In der vorliegenden Arbeit wurden die Ergebnisse von 263 Einzeltierverfolgungen in 12 Betrieben in verschiedenen Regionen in Deutschland, Belgien, Frankreich und der Tschechischen Republik zur Stallkokzidiose der Kälber zusammengefasst ausgewertet. Während diesen Untersuchungen wurden 5840 Kotproben beurteilt. Dabei wurden das Auftreten und die Ausprägung der Eimeriose der Kälber analysiert und potentielle Einflussfaktoren untersucht und ein verlässlicher Schwellenwert für die Bewertung der Oozystenausscheidung ermittelt. Weiterhin wurden in 16 Betrieben bei 23 gemeinsam aufgestallten Kälbergruppen Spezies-Prävalenzuntersuchungen über einen Zeitraum von fünf Wochen durchgeführt. Hierfür wurden 5133 Proben ausgewertet, davon 3519 mit Teil- und 1614 mit vollständiger Differenzierung. In allen Betrieben traten die Kotkzidiosen als eine Mischinfektion verschiedener Eimeria-Arten auf. Dabei herrschte in der Regel in jedem Betrieb eine der beiden pathogensten Spezies vor. Diese Prädominanz blieb auch über mehrere Jahre gleich in den Betrieben. Die Herkunft der Kälber hatte einen Einfluss auf den Infektionsverlauf. In Betrieben mit ausschließlich eigener Nachzucht verläuft die Kokzidiose als eingipflige Infektion, bei Zukaufbetrieben ist der Infektionsverlauf zweigipflig. Ein signifikant erhöhtes Risiko des Auftretens einer klinisch ausgeprägten Kokzidiose bei Aufstallung auf Stroheinstreu im Vergleich zur Haltung auf Spaltenboden konnte bewiesen werden (p = 0,005). In der Verfolgungsuntersuchung korrelierten die Kokonsistenzwerte mit den nachgewiesenen OpG in den Kotproben positiv signifikant (0,135 Korrelationskoeffizient; p = 0,000). Für das Auftreten von Durchfall konnte eine statistisch bewiesene lineare Korrelation mit der Oozystenausscheidung für diverse Schwellenwerte festgestellt werden (p = 0,000). Bei einem Grenzwert von 500 OpG lag der Korrelationskoeffizient bei 0,149. Die Korrelationswerte erhöhten sich nicht wesentlich bei Festlegung eines höheren Grenzwertes für die Oozystenausscheidung oder sanken sogar (0,153 bis 0,121). Bei der Verrechnung von Durchfallvorkommen mit gleichzeitiger, potentiell relevanter Oozystenausscheidung mit den verschiedenen Schwellenwerten der Oozystenausscheidung konnte der höchste Zusammenhang zwischen dem Durchfallgeschehen und dem Schwellenwert von 500 OpG bewiesen werden (0,633 Korrelationskoeffizient; p = 0,000). Daher kann ein Wert von 500 OpG pathogener Eimeria spp. als geeigneter Schwellenwert für die Feststellung einer relevanten Oozystenausscheidung angesehen werden. Bei gleichzeitigem Auftreten von Durchfall ist von einer maßgeblichen Beteiligung der Eimerien auszugehen. Ein gehäuftes Auftreten von mit Oozystenausscheidung assoziierten Durchfällen trat bei Tieren ohne oder ohne potentiell relevante Oozystenausscheidung (‚rK -’) signifikant seltener auf (p = 0,000) als bei Tieren mit mindestens 500 aufsummierten OpG während des gesamten Beobachtungszeitraumes (‚rK +’). Kälber der Kategorie ‚Kok-Kat 1’ hatten signifikant niedrigere Kotkonsistenzwerte und weniger Durchfälle als Tiere der Subpopulation ‚rK -’ (p = 0,000). Dagegen hatten die Tiere der Auswertungsgruppe ‚Kok-Kat 2’ statistisch bewiesen in allen Durchfall-Kategorien höhere Werte bzw. ein häufigeres Durchfallvorkommen als beide anderen Subpopulationen (p = 0,000 für alle Vergleiche). Wässrige Durchfälle mit Beimengungen traten, mit Ausnahme einer Einzelbeobachtung in Gruppe ‚rK -’, ausschließlich bei Kälbern der Auswertungsgruppe ‚Kok-Kat 2’ auf. Sowohl Kälber der Gruppe ‚rK +’ als auch ‚Kok-Kat 2’-Tiere (jeweils p = 0,000) und Kälber mit potentiell relevanter Oozystenausscheidung, aber ohne gleichzeitiges Durchfallgeschehen, (‚Kok-Kat 1’) (p = 0,005) hatten signifikant geringere relative Gewichtszunahmen als Tiere ohne bzw. ohne potentiell relevante Oozystenausscheidung (‚rK -’). Eine lineare Korrelation der Ausscheidung der pathogenen Spezies E. bovis und E. zuernii mit den absoluten (-0,098 Korrelationskoeffizient; p = 0,005) und relativen Gewichtszunahmen (-0,170 Korrelationskoeffizient; p = 0,000) konnte statistisch bewiesen werden. Bei Haltung auf Stroheinstreu zeigten Tiere ohne bzw. mit weniger als 500 ausgeschiedenen OpG im Untersuchungszeitraum (‚rK -’) signifikant höhere relative Zunahmen im Vergleich zu Tieren mit potentiell relevanter Oozystenausscheidung (p = 0,000). Dabei war es ohne Bedeutung, ob diese Kälber ein gleichzeitiges Durchfallgeschehen zeigten oder nicht. Besonders zum Tragen kommen diese Unterschiede in der Gewichtsentwicklung in den Wochen mit den höchsten Oozystenausscheidungen bei zweigipfligem Infektionsverlauf. Unter den Milchviehkälbern nahmen Tiere ohne relevante Oozystenausscheidung signifikant mehr relatives Gewicht zu als Kälber mit kumulativ mindestens 500 OpG im Untersuchungszeitraum (p = 0,004). Dies galt sowohl für Tiere mit gleichzeitigem Durchfall ‚Kok-Kat 2’ (p = 0,002) als auch tendenziell für Kälber der Gruppe ‚Kok-Kat 1’ (p = 0,059). Mastviehkälber der Gruppe ‚rK -’ zeigten signifikant höhere relative Zunahmen im Vergleich zu Tieren mit potentiell relevanter Oozystenausscheidung ‚rK +’ (p = 0,039). Dies galt auch in Relation zu den Kälbern der Auswertungsgruppe ‚Kok-Kat 1’ (p = 0,029). Während der Prävalenzuntersuchungen wurden insgesamt neun verschiedene Eimeria-Arten nachgewiesen. In Einzelkotproben wurden zwischen einer und neun verschiedene Spezies beobachtet. Unter den in Europa als heimisch bekannten Arten wurden während dieser Untersuchung lediglich E. wyomingensis, E. brasiliensis und E. bukidnonensis nicht gefunden. E. ellipsoidalis hatte sowohl die höchste Inzidenz (20,99 %) als auch die größte Intensität (arithmetischer Mittelwert von 765963,37 OpG), gefolgt von E. bovis und E. zuernii. Zudem wurde in Aufzuchtbetrieben E. ellipsoidalis in der Regel als erste Eimeria-Spezies, gefolgt von E. auburnensis und den pathogenen Arten E. zuernii und E. bovis, nachgewiesen. Die seltensten Spezies waren E. canadensis und E. pellita. Eimeria pellita wurde als letzte Art erst ab der fünften Woche nach Aufstallung beobachtet. E. cylindrica trat vermehrt in den Betrieben in Belgien und Frankreich auf. Diese Art sowie E. canadensis wurden nur in Betrieben in Bayern, Belgien und Frankreich festgestellt. E. pellita hatte, neben E. canadensis, die geringsten Prävalenzen, Nachweise wurden vor allem für zentral gelegene Betriebe sowie im Süden des Untersuchungsgebietes dokumentiert. Die Übereinstimmung der gefundenen Varianzen der Speziesprävalenzen der vorliegenden Untersuchung mit den Daten epidemiologischer Studien in den verschiedenen Regionen aus der Literatur bestätigt einen repräsentativen Charakter der Untersuchungsbetriebe. Dies belegt zusätzlich die Allgemeingültigkeit der festgestellten Einflussfaktoren auf das Auftreten und die Auswirkungen der Stallkokzidiose der Kälber. / A total number of 263 calves housed on 12 different farms in several regions in Germany, Belgium, France and the Czech Republic were followed individually in tracking studies and data was compiled and analysed to investigate factors influencing occurrence and severity of bovine eimeriosis of housed calves. The same data was used for development and verification of a suitable threshold indicating relevant oocyst excretion. Within the tracking studies a total number of 5840 faecal samples were examined for faecal consistency, oocyst counts of pathogenic E. bovis and E. zuernii excretion carried out and individual body weight development was documented regularly. Additionally 23 groups of animals on 16 farms were observed for a period of five weeks and 5133 faecal samples examined for oocyst excretion and Eimeria species differentiated. All study sites were positive for mixed coccidia species infections. Nevertheless all farms except one showed a predominance of one pathogenic Eimeria species, which remained unchanged in different groups of animals and even in different years of investigations. Animal origin, i.e. groups of animals representing own breeding or originating of only one source in contrast to groups of calves coming from several origins, influences the course of the coccidiosis infection. Farms with only one single and permanent animal origin or raising exclusively the own breeding show coccidiosis with a single peak of oocyst excretion. On farms housing groups of animals of various origins the course of infection and oocyst shedding has typically two peaks with an interval of two to three weeks. The risk for development of clinical coccidiosis rises significantly if animals were housed on straw bedding compared to slatted-floor (p = 0.005). Faecal scores correlated significantly (p = 0.000) with the intensity of oocyst excretion with a positive correlation coefficient of 0.135. For occurrence of diarrhoea a positive linear correlation with the oocyst excretion was statistically proved (p = 0.000) for various thresholds. At a threshold of 500 opg of E. bovis and E. zuernii the correlation coefficient rised to 0.149 and correlation coefficients did not rise distinctly or even got down if higher thresholds were used (values between 0.153 and 0.121). Focusing only on potentially coccidiosis related diarrhoea the threshold of 500 opg of E. bovis and E. zuernii proved to result in the highest correlation (0.633; p = 0.000) of all tested threshold levels. Therefore the threshold of 500 opg of E. bovis and E. zuernii can be accounted modest and reliable to detect a relevant oocyst excretion in individual faecal samples as well as in compiled samples. In cases of coincidental diarrhoea coccidiosis can be considered as a major factor. Increased numbers of days with diarrhoea in coincidence with an oocyst excretion (‘Kokass-DF’) within the observation period were seen significantly more often (p = 0.000) in animals with a potentially relevant oocyst excretion (‘rK +’) of at least 500 summed up opg of E. bovis and E. zuernii in comparison to calves without such an oocyst excretion (‘rK -‘). Significantly lower faecal scores and fewer days with diarrhoea were documented for calves of the group ‘Kok-Kat 1’ in contrast to animals of group ‘rK -‘ (p = 0.000). Nevertheless significantly higher faecal scores and more days with diarrhoea than both other groups were calculated for those calves meeting the inclusion criteria for group ‘Kok-Kat 2’ (p = 0.000 for all comparisons). Additionally liquid faeces or faeces with constituencies were seen only in this group, except for one single sample of a calf of group ‘rK -‘. Calves of evaluation group ‘rK +’ as well as both subpopulations representing group ‘Kok-Kat 2’ and calves with potentially relevant oocyst excretion but without diarrhoea associated to an oocyst excretion (‘Kok-Kat 1’) showed significant lower values for relative body weight increases in comparison to animals without relevant oocyst excretion throughout the complete study period of five weeks (‘rK -‘) (p = 0.000 vs. ‘rK +’ and vs. ‘Kok-Kat 2‘; p = 0.005 compared with ‘Kok-Kat 1’). A negative linear correlation between oocyst excretion of pathogenic Eimeria spp. and absolute (-0.098 correlation coefficient; p = 0.005) as well as relative body weight gain (-0.170 correlation coefficient) was verified statistically (p = 0.000). Animals housed on straw bedding and belonging to the group ‘rK -‘ gained relatively more body weight in comparison to calves housed in the same stables and meeting the inclusion criterium of group ‘rK +’, i.e. excreting at least 500 summed up opg of pathogenic E. spp., (p = 0.000) within the total study period. The presence of coincidental diarrhoea had no impact on impaired body weight development of animals with a potentially relevant coccidia excretion. Differences in body weight development were most distinct within the weeks of highest intensities in oocyst excretion according to a course of infection with two peaks. Within the subpopulation of dairy calves those animals belonging to evaluation group ‘rK -‘ developed significantly higher relative body weight gains compared to group ‘rK +’ (p = 0.004). Similar results were found for animals of group ‘Kok-Kat 2’ (p = 0.002) and a statistical tendency was calculated for group ‘Kok-Kat 1’ (p = 0.059) in comparison to group ‘rK -‘. Analogous to the differences in dairy calves animals on fattening farms without relevant oocyst excretion (‘rK -’) had significantly higher relative body weight gains compared to calves of evaluation group ‘rK +’ (p = 0.039) and animals of group ‘Kok-Kat 1’ (p = 0.029) of the same breeds and farms. Nine different Eimeria spp. were detected during the prevalence studies. In single individual samples a minimum of one and up to nine different species were found. Twelve Eimeria spp. are known to be endemic in Europe of which only E. brasiliensis, E. bukidnonensis and E. wyomingensis were not present in any faecal sample in this study. E. bovis and E. zuernii were only second to E. ellipsoidalis which had the highest prevalence (20.99 %) as well as the highest intensity (765963.37 mean opg) in the faecal samples examined. In breeding farms E. ellipsoidalis was the first species to be found in faecal examination in most cases, followed by E. auburnensis and the pathogenic species E. zuernii and E. bovis. E. canadensis and E. pellita were detected only in a low number of samples. E. pellita was observed for the first time at the faecal samplings five weeks after stabling and mainly in farms situated in the central and southern region of the prevalence study. E. canadensis and E. cylindrica were most prominent in farms situated in Belgium and France. Variances in prevalence of the species observed are in conformity with those to be found in recent literature according to the different regions of Europe. This may indicate a representative character of the farms participating in this study and therefore universal validity of the results and impactfactors on coccidiosis in calves described in this manuscript.

Die Dissertation mit dem Titel “Battle and Beating, Water and Waste: Micro-Level Impact Evaluation in Developing and Emerging Economies” beinhaltet die Ergebnisse ökonometrischer Wirkungsevaluierungen, die innerhalb zwei verschiedener Themengebieten des täglichen Lebens in Entwicklungs- und Schwellenländern durchgeführt wurden: Gewalt und Wasser. Im ersten dieser Themengebiete konzentriert sich die Analyse auf die Verhaltens-Reaktionen der Bevölkerung, die in räumlicher Nähe zu gewaltsamem Konflikt lebt. Detailliert die Wirkung solcher Exponierung auf das Auftreten häuslicher Gewalt untersuchend, trägt das erste Kapitel – gemeinsam verfasst mit Dominik Noe – dazu bei, die gesellschaftlichen Kosten kriegsähnlicher Auseinandersetzungen abzuschätzen. Insbesondere die Nachwirkungen auf zwischenmenschliche Beziehungen und soziales Verhalten gegenüber Familie und Freunden werden betrachtet. Wir formulieren die Theorie, dass das Leben in Haushalten in der Nähe zu Orten von extrem gewaltsamen Zwischenfällen die Wahrscheinlichkeit von Frauen in diesen Haushalten erhöht, Opfer häuslicher Gewalt zu werden. Diese Theorie überprüfen wir dann anhand von Daten aus Kolumbien; einem Land, in dem sowohl reichhaltige Daten zu Gefechten als auch zu häuslicher Gewalt vorliegen. Die Kernerkenntnis lautet, dass eine höhere Intensität der gewaltsamen Konflikte mutmaßlich die Wahrscheinlichkeit der Frauen, Opfer häuslicher Gewalt zu werden, deutlich erhöht. Das zweite und dritte Kapitel dieser Dissertation sind dem zweiten Themengebiet gewidmet, und hier insbesondere Aspekten des Anschlusses von Haushalten an Leitungswasser und moderne Abwasser-Entsorgung. Das zweite Kapitel – gemeinsam verfasst mit Stephan Klasen, Tobias Lechtenfeld und Kristina Meier – untersucht die Wirkung des Anschlusses von Haushalten an Leitungswasser und Abwasser-entsorgung auf Gesundheit sowie Schul- und Arbeitsplatz-Anwesenheit. Es trägt zu der derzeit noch überschaubaren Anzahl von Wirkungsevaluierungen im Wasser- und Abwasserbereich bei, und ist nach Kenntnis der Autoren die erste rigorose Wirkungsevaluierung im städtischen Umfeld. Quasi-experimentelle Methoden und Wasserqualitäts-Tests unter Berücksichtigung von ungleichmäßiger Infrastruktur-Ausbreitung erlauben es, die Wirkungen separat einerseits für Anschluss lediglich an Leitungswasser, als auch andererseits für zusätzlichen Anschluss an Abwasserentsorgung, zu schätzen. Die Kernerkenntnis lautet, dass Anschluss an Leitungswasser in jemenitischen Städten schädlich sein kann, wenn die Wasserversorgung unregelmäßig ist; und die Wirkung bei regelmäßiger Versorgung im Vergleich zu traditionellen und alternativen Wasserquellen sehr gering ist. Anschluss an Abwasserentsorgung scheint dagegen bei regelmäßiger Wasserversorgung zu gesundheitlichem Nutzen zu führen. Es ist regelmäßig zu beobachten, dass in Aufbereitungsanlagen entkeimtes Leitungswasser innerhalb des Haushaltes rekontaminiert wird. Wasserqualitäts-Tests an Testpunkten entlang der Versorgungskette innerhalb des Haushaltes erlaubt Rückschlüsse auf Ort und Quelle der Kontaminierung. Der Löwenanteil dieser Verschlechterung der Wasserqualität ist auf Verhalten im Zusammenhang mit Wasser-Handhabung und Hygiene zurückzuführen. Das in Alleinautorschaft verfasste dritte Kapitel baut auf dem zweiten auf und untersucht, welche treibenden Faktoren hinter Verhaltensaspekten stehen, die Rekontaminierung verhindern würden. Spezifisch die Determinanten von Wasserbehandlung und Hygiene werden untersucht, und vor dem Hintergrund der Erkenntnisse aus dem zweiten Kapitel interpretiert. Die Kernerkenntnis lautet, dass Hygiene-Training, Zugang zu Informations- und Kommunikations-Technologie sowie Schulbildung mutmaßlich zu den relevanten, beeinflussbaren Determinanten zählen. Anschluss an Leitungswasser und Abwasserentsorgung – welche üblicherweise bestenfalls mittelfristig ausgebaut werden können – haben scheinbar ebenfalls wünschenswerte Effekte, allerdings in geringerem Maße, und in höherem Maße bei Leitungswasser als bei zusätzlicher Abwasserentsorgung.

The aim of this study was to assess and explore the household environmental health factors associated with the occurrence of diarrhoea in under five children in Sebeta town of Ethiopia, in order to develop environmental health strategies for prevention of childhood diarrhoea. A descriptive, quantitative, contextual and cross-sectional study, using stratified random sampling method, was used to conduct the research. The data collection was carried out from November 6 to 28, 2013 using structured interview schedules and a total of 477 households’ mothers/caregivers with under five children had participated in the study. In analyzing data, both bivariate and multivariate analyses were employed using SPSS software. The finding of the study shows that the prevalence of childhood diarrhoea was 9.9%. A number of risk factors including socio-demographic variables, water and hygienic practices, and knowledge risk factors showed significant association with childhood diarrhoea on bivariate analysis using chi-squared and Fischer's exact tests. Multivariate analysis using binary logistic regression was conducted to examine the significance of identified risk factors in bivariate analysis. The results of multivariate regression analysis shows that four variables were associated with risk of childhood diarrhoea; including type of toilet facility (AOR: 0.37; 95% CI 0.16 – 0.87; p=0.023), availability of specific place for handwashing (AOR: 0.40; 95% CI 0.18 – 0.90; p=0.026), availability of handwashing facility (AOR: 0.20; 95% CI 0.06 – 0.70; p=0.012) and mothers’ knowledge on diarrhoea causation (AOR: 3.09; 95% CI 1.24 – 7.68; p=0.015). Although childhood diarrhoea was found to be less prevalent as compared to national and regional prevalence rates, diarrhoea remains one of the causes of morbidity in children of the studied households. The findings of the study concludes that childhood diarrhoea has a number of environmental determinants, notably due to environmental health risk factors associated with lack of improved sanitation and hand-washing facilities and poor knowledge on diarrhoea causation. The study thus recommends that effective measures to curtail prevalence of diarrhoea in urban contexts should be substantially increased by enhancing urban sanitation promotion programmes with emphasis on accelerating universal access to improved sanitation and handwashing facilities, together with efforts in promoting proper hygiene behaviours. / Health Studies / D. Litt. et Phil. (Health Studies)

The aim of this study was to assess and explore the household environmental health factors associated with the occurrence of diarrhoea in under five children in Sebeta town of Ethiopia, in order to develop environmental health strategies for prevention of childhood diarrhoea. A descriptive, quantitative, contextual and cross-sectional study, using stratified random sampling method, was used to conduct the research. The data collection was carried out from November 6 to 28, 2013 using structured interview schedules and a total of 477 households’ mothers/caregivers with under five children had participated in the study. In analyzing data, both bivariate and multivariate analyses were employed using SPSS software. The finding of the study shows that the prevalence of childhood diarrhoea was 9.9%. A number of risk factors including socio-demographic variables, water and hygienic practices, and knowledge risk factors showed significant association with childhood diarrhoea on bivariate analysis using chi-squared and Fischer's exact tests. Multivariate analysis using binary logistic regression was conducted to examine the significance of identified risk factors in bivariate analysis. The results of multivariate regression analysis shows that four variables were associated with risk of childhood diarrhoea; including type of toilet facility (AOR: 0.37; 95% CI 0.16 – 0.87; p=0.023), availability of specific place for handwashing (AOR: 0.40; 95% CI 0.18 – 0.90; p=0.026), availability of handwashing facility (AOR: 0.20; 95% CI 0.06 – 0.70; p=0.012) and mothers’ knowledge on diarrhoea causation (AOR: 3.09; 95% CI 1.24 – 7.68; p=0.015). Although childhood diarrhoea was found to be less prevalent as compared to national and regional prevalence rates, diarrhoea remains one of the causes of morbidity in children of the studied households. The findings of the study concludes that childhood diarrhoea has a number of environmental determinants, notably due to environmental health risk factors associated with lack of improved sanitation and hand-washing facilities and poor knowledge on diarrhoea causation. The study thus recommends that effective measures to curtail prevalence of diarrhoea in urban contexts should be substantially increased by enhancing urban sanitation promotion programmes with emphasis on accelerating universal access to improved sanitation and handwashing facilities, together with efforts in promoting proper hygiene behaviours. / Health Studies / D. Litt. et Phil. (Health Studies)

[Truncated abstract] The prinicipal aim of this thesis was to explore the relationship between 3rd generation cephalosporin antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea (CDAD). This antibiotic class has been implicated in the aetiology of CDAD; therefore restriction of these antibiotics via antibiotic policies represents a potential strategy for prevention and control of CDAD. Successful control of CDAD in hospitals translates to improved quality of care for patients, and a reduction of pressure on hospital resources. Therefore, the objectives of this study were to determine whether 3rd generation cephalosporins were related to CDAD, to evaluate the effect of changes to antibiotic policy on the incidence of CDAD, and to determine the impact of CDAD on patient length of stay and hospital costs. The study was conducted in Sir Charles Gairdner Hospital (SCGH), a public teaching hospital located in Perth, the capital city of the state of Western Australia. Evidence for an association between 3rd generation cephalosporins and CDAD was obtained from studies of ecologic- and individual-level data. A time series analysis of the relationship between monthly consumption of 3rd generation cephalosporins and the incidence of CDAD in SCGH was undertaken covering the period 1994 to 2000. The results demonstrated a positive relationship between the use of 3rd generation cephalosporins and CDAD. A matched case-control study that involved 193 adult inpatients diagnosed with CDAD and 386 adult inpatients without CDAD, selected from the period 1996 to 2000, was conducted. Information was collected on exposure to 3rd generation cephalosporin antibiotics during hospitalisation, as well as exposure to other antibiotics and medications, procedures, and comorbidities. Results from conditional logistic regression analyses found CDAD cases were six times more likely to be exposed to 3rd generation cephalosporins during their admission, prior to the onset of diarrhoea, than controls (adjusted odds ratio [OR] = 6.17, 95% confidence interval [CI] = 1.56-24.37). Approximately one third of CDAD in the study population could be attributed to 3rd generation cephalosporins. CDAD cases were also four times more likely to have been exposed to either amoxicillin-clavulanate or ticarcillin-clavulanate (adjusted OR=4.23, 95% CI=1.81-9.93). In October 1998, an antibiotic policy was introduced at SCGH that restricted the use of ceftriaxone, the 3rd generation cephalosporin most commonly used by the hospital. During 1999 and 2000, the incidence of CDAD halved as ceftriaxone consumption fell in response to this policy. The effect of this policy was demonstrated in the time series model; during the post-policy period the relationship between ceftriaxone and CDAD that was evident prior to the policy was cancelled out. From the individual-level data, obtained from the case-control study, a reduction in the prevalence of exposure to 3rd generation cephalosporins from 11% to 1% accounted for a 30% reduction in the incidence of CDAD. Data from the case-control study was also used to analyse the independent contribution of CDAD to length of stay and admission costs using multiple linear regression

Orientador: Samir Issa Samara / Banca: Maria da Gloria Buzinaro / Banca: Fumio Honma Ito / Resumo: O presente trabalho teve como objetivo verificar a variação da ocorrência da Rinotraqueíte Infecciosa Bovina (IBR) pela associação com duas doenças virais imunossupressoras: a Diarréia Viral Bovina (BVD) e a Leucose Enzoótica Bovina (LEB), em seis propriedades onde não se adota esquema de vacinação contra essas enfermidades. Amostras de soro sangüíneo foram analisadas no teste de virusneutralização (VN), para constatação de IBR e BVD, e Imunodifusão em Gel de Ágar (IDGA), para a LEB. Foram selecionados cinco rebanhos bovinos, em propriedades localizadas em municípios dos Estados de São Paulo e Minas Gerais, sendo três de exploração leiteira, um de gado de corte e um misto, com animais soropositivos ao BoHV-1, além de um rebanho controle, sem anticorpos contra essa enfermidade. Das 278 amostras analisadas, 54,68% (152/278) foram positivas ao BoHV-1, 69,70% (194/278) ao BVDV-1 e 34,33% (96/278) ao VLEB. Na análise estatística, ao relacionar cada enfermidade com o tipo de exploração do rebanho e a idade dos animais, houve diferença significativa, indicando que estas variáveis são fatores de risco para as enfermidades estudadas. Em relação ao tipo de exploração, os rebanhos leiteiros foram mais suscetíveis ao BoHV-1 e a LEB (81,31% e 49,53% respectivamente, (α = 1 ) enquanto no rebanho de gado de corte o BVDV-1 teve maior ocorrência (94,74%, α = 1). A idade foi fator de risco apenas para o BoHV-1 e a LEB, sendo os animais mais velhos os mais suscetíveis (α = 1). As associações entre o BoHV-1 e o BVDV-1, e o BoHV-1 e a LEB também foram significativas (α = 5 e α = 1 respectivamente), indicando que em rebanhos infectados por BVDV-1 e/ou LEB, a probabilidade de se encontrar o BoHV-1 é maior do que naqueles onde não ocorre essas duas enfermidades. / Abstract: The present research had as objective to verify the variation of the occurrence of Infectious Bovine Rhinotracheitis (IBR) by association with two viral infections that affect the immune system, Bovine Viral Diarrhoea (BVD) and enzootic bovine leukosis (EBL), in six farms where vaccination against these diseases was not adopted. Serum samples had been analyzed by the virus neutralization (VN) test for IBR and BVD diagnosis, and agar gel immunodiffusion (IDGA) test for EBL diagnosis. Five cattle herds with BoHV-1 seropositive animals had been selected in the states of São Paulo and Minas Gerais, three of them exploiting dairy cattle, one exploiting beef cattle and one exploiting mixed cattle, in addition to a control herd without seropositive animals. From 278 analyzed samples, 54.68% (152/278) reacted to the BoHV-1, 69.70% (194/278) to the BVDV-1, and 34.33% (97/278) to the EBLV. The statistic analysis showed a significant difference (α = 1) in infection occurrence according to the kind of exploitation and the age of the animals. Dairy cattle were more sensitive to the BoHV-1 (81.31%) and to the EBLV (49.53%) and less to BVDV-1 infection (45.79%). Among the beef herds, the major occurrence was BVDV-1 infection (94.74%), followed by BoHV-1(34.19%) and EBLV (3.95%). The age was a risk factor (α = 1) only for BoHV-1 and EBLV. The associations between BoHV-1 and BVDV-1 infections (α = 5) and between BoHV-1 and EBLV infections (α = 1) also indicated that among BVDV-1 and/or EBLV infected herds the probability of finding BoHV-1 is higher than among herds where these two infections does not occur. / Mestre

Made available in DSpace on 2014-12-17T14:13:26Z (GMT). No. of bitstreams: 1 IonGMA.pdf: 3523435 bytes, checksum: 77c15e2c31b84a1cc840056d94a495b9 (MD5) Previous issue date: 2008-08-20 / There was a significant decline in hospitalizations for acute diarrhea in children younger than 1 year of age in Brazil between 1992 to 2001. The less economically developed state of Rio Grande do Norte is a case example of the national trend. In this work, we show a significant association between improvements in socioeconomic variables as well as increased access to sanitation and the decreased rate of hospitalization. Additionally, we observed a positive, seasonal correlation between rainfall and hospitalizations. Most notably, however, we show that improvements in income and inflation were positively correlated with a decline in hospitalizations. Improvements in public health infrastructure, socioeconomic variables like education and literacy, and increased investment in health services were important in reducing severe early childhood diarrheas. However, the data suggests that increased buying power and reductions in poverty played an equally crucial role in reducing hospitalizations for acute diarrhea in infants in Brazil. The work includes elements of the demography of the period for the age groups involved, children under one year, women in fertile age and fertility rate / Entre 1992 e 2001 houve um decl?nio significativo dos internamentos por diarr?ia em lactentes no Brasil. O Rio Grande do Norte, um dos estados menos desenvolvidos do Brasil, ? exemplo desta tend?ncia nacional. Neste trabalho foi observada uma associa??o significante entre as melhorias das vari?veis socioecon?micas e de acesso ao saneamento, com o decl?nio das hospitaliza??es por diarr?ia. Adicionalmente foi encontrada uma correla??o sazonal positiva entre chuvas e internamentos por diarr?ia. Associa??o significante entre as vari?veis que monitoraram melhorias na renda e controle da infla??o com o decl?nio dos internamentos por diarr?ia foi tamb?m observada para o per?odo de estudo. Melhorias na infra-estrutura, educa??o, alfabetiza??o e aumento dos investimentos nos servi?os de sa?de foram importantes na redu??o da morbidade das doen?as prevalentes na inf?ncia. Os dados indicam tamb?m que a estabilidade do poder de compra e redu??es dos n?veis de pobreza desempenharam papel igualmente crucial na redu??o dos internamentos por diarr?ia aguda em lactentes no Brasil

Ce mémoire contribue à identifier les facteurs associés à l’occurrence de la diarrhée chez les enfants de moins de cinq ans en Haïti. Après une revue de la littérature sur les déterminants de la diarrhée infanto-juvénile dans les pays en développement, nommément Haïti, nous tirons profit de la mise en commun de quatre bases de données des Enquêtes démographiques et de santé pour nos analyses quantitatives (n = 14 481). Notre étude s’intéresse notamment à l’impact de l’eau potable améliorée, des toilettes améliorées et du réfrigérateur sur la diarrhée infanto-juvénile. Nous déterminons la robustesse des associations entre ces commodités et l’occurrence de la diarrhée par des modèles de régression logistique. La commodité la plus commune est l’eau potable améliorée (58%). La présence de plus d’une commodité est peu courante (17%). En moyenne, la prévalence de la diarrhée s’élève à 29%. L’eau potable améliorée et le réfrigérateur sont corrélés à une faible occurrence de la diarrhée chez les 24-59 mois et les toilettes améliorées à une faible occurrence chez les 1-5 et 12-23 mois. Les enfants de famille ne possédant qu’une commodité ne sont pas statistiquement différents des plus défavorisés, sauf chez les 24-59 mois. Enfin, nous ne trouvons pas de liens significatifs entre les commodités et la diarrhée chez les 6-11 mois. Nos résultats sont inédits pour Haïti, et soulignent, comme piste d’intervention en prévention de la diarrhée, la nécessité d’augmenter le nombre des commodités familiales, particulièrement les toilettes améliorées privées, qui limiteraient la contamination de l’eau et des aliments. / This master’s thesis contributes to the identification of factors linked to the occurrence of diarrhoea among children under five years of age in Haiti. Following a review of the literature on predictors of childhood diarrhoea in low-income countries, namely Haiti, we take advantage of four databases from Demographic and Health Surveys (n = 14 481) to conduct our quantitative analyses. Our study is concerned mainly with the impact of improved drinking water, improved sanitations and refrigerator on childhood diarrhoea. We use logistic regression models to assess the robustness of the associations between selected factors and the occurrence of diarrhoea among children under five years of age. The most common commodity was improved drinking water (58%). The presence of more than one commodity was infrequent (17%). On average, diarrhoea prevalence was 29%. The improved drinking water and the ownership of a refrigerator were associated with a decreased occurrence of diarrhoea for children aged 24-59 months. The improved sanitation was related to a decreased in the occurrence of diarrhea for children 1-5 and 12-23 months. Children whose family owned only one commodity were not statistically different from the most disadvantaged children, except for children 24-59 months. Lastly, there was no significant link between any commodity and diarrhoea for children 6-11 months. In the context of Haiti, these new findings highlight, as an intervention path in the prevention of childhood diarrhoea, the importance of increasing the number of commodities within families, and, more specifically, improving sanitations which may help reduce the contamination of water and food.

MSc (Microbiology) / Department of Microbiology / BACKGROUND: Human norovirus (NoV) is the etiological agent associated with acute gastroenteritis (AGE) in both children and adults worldwide. Children of <5 years of age, the elderly and individuals suffering from chronic diseases are potentially at high risk of NoV-associated illness. High morbidity and mortality rate associated with NoV have been reported worldwide. In children under the age of 5 years about 1.8 million death cases have been reported in developing countries alone. Despite the fact that the virus is affecting people of all age groups, there is lack of data to elucidate the importance and the role of NoV in children of the age above 5 years and adults. OBJECTIVE: To characterize human norovirus in patients with diarrhoea in rural communities of Vhembe district, Limpopo province. MATERIALS AND METHODS : From August 2017 to October 2018, outpatient between 5 and 68 years of age from rural communities of Vhembe district, Limpopo province were recruited for this study. A total of n=80 stool samples were collected from patients with diarrhoea and were kept at 4˚C throughout the transportation to the laboratory and refrigerated at - 20˚C prior to RNA extraction. Stool samples were tested for norovirus using the RIDA©GENE NOROVIRUS I & II real-time RT-PCR. The RNA extracts tested positive for norovirus were subjected to RT-PCR amplification. The RT-PCR products of the amplified fragments were sequenced, and phylogenetic trees were constructed by the neighbor-joining method using MEGA 7 software. RESULTS: NoV was detected in 13(16%) out of 80 stool samples collected, of which 6 (46%) strains belonged to norovirus GII and 7 (54%) strains to norovirus GI. A total of 5 genotypes were detected (GII.Pg, GII.1, GII.2, GII.4 Sydney 2012). The phylogenetic analysis revealed circulation of NoV genotypes with considerable diversity. CONCLUSION: This study illustrates NoV prevalence and substantial genetic diversity in patients above 5 years of age living in rural communities of Vhembe district, Limpopo province. Continued systematic surveillance to evaluate norovirus association with diarrhoea is needed to have a full picture on the epidemiology and disease burden in people of all the age groups. / NRF

PhD (Microbiology) / Department of Microbiology / Diarrhoea is still a major problem worldwide. Enteric pathogens such as Enteroaggregative E. coli (EAEC), Enteropathogenic E. coli (EPEC) and Enterotoxigenic E. coli (ETEC) have been reported to cause diarrhoea in children under the age of 5 years. The incidences of these pathogens are due to factors such as poor water quality, sanitation and hygiene practices. Infections with these pathogens result in diarrhoea and have been reported to result in severe disease outcomes more especially in children under 2 years of age. EPEC infections have been well studied using in vitro analyses, with studies highlighting the adherence traits, proteins and virulence genes involved in pathogenesis and inflammatory responses. EPEC is characterized by localized adherence with microcolony formation at the site of infection. In vivo studies have reported on human EPEC infection. However, the current animal models have not been able to replicate clinical outcomes (such as diarrhoea and weigh loss) of EPEC infection similar to humans. Therefore, there is still a need for a suitable small animal model that mimic clinical outcomes of human EPEC infections in vivo. Children living in poor environmental conditions are more susceptible to diarrhoeal pathogens. Furthermore, the incidences of children being exposed to co-infections (more than one pathogen at the same time) is relatively high. The EAEC/EPEC (A/P) and EPEC/ETEC (P/T) co-infections have been increasingly detected in children with and without diarrhoea. It has been suggested that patients infected with these co-infections might result in severe disease outcome than those infected with single pathogens. Pathogens are constantly evolving and the microbe-microbe interaction in the host can result in these pathogens competing for the same niche and thus result in increased virulence. Interaction of co-infections can lead to increased inflammatory responses thus affecting the infected host. The first objective of this study was to develop an EPEC murine model using weaned C57BL/6 mice that have been pretreated with antibiotic cocktail. Mice were orally infected with wild-type (WT) typical EPEC, bfp- and escN mutant strains. The WT had transient weight loss and wet stools with mucous; and the bfp- infected mice also had transient weight loss and bloody stool appearance. Increase in inflammatory biomarkers MPO, LCN-2, CRP, IL-6 and SAA were observed in the WT and bfp- infected mice. The mice infected with escN mutant did not exhibit any weight changes and the stools were similar to the uninfected mice. Furthermore, no inflammatory biomarkers were observed in mice infected with the escN mutant. Metabolic perturbations were observed in WT EPEC infected mice at day 3 post infection with the TCA cycle metabolites (reduced succinate, citrate, fumarate, cis-aconitate) being excreted at lower quantities indicating that the energy production in the infected mice was greatly affected. The second objective of this study was to determine the interaction between the P/T coinfections using in vitro and in vivo analyses. In vitro, human colorectal tumour 8 (HCT-8) cells were infected with single strains of ETEC, EPEC and both the pathogens and incubated for 3 hours. After infection the cells were analysed for bacterial adherence using real-time PCR. The single strains adhered at the same rate similar to the P/T coinfected cells. IL-8, as a marker of inflammatory response, was measured using ELISA. The results indicated that the P/T co-infected cells had a significant increase in IL-8 response higher than the single infections. The P/T co-infections were further analysed in vivo using the EPEC murine model developed in this study. Interestingly, mice infected with P/T co-infections developed severe diarrhoea accompanied with significant increased weight loss and some mice died during the 3-day infection period. The inflammatory responses MPO, LCN-2 and SAA were higher in the co-infected mice indicating a synergistic effect. The bfp and eltA virulence genes were significantly increased in the P/T co-infections. The third objective of this study was to determine the interaction between A/P coinfections using in vitro and in vivo analyses. HeLa cells and HCT-8 cells were infected with EAEC, EPEC and both the pathogens at the same time in order to determine adherence and inflammatory responses. EAEC adherence was higher than EPEC and A/P co-infections adherence. A/P co-infections did not have increased IL-8 response in HCT-8 cells when compared to EAEC alone. The virulence genes involved in EPEC adherence and Type 3 Secretion System (bfp, eae, tir, ler, per, espB and espA) were significantly reduced in A/P co-infected cells. An interesting adherence trait was observed between the A/P co-infections in HeLA cells, EAEC was found to adhere around EPEC altering the localized adherence pattern. The A/P co-infections were further analysed using the EPEC murine model developed in this study. The A/P infected mice had diminished weight changes and EAEC shedding was enhanced when EPEC was present. Faecal inflammatory biomarkers MPO and LCN-2 in A/P infected mice did not have any additive effect. The findings of this study contributed significantly to the knowledge of human EPEC infection in weaned C57BL/6 mice, highlighting clinical outcomes, inflammatory responses and metabolic perturbations. Furthermore, this study also highlighted the interaction of P/T and A/P co-infections using in vitro and in vivo analyses in order to determine the disease severity and outcomes. It was observed in this study that coinfections can result in either synergistic or antagonistic effects. Further studies are therefore, required in order to understand the underlying mechanisms that are involved during co-infections and this can further assist in the development of therapeutic interventions. / NRF