Student Number : 8044255 - PhD thesis - School of Pathology; Discipline Virology - Faculty of Health Sciences / Knowledge of the timing of mother-to-child transmission (MTCT) of HIV-1 is an important issue in reducing the risk of infant infection. Prior to giving birth therefore an HIV-1 positive mother should be provided with anti-HIV-1 drugs (antiretrovirals) during the shortest time possible to ensure both efficacy and minimal toxicity of the antiretrovirals to the newborn. However, in the absence of timeous administration of nevirapine (NVP) or zidovudine (AZT) to the mother at the onset of labour, infants are given post-exposure prophylaxis (PEP). Despite antiviral prophylaxis some infants still become infected. In an attempt to mimic the in vivo scenario we investigated, in Chapter Three, the replication ability of a primary isolate (M502L) in peripheral blood mononuclear cells (PBMC) isolated from healthy donors exposed to different concentrations of NVP or AZT either prior to or post-infection, but that reflected mean neonatal plasma concentrations measured following maternal dosing. In phytohaemagglutinin (PHA) stimulated cultures M502L exhibited some growth. Maintaining NVP and AZT in the culture medium resulted in decreased viral growth over time. In contrast to that expected certain donors demonstrated elevated p24 antigen levels in the presence of HIV-1 and NVP or AZT. This suggested that cells were more conducive to HIV-1 replication either because of cellular activation or due to cellular production of cytokines/chemokines. The in vitro study highlighted (i) the differential permissiveness of cells from different donors for HIV-1 infection, (ii) different abilities of antiretrovirals (ART) to circumvent infection in different individuals and (iii) immunomodulatory effects of ART in vitro. Commencing in Chapter Four we elected to investigate, in vivo, the immunomodulatory consequences of HIV-1 exposure and infection in two groups of HIV-1-exposed newborns whose mothers either received NVP at the onset of labour or who only received NVP as PEP within 72 hours of birth. Short-course antiretroviral drug regimens are known to reduce the risk of MTCT of HIV-1 but mechanisms affording protection of such interventions remain poorly defined. Since T-cell activation is an important factor in productive HIV-1 infection, we tested the hypothesis that single-dose NVP reduces immune activation, which in turn reduces the likelihood of transmission. We compared concentrations of cord and maternal blood plasma immune activation markers, neopterin, β2-microglobulin (β2-m) and soluble L-selectin (sL-selectin) in the two groups of HIV-1-exposed newborns and among HIV-unexposed controls. In utero exposure of the infant to HIV-1, regardless of NVP exposure, led to demonstrable increases in levels of immune activation markers, this being most notable in the presence of pre-existing infection. Contrary to what was hypothesized, immune activation was increased by pre-birth exposure to single-dose NVP, with this effect being enhanced in infants already infected at birth. Our data suggest that reductions in immune activation do not explain transmission prevention effects of single-dose NVP. Our data also suggest a biological explanation for why HIV-1 infected infants exposed perinatally to antiretroviral drugs might experience hastened disease progression, namely that the immunological mileau in some HIV-1 infected individuals treated with NVP favours increased HIV-1 replication. Cytokines and chemokines function to stimulate, or suppress cellular proliferation and differentiation and have unique immunomodulatory properties. Furthermore, they have the potential to protect against HIV-1 infection or to regulate HIV-1 replication. In Chapter Five we therefore questioned whether exposure to HIV-1 or NVP influences cytokine/chemokine levels of infants born to HIV-1 infected mothers. We compared levels of interleukin (IL)-7, IL-10, stromal cell-derived factor: SDF-1α (CXCL12), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage inflammatory protein-1α: MIP-1α (CCL3), macrophage inflammatory protein-1β: MIP-1β (CCL4) and regulated upon activation, normal T-cell expressed and secreted: RANTES (CCL5) of the two groups of HIV-1-exposed newborns and among the HIV-unexposed controls. HIV-1 exposure in the absence of single-dose NVP was not found to impact significantly on the levels of IL-7, IL-10, GM-CSF, CXCL12, CCL3, CCL4 or CCL5 and single-dose NVP had no appreciable effect on these cytokine/chemokine levels. Cord blood plasma levels of IL-7, CXCL12 and GM-CSF were found to be independent of mothers’ levels. Single-dose NVP reduced the ability of cord blood mononuclear cell (CBMC) to produce GM-CSF spontaneously. Maternal and infant (HIV-1 exposed NVP unexposed) IL-10 levels were significantly correlated. Significantly elevated levels of IL-10 were associated with pre-existing infection in NVP unexposed newborns. CCL3, CCL4 and CCL5 levels in NVP unexposed uninfected infants were not different from those of control infants but correlated significantly with IL-7 levels. HIV-1 specific cellular immune responses are elicited in a proportion of infants born to HIV-1 seropositive mothers and have been associated with protection from maternal HIV-1 transmission. In Chapter Six, levels of the immune activation markers neopterin, β2-m, sL-selectin, the immunomodulatory and haematopoietic factors IL-7, CXCL12, GM-CSF and the immunoregulatory cytokine IL-10 were examined amongst the group of newborns, that received NVP as PEP within 72 hours of birth, of which a proportion had specific cellular responses to HIV-1 envelope (Env) peptides. It was our aim to determine in infants that elicit HIV-1 specific cellular immune responses (Env+) and those that lack the specific responses (Env-), whether these factors could predict transmission and whether the former group of infants exhibit unique immune features that might distinguish them from Env- non-responders. Our data suggested that none of the factors tested were predictive of HIV-1 transmission but confirmed that infants with cellular responses to HIV-1 envelope peptides were associated with lack of subsequent infection. In particular, our data demonstrated an association between HIV-1 specific cellular immune responses, lower maternal viral load and lack of infection suggesting that sustained exposure to antigen (reduced maternal viral load) may be responsible for the strong priming effect. Furthermore, an association between reduced GM-CSF levels and the presence of HIV-1 specific responses was demonstrated, which suggested therefore that newborn infants that elicited HIV-1 specific cellular immune responses exhibited different immune capabilities from those without responses. Finally, in Chapter Seven we looked at how immune activation and priming impact on thymic output of T-cells in newborn infants. Unfortunately, sample volumes of the two groups of HIV-1-exposed newborns used in the previous three Chapters became limited with the result that we chose to address these questions using anonymously collected cord blood samples from infants, some of which were used to supplement the placebo group of the the UNAIDS-sponsored clinical trial of short-course zidovudine-lamivudine (AZT-3TC). At the time the AZT-3TC trial was conducted short-course antiviral prophlyaxis was not the standard of care for the prevention of MTCT of HIV-1. The thymus is known to be essential for establishing diversity of the T-cell pool, and morphological thymic changes and effects on naïve T-cells and T-cell receptor excision circle (TREC) concentrations have been reported in studies of HIV-1 infected children and adults. As it is not known to what extent in utero exposure to HIV-1 and infection affects T-cell division in newborn infants, we elected to determine TREC levels of infants born to HIV-1 seropositive mothers that were not exposed to antiretrovirals. The impact of increased immune activation on TREC levels and the consequence of HIV-1 exposure or infection on circulating levels of IL-7 (raised levels indicative of T-cell depletion) was also investigated. HIV-1 exposure or infection did not result in significant losses of TREC. TREC levels were not affected by immune activation associated with HIV-1 exposure and infection and IL-7 levels were not raised. Infants that elicited HIV-1 specific cellular immune responses exhibit TREC levels that were similar to those of infants without HIV-1 specific responses. These data suggested that newborn infants of HIV-1 seropositive mothers demonstrated no altered thymopoietic ability compared to control infants. Furthermore, HIV-1 specific immune responses, (indicative of post-thymic memory T-cell expansion) did not influence thymic output measured in newborn infants. In conclusion, the in vitro study demonstrated that there is a high degree of variability between PBMC isolated from different donors with respect to viral replication and drug effectivity which suggests that these phenomena are likely to exist within patient (infant as well as adult) populations. While immune activation is considered central to productive infection we demonstrated that immune activation is increased by HIV-1 exposure and by single-dose NVP. Exposure to HIV-1 alone or with NVP did not influence birth levels of IL-7, IL-10, CXCL12, GM-CSF, CCL3, CCL4 and CCL5. Furthermore, levels of these factors did not predict infection outcome in the infant. Immune activation and haematopoietic growth factors are modulated independently of the mother but maternal factors such as IL-10 and exposure to single-dose NVP, which reduces responsiveness of CBMC, could impact on the infant. HIV-1 specific cellular immune responses at birth, which are elicited in a proportion of infants born to HIV-1 positive mothers, are of immunological significance and can predict lack of subsequent infection. Disturbances in thymic output are not readily detectable at birth when using TREC to assess de novo T-cell synthesis, alternatively there is a homeostatic balance between thymic output and peripheral T-cell proliferation in newborns of HIV-1 infected mothers. Overall our data suggests that (i) there are immune consequences of being born to an HIV-1 positive mother, (ii) short-course antiretroviral prophylaxis does impact on the developing immune system of the infant and (iii) while the direct effects of single-dose NVP are not disputed, there are indirect consequences of NVP exposure on immune cells. Despite the consequences of HIV-1 exposure or the result of being born to a HIV-1 seropositive mother or exposure to single-dose NVP, our data proposes that the immune system of newborn infants is capable of responding as demonstrated by the enhanced immune activation. It remains important to determine the correlates of immune protection for the development of novel immuno-therapeutic and vaccine strategies and maternal-infant transmission of HIV-1 provides a model which can address questions of protective immune processes. Understanding the influence of antiretrovirals on immune processes remains an important component of the drug mechanisms, (aside from their direct antiretroviral activity), that may underlie reductions in maternal-infant transmission of HIV-1. Furthermore, how antiretrovirals influence immune processes and immune development (together with exposure to HIV-1/consequences of being born to an HIV-1 seropositive mother), may impact on subsequent immune responsiveness to infectious organisms or childhood vaccines.

Background and purpose: Tuberculosis (TB) is one kind of chronic infectious disease which caused by the mycobacterium tuberculosis, and still widely exists in the world. In Taiwan, there are approximately 15,000 new tuberculosis patients and 1,300 died annually. The incidence and mortality rate rank the number one among the legal reported disease in Taiwan. Therefore, how to prevent and control the tuberculosis becomes a crucial policy for Centers for Disease Control (CDC) in Taiwan. Directly Observed Treatment, Short-course (DOTS) is a TB control program implemented in many countries aggressively by the World Health Organization (WHO) since 1993. The implementation method is that patients are supervised by well-trained health care staff while medication is administered, to assure the clients taking each dose of medicine. This policy is intended to cure the patient in time, cutting off the infectious sources, prevent the efficacy of anti-tuberculosis drugs and cease the emerging of multidrug resistant tuberculosis (MDRTB) . For the long-term planning and the target of ¡§Halve the TB over the next ten years,¡¨ the CDC of Taiwan has been enforced the DOTS program since April 1st, 2006. The rate implementing DOTS in smear- positive case has been exceeded 90%. The purpose of this study is to examine the effect of DOTS policy on the outcomes of Tuberculosis before and after the DOTS policy implementation. Methods: The secondary databases from the study hospital were retrieved. The data included 24 months before and after the DOTS implementing (April 1st, 2006). We investigated if there¡¦s significant improvement in treating tuberculosis after the DOTS. Both descriptive and Chi-square tests were used to depict the study sample and to examine the correlation between treatment outcome and DOTS, respectively. Results: There is no difference on treatment outcome between male and female. Male had higher cavity formation on the chest x-ray. There¡¦s more easy treatment completion when the clients were younger than 65 years old. No cavity on the chest x-ray was statistically associated with negative acid fast stain. The chest x-ray showed cavity was related to higher completion rate of treatment. There¡¦s no correlation between the acid fast stain and treatment completion. There¡¦s no significant difference on treatment outcome after the DOTS implementing. Conclusions: There¡¦s no difference in treatment result between the ¡§DOTS¡¨ and ¡§without DOTS¡¨ group after April 2006. The reason we deliberate that may be the study hospital is located at the urban area, which is high prevalence area in tuberculosis and thus have been under control for years. The completion rate in tuberculosis treatment is already high enough. No wonder there¡¦s no such difference. Anyway, we can not ignore the policy of the DOTS, we must keep cooperation with this policy, make great efforts on tuberculosis prevention and control in Taiwan.

Community developers are often solicited to teach essential core concepts and strategies in the field but lack the consensus among their peers on which theories constitute the fundamentals. This study examines leading community development theories, concepts and approaches to establish the essential elements for a weeklong short course. In addition to content research, leading teaching theories were also explored to establish the core methods for teaching such a course. Active learning techniques were utilized to increase student participation in the learning process while building solidarity and capacity in the class. Finally, the short course was taught to a group in Banda Aceh, Indonesia and was evaluated for knowledge and attitude change through pretests, posttests, and journal entries.

Magister Public Health - MPH / Tuberculosis (TB) is a major health problem worldwide, with an estimated 9 million new cases accounting for an estimated 1.5 million deaths in 2012. Non-compliance with TB treatment has become a major barrier to achieving global TB control targets. Namibia is one of the worst affected countries in Africa with a high case notification rate (CNR) of all forms of TB and relatively low treatment success rate compared to the WHO targets. The study aimed at investigating TB treatment compliance and measuring its association to patient characteristics and treatment outcomes, in determining the effects of compliance on treatment outcomes in Windhoek District. This information is crucial for TB programme management and development of targeted strategies. A quantitative observational analytic study using a retrospective cohort design was adopted. New adult Pulmonary Tuberculosis (PTB) patients treated under DOTS in Windhoek District between 1st January 2013 and 31st December 2013 were included in the study based on specified criteria. Data was collected from the patients TB treatment cards using an extraction tool. Selection and information bias was eliminated by using clearly defined inclusion and exclusion criteria using a pre-tested standardised tool. Statistical analysis using descriptive and analytic statistics was done using Epi Info 7 to determine compliance, treatment outcomes and to measure the associations. Overall treatment compliance (89%), initial phase compliance (97.2%) and continuation phase compliance (88.1%) were reported in the study. Age (OR=4.3 95% CI (1.72 – 9.90), p-value=<0.01) and type of area (OR=0.02 95% CI (1.00 – 1.13), p-value=0.05) were associated with compliance in the continuation phase. Overall, type of area (OR=0.03 95% CI (0.00 – 0.91), p-value=0.04) remains associated with treatment compliance. Treatment success is reported among 86.1% of patients. Poor treatment outcomes are associated with non-compliance in the initial phase ( =49.98, p-value=<0.01), continuation phase ( =98.81, p-value=<0.01) and overall ( =110.02, p-value=<0.01). Overall treatment compliance (89%) although higher than expected was lower than the WHO recommended 90% compliance. Very high compliance (97.2%) were reported in the initial phase of treatment whilst compliance was also lower than desired (88.1%) in the continuation phase. Non-compliance recorded in the continuation phase is in agreement with the literature. Age and type of area are associated with compliance as reported in the continuation phase and overall in this study is new contribution of knowledge. The findings suggest that treatment compliance is associated with treatment success in both phases of treatment and overall. Low compliance especially in the continuation phase could lead to poor treatment outcomes such as prolonged infections, relapse, high TB mortality and drug resistance leading to increased programme costs. The study concludes that non-compliance results in poor treatment outcomes highlighting the need for interventions that address compliance in all phases but specifically within the continuation phase and amongst those at risk of having reduced compliance such as those in rural areas and young adult patients aged (15 – 34 years). Recommendations to the District Management Team and TB Programme Managers include: identification of measures that promote treatment compliance; support and monitoring of TB patients’ compliance continuously; strengthening CB-DOT by increasing CB-DOT points and enhancing CB-DOT supporters’ capacity as well as strengthening record keeping as a monitoring tool to increase compliance and improve treatment outcomes.

Tuberculosis is one of the worlds? deadliest infectious diseases, and is one of the major causes of morbidity and mortality especially in poor countries. In Zambia, Tuberculosis remains a major health problem and is among the top ten causes of morbidity and mortality. Tuberculosis notifications have increased 5- fold in the last 20 years, mainly due to HIV/AIDS, it is estimated that approximately 70 % of all detected tuberculosis cases are also co-infected with HIV. The interaction of tuberculosis with the human immunodeficiency virus (HIV) infection has complicated and made difficult the Tuberculosis control program. Tuberculosis has become the leading cause of death among people living with HIV/AIDS. The management of tuberculosis in Zambia is faced with many challenges, such as lack of compliance to treatment by patients, poverty as well as lack of adequate finance for diagnosis, treatment and follow-up care. The main aim of my thesis was monitoring the problem of tuberculosis in Zambia, other accompanying aims were to find out how well informed the Zambian population is, about tuberculosis, monitor the diagnostic procedure for tuberculosis, analyse the tuberculosis treatment regime and lastly to analyse the preventive measures that have been implemented and how effective they have been. In this thesis, both qualitative and quantitative types of research were used. With the qualitative research, secondary analysis of data was used. Data from different sources of information like books, publications and research findings of various surveys and researches that were done not only by the Zambian Ministry of Health but also by other organizations was used. With the quantitative research, a questionnaire was formulated whose main aim was to find out about how well informed the Zambian people are about tuberculosis. This was done only in the capital city of Zambia which is Lusaka, and the number of respondents was 100. From the results obtained, the tuberculosis burden in Zambia still remains high and tuberculosis continues to be a serious public health problem. The implementation of the various preventive measures, though still facing difficulties, has however yielded positive results. There have been improvements in the treatment success rates from 77 % in the year 2000 to the current 86 %, the incidence rate per 100 000 population has also reduced from 504 in the year 2000 to the current 365 per 100 000 population. This reduction in incidence rates can be attributed to the preventive measures like the expansion of directly observed therapy treatment ? shortcourse (DOTS)strategy to all the districts in the country, the strengthening of the National Tuberculosis Control program and many others. This work can be used as a source of reference for future research in relation to the topic of tuberculosis in Zambia.

Magister Public Health - MPH / Background: The incidence of tuberculosis in South Africa last measured at 834 in 2015 as reported by the World Bank. Out of these cases, only 54% cured and 13% of patients stop taking treatment. In Pretoria, Gauteng, comprehensive TB services are available in 87% of clinics and all these clinics offer the Directly Observed Treatment Short-course (DOTS) programme and help to diagnose TB and trace contacts. However, the average Pretoria district DOTS coverage has decreased from 88.8% to 84.7% in the last few years. The health district's cure rate as at 2012 is 61%, and its average rate of successful treatment of all new smear positive cases is 66% since 2005. Certain factors that determine patients' adherence towards TB treatment have been identified to include demographic, psychosocial and health system related factors. However, the WHO identified factors responsible for or predisposing patients to discontinue the DOTS programme have not been investigated in the study setting. Aim: The aim of this study was to assess the determinants of adherence to DOTS therapy amongst TB patients who commenced TB treatment at the TB clinic of a district hospital during April – June 2014. Methodology: A quantitative study was conducted using a descriptive cross-sectional design. An inclusive sample was drawn from adults in the DOTS programme receiving first line treatment during the 6-month period prior to commencement of the research. The calculated sample size was 234 individuals. The data collection tools included a questionnaire, 2-day recall and 30-day recall instruments and pill counts. Data were analysed using EPI info version 7 which included descriptive statistics to measure level of adherence. Associations between identified factors and adherence to TB treatment were also determined. Results: The final sample size was 80 participants of which 76% were male. The mean composite adherence rate was found to be 94% while the proportion of the patients who achieved adherence of 95% and above was 75%. Identified barriers to adherence include forgetfulness, lack of transport fare on clinic appointment days, patients not feeling well and so were not strong enough to attend clinic appointments. On the other hand, the role of treatment supporters and counseling were found to have a positive impact on adherence to DOT in this setting. The use of reminders such as cell phones and alarm-radios were also identified as facilitators to adherence. Patients' knowledge of consequences for not taking medications as prescribed, which is closely linked with counseling, was found to be significantly associated with adherence in this study. Education status of participants was found to be significantly associated with adherence to DOTS (p = 0.01), when considering the pharmacy refill pill count as the adherence measure. Significant association was found between DOTS treatment regimens and 30-day recall adherence measures (p = 0.002). Significant association was also found for medication side effects and the adherence measures of 2-day recall, 30-day recall and pill count with p = 0.04; p = 0.03; p = 0.05 respectively There were significant associations between age and adherence with two of the adherence measures (30-day recall and pill count) at p = 0.002 and p = 0.003 level of significance respectively. Significant association was observed between duration of DOTS treatment when dichotomised using the mean treatment period (17 weeks) as the cut-off point and any of the adherence measures. Conclusion: The factors identified in this study can be classified into patient related factors, economic factors, social factors and health care workers and health system related factors. Furthermore, the factors at these different levels impact on one another and their improvements need to be made at all these levels to address the challenges facing TB patients to achieve optimal treatment adherence. This study is the first study of its kind in the study location and the findings have provided useful baseline data on the adherence rates and some insights into the major factors that affect adherence among patients on DOTS at a Pretoria West District Hospital. However further qualitative and quantitative studies are required to explore the factors influencing adherence further.

Abstract The thesis presents a case-study through which the linguistic purpose and historical and social context of the University of London Holiday Course in English Language for Foreign Teachers, is analysed and interpreted. The study foregrounds the context, content and development of one of the smallest academic units, a four-week short course, to contribute to our understanding of how international students of English language were taught and assessed in a particular university context in the early 20th century. The period from 1903 to 1952 is examined in order to understand why the course was successful and the impact of the work of Walter Ripman (1869-1947) who directed the course until 1939. Ripman is better known as a teacher of German and a significant figure in the German Reform Movement, which originated in 19th century Germany, but his approach to culture, phonetics and vocabulary acquisition in English language teaching and learning is less well known. The study goes beyond a history of his methodology to investigate and critically assess the formula that Ripman developed for the design of the short, university English language course and compares it with a similar course run at University College London by Daniel Jones. The changes that were made to the content and purpose of the course, following Ripman’s retirement in 1939, are examined as to how far they reflected the effects of war and the continued desire to internationalise the University itself by aligning the content of the courses more closely to the University programmes. The nature and importance of the web of relationships between staff in the success and longevity of the course are analysed and in particular the contribution of women to better understand their role in the learned world at that time. / Tiivistelmä Tässä tapaustutkimuksessa analysoidaan ja tulkitaan Lontoon yliopiston ulkomaisille opettajille suunnatun englannin kielen lomakurssin kielellisiä tavoitteita sekä historiallista ja sosiaalista kontekstia. Tutkimus nostaa tarkastelun kohteeksi yhden pienimmistä akateemisista opintokoko-naisuuksista eli neliviikkoisen lyhytkurssin ja sen kontekstin, sisällön ja kehityksen. Tavoitteena on syventää ymmärrystä siitä, kuinka kansainvälisiä englannin kielen opiskelijoita opetettiin ja arvioitiin tässä yliopistokontekstissa 1903–1952. Tutkimuksen tarkoituksena on selvittää, miksi kurssi oli menestyksekäs ja mikä rooli tässä oli Walter Ripmanilla (1869–1947), joka johti kurssia vuoteen 1939 asti. Ripman tunnetaan saksan kielen opettajana ja tärkeänä hahmona kieltenopetuksen uudistustyössä, joka alkoi 1800-luvulla Saksassa, mutta hänen englannin opetukseen ja oppimiseen liittyvät näkemyksensä kulttuurista, fonetiikasta ja sanaston oppimisesta ovat vähemmän tunnettuja. Tutkimuksessa tarkastellaan Ripmanin metodologian historiaa mutta arvioidaan myös kriittisesti yliopistollisen englannin kielen lyhytkurssin toimintamallia, jota hän kehitti. Mallia verrataan vastaavaan kurssiin, jota Daniel Jones johti Lontoon University Collegessa. Työssä tutkitaan niitä muutoksia, joita tehtiin kurssin sisältöön ja tavoitteisiin sodan jälkeen, kun Ripman oli jo siirtynyt eläkkeelle. Muutoksia tarkastellaan suhteessa yliopiston kansainvälistämispyrki¬myksiin ja toiveisiin suunnata kurssisisältöä yliopiston tutkinto-ohjelmien mukaisesti. Lisäksi tutkimuksessa kiinnitetään huomiota henkilökunnan keskinäisten verkostojen luonteeseen ja merkitykseen kurssin menestykselle ja pitkäikäisyydelle sekä erityisesti naisten panokseen ajan akateemisessa maailmassa.

Η φυματίωση είναι λοιμώδης νόσος μεταδιδόμενη αερογενώς και προκαλούμενη από βακτήρια τα οποία ανήκουν στην ομάδα των Μυκοβακτηριδίων και ιδιαίτερα στο σύμπλοκο της φυματιώσεως (Mycobacterium tuberculosis complex). Τα τελευταία χρόνια αποτελεί ένα επιδεινούμενο πρόβλημα δημόσιας υγείας ανά την υφήλιο, με επίπτωση παγκοσμίως για το 2007 139/100.000 πληθυσμό, ενώ για την Ευρώπη 54/100.000 και για την Ελλάδα 5,9/100.000 πληθυσμό. Η σωστή καταγραφή των κρουσμάτων, συμβάλλει στην πραγματική αποτύπωση του μεγέθους του προβλήματος και των χαρακτηριστικών της νόσου και θα οδηγήσει σε αποτελεσματικές θεραπευτικές παρεμβάσεις, ώστε να επιτευχθούν και στη χώρα μας οι στόχοι που έχει θέσει η ΠΟΥ, δηλαδή ο περιορισμός κατά το ήμισυ της νοσηρότητας και των θανάτων από φυματίωση έως το 1015, συγκριτικά με το 1990 και η εκρίζωση της νόσου έως το 2050. Στην παρούσα μελέτη έγιναν αρχικά δύο επιδημιολογικές έρευνες που αφορούσαν: α) την επιδημιολογία της φυματίωσης στη Δυτική Ελλάδα και την αξιολόγηση της πληρότητας των υποχρεωτικών δηλώσεων (2000-2003) καθώς και β) την εκτίμηση του δείκτη διαμόλυνσης σε μαθητικό πληθυσμό του Νομού Ηλείας (1994-2000). Σκοπός μας ήταν να περιγραφεί και να αναλυθεί η επιδημιολογία της φυματίωσης στη Δυτική Ελλάδα (Νομοί Ηλείας, Αχαΐας, Αιτωλοακαρνανίας), ώστε να εξετασθεί η επάρκεια ολόκληρου του συστήματος επιτήρησης και ελέγχου για τη δηλωτέα αυτή νόσο στο ΚΕΕΛΠΝΟ, καθώς και να αξιολογηθεί η εξέλιξη του δείκτη διαμόλυνσης της φυματίωσης στο νομό Ηλείας, στα πλαίσια πρόληψης της νόσου. Για τον λόγο αυτό, χρησιμοποιήθηκαν επίσημα στοιχεία από την ΠΟΥ, το ΚΕΕΛΠΝΟ, τις Νομαρχιακές αυτοδιοικήσεις, αλλά και αρχεία των νοσοκομείων ENΝΘΔΕ, του ΠΓΝ Πατρών, καθώς και του Κέντρου Υγείας Γαστούνης. Εν συνεχεία, μελετήθηκε η εφαρμογή της Άμεσα Επιτηρούμενης Θεραπείας (DOTS) σε 13 νεοδιαγνωσθέντες ασθενείς με φυματίωση, συγκριτικά με την έκβαση 41 πρώην διαγνωσθέντων ασθενών (μάρτυρες) χωρίς ΑΕΘ, αλλά με την έως τώρα συντηρητική αντιμετώπιση, όλοι κάτοικοι του Νομού Ηλείας. Για την ολοκλήρωση της μελέτης υπήρξε συνεργασία του Πνευμονολογικού Ιατρείου του Γ.Ν. Πύργου με τον ειδικά εκπαιδευμένο Γενικό/Οικογενειακό Ιατρό, ο οποίος πραγματοποιούσε τις κατ΄ οίκον επισκέψεις και προσωπικές συνεντεύξεις στους νέους ασθενείς, στους μάρτυρες αλλά και στα μέλη των οικογένειών τους. Για την στατιστική ανάλυση των αποτελεσμάτων μας, χρησιμοποιήθηκε το πρόγραμμα SPSS (11,0 – 15,0). Από επιδημιολογικές μελέτες προκύπτει ότι οι χώρες της Ευρωπαϊκής Ένωσης παρουσιάζουν μια σταθερή μείωση του μέσου όρου επίπτωσης της φυματίωσης το διάστημα 1986-2006, με την Ελλάδα να έχει τις μικρότερες τιμές (4,7/100.000 το 2001 και 6/100.000 το 2007). Με βάση όμως «ενδεικτικές» επιδημιολογικές μελέτες-έρευνες της φυματίωσης στον Ελλαδικό χώρο σε αντίστοιχα διαστήματα, προκύπτει διακύμανση της επίπτωσης από 16 – 73/100.000. Αναφορικά με την έρευνά μας στη Δυτική Ελλάδα, η μέση ετήσια επίπτωση βρέθηκε να είναι 5,4 ανά 100.000 άτομα (4 Αχαΐα, 6 Αιτωλοακαρνανία, 7,2 Ηλεία), ενώ τα επίσημα στοιχεία από το ΚΕΕΛΠΝΟ παρουσιάζουν μόνο 3,8 κρούσματα ανά 100.000 πληθυσμό. Στην μελέτη μυκοβακτηριδιακής διαμόλυνσης για τον μαθητικό πληθυσμό του νομού Ηλείας, συγκρίνοντας τις δύο τριετίες 1994-1996 και 1998-2000, ο Μ.Ο. εξάπλωσης του ΔΜΔ για τους μαθητές του Δημοτικού μειώθηκε από 0,7% σε 0,16%, ενώ στους μαθητές του Γυμνασίου παρατηρήθηκε μια μικρή πτώση, από 2,51% σε 2,41%. Σε επίπεδο γειτονικών νομών (αλλά και αναπτυγμένων χωρών), ο μέσος φυματινικός δείκτης είναι <1%, ενώ ως εκρίζωση κατά την Π.Ο.Υ. νοείται ο περιορισμός του Δ.Δ.<0,1%. Με βάση τις διεθνείς οδηγίες, η θεραπευτική αντιφυματική αγωγή αποτελείται από INH, RIF, PZA και EMB για 2 μήνες και για τους επόμενους 4 μήνες χορηγούνται μόνο INH και RIF. Κατόπιν αξιολόγησης των αποτελεσμάτων της προοπτικής μας μελέτης υπό το πρόγραμμα DOTS, προκύπτει ότι τα ποσοστά επιτυχούς θεραπείας ήταν 84,6% (προσεγγίζοντας το κατώτερο 85% που έχει θέσει ο WHO), εκ των οποίων 69,2% είχαν αρνητικά πτύελα στο τέλος της θεραπείας και 15,4% ολοκλήρωσαν την θεραπεία χωρίς μικροβιολογική εξέταση πτυέλων (2 αθίγγανοι που δε συνεργάστηκαν). Αξίζει να σημειωθεί, ότι ένας ασθενής απεβίωσε και ένας εξαφανίστηκε, λόγω αλλαγής πόλης στην οποία εργαζόταν. Αντίθετα, για τους μάρτυρες μόνο το 75,6% επιβεβαιώνουν αποτελεσματικότητα της θεραπείας, το 49% έλαβε 9μηνη αντιφυματική αγωγή και το 36% 12μηνη. Η σημαντικότητα της κατ’ οίκον επιτηρούμενης θεραπείας, πέραν της επιτυχούς θεραπείας των ασθενών, παρουσιάζει οφέλη και για τα μέλη. Πριν την κατ’ οίκον επίσκεψη δεν είχε γίνει η διενέργεια Mantoux στο 43,3%, από τα μέλη των ασθενών, στους οποίους και έγινε κατά την επίσκεψη στις οικίες τους από το Γενικό Ιατρό. Αντίθετα, το ήμισυ από τα μέλη των οικογενειών των μαρτύρων, κατά την διάγνωση του ασθενούς τους, δεν προσήλθαν στο νοσοκομείο για διενέργεια Mantoux. Μετά τις επισκέψεις στις οικίες από τον Γενικό Ιατρό, τηρήθηκε απόλυτα η εφαρμογή των μέτρων πρόληψης και συνθηκών διαβίωσης (αερισμός, φωτεινότητα, καθαριότητα, συγχρωτισμός, κ.τ.λ.) στα μέλη των ασθενών. Στα δε μέλη των μαρτύρων ούτε εκεί εφαρμόζονταν σωστά (92,3%) μέτρα πρόληψης – προφύλαξης και αυτό συνέβη καθ’ όλη την διάρκεια θεραπείας του ασθενούς. Σχετικά με τη νοσηρότητα των μελών, από τους 30 συγγενείς – μέλη των ασθενών, οι 4 (13,3%) χρειάστηκαν χημειοπροφύλαξη, ενώ από τους 111 συγγενείς – μέλη των μαρτύρων, οι 14 (12,6%) χρειάστηκαν χημειοπροφύλαξη και οι 7 (6,3%) νόσησαν και έλαβαν θεραπεία. Συμπερασματικά, η σωστή αντιμετώπιση του προβλήματος δεν έγκειται μόνο στην έγκαιρη διάγνωση και θεραπεία, αλλά και στην αξιόπιστη καταγραφή των κρουσμάτων που θα μας ευαισθητοποιήσουν στο να αντιληφθούμε την πραγματικά ανησυχητική διάσταση του προβλήματος και να χρησιμοποιήσουμε αποτελεσματικότερους τρόπους πρόληψης και αντιμετώπισης. Για την πληρέστερη δήλωση των κρουσμάτων, θα πρέπει να υπάρχει ευαισθητοποίηση και ένα εύκολο και προσιτό δίκτυο επικοινωνίας μεταξύ του ΚΕΕΛΠΝΟ, των Νοσοκομειακών αλλά και των ιδιωτών ιατρών, των Κ.Υ. αλλά και των Νομαρχιακών Αυτοδιοικήσεων, προκειμένου να κατανοηθεί επακριβώς ο τρόπος καταγραφής και αποστολής των στοιχείων, κατόπιν διάγνωσης των κρουσμάτων. Η άμεσα επιτηρούμενη θεραπεία, στοχεύει όχι μόνο στη σωστή παρακολούθηση και ίαση των ασθενών με φυματίωση, αλλά και στην εκπαίδευση των μελών των οικογενειών τους σε θέματα πρόληψης και βελτίωσης των επιβαρυντικών παραγόντων διαβίωσης, μειώνοντας σημαντικά τη νοσηρότητα του πληθυσμού. / Tuberculosis is an infectious disease transmitted aerogen and caused by bacteria which belong to the Mycobacterium tuberculosis complex. In the past few years it constitutes an increasing problem of public health with a worldwide incidence rate of 139/100 000 population in the year 2007, while in Europe the incidence was 54 and in Greece 5.9, respectively. The accurate recording of cases contributes to the actual mapping of the burden of the disease leading thus to focused therapeutic interventions, which can be also achieved in our country, according to the goals set by WHO, i.e. the decrease of morbidity and mortality from tuberculosis at least the half until 2015, in comparison to 1990 and the eradication of the disease until 2050. In the present research two epidemiologic studies were carried out, concerning a) the epidemiology of tuberculosis in Western Greece and the evaluation of completeness of TB notifications (2000-2003), b) the estimation of tuberculin status in school population in the Prefecture of Ilia (1994-2000). The aim of the studies was to described and analyze the epidemiological characteristics of tuberculosis in Europe in comparison to Greece, to describe and analyze the epidemiology of tuberculosis in Western Greece (Prefectures Ilia, Achaia, Etoloakarnania) and to evaluate the completeness of TB notifications in order to examine the effectiveness of the surveillance system and the effectiveness of disease control and prevention, as well as to evaluate the tuberculin status in the prefecture of Ilia, in order to examine if satisfactory progress has been achieved in the control and prevention of tuberculosis. For these purposes, official data of WHO, KEELPNO (Hellenic Centre of Disease Control), the local and prefectoral self-administrations were used, as well as records of the hospitals in the examined area and of the Health Centre of Gastouni. Furthermore, a study was carried out, implementing a Directly Observed Treatment Short Course (DOTS) programme in the prefecture of Ilia (Western Greece) and assessing the efficacy of the WHO-recommended strategy in 13 newly detected pulmonary tuberculosis cases in comparison to 41 TB cases managed conventionally. In collaboration with the clinic of pulmonology of the general hospital of Pyrgos a general practitioner who was educated in DOTS strategy carried out home visits and completed a questionnaire in a face-to-face interview with the newly diagnosed patients, the past treated patients as well as the household members of the patients. All statistical analyses were performed using SPSS for Windows (v.11.0 – v.15.0). According to the results of the epidemiological studies, the countries of the European Union present a steady decline of the average incidence of tuberculosis (<20/100 000), with Greece presenting the lowest rates (4.7/100 000, 2001). Based on other “indicative” epidemiological studies carried out in Greece, the incidence of tuberculosis varies from 16 – 73, respectively. In regard to the study performed in Western Greece, the mean annual incidence was found to be 5.4 (4 in Achaia, 6 in Etoloakarnania and 7.2 in Ilia), respectively, while the official data from KEELPNO for Western Greece revealed only 3.8 cases per 100 000 population. Finally, for the school population in the prefecture of Ilia, comparing the two three-year periods from 1994-1996 and 1998-2000, the mean prevalence of positive tuberculin status in the primary schoolchildren declined from 0.7% to 0.16%, while in the secondary schoolchildren we observed a very small decline, from 2.51% to 2.41%. In the neighboring prefectures (but also in developed countries), the mean prevalence of positive tuberculin status is <1%, while as indicator for eradication WHO determine a positive tuberculin status<0.1%. Based on the international guidelines, the antituberculosis therapy comprises INH, RIF, PZA and EMB for 2 months and for the following next 4 months only INH and RIF are taking. The evaluation of the results of the prospective DOTS study shows treatment success in 84.6% (approximating the lower limit of 85% set by the WHO), out of them 69.2% had negative saliva swab test at the end of treatment and 15.4% completed the treatment without microbiological examination of the saliva (2 gypsies who showed non compliance). One case under DOTS programme died during the study and one was lost to follow-up, because of change of residence. On the contrary, among the past treated cases 75.6% confirmed treatment effectiveness, in 49% after 9 month therapy duration and in the 36% after 12, respectively. The importance of the Directly Observed Treatment Short Course, beyond the successful treatment of patients, presents benefits also for the household members. Before the 1st home visit, Mantoux test was not carried out in 43.3% of the household members, but performed in all members during the 1st home visit by the general practitioner. On the contrary, 50% of the household members of the past treated patients had not carried out Mantoux test after diagnosis confirmation in the past treated patients, since they did not visit the hospital/health center for vaccination. After the doctor’s home visits, the family members adhered to the preventive measures and adequate living conditions (airing, brightness, cleanness, etc.). In the members of past treated patients the preventive measures were not met in 92.3% during the whole treatment period. With regard to the morbidity of the members of DOTS patients, from the 30 household members 4 (13.3%) needed chemoprophylaxis, while from the 111 members of past treated patients, 14 (12.6%) needed chemoprophylaxis and 7 (6.3%) antituberculosis treatment. In conclusion, the adequate confrontation of the problem does not lie only in the early diagnosis and treatment of TB, but also in the reliable notification of cases, in order to create public awareness of the burden and to implement more effective control and prevention measures. For optimal monitoring a more accurate and to all accessible communication network with proper and sincere co-operation between all actors (KEELPNO, hospitals, doctors in private praxis, health centers and prefectoral self-governments) is needed, in order to improve the accuracy of the notification system. The Directly Observed Treatment Short Course aims not only in the appropriate control and cure of the TB patients, but also in the education of the household members, in regard to prevention and improvement of aggravating risk factors, decreasing thus considerably the burden of the disease.

The purpose of this study is to explore and describe the knowledge, attitudes and experiences of health care workers who care for patients receiving treatment under DOTS strategy at public health facilities in the Windhoek District of the Khomas Region. A qualitative explorative, descriptive and contextual research design was used in this study. A purposive sampling was used to select participants who met the inclusion criteria for the study. The inclusion criteria was to be a health care worker who at the time of the study was working with patients who are on DOT for at least 6 months. A semi-structured interview guide was used to collect data. The study was conducted in the Windhoek district of the Khomas region, with a sample of 14 health care workers. Data was analysed by means of content analysis, a process of organizing and integrating narrative, qualitative data according to emerging themes and concepts. The three themes, which emerged from data analysis, were the knowledge of health care workers regarding the implementation of DOTS, the attitudes of health care workers towards patients on DOT which may affect the success of their treatments, and the experiences of health care workers when attending to patients on DOTS. The findings from the study may be used to engage stakeholders to address the shortcomings that exist in the implementation of the DOTS strategy in the district. / Health Studies / M.A. (Nursing Science)

The purpose of the study was to develop a short course to inculcate the spirit of Ubuntu amongst the student nurses at Limpopo College of Nursing at Limpopo Province. A sequential explanatory research design was used and data was collected from one hundred and fifteen student nurses at the three (3) campuses for quantitative phase by means of structured interviews and ten (10) level III student nurses from each campus for qualitative phase by means of focus group discussions and reflective diaries. Ten (10) lecturers at the three campus participated in focus group discussions. Quantitative data analysis was done through descriptive analysis and findings were presented in frequencies, tables and charts. The qualitative data analysis was done through Tesch’s eight steps. There were similarities and differences in the themes and subthemes that were presented by all participants. There were also conflicting views from the same participants during qualitative and quantitative phases. The excerpts were presented to support all themes. The study found that Ubuntu needs to be inculcated through formal teaching and mentoring and that Ubuntu should be included in curriculum. Limpopo College of Nursing consists of student nurses from diverse cultures most of which are: Tsonga, Venda and Northern Sotho. They render nursing care to people of diverse cultures as globalisation has encouraged people to travel to different places. Media portrayal of the nursing care in public hospitals and clinics in South Africa is that of negativity. This is partially valid because, for example, the deterioration in nursing care in the public hospitals and clinics is as well evident in Limpopo Province in Mopani District (Bond 2002:1; Mohale & Mulaudzi 2008:61). Furthermore, Ubuntu is not effective if there is no correlation of theory and practice and evaluation of it in the clinical areas. Based on the findings and conclusion of the study, a short course on Ubuntu was developed after the consensus was reached among the participants and the experts who were consulted. / Health Studies / D. Lit. et Phil. (Health Studies)