vaccine use included: single or multiple vaccine supplier routes; hemisphere variation; historical pandemic legacy; targeted populations; setting vaccination priorities; side effect concerns; perceived effectiveness of vaccines during the pandemic influenza response. The themes which were most prominent comprised the sourcing and distribution of the vaccines during the response and the associated communication challenges. The necessary prioritisation of vaccines caused extensive discussions and uneasiness by the pandemic influenza response personnel as the initial vaccines arrived in small quantities and required allocation, especially in circumstances where country’s intended for all/most citizens to eventually have access to the vaccine. The variation in timing of the vaccination campaigns and disease activity would suggest that subsequent influenza wave morbidities and mortalities could have been reduced if vaccines had been available more promptly. The southern hemisphere country, New Zealand, exemplified the circumvention of vaccine safety concerns through the use of a trivalent vaccine inclusive of H1N1. Conclusions: Pandemic vaccines were the cornerstone of two countries responses and were associated with high uptake rates. Vaccine discussions, such as prioritisation and essential workers estimates, can be established during interpandemic phases by pandemic influenza response personnel. The use of annual seasonal influenza vaccines that are inclusive of the novel pandemic influenza strain should play a greater role in future pandemic influenzas, should the vaccination campaign timing be appropriate, as this may reduce public anxiety concerning the perceived safety of novel vaccines. The use of the 2009-10 influenza A(H1N1) pandemic vaccines had varied in success and the lessons learnt from this event have important implications for future policy. Pandemic influenza response personnel are recommended to prepare as fully as possible during this interpandemic period.

Epstein Barr Virus (EBV) is a major risk factor in Multiple Sclerosis (MS), via as yet unclear mechanisms. Several hypotheses have been proposed to explain how EBV infection could cause MS and the aim of this thesis was to better understand the mechanisms of action of EBV in the context of MS studying a) the role of EBV in myelin antigen presentation by B cells and b) the association of HERVs with MS. In a non-human primate experimental autoimmune encephalomyelitis (EAE) model, an EBV-related lymphocryptovirus enables B cells to protect a proteolysis-sensitive immunodominant myelin oligodendrocyte glycoprotein (MOG) peptide (residues 35- 55) against destructive processing. This facilitates its cross-presentation to autoaggressive cytotoxic MHC-E-restricted cytotoxic T cells. The present study extends these observations to human B cells and identifies a key role of autophagy. EBV infection upregulated antigen presentation-related markers on B cells and activated the cross-presentation machinery. Although human MOG protein was degraded less in EBV-immortalized B-lymphoblastoid cell lines (LCL) than in uninfected B cells, induction of cathepsin G activity by EBV led to total degradation of the immunodominant peptides. Inhibition of cathepsin G or citrullination of the arginine residue within a LC3-interacting regions (LIR) motif of immunodominant MOG peptides abrogated their degradation. Internalized MOG co-localized with autophagosomes, which may protect it from destructive processing. Thus, EBV infection switched MOG processing in B cells from destructive to productive possibly facilitating cross-presentation of disease-relevant epitopes to CD8+ T cells. This mechanism could facilitate presentation of myelin autoantigens that may be involved in MS induction and progression. The first part of this thesis shows a possible EBV-mediated mechanism involved in MS pathogenesis, but it is likely that different mechanisms act alternatively or cumulatively in different individuals based on environmental and genetic differences. A further mode of action of EBV is through the activation of Human Endogenous Retroviruses (HERVs). In normal conditions HERVs are silenced or expressed at low levels, but in some pathological cases, like MS, their expression is higher than in the healthy population. We performed a systematic review and meta-analysis of the literature on the association between HERVs and MS. The systematic review suggested a strong association between HERV expression and MS, in particular with the HERV-W family. The meta-analysis showed odds ratios of 22, 44, and 6 for the expression of MSRVpol in serum/plasma, MSRVenv in PBMC and MSRVpol in CSF respectively. Furthermore, we confirmed the association experimentally. An increased expression of MSRV/HERV-Wenv and TLR4 RNA was detected in blood of MS patients compared with control groups and the viral protein Env was expressed mainly by B cells and monocytes, but not by T cells. Our finding that EBV infection can induce the expression of MSRV/HERV-Wenv is consistent with previous reports in the literature. We also established that such increased expression was not due to a repression of retroviral restriction factors in LCL. A further connection between HERVs and MS is supported by the observation that people infected by HIV may have a lower risk of developing MS than the HIV non- infected, healthy population. We found that the expression of MSRV/HERV-Wenv RNA in HIV-infected people was lower than in MS patients and similar to healthy controls. Nevertheless, there was no difference in MSRV/HERV-Wenv expression between antiretroviral drug -treated and -untreated HIV patients. The expression of MSRV/HERV-Wenv was also detected in vitro in LCL treated with different classes of antiretroviral treatments (ART) and only Efavirenz (NNRI) reduced MSRV/HERV- Wenv expression. In conclusion, taking in consideration the multifactorial aetiology of MS, it is likely that EBV infection and increased expression of MSRV/HERV-W are significant contributing factors in genetically predisposed individuals. This thesis helps to better understand the mechanisms of action of EBV and HERVs in the context of MS.

Background Community acquired pneumonia (CAP) is a common illness in patients admitted to hospital, accounting for nearly 10% of acute medical admissions. Despite widespread use of antimicrobial therapy, morbidity and mortality from this disease remains high. In recent years in the UK, there have been significant developments in both preventative and treatment strategies for this illness. To understand the impact of these changes and direct future management strategies, it is important that the epidemiology of this disease is fully understood. This thesis investigates changes in epidemiology and outcomes in adult patients admitted to UK hospitals with a primary diagnosis of CAP, in recent years and with reference to the herd protection effect of the conjugate Streptococcus pneumoniae vaccine. Methods There are 3 study populations presented in this thesis. Data were derived from (a) the British Thoracic Society national CAP audit database, (b) a longitudinal cohort study of adults hospitalised with CAP, within the Greater Nottingham area, and (c) an observational study of adults admitted to four hospitals within the East Midlands area with a diagnosis of CAP. The specific methods used for the identification of study participants, laboratory and statistical analysis are described in detail in ensuing chapters. Results Across the UK, there was a significant reduction in 30-day mortality between 2009 and 2014; this improvement in outcome may be attributable in some part to improved processes of care. Whilst data derived from coding databases have previously been used to report CAP related mortality trends, this thesis has demonstrated significant variation in coding accuracy across UK institutions and that miscoded cases of pneumonia had lower odds of 30 day mortality compared to those individuals with CAP. Consequent to herd effects from national infant vaccination programmes and changes in nasopharyngeal carriage of S pneumoniae, this thesis shows that (a) school holiday periods were associated with increased incidence of pneumococcal CAP in hospitalised adults, (b) older adults at high risk of pneumococcal disease were less likely to be hospitalised with vaccine serotype CAP compared to non-vaccine-serotype pneumococcal CAP, and (c) there was a decrease in the overall burden of vaccine-serotype pneumococcal CAP compared to non-vaccine-serotype pneumococcal CAP. Conclusion Important changes in the epidemiology of adult CAP in the UK over recent years are reported in this thesis. This includes temporal decreases in mortality rates of all cause CAP, as well as a significant ongoing burden of non-vaccine serotype pneumococcal CAP. This data on the current burden of disease and associated outcomes should help inform future CAP management strategies.

Background Malaria and pneumonia are the leading causes of under-five mortality in sub-Saharan Africa especially in Nigeria. The Integrated Management of Childhood Illness (IMCI) guidelines were developed by the World Health Organisation (WHO)/United Nations Children’s Fund (UNICEF) as a strategy to reduce the burden of these and other preventable childhood diseases. However, there appears to be a paucity of evidence on the diagnostic performance of the revised IMCI guidelines and whether they offer an advantage over lay diagnosis (caregiver) for malaria and pneumonia management in Nigeria. Aim and specific objectives This study evaluates early diagnostic approaches (IMCI guidelines and lay diagnosis) for malaria and pneumonia in children under-five at the primary healthcare level. To address the overarching aim of the study, the following four specific objectives were studied: I. To assess the diagnostic accuracy of the IMCI guidelines and lay diagnosis (caregiver) for malaria and pneumonia in comparison to reference diagnostic approaches (microscopy and chest X-ray for malaria and pneumonia respectively). The extent of agreement between caregivers’ and health workers’ diagnosis of malaria and pneumonia is also assessed. II. To estimate the burden of malaria and pneumonia among children under-five presenting to study primary healthcare centres (PHCs) according to various diagnostic approaches. III. To determine the clinical outcomes in children diagnosed with malaria and pneumonia according to the IMCI guidelines and risk factors for severe outcomes. IV. To qualitatively explore caregivers’ and health professionals’ perspectives on lay diagnosis and IMCI guidelines as diagnostic approaches for childhood malaria and pneumonia. Methods A mixed methods approach was used for this study. The quantitative component used a consecutive sampling approach to recruit 903 children aged 2–59 months who met study eligibility criteria for malaria and pneumonia assessment according to the IMCI guidelines at presentation to five study PHCs in Benin City, Nigeria. Caregivers of these children were also asked what they thought the diagnosis was (lay diagnosis). Diagnostic accuracy was assessed in terms of sensitivity, specificity, positive and negative predictive values, Area under the Receiver Operating Characteristic Curves (AUROC) values and 95% Confidence Intervals (C.I). The extent of agreement was assessed in terms of Cohen’s kappa statistic (k) and 95% CI. The estimated burden of malaria and pneumonia during the study period was assessed using proportions and 95% C.I. Clinical outcomes in children diagnosed with malaria and pneumonia by the IMCI guidelines were described in terms of frequency and percentages, while the potential risk factors associated with clinical outcomes were assessed using odds ratios (ORs) and 95% C.I. For the qualitative component, health stakeholders (17 health professionals and 13 caregivers) who met the study eligibility criteria were purposively recruited and interviewed using semi-structured interviews. An inductive approach to thematic analysis was used for data analysis. Results Compared to microscopy, the diagnosis of malaria by health workers using the IMCI guidelines was poorly accurate with an AUROC value of 0.57 (with sensitivity and specificity of 51.8% and 61.3% respectively). Similarly, caregivers’ diagnosis of malaria was poor with an AUROC value of 0.55 (with sensitivity and specificity of 31.1% and 79.5% respectively) as compared to microscopy. Using the IMCI guidelines as the reference diagnostic test, caregivers’ diagnosis of malaria was more accurate (AUROC 0.60) in comparison to that of pneumonia (AUROC 0.54). There was a slight or minimal level of agreement (k=0.14; 95% CI: 0.09-0.19) between caregivers and health workers in the diagnosis of malaria and pneumonia. The estimated burden of malaria and pneumonia was relatively low, varying by the study local government areas, PHCs and seasonality, irrespective of the diagnostic approach. Where follow-up data were available, approximately 57% (172/304) and 78% (81/104) of the children diagnosed with malaria and pneumonia, respectively, recovered without complications within 30 days. Self-medication prior to presenting to study PHCs and use of preventive measures against malaria were independently and significantly associated with improved clinical outcomes. In contrast, exposure to solid fuels increased the odds of severe illness following malaria or pneumonia diagnosis. The qualitative component of the study found that caregivers rely on lay diagnosis despite the awareness of its limitations. The perceptions of malaria and pneumonia appeared to influence caregivers’ home management practices and health seeking behaviours. Caregivers showed willingness to be trained in the IMCI guidelines for improved home-based management of malaria and pneumonia. Health professionals believed that the IMCI guidelines were useful for managing both malaria and pneumonia. However, there are some recurring challenges to the wide-scale and sustainable implementation of the IMCI strategy in Nigeria. These include inaccurate diagnosis of malaria and inadequate funding. Conclusion The IMCI guidelines are crucial in the effective management (diagnosis and treatment) of malaria and pneumonia at the primary healthcare level in Nigeria. Although not perfect, lay diagnosis has an important contribution in the early detection and management of malaria and pneumonia at the community level in Nigeria. However, there is need for further investment in the training of both health professionals and caregivers in the IMCI guidelines for better health outcomes in under-five population. The training of caregivers in the IMCI guidelines and potential for a scale-up will benefit from careful design, piloting, implementation, and monitoring.

Background Papular pruritic eruption (PPE) of human immunodeficiency virus (HIV) infection is common HIV-infected populations who live in tropical and subtropical regions. It is characterized by chronic and intensely itchy papules that are usually more highly concentrated on the extremities, adversely impacting on quality of life. Its aetiology has been postulated to be an altered and exaggerated immunological response to insect bites or stings. It has been reported to diminish in severity or resolve with antiretroviral therapy (ART). Its presence after at least six months of ART has been proposed as one of several clinical markers of failure of antiretroviral treatment. Objectives 1. To systematically summarise the evidence of interventions for PPE 2. To translate, culturally adapt, and test oral administration of a Runyankore-version of Skindex-16 for use in dermatology research in Mbarara, Uganda 3. To determine factors associated with PPE in HIV-infected Ugandan adults receiving ART for at least 15 months 4. To describe the natural history of PPE in HIV-infected Ugandan adults over two years from the time of ART initiation and explore the association between recurrent or persistent PPE and antiretroviral treatment failure Methods Systematic review of interventions for PPE Electronic searches of Medical Literature Analysis And Retrieval System Online (Medline), Excerpta Medica Database (Embase), Cumulative Index To Nursing And Allied Health Literature (CINAHL), Global Health Library, Cochrane Library, World Health Organization (WHO) International Clinical trials registry and National Library Of Medicine (NLM) gateway were carried out from January 1980 to July 2014. Studies of any design were included. The primary outcome measure for this review was resolution of skin disease. The quality of evidence was assessed using the Newcastle-Ottawa quality assessment scale and Grading Of Recommendation, Assessment, Development And Evaluation (GRADE) approach, where appropriate. Two authors carried out data extraction and quality assessment of studies independently. Runyankore-version of Skindex-16 for oral administration in Mbarara, Uganda Skindex-16 in English was translated to Runyankore, and then back-translated to English. The original and back-translated versions of Skindex-16 were compared for fidelity of translation. The Runyankore-version was administered orally to 47 dermatology patients and 47 random hospital visitors. Study participants were also asked about the characteristics of their skin condition including its duration, presence of skin colour change and ease or difficulty of concealment as well as an open question on how their skin condition has affected them. Case control study examining factors associated with PPE in the ART era This is a case–control study nested within a 515-person cohort receiving care at the HIV clinic of a teaching hospital in Mbarara, Uganda. Forty-five cases and 90 controls were enrolled. Cases had received ART for ≥15 months, fulfilled the clinical case definition of PPE and had skin biopsy findings consistent with PPE. Each case was individually matched with two controls for age, sex and ART duration. Cohort study describing the natural history of PPE over two years from ART initiation This is a cohort study of HIV-infected Uganda adults initiating ART and receiving care at the HIV clinic of a teaching hospital in Mbarara, Uganda who fulfilled the clinical case definition of PPE and had skin biopsy findings consistent with PPE. Standardised interviews, clinical photography, HIV viral load, CD4 counts and CD8+ T-cell activation markers were measured at three-month intervals for two years. Results Systematic review of interventions for PPE No randomised controlled trials were identified. Thirteen studies with a total 188 participants were included. ART was associated with resolution of PPE in a prospective observational study that had high loss to follow-up rates. Two observational studies reported positive responses of PPE to oral antihistamines (promethazine and cetirizine). Pentoxifylline was associated with diminished signs and symptoms of PPE in an uncontrolled open trial and superior to dapsone and a combination of antihistamine and topical corticosteroids in a parallel group non-randomised trial. Resolution of PPE was reported with a combination of topical corticosteroids and oral antihistamines in a case report. The efficacy of ultraviolet B (UVB) phototherapy was reported in an observational study with eight participants and three case studies with a total of five participants. Runyankore-version of Skindex-16 for oral administration in Mbarara, Uganda Oral delivery was feasible, taking ≤10 minutes per subject. High Cronbach α values (0.86, 0.88 and 0.85 for Symptoms, Emotions and Functioning subscales, respectively) demonstrated internal consistency reliability. As hypothesised, subjects with reported skin problems, dyspigmentation and difficulty in concealment had higher mean Skindex-16 scores, indicating construct validity. A large proportion (72.4%) of responses to the open-ended question were addressed in Skindex-16, indicating content validity. Case control study examining factors associated with PPE in the ART era Twenty-five of 45 cases (56%) had histological findings consistent with PPE (known as PPE cases). At skin examination and biopsy (study enrolment), a similar proportion of PPE cases and their matched controls had plasma HIV RNA <400 copies/ml (96% vs. 85%, p=0·31). The odds of having PPE increased four-fold with every log increase in viral load at ART initiation (p=0.02) but not at study enrolment. CD4 counts at ART initiation and study enrolment, and CD4 gains and CD8 T-cell activation measured 6 and 12 months after ART commencement were not associated with the presence of PPE. Study participants who reported daily insect bites had greater odds of being cases [odds ratio (OR) 8.3, p<0.001] or PPE cases (OR 8.6, p=0.01). Cohort study of natural history of PPE over 2 years from ART initiation Seventeen (15 female and 2 male) participants with a median age of 29.8 years were enrolled. Median CD4 count and HIV viral load at ART commencement was 108 cells/mm3 and 114,442 copies/ml, respectively. Resolution of PPE occurred in 13 of 17 (76%) study participants at a median time of 8.5 months after ART initiation, although PPE recurrence was observed at seven participants during the study period. Two participants had persistent PPE. Virological failure was not detected in any study participant. HIV RNA was less than 400 copies/ml at a median time of three months from ART initiation in all study participants. Conclusions 1. The evidence base of interventions for PPE is of low quality. There is some evidence of the efficacy of ART in the management of PPE. Pentoxifylline and phototherapy may have a role in its management but are unlikely to be available in resource-limited settings. Oral antihistamines and topical corticosteroids may be helpful in some individuals affected by PPE. 2. The orally administered Runyankore-version of Skindex-16 is reliable, with construct and content validity, and feasible for use in dermatology research in Mbarara, Uganda. 3. PPE in HIV-infected Ugandan adults receiving ART for at least 15 months was associated with reported daily insect bites and greater HIV viraemia at ART commencement, independent of CD4 count. 4. Recurrent or persistent PPE in HIV-infected Ugandan adults observed over two years from initiation of ART was not associated with virological failure in participants of this study.

Frontline healthcare workers (HCWs) in the UK have been prioritised for free occupational immunisation against seasonal influenza since 1999. During the 2009-10 influenza pandemic, they were identified as a priority group to receive the strain-specific vaccine. Nevertheless, take-up rates among HCWs have rarely exceeded 50%, even during the pandemic. Most attempts to change this situation have been predicated on the assumption that these low rates are the result of reluctance or resistance by individual HCWs, who must be persuaded or coerced to comply with employer directives. To gain a novel understanding of this immunisation programme, an actor-network theory approach is adopted to trace the journeys of vaccines through two Local Health Boards in Wales during the 2009-10 H1N1 influenza pandemic and in the following winter influenza season (i.e. during 2010-11). The research reported shows that low uptake is largely the result of complex social, organizational and cultural processes. Only when these have been changed will it be appropriate to frame the remaining problem as reluctance or resistance by individual HCWs. The study reveals that this immunisation programme is inherently unstable and subject to ambivalence from actors at all levels. Suggestions for practical improvement are given.

Magister Public Health - MPH / The prevalence of non-communicable diseases such as hypertension and diabetes including obesity has increased among the black population over the past few years. The increase in these diseases has been associated with increased urbanization and lifestyle changes. No studies have documented the experiences of people who have migrated to urban areas. Aim: To describe the type of lifestyle changes, reasons for the lifestyle changes and the barriers to adopting a healthy lifestyle among people who have migrated from rural areas to urban areas in the past 5 years and reside in Khayelitsha. Objectives: (1) To identify people who have moved from rural to urban areas in the past 2-5 years; (2) To explore reasons for moving to the city; (3) To explore experiences of respondents on moving to the city; (4) To identify the types of lifestyle changes related to chronic diseases among respondents on arrival to the city; (5) To identify reasons for the lifestyle changes among respondents; (6) To identify coping strategies that have been adopted by respondents; (7) To identify barriers to healthy lifestyle among respondents; (8) To make recommendations for development of appropriate interventions that will enable migrating populations to adjust better to city life. Rural-urban migration (urbanization) was associated with factors such as seeking employment, better life and working opportunities. On arrival in the city migrants face a number of challenges such as inability to secure employment and accommodation. Faced with these challenges, migrants change their lifestyle including buying fatty foods, increasing frequency in food consumption and decreasing in physical activity. In the city factors such as poverty, environment including lack of infrastructure, and lack of knowledge about nutrition, social pressures and family preferences were identified as hindrances to a healthy lifestyle. Conclusion: This study identified various factors that influence the decision to migrate from rural areas. Lifestyle changes in an urban setting are due to socio-economic, environmental and individual factors. Perceived benefits of moving to urban areas can pose challenges to health and this may have negative health-outcomes. / South Africa

A rapid, objective indicator of pyogemc infection would be of great value in the practice of clinical medicine. On the basis of earlier studies it was claimed that the nitroblue tetrazolium ( NBT) test might fulfill such a role. In view of the potential value of this test, it was reassessed m order to determine its diagnostic accuracy and clinical value. The results obtained in this study did not conform with those previously published. Elevated NBT scores were not diagnostic of pyogenic infection, there was a wide overlap of the results of tests performed on patients with pyogenic disease, patients with other diseases and normal subjects. In addition, there was a significant observer error in the interpretation of the slide preparations. The extent of this error was reduced with experience, but was still considerable in the hands of experienced observers. In the NBT test, the dye enters neutrophils by phagocytosis of NBT in particulate form, complexed to heparin and/or '·fibrinogen. The proportion of neutrophils which phagocytose these complexes seems to be related to the severity of illness of the patient. As serum from these patients is capable of enhancing phagocytosis of complexed dye by normal cells, a humeral factor could be responsible for the increased phagocytosis of complexed NBT indicated by a positive test. , Of the compounds tested, man m vitro model system designed to simulate the NBT test, 3 a,l_acid glycoprotein, immunoglobulins and endotoxin, in concentrations that occur in vivo, enhanced NBT reduction. Any one of these compounds, singly or in combination, could be responsible for positive NBT tests.